Gastritis and Gastropathies Gastritis and Gastropathies

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Pathology and Imaging of the Pathology and Imaging of the Esophagus and StomachEsophagus and Stomach

Robert E. Petras, M.D., FCAP, FACGRobert E. Petras, M.D., FCAP, FACG

National Director GI Pathology ServicesNational Director GI Pathology Services

AmeriPath Inc.AmeriPath Inc.

Associate Clinical Professor of PathologyAssociate Clinical Professor of Pathology

Northeastern Ohio Universities College of MedicineNortheastern Ohio Universities College of Medicine

Robert E. Petras, M.D.Robert E. Petras, M.D.DisclosuresDisclosures

Salaried employee of AmeriPath Inc.Salaried employee of AmeriPath Inc.

Wholly owned subsidiary of Quest Wholly owned subsidiary of Quest Diagnostics Inc.Diagnostics Inc.

Stock holder Stock holder –– Quest Diagnostics Inc.Quest Diagnostics Inc.

Advisory Board Advisory Board –– Genomic Health Inc.Genomic Health Inc.

Research collaborator Research collaborator –– CSA Medical Inc.CSA Medical Inc.

Pathology and Imaging of the Pathology and Imaging of the Esophagus and StomachEsophagus and Stomach

Gastritis Gastritis –– a pragmatic approacha pragmatic approach

Gastric carcinoids & microcarcinoidosisGastric carcinoids & microcarcinoidosis

Gastrointestinal stromal tumorsGastrointestinal stromal tumors

Gastroesophageal reflux and Gastroesophageal reflux and eosinophilic esophagitiseosinophilic esophagitis

BarrettBarrett’’s esophagus and dysplasias esophagus and dysplasia

Gastritis and GastropathiesGastritis and Gastropathies

Definitions varyDefinitions vary

Symptoms, endoscopic appearance, Symptoms, endoscopic appearance, histologyhistology

Poor correlation between histologic gastritis Poor correlation between histologic gastritis and symptoms (epigastric pain, nausea, and symptoms (epigastric pain, nausea, vomiting, bleeding)vomiting, bleeding)

Poor correlation between histologic gastritis Poor correlation between histologic gastritis and endoscopyand endoscopy

Gastritis and GastropathiesGastritis and Gastropathies

No uniformly accepted classification schemeNo uniformly accepted classification scheme

The Sydney System and updates cumbersomeThe Sydney System and updates cumbersome

Five biopsy specimens from three labeled sites Five biopsy specimens from three labeled sites recommendedrecommended

Five histologic features assessed on a 4 grade Five histologic features assessed on a 4 grade scalescale

Eight nonEight non--graded histologic variables graded histologic variables

1862 combinations 1862 combinations

Histologic GastritisHistologic GastritisPattern ApproachPattern Approach

Erosive gastritis/reactive gastropathyErosive gastritis/reactive gastropathy

““ChemicalChemical”” gastritisgastritis

Chronic antral gastritis Chronic antral gastritis –– H. pyloriH. pylori

Chronic superficial gastritis Chronic superficial gastritis ––

Chronic superficial and deep gastritisChronic superficial and deep gastritis

MAG, autoimmune, autoimmune pangastritisMAG, autoimmune, autoimmune pangastritis

Gastric carditis Gastric carditis -- refluxreflux

Special typesSpecial types

Lymphocytic, collagenous, granulomatous, Lymphocytic, collagenous, granulomatous, eosinophiliceosinophilic

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Helicobacter pyloriHelicobacter pyloriIsolation and IdentificationIsolation and Identification

Selective media Selective media –– microaerophilicmicroaerophilic

Slow growth Slow growth –– 3 to 6 days3 to 6 days

Gram negative spiral bacillusGram negative spiral bacillus

Oxidase + Catalase +Oxidase + Catalase +

Urease + Indole Urease + Indole --

Does not reduce nitrates to nitritesDoes not reduce nitrates to nitrites

Hippurate hydrolysis Hippurate hydrolysis -- negativenegative

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Helicobacter pyloriHelicobacter pyloriDiagnosisDiagnosis

Invasive techniques Invasive techniques –– gastric specimen gastric specimen required.required.

CultureCultureHistologyHistologyUrease testUrease test

Noninvasive techniquesNoninvasive techniquesSerologySerology1313CC -- breath testbreath test1414CC –– breath test*breath test*Stool antigenStool antigen

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Helicobacter pyloriHelicobacter pyloriACG GuidelinesACG Guidelines for Treatmentfor Treatment

ClarithromycinClarithromycin--based triple therapy 14 daybased triple therapy 14 day

PPI bid, Amoxicillin 1000 mg bid or PPI bid, Amoxicillin 1000 mg bid or Metronidazole 500 mg bid and Metronidazole 500 mg bid and Clarithromycin 500 mg bidClarithromycin 500 mg bid

Bismuth quadruple therapy 10Bismuth quadruple therapy 10--14 day14 day

PPI bid or HPPI bid or H22RA, Bismuth 2 tabs qid, RA, Bismuth 2 tabs qid, Metronidazole 250 mg tid, Tetracycline Metronidazole 250 mg tid, Tetracycline 500 mg qid500 mg qid

Chey WD and Wong BCY. Chey WD and Wong BCY. Am J GastroenterolAm J Gastroenterol 102:1808, 2007102:1808, 2007

Gastric SpirocheteGastric Spirochete--Like OrganismsLike Organisms

•• Prevalence range from 0.1% Prevalence range from 0.1% (Italy) to 6.2% (Thailand)(Italy) to 6.2% (Thailand)

Mild chronic active gastritisMild chronic active gastritis

Duodenal ulcer, gastric Duodenal ulcer, gastric carcinoma and MALT carcinoma and MALT lymphoma have been observedlymphoma have been observed

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Gastric SpirocheteGastric Spirochete--Like OrganismsLike Organisms

Nomenclature:Nomenclature:? true spirochete (order Spirochaetales)? true spirochete (order Spirochaetales)

? ? Spirilla rappiniSpirilla rappini (order Pseudomondales)(order Pseudomondales)

Gastrospirillum hominisGastrospirillum hominis

Helicobacter heilmanniiHelicobacter heilmannii

Reservoir:Reservoir: Domestic animalsDomestic animals

Association with disease:Association with disease: Human gastritisHuman gastritis

Treatment:Treatment: Lansoprazole (30 mg/day), amoxicillin Lansoprazole (30 mg/day), amoxicillin (750 mg/day), clarithromycin (750 mg/day), clarithromycin (400 mg/day) for 1 week(400 mg/day) for 1 week

Helicobacter pyloriHelicobacter pyloriDisclaimerDisclaimer

Suggestive morphology but no organisms Suggestive morphology but no organisms on special stain on special stain ++ immunostainimmunostain

-- Prior antibiotic exposurePrior antibiotic exposure

Migration of Migration of H. pyloriH. pyloripresence of proton pump inhibitorspresence of proton pump inhibitors

Acute Erosive Gastritis/Reactive Acute Erosive Gastritis/Reactive GastropathyGastropathy

A.K.A. A.K.A. –– Chemical gastritisChemical gastritis

Associations:Associations:

Post gastrectomy/bile Post gastrectomy/bile refluxreflux

SteroidsSteroids

NSAIDsNSAIDs

AlcoholAlcohol

Stress ulcersStress ulcers





Chronic superficial gastritis Chronic superficial gastritis –– H. pyloriH. pylori






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Atrophic Gastritis and ECLAtrophic Gastritis and ECL--Cell Cell Hyperplasia/CarcinoidHyperplasia/Carcinoid

Treatment OptionsTreatment Options

•• Endoscopic resection and Endoscopic resection and surveillancesurveillance

Subtotal gastrectomySubtotal gastrectomy

SST analoguesSST analogues

AntrectomyAntrectomy

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Atrophic Autoimmune PangastritisAtrophic Autoimmune PangastritisJevremovic D, et al. Jevremovic D, et al. Am J Surg PatholAm J Surg Pathol 30:1412, 200630:1412, 2006

Eight patients reported Eight patients reported –– 3 mo to 75 years3 mo to 75 yearsInflammation with atrophy of body and antrum Inflammation with atrophy of body and antrum with decreased neuroendocrine cells, apoptosis, with decreased neuroendocrine cells, apoptosis, lymphocytic gastritislymphocytic gastritisAbsence of hypergastrinemia and antiAbsence of hypergastrinemia and anti--parietal cell parietal cell and antiand anti--intrinsic factor antibodiesintrinsic factor antibodiesFour with autoimmune enterocolitis; SLE, Four with autoimmune enterocolitis; SLE, refractory sprue, fibromyalgia, hemolytic anemia refractory sprue, fibromyalgia, hemolytic anemia (one each)(one each)Improvement reported after treatment with Improvement reported after treatment with prednisone +/prednisone +/-- azathioprineazathioprine





Chronic superficial gastritis Chronic superficial gastritis –– H. pyloriH. pylori






Lymphocytic GastritisLymphocytic GastritisClinical AssociationsClinical Associations

Past or present Past or present H. pyloriH. pyloriinfectioninfection

Celiac sprueCeliac sprue

Lymphocytic colitisLymphocytic colitis

MenetrierMenetrier’’s diseases disease--like like protein losing gastropathyprotein losing gastropathy

Varioliform (Varioliform (““octopus octopus suckersucker””) gastritis) gastritis

CD3CD3

Collagenous GastritisCollagenous GastritisClinical SubsetsClinical Subsets

Children:Children:AnemiaAnemiaNodules on endoscopyNodules on endoscopyDisease limited Disease limited to the stomachto the stomach

Adults:Adults:Associated collagenous Associated collagenous colitis (colitis (++ ““celiac sprue/collagenous sprueceliac sprue/collagenous sprue””) )

presenting with chronic watery diarrheapresenting with chronic watery diarrheaLagorceLagorce--Pages C, et al. Pages C, et al. Am J Surg PatholAm J Surg Pathol 25:1174, 200125:1174, 2001

Granulomatous GastritisGranulomatous Gastritis

Infection (e.g., tuberculosis, Infection (e.g., tuberculosis, ??H. pyloriH. pylori))

CrohnCrohn’’s diseases disease

SarcoidosisSarcoidosis

Foreign body giant cell Foreign body giant cell reaction (reaction (““cerealcereal”” granuloma, granuloma, mucin granuloma)mucin granuloma)

Reaction to neoplasiaReaction to neoplasia

Idiopathic granulomatous Idiopathic granulomatous gastritisgastritis

Eosinophilic GastritisEosinophilic Gastritis

Eosinophils in large Eosinophils in large numbers within the mucosanumbers within the mucosaChildren and adolescentsChildren and adolescentsSymptoms: abdominal pain, Symptoms: abdominal pain, nausea, vomiting, diarrhea, nausea, vomiting, diarrhea, anemia, proteinanemia, protein--losing losing gastroenteropathygastroenteropathySometimes linked to food Sometimes linked to food allergiesallergiesTreatment: dietary therapy, Treatment: dietary therapy, corticosteroids, mast cell corticosteroids, mast cell stabilizers, antihistaminesstabilizers, antihistamines

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Gastrointestinal Stromal TumorsGastrointestinal Stromal TumorsEvolution of ThoughtEvolution of Thought

19301930’’s to 1980s to 1980’’s s -- tumors thought to be of smooth tumors thought to be of smooth muscle origin despite:muscle origin despite:

Ultrastructure only rarely showing smooth Ultrastructure only rarely showing smooth muscle differentiationmuscle differentiation

EM and immunohistochemistry occasionally EM and immunohistochemistry occasionally showing Neural/Schwann cell differentiation.showing Neural/Schwann cell differentiation.

1983 1983 –– Mazur and Clark introduce the term Mazur and Clark introduce the term stromal tumors.stromal tumors.

1990 to present 1990 to present -- cc--Kit, CD117.Kit, CD117.

Gastrointestinal Stromal TumorsGastrointestinal Stromal TumorsEvolution of ThoughtEvolution of Thought

•• GISTs express cGISTs express c--Kit as demonstrated by Kit as demonstrated by CD117 and CD34 immunostaining.CD117 and CD34 immunostaining.Interstitial cells of Cajal express CD117 Interstitial cells of Cajal express CD117 and CD34and CD34ICCs related to both smooth muscle and ICCs related to both smooth muscle and nerve.nerve.Explanation for historical observation.Explanation for historical observation.

GISTGIST

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Epithelioid Epithelioid GISTGIST

Gastrointestinal Stromal TumorsGastrointestinal Stromal TumorsObservations on Biologic BehaviorObservations on Biologic Behavior

Obviously malignantObviously malignant

Concurrent metastasisConcurrent metastasis

High cellularity, high mitosis rate, High cellularity, high mitosis rate, large sizelarge size

Probably benign Probably benign

Small tumors, low cellularitySmall tumors, low cellularity

Low mitosis rateLow mitosis rate

Indeterminate biologic behaviorIndeterminate biologic behavior

Defining Risk Groups in Defining Risk Groups in Gastrointestinal Stromal TumorsGastrointestinal Stromal Tumors

Consensus ApproachConsensus ApproachRelative RiskRelative Risk SizeSize Mitotic CountMitotic Count

Very low Very low < 2 cm < 5/50< 2 cm < 5/50

Low Low 22--5 cm5 cm < 5/50< 5/50

Intermediate Intermediate < 5 cm < 5 cm 66--10/50 10/50 55--10 cm < 5/5010 cm < 5/50

HighHigh > 5 cm > 5/50> 5 cm > 5/50

> 10 cm > 10 cm Any Any

Any size Any size > 10/50> 10/50Fletcher CDM, et al. Fletcher CDM, et al. Hum PatholHum Pathol 33:459, 2002.33:459, 2002.

Gastrointestinal Stromal TumorsGastrointestinal Stromal Tumorsof the Stomachof the Stomach

Prognosis by Risk GroupPrognosis by Risk Group

Risk groupRisk group Adverse outcome*Adverse outcome*

Very lowVery low 0%0%LowLow 1.8%1.8%IntermediateIntermediate 7.3%7.3%HighHigh 45.9%45.9%

*Reports 1068 patients having follow*Reports 1068 patients having follow--up of approximately up of approximately 15 years.15 years.

Modified from Miettinen M, et al. Modified from Miettinen M, et al. 29:52, 200529:52, 2005

Imatinib MesylateImatinib MesylateSynonymsSynonyms

•• STI 571STI 571

GlivecGlivec

GleevecGleevec

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Imatinib MesylateImatinib MesylateInhibitor of specific tyrosine kinasesInhibitor of specific tyrosine kinases

Targeted to PDGFrTargeted to PDGFr

Found to inhibit BCRFound to inhibit BCR--ABL fusion ABL fusion product of CMLproduct of CML

Inhibitor of cInhibitor of c--Kit in GISTsKit in GISTs

Shown to be effective in treatment of Shown to be effective in treatment of CML and metastatic GISTsCML and metastatic GISTs

FDA approval 2002 FDA approval 2002

CD117CD117

Gastrointestinal Stromal TumorsPathologic Diagnosis

• Must be considered for all spindle cell/mesenchymal tumors involving gut wall, mesentery, omentum

• Immunohistochemical panel – CD117, CD34, SMA, desmin, cytokeratin, S100, Melan A

• 96%+ overexpress c-Kit (CD117, CD34)Activating mutations in KIT genes/imitanib response – exons 11 (65%/80%), 9 (20%/50%), 13 & 17 (< 5% each/response rare)PDGFRA mutations (exons 12, 14 & 18*) in wild-type KIT

Imatinib Mesylate Imatinib Mesylate ResistanceResistance

Gentically develop multiple new mutations Gentically develop multiple new mutations in KIT and/or PDGFRAin KIT and/or PDGFRASunitinib considered standard therapy for Sunitinib considered standard therapy for Imatinib Mesylate resistanceImatinib Mesylate resistance

Other drugs may have activity (e.g., Other drugs may have activity (e.g., Hsp90 inhibitors, Sorafenib, Nilotinib)Hsp90 inhibitors, Sorafenib, Nilotinib)

Should combinations be given initially?Should combinations be given initially?Should high risk GISTs receive adjuvant Should high risk GISTs receive adjuvant therapy?therapy?

Inflammatory Fibroid PolypInflammatory Fibroid PolypUsually solitaryUsually solitaryMyxoid fibrous tissue; Myxoid fibrous tissue; layered in whorllayered in whorl--like like fashion around blood fashion around blood vesselsvesselsRich in plasma cells Rich in plasma cells and eosinophilsand eosinophilsCD34 positive; CD117 CD34 positive; CD117 negativenegativePDGFRA mutations PDGFRA mutations (Schildhaus (Schildhaus J PatholJ Pathol216:176,2008)216:176,2008)

Gastroesophageal RefluxGastroesophageal RefluxEndoscopic ChangesEndoscopic Changes

•• Normal appearanceNormal appearance

HyperemiaHyperemia

ErosionErosion

UlcersUlcers

StrictureStricture

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••PapillomatosisPapillomatosis

••Basal Cell HyperplasiaBasal Cell Hyperplasia

Reflux EsophagitisReflux EsophagitisDifferential DiagnosisDifferential Diagnosis

•• Infectious esophagitisInfectious esophagitis

-- HSV, CMV, Candida speciesHSV, CMV, Candida species

““PillPill”” esophagitisesophagitis

Allergic esophagitis Allergic esophagitis

Squamous dysplasia/carcinomaSquamous dysplasia/carcinoma

Allergic Esophagitis in Allergic Esophagitis in ChildrenChildren

Dysphagia or Dysphagia or ““Food catchingFood catching””Allergic historyAllergic historyNormal or borderline pH probe Normal or borderline pH probe studiesstudiesLarge numbers of intraepithelial Large numbers of intraepithelial eosinophils in esophageal biopsy eosinophils in esophageal biopsy specimensspecimens

Allergic Esophagitis in ChildrenAllergic Esophagitis in ChildrenGroup A Group A –– 12 patients12 patients

-- No response to acid suppressionNo response to acid suppression

-- Normal pH probe studyNormal pH probe study

Group B Group B –– 10 patients10 patients

-- No response to acid suppressionNo response to acid suppression

-- No data or borderline pH studyNo data or borderline pH study

Group C Group C –– 13 patients13 patients

-- Improved with acid suppressionImproved with acid suppression

-- Abnormal pH probe studyAbnormal pH probe studyWalsh SV, et al. Walsh SV, et al. Am J Surg PathAm J Surg Path 23:390, 199923:390, 1999

Allergic Esophagitis in ChildrenAllergic Esophagitis in Children

Group A & BGroup A & B Group CGroup C(22 patients)(22 patients) (13 patients)(13 patients)

DysphagiaDysphagia 1111 22““Food catchingFood catching”” 1313 00Allergic HistoryAllergic History 2121 44Eosin/HPFEosin/HPF 2424 22Eosin AggregateEosin Aggregate 77 00Superficial EosinSuperficial Eosin 1010 00

Walsh SV, et al. Walsh SV, et al. Am J Surg PathAm J Surg Path 23:390, 1999.23:390, 1999.

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Eosinophilic (Eosinophilic (““AllergicAllergic””) ) Esophagitis in AdultsEsophagitis in Adults

Predominantly affects men (3:1)Predominantly affects men (3:1)Onset ages 20Onset ages 20--4040Acute or recurrent dysphagia, Acute or recurrent dysphagia, rarely pyrosisrarely pyrosisImpaction of solid foodsImpaction of solid foodsHistory of atopyHistory of atopy


•• Endoscopy Endoscopy –– rings, corrogated appearance, rings, corrogated appearance, vertical erosions, white plaques/vesicles, vertical erosions, white plaques/vesicles, proximal esophageal stricture, diffuse small proximal esophageal stricture, diffuse small caliber esophaguscaliber esophagus

•• Molecular/genetic Molecular/genetic –– OverOver--expression of expression of eotaxineotaxin--3; susceptibility locus 5q22 (TSLP)3; susceptibility locus 5q22 (TSLP)

Treatment Treatment –– elemental diets, corticosteroids, elemental diets, corticosteroids, fluticasone, mast cellfluticasone, mast cell stabilizers, anti ILstabilizers, anti IL--5, 5, anti ILanti IL--13, oral viscous budesonide13, oral viscous budesonide

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Endoscopy Endoscopy –– rings, corrogated appearance, rings, corrogated appearance, vertical erosions, white plaques/vesicles, vertical erosions, white plaques/vesicles, proximal esophageal stricture, diffuse small proximal esophageal stricture, diffuse small caliber esophaguscaliber esophagus

Molecular/genetic Molecular/genetic –– OverOver--expression of expression of eotaxineotaxin--3; susceptibility locus 5q22 (TSLP)3; susceptibility locus 5q22 (TSLP)

Treatment Treatment –– elemental diets, corticosteroids, elemental diets, corticosteroids, fluticasone, mast cellfluticasone, mast cell stabilizers, anti ILstabilizers, anti IL--5, 5, anti ILanti IL--13, oral viscous budesonide13, oral viscous budesonide

Eosinophilic Esophagitis in Eosinophilic Esophagitis in Children and AdultsChildren and Adults

Consensus Recommendations for DiagnosisConsensus Recommendations for Diagnosis

Symptoms of esophageal dysfunctionSymptoms of esophageal dysfunction

15 or more eosinophils in one high 15 or more eosinophils in one high magnification fieldmagnification field

No response to high dose (2 mg/kg/day) No response to high dose (2 mg/kg/day) PPIPPI

Normal distal esophageal pH Normal distal esophageal pH Furuta GT, et al. Furuta GT, et al. Gastroenterol Gastroenterol 2007;133:1342.2007;133:1342.

BarrettBarrett’’s Esophaguss EsophagusACG DefinitionACG Definition

A change in esophageal epithelium of any A change in esophageal epithelium of any lengthlengthRecognized at endoscopyRecognized at endoscopyConfirmed to contain intestinal Confirmed to contain intestinal metaplasiametaplasia

Wang KK & Sampliner RE. Wang KK & Sampliner RE. Am J GastroAm J Gastro 103:788, 2008103:788, 2008Sampliner RE. Sampliner RE. Am J GastroAm J Gastro 97:1888, 200297:1888, 2002Sampliner RE. Sampliner RE. Am J GastroAm J Gastro 93:1028, 199893:1028, 1998

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Alcian Blue/PASAlcian Blue/PAS

BarrettBarrett’’s Esophaguss EsophagusACG Practice GuidelinesACG Practice Guidelines

The recognition of intestinal The recognition of intestinal metaplasia on biopsy is increased by metaplasia on biopsy is increased by use of alcian blue stain.use of alcian blue stain.-- Decreases chance of missing goblet Decreases chance of missing goblet

cells.cells.-- Decreases chance of misinterpreting Decreases chance of misinterpreting

cells with cytoplasmic vacuoles as cells with cytoplasmic vacuoles as goblet cells.goblet cells.

Sampliner RE. Sampliner RE. 97:1888,200297:1888,2002

BarrettBarrett’’s Esophaguss EsophagusPathology ReportPathology Report

Classify type of epitheliumClassify type of epitheliumNote presence or absence of Note presence or absence of intestinal metaplasia (specialized intestinal metaplasia (specialized columnar epithelium)columnar epithelium)

BarrettBarrett’’s Associated Carcinoma: s Associated Carcinoma: Analysis of RiskAnalysis of Risk

Prospective StudiesProspective Studies

First AuthorFirst Author Yearly Incidence/10Yearly Incidence/1066 Increased RiskIncreased Risk

Robertson (1988)Robertson (1988) 17861786 350x350x

Hameeteman (1988)Hameeteman (1988) 19201920 125x125x

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BarrettBarrett’’s Esophaguss EsophagusACG RecommendationsACG Recommendations

Systematic biopsy is required to document Systematic biopsy is required to document intestinal metaplasia and to detect intestinal metaplasia and to detect dysplasia.dysplasia.

The grade of dysplasia determines The grade of dysplasia determines endoscopy interval.endoscopy interval.

An abnormal surface requires special An abnormal surface requires special sampling.sampling.

Sampliner RE. Sampliner RE. Am J GastroAm J Gastro 97:1888, 200297:1888, 2002

Dysplasia in BarrettDysplasia in Barrett’’s s EsophagusEsophagus

Unequivocal neoplastic changeUnequivocal neoplastic change

May not only be marker or May not only be marker or precursor of carcinoma, but may precursor of carcinoma, but may itself be malignant and associated itself be malignant and associated with direct invasionwith direct invasion

Dysplasia in BarrettDysplasia in Barrett’’s Esophaguss EsophagusProposed ClassificationProposed Classification

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Indefinite for dysplasiaIndefinite for dysplasia

Positive Positive –– low grade dysplasialow grade dysplasia

Positive Positive –– high grade dysplasiahigh grade dysplasia

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p53p53

p53p53

p53 Null p53 Null MutationMutation

Racemase Racemase (P504S)(P504S)

Dysplasia/Carcinoma in BarrettDysplasia/Carcinoma in Barrett’’s s EsophagusEsophagus

Ancillary testingAncillary testingDNA aneuploidy, racemase DNA aneuploidy, racemase OncogenesOncogenes-- Cyclin D1, TGFCyclin D1, TGFαα, EGFR, Ras, , EGFR, Ras, ββ--catenincatenin

Tumor suppressorsTumor suppressorsRb, p53, p16, APCRb, p53, p16, APC

AntiAnti--apoptosisapoptosisp53, COX2p53, COX2

AntiAnti--senescencesenescenceTelomeraseTelomerase

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BarrettBarrett’’s Esophaguss EsophagusACG Surveillance RecommendationsACG Surveillance Recommendations

Negative Negative -- Two negative EGDs in one yearTwo negative EGDs in one year–– EGD q3 yearsEGD q3 yearsLGD LGD –– Expert pathologist confirmation; repeat exam in 6 Expert pathologist confirmation; repeat exam in 6 mo; then q 1 year; mo; then q 1 year; HGD with mucosal irregularity HGD with mucosal irregularity –– EMREMRHGD HGD –– Repeat EGD with biopsy to rule out Repeat EGD with biopsy to rule out cancer/document HGD within 3 mo, expert pathologist cancer/document HGD within 3 mo, expert pathologist confirmation.confirmation.-- Intervention (ablation, photodynamic therapy, surgical Intervention (ablation, photodynamic therapy, surgical

resection) depending upon local expertise, patientresection) depending upon local expertise, patient’’s age, s age, comorbidities, patient preference. comorbidities, patient preference.

Wang KK and Sampliner RE. Wang KK and Sampliner RE. Am J GastroAm J Gastro

Definition of Barrett’s EsophagusThe British Are Coming!

A Plea for Sanity from One American

BSG rationale for not requiring intestinal metaplasia based on sampling error and not a rejection of concept

Research to establish adequate guidelines for number of samples over time requiredDoes antireflux treatment effect conversion to intestinal metaplasia?

Were studies establishing intestinal metaplasia as an important precursor to cancer flawed?Are studies linking non goblet cell mucosa to DNA abnormalities and cancer sound technically and in design?

BarrettBarrett’’s Esophaguss EsophagusSummarySummary

Definition Definition –– Endoscopic abnormality Endoscopic abnormality containing intestinal metaplasia.containing intestinal metaplasia.

Endoscopic surveillance interval Endoscopic surveillance interval determined by the degree of dysplasia.determined by the degree of dysplasia.

Dysplasia confirmed by an expert Dysplasia confirmed by an expert pathologist should prompt increased pathologist should prompt increased scrutiny or an intervention.scrutiny or an intervention.

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Gastritis and Gastropathies Gastritis and Gastropathies