Gastritis and Gastropathies Gastritis and Gastropathies
Transcript of Gastritis and Gastropathies Gastritis and Gastropathies
1
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
2
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
3
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
4
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
5
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
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 –– H. pyloriH. pylori
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
6
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
7
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
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 –– H. pyloriH. pylori
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
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
8
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
9
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
10
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
11
••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.
12
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
Eosinophilic (Eosinophilic (““AllergicAllergic””) ) Esophagitis in AdultsEsophagitis in Adults
•• 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
13
Eosinophilic (Eosinophilic (““AllergicAllergic””) ) Esophagitis in AdultsEsophagitis in Adults
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
14
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
15
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
•
Indefinite for dysplasiaIndefinite for dysplasia
Positive Positive –– low grade dysplasialow grade dysplasia
Positive Positive –– high grade dysplasiahigh grade dysplasia
16
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
17
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.