GI Grand Rounds October 1, 2004 Yoshi Makino, M.D. USC Department of Internal Medicine.

GI Grand RoundsGI Grand RoundsOctober 1, 2004October 1, 2004

Yoshi Makino, M.D.Yoshi Makino, M.D.USC Department of Internal MedicineUSC Department of Internal Medicine

Case PresentationCase Presentation

Patient F.B. is a 64 year old African-Patient F.B. is a 64 year old African-American male, referred from an outside American male, referred from an outside M.D. for OB(+) stool and anemia. Patient M.D. for OB(+) stool and anemia. Patient was scheduled for colonoscopy based on was scheduled for colonoscopy based on the above indications.the above indications.PSH: nonePSH: nonePMH: PMH: – HTNHTN– hyperlipidemiahyperlipidemia

Case PresentationCase Presentation

SH:SH:– EtOH: EtOH: 1-2 beers/day, 1-2 beers/day,

6-pack on weekends x 40 years6-pack on weekends x 40 years– Tobacco: ¾ ppd x 40 yearsTobacco: ¾ ppd x 40 years– Drugs: Marijuana in youth; without h/o IVDADrugs: Marijuana in youth; without h/o IVDA

ROS:ROS:– Denies h/o BRBPR, melena, stool caliber Denies h/o BRBPR, melena, stool caliber

changes, nor weight loss. Without h/o GERD changes, nor weight loss. Without h/o GERD or other upper GI complaints.or other upper GI complaints.

Case PresentationCase Presentation

Allergies: NKDAAllergies: NKDAMedicationsMedications– Pravachol 40 mg PO dailyPravachol 40 mg PO daily– HCTZ 25 mg PO dailyHCTZ 25 mg PO daily– Atenolol/Chlorthalidone 50 mg / 25 mg PO dailyAtenolol/Chlorthalidone 50 mg / 25 mg PO daily– Quinapril 40 mg PO dailyQuinapril 40 mg PO daily– Norvasc 10 mg PO dailyNorvasc 10 mg PO daily– Cardura 2 mg PO dailyCardura 2 mg PO daily– EC ASA 81 mg PO dailyEC ASA 81 mg PO daily– Darvocet or Tylenol 500 mg prn pain/HADarvocet or Tylenol 500 mg prn pain/HA

LaboratoriesLaboratories

140 103 14

3.8 20 0.8785.3 278

13.0

39.1

MCVMCV 81.681.6 Alk PAlk P 129129 ASTAST 2929RDWRDW 17.617.6 TProtTProt 7.97.9 ALTALT 1818FerrFerr 191191 AlbAlb 4.34.3TIBCTIBC TBiliTBili 0.50.5FeFe 5555 DBiliDBili 0.10.1%Sat%Sat

ColonoscopyColonoscopy

Poor prepPoor prep

Anus: small IHAnus: small IH

Sigmoid: 2 cm flat polyp, s/p bxSigmoid: 2 cm flat polyp, s/p bx

Transverse colon: one diminutive polyp Transverse colon: one diminutive polyp and a 1.5 cm sessile polyp, s/p bxand a 1.5 cm sessile polyp, s/p bx

Ascending colon: multiple 2-9mm sessile Ascending colon: multiple 2-9mm sessile polyp, s/p bxpolyp, s/p bx

Biopsy ResultsBiopsy Results

8 of 11 polyps biopsied showed tubular 8 of 11 polyps biopsied showed tubular adenomaadenoma

Of these 8 polyps, 2 also showed areas of Of these 8 polyps, 2 also showed areas of focal increased glandular complexity and focal increased glandular complexity and high grade dysplasiahigh grade dysplasia

Colonoscopy ImagesColonoscopy Images

Colonoscopy ImagesColonoscopy Images

What Now?What Now?

Family HistoryFamily HistoryColon CA; Age 70’s

Colon CA; Age 68

Colon CA; dx age 46;Presently 66

1 adenomatous polyp@ age 42, now 46

“Bone” CA; Age 64

Unscreened

Attenuated FAPAttenuated FAP

ObjectivesObjectives

OverviewOverview

Clinical FeaturesClinical Features

DiagnosisDiagnosis

GeneticsGenetics

ManagementManagement

FAP OverviewFAP Overview

Familial colorectal cancers account for Familial colorectal cancers account for < 5% of all cases of colon cancer< 5% of all cases of colon cancer

Yangming et al. AJG 2002;97(7)1822-1827.Yangming et al. AJG 2002;97(7)1822-1827.

Familial Adenomatous Polyposis (FAP) was first Familial Adenomatous Polyposis (FAP) was first described by Lockhart-Mummery in 1925 as a described by Lockhart-Mummery in 1925 as a disease with clear dominant inheritancedisease with clear dominant inheritance

Adenomatous Polyposis Coli (APC: 5q21) gene Adenomatous Polyposis Coli (APC: 5q21) gene identified by Kinzer and Groden in 1991identified by Kinzer and Groden in 1991

Attenuated FAPAttenuated FAP

In 1990, Lynch et al described two families with In 1990, Lynch et al described two families with “right-sided colonic flat adenomas” with more “right-sided colonic flat adenomas” with more polyps than HNPCC but fewer than FAPpolyps than HNPCC but fewer than FAP

Lynch also observed later age of onset of colon Lynch also observed later age of onset of colon cancer, and a paucity of rectal adenomascancer, and a paucity of rectal adenomas

Lynch et al. Cancer. 1990 Sep 1;66(5):909-15.Lynch et al. Cancer. 1990 Sep 1;66(5):909-15.

Initially called “hereditary flat adenoma Initially called “hereditary flat adenoma syndrome”, later called attenuated FAPsyndrome”, later called attenuated FAP

Clinical FeaturesClinical Features

Less than 100 adenomas, typically Less than 100 adenomas, typically morphologically flatmorphologically flat

Polyps primarily located proximal to the Polyps primarily located proximal to the splenic flexure, sparing the rectumsplenic flexure, sparing the rectum

Diagnosed at mean age of 44 years, and Diagnosed at mean age of 44 years, and cancers at a mean of 56 yearscancers at a mean of 56 years

Hernegger et al. Dis Colon Rectum. 2002 Jan;45(1):127-136Hernegger et al. Dis Colon Rectum. 2002 Jan;45(1):127-136..

Extracolonic ManifestationsExtracolonic Manifestations

High association with gastric fundic polypsHigh association with gastric fundic polypsExtracolonic cancers similar to FAP, including:Extracolonic cancers similar to FAP, including:– duodenal and periampullary tumors (5-10%)duodenal and periampullary tumors (5-10%)– pancreatic (2%)pancreatic (2%)– thyroid (2%)thyroid (2%)– Gastric (0.5%)Gastric (0.5%)

Congenital Hypertrophic Retinal Pigment Congenital Hypertrophic Retinal Pigment Epithelium (CHRPE), osteomas and desmoids Epithelium (CHRPE), osteomas and desmoids are rarely seenare rarely seen

Hernegger et al. Dis Colon Rectum. 2002 Jan;45(1):127-136Hernegger et al. Dis Colon Rectum. 2002 Jan;45(1):127-136..

Comparison of Hereditary Comparison of Hereditary Colorectal DiseasesColorectal Diseases

FAPFAP AFAPAFAP HNPCCHNPCC

InheritanceInheritance DominantDominant DominantDominant DominantDominant

IncidenceIncidence 1:10,0001:10,000 1:100,0001:100,000 1:2,0001:2,000

Gene DefectGene Defect APCAPC APC / MYH ?APC / MYH ? MMRMMR

Colonic PolypsColonic Polyps Always > 100, Always > 100, often >1000often >1000

10 - 100, usually 10 - 100, usually proximalproximal

Few, sporadicFew, sporadic

Lifetime CRC RiskLifetime CRC Risk Near 100%Near 100% 70-80%70-80% > 80%> 80%

Average age of CRCAverage age of CRC 3939 4949 4444

Adapted from Grady. Gastro. 2003;124:1574–1594

Distinguishing Flat PolypsDistinguishing Flat Polyps

Eisen et al. Gastrointest Endosc 2002;55:687-94.

High-resolution ChromoendoscopyHigh-resolution Chromoendoscopy

Eisen et al. Gastrointest Endosc 2002;55:687-94.

“Pit” pattern “Grooves”

Adenomatous PolypHyperplastic Polyp

High-resolution ChromoendoscopyHigh-resolution Chromoendoscopy

Conventional dyes (e.g. 0.9% indigo carmine) or florescent dyes used in conjunction with a high-resolution endoscope (410k – 850k pixels vs standard scopes 100k – 200k pixels pixels)Hyperplastic polyps– a characteristic “pit” pattern of orderly arranged circular “dots,”

morphologically similar to surrounding normal mucosa.

Adenomatous Polyps– surface “grooves” occasionally with a sulcus-like appearance

In a recent multicenter trial by Eisen et al., In a recent multicenter trial by Eisen et al., chromoendoscopy had a sensitivity of 82% and chromoendoscopy had a sensitivity of 82% and specificity of 82% in distinguishing the above polypsspecificity of 82% in distinguishing the above polyps

Eisen et al. Gastrointest Endosc 2002;55:687-94.

Gastric Fundic Gland PolypsGastric Fundic Gland Polyps

Fundic gland polyps account for 50% of all Fundic gland polyps account for 50% of all gastric polyps and are observed in 0.8-1.9% of gastric polyps and are observed in 0.8-1.9% of all patients undergoing EGDall patients undergoing EGDStudies estimate 52-88% of FAP patients have Studies estimate 52-88% of FAP patients have gastric fundic glands polypsgastric fundic glands polypsUnlike colonic adenomas, the number of gastric Unlike colonic adenomas, the number of gastric fundic gland polyps fundic gland polyps is not attenuated in AFAPis not attenuated in AFAP

Burt. Gastro 2003;125:1462-1469.

Prevalence of duodenal and gastric adenomas is Prevalence of duodenal and gastric adenomas is unknown, varying from 93% in one series to 0% unknown, varying from 93% in one series to 0% in another in another

Lynch. Cancer. 1995. / Rozen. Jpn J Cancer Res. 1999Lynch. Cancer. 1995. / Rozen. Jpn J Cancer Res. 1999

Endoscopic FeaturesEndoscopic Features

Polyps are sessile, hemispherical elevations, at Polyps are sessile, hemispherical elevations, at times with a “waist” but no clear stalktimes with a “waist” but no clear stalk1 mm to 5 mm in diameter1 mm to 5 mm in diameterColor is pale, pink, resembling surrounding Color is pale, pink, resembling surrounding mucosamucosaOn biopsy, polyps “chunk off” or detach entirely On biopsy, polyps “chunk off” or detach entirely at the baseat the baseUsually fewer than 10 polyps in sporadic cases, Usually fewer than 10 polyps in sporadic cases, versus hundreds in FAP and AFAPversus hundreds in FAP and AFAP

Burt. Gastro 2003;125:1462-1469.

Gastric Fundic Gland PolypsGastric Fundic Gland Polyps

FAP AFAP

Burt. Gastro 2003;125:1462-1469.

Diagnostic Criteria for AFAPDiagnostic Criteria for AFAP

Leppert et al suggest a set of diagnostic Leppert et al suggest a set of diagnostic criteria for the diseasecriteria for the disease

– A positive family history of colorectal cancer with at A positive family history of colorectal cancer with at least one of the following criterialeast one of the following criteria

CRC at any ageCRC at any age

> 5 colorectal adenomas> 5 colorectal adenomas

2-4 adenomas and multiple gastric fundic polyps2-4 adenomas and multiple gastric fundic polypsLeppert et al. N Engl J Med 1990; 322:9.Leppert et al. N Engl J Med 1990; 322:9.

Later studies suggest a fourth criteriaLater studies suggest a fourth criteriaNumber of colorectal adenomas must be < 100Number of colorectal adenomas must be < 100

Knudsen et al. Familial Cancer. 2003;2:43-55

Problems with the CriteriaProblems with the Criteria

No consensus exists on the exact definition of No consensus exists on the exact definition of AFAPAFAP– Cases of AFAP have been reported with Cases of AFAP have been reported with

adenomatous polyps in excess of 100adenomatous polyps in excess of 100– The age at which adenoma counts should be The age at which adenoma counts should be

made is undefinedmade is undefined

Burt et al investigated 120 patients from 2 families Burt et al investigated 120 patients from 2 families with AFAP (5’ mutation) revealing median number with AFAP (5’ mutation) revealing median number of 25 polyps, with a range of of 25 polyps, with a range of 0-470 polyps0-470 polyps Burt et al. Gastro. 2004;127:444-451Burt et al. Gastro. 2004;127:444-451

Extreme Phenotypic VariabilityExtreme Phenotypic Variability

Burt et al. Gastro. 2004;127:444-451Burt et al. Gastro. 2004;127:444-451

The Genetics of AFAPThe Genetics of AFAP

Spirio et al in 1993 identifies four mutations at Spirio et al in 1993 identifies four mutations at the 5’ end (exon 3) of the APC gene in seven the 5’ end (exon 3) of the APC gene in seven families with AFAPfamilies with AFAP

Spirio et al. Cell. 1993; 75: 951-7.Spirio et al. Cell. 1993; 75: 951-7.

Since then, 38 distinct mutations have been Since then, 38 distinct mutations have been identifiedidentified– 5’ to codon 175 (15)5’ to codon 175 (15)– 3’ to codon 1596 (12)3’ to codon 1596 (12)– Exon 9 (10)Exon 9 (10)– Deletion of entire allele (1)Deletion of entire allele (1)

APC Gene MutationsAPC Gene Mutations

Nicola et al. Human Molecular Genetics. 2001.

APC Mutation PhenotypesAPC Mutation Phenotypes

Colored regions = mutations / Grey areas = translated regions

Nicola et al. Human Molecular Genetics. 2001;10:7.

A Model for Mutation and FAPA Model for Mutation and FAP

APC gene is a classic tumor suppressor gene, APC gene is a classic tumor suppressor gene, primarily down-regulating intercellular primarily down-regulating intercellular ββ-catenin -catenin activity and ultimately slowing cell cycle entry activity and ultimately slowing cell cycle entry and progressionand progression

““Dominant negative model” suggests that the Dominant negative model” suggests that the mutated gene product forms homodimers with mutated gene product forms homodimers with the wild-type protein, causing lowered or the wild-type protein, causing lowered or abolished tumor suppressor activityabolished tumor suppressor activity

APC, APC, ββ-catenin and E-cadherin-catenin and E-cadherin

Fearnhead et al. Hum Mol Gen. 200`;`0(7):721-733.

An Explanation for Attenuation?An Explanation for Attenuation?

5’ to codon 1755’ to codon 175– Mutation in this region affect the homodimer forming Mutation in this region affect the homodimer forming

domain of the APC gene (amino acids 6-57)domain of the APC gene (amino acids 6-57)– Interactions between mutated and wild-type proteins Interactions between mutated and wild-type proteins

are reducedare reduced

3’ to codon 15963’ to codon 1596– Gene product not detectable by Western blot analysisGene product not detectable by Western blot analysis– Suggests mRNA or protein degradationSuggests mRNA or protein degradation

Exon 9Exon 9– Even wild-type allele undergoes significant Even wild-type allele undergoes significant

physiological splicing in this regionphysiological splicing in this region– Alternate splicing pathways may “skip over” mutationAlternate splicing pathways may “skip over” mutation

MYH MutationsMYH Mutations

MYH along with OGG1 and MTH1 are MYH along with OGG1 and MTH1 are proteins involved in the repair G:C to T:A proteins involved in the repair G:C to T:A transversions due to oxidative stress from transversions due to oxidative stress from 8-hydroxyguanine8-hydroxyguanineRecently, inherited variants of the MYH Recently, inherited variants of the MYH gene have been associated with colorectal gene have been associated with colorectal polyposis with a recessive pattern of polyposis with a recessive pattern of inheritanceinheritance

Al Tassan et al. Nat Genet. 2002;30:227-232.Al Tassan et al. Nat Genet. 2002;30:227-232.Jones et al. Hum Mol genet. 2002;11:2961-2967.Jones et al. Hum Mol genet. 2002;11:2961-2967.

MYH Mutation and AFAPMYH Mutation and AFAP

MYH-associated polyposis is MYH-associated polyposis is phenotypically similar to attenuated FAPphenotypically similar to attenuated FAP– Later age of onset of polyposis than FAPLater age of onset of polyposis than FAP– Polyps usually < 100, but counts of 500 have Polyps usually < 100, but counts of 500 have

also been reportedalso been reported

Mutations in MYH may lead to G:C to T:A Mutations in MYH may lead to G:C to T:A transversions in the APC genetransversions in the APC gene

However, autosomal recessive patternHowever, autosomal recessive patternWang et al. Gastro. 2004;127:9-16.Wang et al. Gastro. 2004;127:9-16.

MYH Mutation and AFAPMYH Mutation and AFAP

In a recent study, Wang et al analyzed 984 In a recent study, Wang et al analyzed 984 patients with high risk for genetic mutationpatients with high risk for genetic mutation– 313 patients with 1-3 adenomatous polyps on colonoscopy313 patients with 1-3 adenomatous polyps on colonoscopy– 444 patients with history of CRC444 patients with history of CRC– 140 patients referred for probable FAP140 patients referred for probable FAP

18 patients with biallelic mutations were 18 patients with biallelic mutations were identifiedidentified– 2 patients with colorectal cancer at age > 512 patients with colorectal cancer at age > 51– 16 patients with 20 - 500 adenomatous polyps16 patients with 20 - 500 adenomatous polyps– No patients with polyp counts < 20 had a biallelic MYH mutaitionNo patients with polyp counts < 20 had a biallelic MYH mutaition

Wang et al. Gastro. 2004;127:9-16.Wang et al. Gastro. 2004;127:9-16.

Genetic Testing for AFAPGenetic Testing for AFAP

Clinical criteria for AFAP met– Greater than 5 to 10 and less than 100 colorectal Greater than 5 to 10 and less than 100 colorectal

adenomasadenomas– 2-4 adenomas and multiple gastric fundic polyps2-4 adenomas and multiple gastric fundic polyps

First-degree relatives of a person with a known APC mutation, regardless of polyp status

A person with multiple adenomas who is a relative of a person with a known APC mutation

Grady. Gastro.Grady. Gastro. 2003;124:1574–1594

Role of MYH Testing in AFAPRole of MYH Testing in AFAP

“At this time, there are insufficient clinical data regarding the role of MYH mutations… in people with adenomatous polyposis to make any recommendations regarding the use of MYH mutation analysis in the clinical management of these individuals.”

Grady. Genetic Testing for High-Risk Colon Cancer Patients. Gastro 2003;124:1574–1594

Recap of Disease CourseRecap of Disease Course

Generally age at onset and progression to Generally age at onset and progression to cancer (44 and 56 years respectively) is cancer (44 and 56 years respectively) is 15 years later than that of classic FAP15 years later than that of classic FAP

Lesions usually proximal to the splenic Lesions usually proximal to the splenic flexureflexure

Rectal sparingRectal sparing

Gastric fundic gland polyps commonly Gastric fundic gland polyps commonly seenseen

Surveillance RecommendationsSurveillance Recommendations

Surveillance must be by colonoscopySurveillance must be by colonoscopy– Due to lesions proximal to splenic flexureDue to lesions proximal to splenic flexure– Contrasts with screening by flexible Contrasts with screening by flexible

sigmoidoscopy in classic FAPsigmoidoscopy in classic FAP

Colonoscopy starting at 10–17 years, annually

EGD starting at 30 years, every 1–3 years, depending on polyp status in duodenum

Grady. Gastro.Grady. Gastro. 2003;124:1574–1594

ManagementManagement

Increased risk of colon cancer, but exact risk remains Increased risk of colon cancer, but exact risk remains unknown (general consensus is roughly 60-80%)unknown (general consensus is roughly 60-80%)Similar to FAP, disease progression from adenoma to Similar to FAP, disease progression from adenoma to carcinoma is not acceleratedcarcinoma is not acceleratedColonoscopyColonoscopy– Unlike FAP, there is a sufficiently low number of Unlike FAP, there is a sufficiently low number of

colonic polyps to make polypectomy practicalcolonic polyps to make polypectomy practicalBurt et all. Gastro. 2004;127:444-451.Burt et all. Gastro. 2004;127:444-451.

EGDEGD– Best treatment of gastric fundic gland polyps is Best treatment of gastric fundic gland polyps is

presently unknownpresently unknownBurt. Gastro 2003;125:1462-1469.

When to Perform Colectomy?When to Perform Colectomy?

The exact risk of colon cancer is unknown in AFAP, but The exact risk of colon cancer is unknown in AFAP, but estimated between 60 – 80%estimated between 60 – 80%In FAP patients, The American Society of Colon and Rectal Surgeons recommends colectomy between ages 15 to 18

Church and Simmang. Dis Colon Rectum, August 2003.

No clear consensus exists for AFAPNo clear consensus exists for AFAP– 15 year delay in onset of disease would suggest 15 year delay in onset of disease would suggest

colectomy at age 30colectomy at age 30– In a series of 120 patient with AFAP by Burt et al., first In a series of 120 patient with AFAP by Burt et al., first

CRC was at a mean age of 58 years (range of ages CRC was at a mean age of 58 years (range of ages 29 to 81), with 12 patients over the age of 60 with 29 to 81), with 12 patients over the age of 60 with intact colonsintact colons

Burt et all. Gastro. 2004;127:444-451.Burt et all. Gastro. 2004;127:444-451.

Type of SurgeryType of Surgery

Three main surgical options– Colectomy and ileorectal anastomosis (IRA),– Proctocolectomy with ileostomy (TPC)– Proctocolectomy with ileal pouch-anal anastomosis

(IPAA)

As AFAP almost always spares the rectum, present consensus is for IRA, with subsequent surveillance by flexible sigmoidoscopy annually

Bülow et al. Gastro. Bülow et al. Gastro. 2000;119:1454–1460.

Church and Simmang. Dis Colon Rectum, August 2003.

Pharmacologic TherapyPharmacologic Therapy

Treatment with sulindac and celecoxib may also Treatment with sulindac and celecoxib may also reduce polyp burdenreduce polyp burden

Giardiello et al. Giardiello et al. N Engl J Med 1993;328:1313-1316N Engl J Med 1993;328:1313-1316..Steinbach et al. N Engl J Med 2000;342:1946–52.Steinbach et al. N Engl J Med 2000;342:1946–52.

In 1999, FDA approves celecoxib as a treatment In 1999, FDA approves celecoxib as a treatment for patients with FAPfor patients with FAP– Dosage: celecoxib 400 mg PO BIDDosage: celecoxib 400 mg PO BID– ““To reduce the number of adenomatous colorectal To reduce the number of adenomatous colorectal

polyps in familial adenomatous polyposis (FAP), as polyps in familial adenomatous polyposis (FAP), as an adjunct to usual care (e.g., endoscopic an adjunct to usual care (e.g., endoscopic surveillance, surgery).”surveillance, surgery).”

FDA Application NDA 21-156 & 20-998/S007FDA Application NDA 21-156 & 20-998/S007

Celecoxib and FAPCelecoxib and FAP

Steinbach et al. N Engl J Med 2000;342:1946–52.Steinbach et al. N Engl J Med 2000;342:1946–52.

Sulindac and FAPSulindac and FAP

15 case series and at least 4 randomized, controlled trials have proven the efficacy of NSAIDs (primarily sulindac) in reducing the adenoma burden of persons with FAPHowever, in a recent trial by Giardiello, sulindac did not significantly reduce or delay the emergence of colorectal adenomas in prephenotypic FAP patientsDefinitive clinical outcomes (e.g., reductions in CRC morbidity and mortality or changes in surveillance practices) have yet to be proven.

Hawk et al. Gatro. 204;126:1423–1447.Giardiello et al.N Engl J Med 2002;346:1054–1059.

ConclusionsConclusions

Attenuated FAP is a rare cause of CRC, accounting for Attenuated FAP is a rare cause of CRC, accounting for <0.1% annually<0.1% annuallyHowever, distinguishing AFAP from sporadic polyps is However, distinguishing AFAP from sporadic polyps is critical as the lifetime risk for CRC may be as high as 60-critical as the lifetime risk for CRC may be as high as 60-80%80%Suspicion for AFAP should be heightened in: Suspicion for AFAP should be heightened in: – the presence of > 5-10 colonic polyps (especially proximal the presence of > 5-10 colonic polyps (especially proximal

distribution)distribution)– 2-4 adenomas and multiple gastric fundic polyps2-4 adenomas and multiple gastric fundic polyps

Family history should be obtained, and genetic testing Family history should be obtained, and genetic testing should be offered to all first degree relativesshould be offered to all first degree relatives

ConclusionsConclusions

Annual colonoscopy with polypectomy Annual colonoscopy with polypectomy may be sufficient to prevent progression of may be sufficient to prevent progression of diseasediseasePharmacologic therapy with celecoxib/ Pharmacologic therapy with celecoxib/ sulindac may further aid in reducing polyp sulindac may further aid in reducing polyp burdenburdenNo consensus yet regarding need for No consensus yet regarding need for colectomy, however when required, IRA is colectomy, however when required, IRA is believed to be sufficientbelieved to be sufficient

The Future of AFAPThe Future of AFAP

AFAP remains a poorly defined entityAFAP remains a poorly defined entity– While most literature associates AFAP with specific While most literature associates AFAP with specific

APC mutations, recent literature suggest MYH APC mutations, recent literature suggest MYH mutations may also be seen in this disease mutations may also be seen in this disease Wang et al. Gastro. 2004;127:9-16.Wang et al. Gastro. 2004;127:9-16.

– Consensus on a gold-standard test for AFAP is Consensus on a gold-standard test for AFAP is required to reliably report and follow the course of this required to reliably report and follow the course of this diseasedisease

Cumulative lifetime polyp countsCumulative lifetime polyp counts– To better understand progression of diseaseTo better understand progression of disease– To reach a consensus regarding age that polyp count To reach a consensus regarding age that polyp count

should be madeshould be made

Patient Follow-upPatient Follow-up

Patient had an EGD on 9/20/2004 to Patient had an EGD on 9/20/2004 to evaluate for gastric fundic gland polyps evaluate for gastric fundic gland polyps and periampullary diseaseand periampullary disease– No significant lesions foundNo significant lesions found

Patient underwent genetic counseling at Patient underwent genetic counseling at Norris Comprehensive Cancer Center on 9/24/2004, and is presently pending results of genetic testing

Acknowledgements

Dr. Laurie DeLeveDr. Laurie DeLeve

Dr. Mark EwingDr. Mark Ewing

GI Consult TeamGI Consult Team

This presentation is available at:This presentation is available at:

http://www.makino.net/gastrohttp://www.makino.net/gastro

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