Case Case Presentaion Presentaion : : Duodenal Duodenal Adenomatosis Adenomatosis and and Polypharmacy Polypharmacy John Weaver John Weaver Department of General Surgery Department of General Surgery University of Colorado University of Colorado October 27, 2008 October 27, 2008
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Case Case PresentaionPresentaion::Duodenal Duodenal Adenomatosis Adenomatosis and and PolypharmacyPolypharmacy
John WeaverJohn WeaverDepartment of General SurgeryDepartment of General SurgeryUniversity of ColoradoUniversity of ColoradoOctober 27, 2008October 27, 2008
SHSH
67 67 y/o y/o female with FAPfemale with FAP Total Total colectomy colectomy in 1950in 1950’’ss
Duodenal polyps on EGD since 1990Duodenal polyps on EGD since 1990 Surveillance BiopsiesSurveillance Biopsies
high grade dysplasiahigh grade dysplasia EUS EUS –– mucosal thickening/stricture of pancreatic ductmucosal thickening/stricture of pancreatic duct
Referral forReferral for a a pancreaticoduodenectomypancreaticoduodenectomy
SHSH PMHxPMHx
FAP FAP s/p s/p total total colectomy colectomy with IRA in 1950with IRA in 1950 Rectal polypsRectal polyps C1C1--C2 fusionC2 fusion D/C 1972; tubal ligation 1979D/C 1972; tubal ligation 1979 Rheumatoid ArthritisRheumatoid Arthritis Multiple GI bleeds Multiple GI bleeds –– ulcerations in rectumulcerations in rectum BipolarBipolar GerdGerd
PSHxPSHx Bilat Bilat total hips; left femur ORIF;total hips; left femur ORIF; C1C1--2 fusion2 fusion
Family HistoryFamily History FAPFAP
SocialSocial No ETOH or tobaccoNo ETOH or tobacco
SHSH
MedicationsMedications –– (active medications at pre(active medications at pre--op)op)
Patients will develop duodenal adenomasPatients will develop duodenal adenomas 100% by age 75100% by age 75
200 fold higher risk of duodenal cancer200 fold higher risk of duodenal cancer 5% with duodenal polyps develop cancer5% with duodenal polyps develop cancer 50% develop stage 4 disease by 7050% develop stage 4 disease by 70
40% cumulative cancer risk40% cumulative cancer risk
Pandolfi M, et al. JOP. 2008;9:1-8.
SpigelmanSpigelman’’s s ClassificationClassification
Sarin G, et al. J Clin Onc 2004; 22:493-499.
Duodenal cancer in patients with familial Duodenal cancer in patients with familial adenomatous polyposisadenomatous polyposis: : results from a 10 year prospective studyresults from a 10 year prospective study
Prospective Study 1988Prospective Study 1988--19981998
Endoscopic analysis with multiple biopsiesEndoscopic analysis with multiple biopsies 11stst, 2, 2ndnd, 3, 3rdrd portions of duodenumportions of duodenum
114 patients114 patients 99 patients with full endoscopic follow over 10 years99 patients with full endoscopic follow over 10 years
Germline Germline mutationsmutations 73% precise 73% precise germline germline analysis analysis –– no conclusions based on no conclusions based on
stagestage
Groves C, et al. Gut. 2002;50:636-641
Duodenal cancer in patients with familial Duodenal cancer in patients with familial adenomatous polyposisadenomatous polyposis: : results from a 10 results from a 10 year prospective studyyear prospective study
OutcomeOutcome 6/114 patients developed cancer (median 6 years)6/114 patients developed cancer (median 6 years)
–– Median age 68 at diagnosisMedian age 68 at diagnosis
Stage 1Stage 1 (0/15)(0/15)
–– Stage progression 20%Stage progression 20%
Stage 2Stage 2 (1/43) (1/43) –– 2.3% risk of CA2.3% risk of CA
–– Stage progression 15.9%Stage progression 15.9%
Stage 3Stage 3 (1/41) (1/41) –– 2.4% risk of CA2.4% risk of CA
–– Stage progression 12.2%Stage progression 12.2%
Stage 4Stage 4 (4/11) (4/11) –– 36.4% risk of CA36.4% risk of CA
–– Dx Dx between 5between 5--10 years of initial screen10 years of initial screen–– Stage progression 36.4%Stage progression 36.4% Groves C, et al. Gut. 2002;50:636-641
Duodenal Duodenal adenomatosis adenomatosis in in familial familial adenomatous polyposisadenomatous polyposis
Prospective 5 nation study Prospective 5 nation study -- largest studylargest study
Duodenal Duodenal adenomatosis adenomatosis in familial in familial adenomatous polyposisadenomatous polyposis
-50% progression from stage 0 in 6yr
68% progression in 8yr
-15% progression to stage 4 in 8
years
-52% stage 4 by age 70
Bulow S, et al. Gut 2004;53:381-386.
Duodenal Duodenal adenomatosis adenomatosis in in familial familial adenomatous polyposisadenomatous polyposis
Time from entryTime from entry Increase in size (p <0.0001)Increase in size (p <0.0001) Increase in numbers (p <0.0001)Increase in numbers (p <0.0001) Minimal change in dysplasia (p = 0.07)Minimal change in dysplasia (p = 0.07)
2/26 (7.7%) stage 4 developed cancer2/26 (7.7%) stage 4 developed cancer Median age 52Median age 52 0.7% stage 3 developed cancer0.7% stage 3 developed cancer
1.6% developed duodenal cancer (4 pts)1.6% developed duodenal cancer (4 pts) Lifetime risk of duodenal cancer 3Lifetime risk of duodenal cancer 3--5%5%
Bulow S, et al. Gut 2004;53:381-386.
Endoscopic Surveillance Endoscopic Surveillance RecommendationsRecommendations Initial surveillance Initial surveillance –– 2525--30 years old30 years old
Stage 0Stage 0--11 5 year endoscopic follow up5 year endoscopic follow up No progression beyond stage 2 in 10 yearsNo progression beyond stage 2 in 10 years
Stage 2Stage 2--33 22--3 year endoscopic follow up3 year endoscopic follow up 2% developed CA in 10 years2% developed CA in 10 years 1212--15% progressed in stage in 10 years15% progressed in stage in 10 years Endoscopic treatment of polyps/ChemopreventionEndoscopic treatment of polyps/Chemoprevention
Stage 4 Stage 4 (or severe dysplasia)(or severe dysplasia)
Offer surgery Offer surgery –– PD vs. PSDPD vs. PSD
Groves C, et al. Gut. 2002;50:636-641
Treatment Options for Treatment Options for Duodenal PolypsDuodenal Polyps
Outcomes Outcomes -- Endoscopic resection for stage 2/3 or LGDEndoscopic resection for stage 2/3 or LGD FollowFollow--up 19up 19--66 months 66 months –– no progression to cancerno progression to cancer NonNon--surgical candidatessurgical candidates
Pandolfi M, et al. JOP. 2008.
Treatment Options for Duodenal Treatment Options for Duodenal PolypsPolyps Endoscopic RemovalEndoscopic Removal Transduodenal polypectomyTransduodenal polypectomy
High recurrence rates in FAPHigh recurrence rates in FAP Extensive Extensive polyposispolyposis
PancreasPancreas--sparing sparing duodenectomyduodenectomy Easier followEasier follow--up up survelliancesurvelliance Similar complication rateSimilar complication rate
PancreaticoduodenectomyPancreaticoduodenectomy HGD in FAP Suspicion/evidence of invasion on EUS
Alternative Alternative treatementstreatements
Celocoxib Celocoxib TrialTrial 800mg daily800mg daily Reduction in duodenal Reduction in duodenal adenomatosisadenomatosis ? Cancer? Cancer benefitbenefit
Sulindac Sulindac Trial Trial -- little to no effectlittle to no effect AspirinAspirin RanitidineRanitidine Photodynamic therapy Photodynamic therapy -- no long term datano long term data NdNd:YAG laser :YAG laser -- high risk of perforationhigh risk of perforation
Polypharmacy Polypharmacy and the and the Geriatric PatientGeriatric Patient By 2040, By 2040, ¼¼ of the worldof the world’’s population is s population is
estimated to be over 65 years oldestimated to be over 65 years old
44% of men and 57% of women over 65 44% of men and 57% of women over 65 use 5+ drugs/weekuse 5+ drugs/week
12% use 10 or more meds12% use 10 or more meds
44% of patients over 65 with home health 44% of patients over 65 with home health receive 9+ medsreceive 9+ meds
Drug use in elderlyDrug use in elderly
elderly aged 65+population
65+ years<65 years
30% of all prescription drug use among those aged 65+
12% of population aged 65+
aged 65+<65 years
50% of all OTC drug use among those 65+
Adverse Drug ReactionsAdverse Drug Reactions
82%82% risk of ADR at 6 medicationsrisk of ADR at 6 medications
$177 billion spent in 2000$177 billion spent in 2000
Every $1 spent on drugs, $1 spent on Every $1 spent on drugs, $1 spent on ADRADR’’ss
95% considered predictable95% considered predictable
7 fold increase in elderly7 fold increase in elderly
Exponential Relation between Exponential Relation between ADR and ADR and PolypharmacyPolypharmacy
0102030405060708090
100
drug moredrugs
even moredrugs
lots-o-drugs
65+
Nolan L, et al. JAGS. 1998;36:142-149.
Ris
k of
AD
R
PharmacodynamicsPharmacodynamics Affinity for the site of action is inherentAffinity for the site of action is inherent
ResponseResponse of patient to drug at receptor of patient to drug at receptor changeschanges
Exaggerated response to analgesic effects Exaggerated response to analgesic effects but less sensitive to but less sensitive to betabeta--agonists/antagagonists/antag
50% decreased in 50% decreased in benzodiazapine benzodiazapine dose dose needed for sedationneeded for sedation
may be explained by changes at may be explained by changes at GABAGABA--benzo benzo receptor receptor complexcomplex
PharmacokineticsPharmacokinetics
AbsorptionAbsorption Increased lean body mass Increased lean body mass Slow GI motilitySlow GI motility Decreased gastric emptyingDecreased gastric emptying
DistributionDistribution Increased fat mass, decrease muscle massIncreased fat mass, decrease muscle mass Decreased total body waterDecreased total body water Decreased albuminDecreased albumin
EliminationElimination Altered renal function Altered renal function –– low GFR, loss of tubular functionlow GFR, loss of tubular function Decreased renal blood flowDecreased renal blood flow Clinically very important Clinically very important -- changes dosingchanges dosing
MetabolismMetabolism Decreased hepatic mass and blood flowDecreased hepatic mass and blood flow Cp450 Cp450 –– affecting metabolism of other medicationsaffecting metabolism of other medications
Updating the Beers Criteria for potentially Updating the Beers Criteria for potentially inappropriate medication use in older adults inappropriate medication use in older adults ––est. 1997est. 1997
30% of hospital admissions in the elderly 30% of hospital admissions in the elderly are related to drug problems or toxic drug are related to drug problems or toxic drug effectseffects
ADEs ADEs –– related to depression, falls, related to depression, falls, constipation, immobility, confusion and hip constipation, immobility, confusion and hip fracturesfractures
Of Of ADEs ADEs –– 1/7 require hospital admission1/7 require hospital admission Cause 106,000 deaths annuallyCause 106,000 deaths annually
Fick, D et al. Arch Intern Med 2003;163:2716-2723
Updating the Beers Criteria for potentially Updating the Beers Criteria for potentially inappropriate medication use in older adultsinappropriate medication use in older adults
23% decrease in PIM (potentially 23% decrease in PIM (potentially inappropriate medication use) with use of inappropriate medication use) with use of Beers list in review of Beers list in review of medicare/medicaid medicare/medicaid populationpopulation
Limit new drug prescribingLimit new drug prescribing–– Once daily dosingOnce daily dosing–– Increased meds = decreased complianceIncreased meds = decreased compliance
Review BeerReview Beer’’s Lists List–– Know most common DDIKnow most common DDI
Follow up planning with geriatricianFollow up planning with geriatrician–– Inpatient geriatrics consultInpatient geriatrics consult
ReferencesReferences Bulow S, Bulow S, Bjork Bjork J, Christensen J, J, Christensen J, Fausa Fausa O, O, Jarvinen Jarvinen J, J, Moesgaard Moesgaard F, F, Vasen Vasen H. Duodenal H. Duodenal
adenomatosis adenomatosis in familial in familial adenomatous polyposisadenomatous polyposis. Gut 2004; 53:381. Gut 2004; 53:381--386.386. Cameron J. Current Surgical Therapy 9Cameron J. Current Surgical Therapy 9thth Ed. 2004.Ed. 2004. Fick Fick D, Cooper J, Wade W, Waller J, Maclean R, Beers M. Updating the D, Cooper J, Wade W, Waller J, Maclean R, Beers M. Updating the Beers Criteria for Beers Criteria for
Potentially Inappropriate Medication Use in Older Adults. Arch IPotentially Inappropriate Medication Use in Older Adults. Arch Intern Med 2003;163:2716ntern Med 2003;163:2716--2723.2723.
Groves C, Saunders B, Groves C, Saunders B, Spigelman Spigelman A, Philips R. Duodenal cancer in patients with familial A, Philips R. Duodenal cancer in patients with familial adenomatous polyposisadenomatous polyposis: results from a 10 year prospective study. Gut 2002;50:636: results from a 10 year prospective study. Gut 2002;50:636--641.641.
Hayes B, Klein W, Hayes B, Klein W, Barrueto Barrueto F. F. Polypharmacy Polypharmacy and the geriatric patient. and the geriatric patient. Clin Geriatr Clin Geriatr Med Med 2007; 23:3712007; 23:371--390.390.
Gozansky Gozansky W. W. PolypharmacyPolypharmacy. CRIT 2008.. CRIT 2008. Pandolfi Pandolfi M, Martino M, M, Martino M, Gabbrielli Gabbrielli A. Endoscopic treatment of A. Endoscopic treatment of ampullary ampullary adenomas. JOP adenomas. JOP