Hopkins Review

Hopkins
General
Surgery
ReviewManual
HopkinsGeneralSurgeryManual
Introduction
ThismanualisacompilationofstudynotesIhavemadeoverthepast5yearsbasedona
numberofsources,includingthoselistedhere:
Textbooks(seereferencelist)
Reviewbooks(seereferencelist)
DidacticlecturesandconferencesatbothJohnsHopkinsandtheNCISurgeryBranch
PresentationsIgaveduringweeklyconferencesatNCI
Primaryandreviewarticles
PointsmadebyattendingsandotherresidentsonroundsorintheOR
InternSundaymorninglecturewithDr.Cameron(20012002)
Halstedquizzes
SESAPquestions
UpToDate
Disclaimer:Individualillustrationsandmaterialmaybelongtoathirdparty.
UnlessotherwisestatedallfiguresandtablesbyPeterAttia
WhenIbeganputtingmynotestogetheronrandompiecesofpaperandmyPalmPilot,Ididnot
intendtodomuchelsewiththem.However,intime,theybecamesonumerousthatIneededto
organizetheminabetterway.AresidentfromtheBrighamwhomIworkedwithinthelabat
NIHencouragedmetoputthemtogetherinwhathejokinglyreferredtoasanAttiaBibleof
surgicalwisdom,somethinghehaddonewithhisownnotes.Theintentofthesenoteswasnotas
muchtobeareviewforaspecifictestperse,asitwasanallpurposecompilationofsalient
pointstoconsiderasIgothroughresidency.
Ofcourse,thesenotescomewiththestandarddisclaimerthattheyarenotmeanttoreplace
readingfromprimarysources,rathertosupplementit.Inaddition,whileIhavetriedtobeas
accurateaspossible,duringmyreadingsIencounteredseveralfactsthatwereeither
contradictorytofactsIhadbeentaughtasaresidentorreadinothersources.ForthisreasonI
canmakenoguaranteesaboutthevalidityofeachstatementmadehere.Ihavetriedmybestto
amalgamateeachsetoffactsintoasomewhatconcise,yetaccuratedocument.
Hopefully,thesenoteswillprovideyouwithsomebenefitaswell.Iwelcomeallcriticismand
correctionandlookforwardtosupplementingandaugmentingthisfirsteditionmanytimesover.
PeterAttia,MD
SurgicalResident
TheJohnsHopkinsHospital
pete_attia@yahoo.com
Copyright,PeterAttia,2005.Allrightsreserved.
ReferenceList
1. VascularSurgery3rdEd.HouseOfficerSeries.FaustGR,CohenJR.,1998.
2. ABSITEKiller.LipkinAP,2000
3. RushUniversityReviewofSurgery3rdEd.Deziel,Witt,Bines,etal.,2000.
4. CurrentSurgicalTherapy6thEd.CameronJL,1998.
5. CurrentTherapyofTrauma4thEd.TrunkeyDDandLewisFR,1999.
6. Surgery:ScientificPrinciplesandPractice3rdEd.GreenfieldLJ,etal.,2001.
7. ShackelfordsSurgeryoftheAlimentaryTract5thEd.YeoCJandZuidemaGD.VolumesIV,2001.
8. AtlasofHumanAnatomy8thEd.NetterFH,1995.
9. AtlasofSurgicalOperations7thEd.Zollinger&Zollinger,1993.
10. GeneralSurgeryBoardReview3rdEd.GoldMS,ScherLA,andWeinbergG,1999.
11. GeneralSurgeryReview.MakaryMA,2004.
12. AdvancesinSurgeryVol33.Ed.CameronJL,etal.,1999.
13. PitfallsofDataAnalysis.ClayHelberg,1995.
14. PrinciplesofBiostatistics.2ndEd.PaganoMandGauvreauK.2000.
Editors
Thefollowingindividualshavebeengenerouswiththeirtimeandthoughts,andhavemadeseveralchangesand
additionstomyoriginalmanual.
H.RichardAlexander
WilliamA.Baumgartner
JohnL.Cameron
MichaelA.Choti
PeterL.Choyke
PaulM.Colombani
MatthewCooper
EdwardE.Cornwell,III
ToddDorman
FredericE.Eckhauser
DavidT.Efron
AnneC.Fischer
JulieA.Freischlag
SusanL.Gearhart
VincentL.Gott
McDonaldHorne
UdaiS.Kammula
HerbertKotz
StevenK.Libutti
PamelaA.Lipsett
MartinA.Makary
BruceJ.Perler
PeterA.Pinto
JorgeD.Salazar
AnthonyP.Tufaro
PeterS.Walinsky
StephenS.Yang
CharlesJ.Yeo
MarthaA.Zeiger
SurgeryBranch,NationalCancerInstitute
DepartmentofRadiology,NationalInstitutesofHealth
TheUniversityofMaryland
DepartmentofHematology,NationalInstitutesofHealth
DepartmentofGynecology,NationalCancerInstitute
UrologyBranch,NationalCancerInstitute
UniversityofTexas,SanAntonio,TX
PresbyterianHeartGroup,Albuquerque,NM
ThomasJeffersonUniversity
TableofContents
BreastDisease ................................................................................................................................................................................... 5
Head&NeckDisease...................................................................................................................................................................... 9
ThyroidGlandandDisease ......................................................................................................................................................... 12
ParathyroidGlandandDisease................................................................................................................................................... 15
MultipleEndocrineNeoplasia(MEN) ....................................................................................................................................... 18
Gastrinoma ...................................................................................................................................................................................... 21
Glucagonoma .................................................................................................................................................................................. 22
Insulinoma ...................................................................................................................................................................................... 23
AdrenalGland ................................................................................................................................................................................ 24
Pheochromocytoma........................................................................................................................................................................ 27
PituitaryGland ............................................................................................................................................................................... 28
ThoracicSurgery ............................................................................................................................................................................ 29
MediastinalDisease ...................................................................................................................................................................... 32
CardiacSurgery:CongenitalDefects ......................................................................................................................................... 34
CardiacSurgery:AcquiredDefects............................................................................................................................................. 36
VascularSurgery ............................................................................................................................................................................ 42
Urology............................................................................................................................................................................................. 54
OrthopedicSurgery ....................................................................................................................................................................... 55
GynecologicPathology ................................................................................................................................................................. 56
Neurosurgery .................................................................................................................................................................................. 57
CancerEpidemiology .................................................................................................................................................................... 58
EsophagealDisease........................................................................................................................................................................ 59
Stomach&GutPhysiologyandDisease ................................................................................................................................... 63
SmallBowelPhysiologyandDisease ........................................................................................................................................ 67
ColorectalDisease.......................................................................................................................................................................... 71
PediatricSurgery ............................................................................................................................................................................ 79
SpleenandSplenectomy .............................................................................................................................................................. 84
HepatobiliaryAnatomy,Physiology,andDisease .................................................................................................................. 86
Pancreas............................................................................................................................................................................................ 97
Sarcoma .......................................................................................................................................................................................... 102
Melanoma ...................................................................................................................................................................................... 103
Hernia&AbdominalWall ......................................................................................................................................................... 105
TraumaPrinciples ........................................................................................................................................................................ 106
CriticalCare................................................................................................................................................................................... 117
Hemostasis&Transfusion ......................................................................................................................................................... 126
Metabolism.................................................................................................................................................................................... 130
TransplantSurgery ...................................................................................................................................................................... 131
Nutrition ........................................................................................................................................................................................ 134
Fluids&Electrolytes ................................................................................................................................................................... 136
RenalPhysiology.......................................................................................................................................................................... 137
Immunology/Infections .............................................................................................................................................................. 139
Burns............................................................................................................................................................................................... 140
Skin&WoundHealing............................................................................................................................................................... 141
Pharmacology................................................................................................................................................................................ 142
Radiology....................................................................................................................................................................................... 143
StatisticsinMedicine .................................................................................................................................................................. 149
Notes............................................................................................................................................................................................... 154
BreastDisease
SurgicalAnatomy:
Intercostobrachialnerve(off2ndintercostalnerve)sensationtomedialarmcansacrifice
Longthoracicnerve:toserratusanteriorwingedscapula
Thoracodorsalnerve:tolatissimusdorsiweakarmadduction
Medialpectoralnervetopecminorandmajor;lateralpectoralnervetopecminoronly
Batsonsplexus:valvelessvertebralveinsallowdirectmetastasestospine
Polandsyndrome:amastia,hypoplasticshoulder,nopecs
Mastodynia:Rxwithdanazol,OCP
Mondorsdisease:thrombophlebitisofsuperficialveinofbreastRxwithNSAID
DCIS
Highlycurablewithsurvivalof94100%
50%ofrecurrencesareinvasive
ExcisionandradiotherapyORmastectomy;axillarylymphnodedissection(ALND)notrequired
(only1%havepositivenodes).NSABP17showedthatlumpectomyalonehad13.4%recurrent
DCISand13.4%recurrentinvasivecancervs.8.2%and3.9%,respectivelyforlumpectomy+
radiation.
TamoxifendecreasesrateofipsilateralandcontralateralbreastcancerinERpositivewomen,rolein
ERnegativewomen,ifany,unknown;butmustbebalancedagainstriskfactors(12%DVT,PE;
Endometrialcancer).TamoxifenhasNOTbeenshowntoincreasesurvival,onlytodecreaserate
ofrecurrence(DCISandipsilateral/contralateralinvasivebreastcancer).Severallargestudies
havebeendone(NSABP24,1800patients,[FisherB,etal.Lancet1999;353:1993])andfailedtoidentifya
survivaladvantage,despiteadequatepower.
Ongoingresearchtoidentifysubsetofpatientswhocouldbetreatedwithoutradiation
RoleofSentinelLymphisundefined.NOevidencetosupportuseasof2004.
VanNuysclassificationMAYidentifypatientswhocanbenefitfromlumpectomyalone(lowgrade,
withoutnecrosis;margin>1cm;lesion<1.5cm)
LCIS
1. AkaLobularNeoplasia,encompassesLCIS(>50%lobularinvolvement)andAtypicalLobular
Hyperplasia(ALH,<50%lobularinvolvement)
2. Notclinically,radiographically,grosslydetectable
3. 710xincreasedriskofinvasivecancerineitherbreast(especiallyinyoungwomenwithafamily
history)
4. 17%riskat15years,5.6%at5years;20%lifetimerisk(70%ofwhichwillbeductalinvasive,30%
willbelobularinvasive);1%peryear
5. Marginsareirrelevant,diseaseisdiffuse(unlikeDCIS)
6. LCISisnotitselfprecancerous,itissimplyamarkerofasusceptiblefield
Phyllodestumor:10%malignant;large;rarenodes(spread,ifany,hematogenous):RxWLE,mastectomy
notnecessary;NOALND
Intraductalpapilloma:Noriskofcancer;#1causeofbloodynippledischarge
Comedobreastcancer:Likelymulticentric;domastectomy;poorprognosis
Pagetsdiseaseofthebreast:EczematouslesiononnippleunderlyingDCISorductalCA
Mostrecentscreeningrecommendations:Firstat40;q12yearsuntil50;yearlythereafter
RadialScar:associatedwithcarcinomaanywhereinthescar;donotstereotacticallybiopsy(chanceof
samplingerror),insteadexcisionalbiopsy
Staging:
T1:<2cmT2:2.15cmT3:>5cmT4:skininvolvement(inflammatorydermallymphaticinvasion)
N1:+axnodes
N2:matted/fixed
N3:internalmammarynodes
StageI:T1
StageII:uptoT2N1orT3N0
StageIII:T4orN3 StageIV:anyM
Survivalbystage(5years):
I:9095%
II:5080% III:3050% IV:1520%
Note:FNAcannotdistinguishbetweenDCISandinvasive
Whogetschemotherapy?
1.Premenopausal:
ER/PR
T>1cm
AnyN,includingmicro(SN+)
2.Postmenopausal(upto90%areER/PR+gettamoxifen):
ER/PR&T>2cm
4nodesORmattednodes(regardlessofER/PR)
(Hence,ER/PR+,3unmattednodesnochemo)
Whogetsaxillaryradiation?(Ingeneral,wanttoavoidaxillaryradiationfollowingdissection)
+supraclavicularnode
mattednodes(extracapsularextension)
4nodes
Whogetsbreastirradiation?
anysegmentalresectionforinvasiveorDCIS
inflammatorydisease(T4/skininvolvement);someT3
Majorstudiesevaluatingroleofadjuvantradiation*therapy:
1. Theadditionofpostopirradiationtochemotherapy(CMF)forwomenwithstageIIorIIIbreast
cancerfollowingmastectomyincreasedoverallsurvivalandreducedlocoregionalrecurrence.
[Postoperativeradiotherapyinhighriskpremenopausalwomenwithbreastcancerwhoreceiveadjuvantchemotherapy.
DanishBreastCancerCooperativeGroup82bTrial.OvergaardM,etal.NEJM1997;337:949].
2. Radiotherapycombinedwithchemotherapy(CMF)aftermodifiedradicalmastectomydecreases
ratesoflocoregionalandsystemicrelapseandreducesmortalityfrombreastcancer.[Adjuvant
radiotherapyandchemotherapyinnodepositivepremenopausalwomenwithbreastcancer.RagazJ,etal.NEJM
1997;337:956].
*Trentalisveryeffectiveintreatingradiationmastitis
LocallyAdvancedBreastCancer
LocallyAdvancedBreastCancer(LABC)&InflammatoryBreastCancer(IBC)sometimes
(incorrectly)usedinterchangeably
Strictlyspeaking,LABCincludes:T3+N13orT4+N03oranyT+N23(i.e.StageIIIA/Bdisease)
TermIBCfirstusedin1924byLeeandTannenbaumatMemorialHospitaltodescribeclinical
presentationof28patientswith:breastofaffectedsideusuallyincreasedinsizeskinbecomes
deepredorreddishpurpletothetouchbrawnyandinfiltratedafterthefashionoferysipelas
Accountsfor16%ofallbreastcarcinomas(IBC)
5075%axillaryinvolvementatdiagnosis
Overallprognosismediansurvival:2years
DiagnosisbasedonhistologyofinvasivecarcinomaPLUS
1. Erythema
2. Edema,orpeaudorange
3. Wheals,orridgingoftheskinsecondarytodermallymphaticinvasion(althoughtumor
invasiononlyseenin30%)
Neoadjuvanttreatmentandearlydiagnosiscrucialforsuccessfultreatment
Approximately75%undergoCRorPRtoinductiontherapyresponsepredictsoutcome
EffectivenessofmastectomybyresponsetoinductionchemotherapyforcontrolofInflammatoryBreast
Cancer[FlemingR,etal.AnnSurgOnc19974:452]
InitialResponsetoInductiontherapy:
CRmediansurvival:120months(12%)
PRmediansurvival:48months(62%)
NRmediansurvival:<24months(26%)
FurtherBreakdown:
If>1cm3residualtumormediansurvival:36months
If<1cm3residualtumor70%aliveat5years
RoleofMastectomy:
IfCRorPRChemo+RT+Mastectomyincreasedmediansurvivalfrom48to120months(vs.
Chemo+RT)
IfNRChemo+RT+Mastectomydidnotinfluencemediansurvival(<24months),ordisease
freeinterval
SummaryforTreatmentforInflammatorybreastcancer:
1.Neoadjuvantchemo(cytoxan/adriamycin);responsetothispredictssurvival(10%CR,80%PR)
2.MRM(ifPRorCR)
3.Adjuvantchemo(taxanebased)
4.Radiationtochestwall
Chemotherapy/Hormonal*Treatment:
Premenopausal
Postmenopausal
chemoforalmostanytumor>1cm(regardlessof
nodalstatus)
cytoxan&adriamycin
addtaxaneifnodepositive
tamoxifenifER/PRpositive
arimidexandaromataseinhibitorsnoteffectivein
premenopausalsincecantcompetewith
estrogenproduced
tamoxifenorarimidexifnodenegativeandER/PR+
Chemoifpoorlydifferentiatedand>1cm(evenifnode
negative)
cytoxan&adriamycintaxaneifnodepositive
tamoxifenoradriamycinifelderly,nodepositive,and
ER/PR+
*Responsestohormonaltherapybymarker:
ER/PR+
80%
ER/PR+
45%
ER+/PR
35%
ER/PR
10%
InheritedBreastCancerSyndromes:4appeartobeimportant
1.LiFraumeniSyndromemutationofp53
2.Mutationofbcl2(18q21)expressionofbcl2,whichisantiapoptotic
3.BRCA1onlongarmof17
4.BRCA2onshortregionof13q1213
BRCA1
Ch17q21;reported1990,positionallycloned1994
Riskofbreastcancer(85%)andovariancancer(4050%)
BRCA2
Ch13q1213;reported1994;positionallycloned1995
Riskofbreastcancer(85%)andovariancancer(10%)
Riskofmalebreastcancer(6%)
RisksofTamoxifenuse
Uterineadenocarcinoma,sarcoma
Cataracts
DVT,PE
osteoporosis
Nochangeinincidenceofheartdisease
Head&NeckDisease
Parotiditis:Usuallycausedstaphspp;seeninelderly,dehydrated;Rx:antibioticsdrainageofabscessif
notimproving
Ludwigsangina:Sublingualspaceinfection(severedeepsofttissueinfectionofneckinvolvingthefloor
ofthemouth);ifairwaycompromiseperformawaketracheostomyunderlocalanestheticoperative
debridement
Leukoplakiacanbepremalignant;erythroplakiaispremalignant(andofmuchmoreconcern)
Head&NeckSCC: StageI,II(upto4cm,nonodes)singlemodalitytreatment(surgeryorRT)
StageIII,IVcombinedmodality
PerformFNA,notexcisionalbiopsyforsuspiciousmasses
NasopharyngealSCC:associatedwithEBV;50%presentlateasneckmass;drainagetoposteriorneck
nodes;mostcommonnasopharyngealcancerinadults(lymphomaismostcommoninkids).Oftenseein
Asianpopulation
GlotticCancer:ifcordsnotfixedRT;iffixedsurgery+RT.Chemo+RTusedmoreoftenfororgan
preservation
LipCancer(99%epidermoid[i.e.squamous]carcinoma):Lower>upperlip(becauseofsunexposure)
resectwithprimaryclosureif<lip;otherwiseflap
TongueCancer:usuallysurgery+RT;seeninPlummerVinson(dysphagia,spoonfingers,anemia).More
commonlyseeninsmokers/drinkers
Assalivaryglandsize[sublingual(60%),submandibular(50%),parotid(20%)]incidenceofmalignant
disease
Pharyngealcancershaveworseprognosisthanoralcancers
Mucoepidermoidcarcinoma:#1malignantsalivarytumoroverall
Adenoidcysticcarcinoma:#1malignantsalivarytumorofsubmandibular/minorglands.Overall:poor
prognosis
Pleomorphicadenomamixedparotidtumor=#1benigntumor(4070%ofallsalivaryglandtumors)
DoNOTenucleate(orwillrecur)needssuperficialparotidectomy(spareCNVII).
Ifmalignanttakewholegland+CNVII;
Ifhighgrade(anaplastic)needneckdissection
Warthinstumor(adenolymphoma)#2benignsalivarytumor;malepredominance;10%bilateral;70%of
bilateralparotidtumorsareWarthinstumor;Rxsuperficialparotidectomy
FreysSyndrome:latecomplicationofparotidectomy(occurs50%whenfacialnerveispreserved);perfuse
perspirationovercheekfollowingsalivarystimulation.IntracutaneousinjectionofBotoxA100%effective
intreatment,butresponsesmaybeshortlived(canberepeated).Usuallyselflimiting.
Ipsilateraldroolingfollowingsubmandibularglandresection:likelyinjurytomarginalmandibularnerve
Radicalneckdissection:takesCNXI,SCM,IJ,submandibulargland;mostmorbidisCNXI
ClassificationofCervicalLymphNodes
[ACSSurgeryPrinciplesandPractice,2004]
Level
I
II
III
IV
V
VI
Nodes
Submental,submandibularnodes
UpperIJnodes
MiddleIJnodes
LowerIJnodes
Spinalaccessorynodes,Transversecervicalnodes
Treacheoesophagealgrovenodes
10
CancersoftheoralcavityusuallymetastasizetothenodesinlevelsIIII.
LaryngealcancerstypicallymetastasizetothenodesinlevelsIIIV.
PresenceofHornerSyndrome(paralysisofthevagusnerve,phrenicnerve,invasionofbrachialplexus,
and/orparavertebralmusculature)generallyindicatestumorunresectability
Tracheoinnominatefistula
Massivebleedingfromtracheaisinnominatearteryuntilprovenotherwise;avoidbymaking
tracheostomynolowerthan3rdring
Usuallyoccurs23weeksposttracheostomy;poornutritionandsteroidsusemaycontribute
Mortality80%
SentinelbleedtoORforbronchoscopy
Temporarycontrol(onroutetoOR)viacuffhyperinflationorfingercompressionofinnominate
artery(anteriorpressure)
Treatmentisligationofinnominateartery
Mostcommonlocationsformandibularfractures:angle(25%)andsubcondyl(30%);themostcommon
longtermcomplicationofmandibularfractureismalocclusion
Carotidbody:chemoreceptorwithintheadventitiaoftheCCA(posteromedialside);respondstoO2
tension,CO2tension,bloodacidity,andbloodtemperaturebyHR,BP,andrate&depthof
respirationinanattempttoovercometheabovestimuli
Carotidsinus:pressuresensorwithinwallofproximalICA;respondstoBPbyHRandBP
11
ThyroidGlandandDisease
fromtheGreekworkTheros(shield)andeidos(form)
secreteshormones(T4,T3,calcitonin)frombasalmembraneside(intobloodstream)
antithyroidagentsimpair(i)iodinationand(ii)couplingofDIT/MIT
T4T3peripherally(kidney,liver)(T3;10xmoreactivethanT4).Propothiouracil(PTU)blocks
peripheralconversionofT4T3
Note:SuppressionofiodineuptakeinpatientswithincreasedT3andT4levelsispathognomonicfor
subacutethyroiditis
UsualCausesofHyperthyroidism:
1. Toxicnodule
2. Toxicmultinodulargoiter
3. Gravesdisease
4. Earlysubacutethyroiditis
WaystoTreatHyperthyroidism:
1. Medical(PTU,methimazole):interferewithiodineconversion;upto60%recur
2. RadioiodineAblation(I131):weekstomonths;1stchoicebymanyexceptinpregnancy
3. Surgery:risksofsurgery
ThyroidStorm:untreatedhyperthyroidism+stress(trauma,infection,pregnancy,DKA,etc)
Rx:fluids,O2,glucose,antithyroiddrugs,butfirsttreatunderlyingcause;
NB:donotuseASA,asitdisplacesT4fromthyroglobulin
(Differentiated)ThyroidCancer
15,00020,000cases/yrUS
15,000,000nodules/yr(510%harborcancer)
mortality<1%
Risks
age<14,>65
previousthyroidcancer
familyhistory
enlargingnoduleonthyroidhormonesuppression
exposuretolowdoseradiation
Gravesdiseaseorthyroiditis
syndromes(MENII,Carneys)
CancerHistology
Papillary(60%)
Follicularvariantofpapillary(20%)
Follicular(<5%)*
Hrthlecellcarcinoma(<5%)
Medullary(5%)
Anaplastic(1%)
Other(1%)
*difficultonFNAtodifferentiatefollicularadenomafromcarcinoma
12
OfFNAedlesionsinadults*
Inadequate,
15%
Carcinoma,
5%
Suspicious,
10%
Benign,70%
*Childrenhavehigherincidenceofcarcinoma:2050%
OneoptionforlesionsdeemedbenignonFNAishormonesuppression:ifregressesfollow;
Ifgrowsremove;ifsamerepeatFNA
Surgicalmanagement
Lobectomy:unclearpath(gobackforcompletion,ifnecessary)
Lobectomy+isthmusectomy:papillary<1cm,benignunilaterallesionsorsuspiciouslesions
Totalthyroidectomy(followedbyRAI):papillary1cm,follicular,Hrthle,medullary
IFplanningpostopRAImustdototalthyroidectomy,regardlessofsize(RAIonlyusefulinwell
differentiatedcancersnotMTC)
Medullaryistheonlyhistologywhereyoudocentraldissection(levelVIandVII)prophylactically(in
additiontototalthyroidectomy)andmodifiedradicalneckdissection(levelsIIV)onaffectedside
*PerformingatotalthyroidectomyallowsuseofthyroglobulinforrecurrencemonitoringanduseofRAI
formicroscopicdisease
[FiguretakenfromtalkgivenbyH.R.Alexander,NCI,2003]
13
MedullaryThyroidCancer:20%ofthosewithMTChaveMENII(100%ofthosewithMENIIhaveMTC).
MENIIassociatedMTCtendstobebilateral,younger,worseprognosis,RETprotooncogene;
aggressivenessasfollows:MENIIB[performthyroidectomyby6monthsold]>MENIIA[perform
thyroidectomyby5yearsold]>FMTC
Mayseeamyloidonpathology
serumcalcitonin(canuseserumcalcitoninlevelstomonitorforrecurrence)
OriginatesfromparafollicularCcells,whichproducecalcitoninandhencedonotconcentrate
iodine.
Anaplastic:Onlyoperationthatshouldbeconsideredistracheostomy.Minimalroleforpalliativeresection
Medicalmanagement
Thyroidhormonesuppression
Radioactiveiodineablation(RIA)
Cytomel(T3)[halflife34days]vs.Synthroid(T4)[halflife4weeks]
*HenceuseT3replacementpostopbeforeRIA
Thyroglobulincanonlyserveasatumormarkerwhenthefollowing2conditionsaremet:
1. Thetumoriswelldifferentiated(sinceitsproducedbyfollicularcells)
2. Thepatienthashadatotalthyroidectomy
Lymphnodes
Fordifferentiatedcancer:noroleforprophylacticLNDonlyforpalpableorFNA+nodesregional
dissection(RadicaltakeslevelsIVI+jugular+CNXI;ModifiedtakeslevelsIIVII,sparesIJV,SCM,
spinalaccessorynerveXI).LevelsmostatriskareIIVI
Prognosis(forwelldifferentiatedthyroidcancer):
AGES/AMES:age,grade/mets,extent,size;TNM;
However,age,grade(histology),sizemostimportant
Age(>45,or<14)issinglegreatestfactor
Superiorlaryngealnerve(bothsensoryandmotor),Externalbranch:motortocricothyroid;injurylose
projection,highpitchtone;providessensorytosupraglottis
Recurrentlaryngealnerve:innervatesalloflarynxexceptcricothyroid;bilateralinjuryairwayocclusion
Note:AlwaysassesscordfunctionbeforeanyoperationonthyroidtodocumentRLNfunction
14
ParathyroidGlandandDisease
Superiorparathyroidglandsfrom4thpharyngealpouch;Inferior(andthymus)from3rdpharyngealpouch
morevariableposition(sincelongerdistancetraveled)
Allparathyroidglandsgenerallyreceivebloodsupplyfromtheinferiorthyroidartery
Ifonly3glandsfoundatsurgery,fourthmaybein:
Thymus,anteriormediastinum
Thyroid
Carotidsheath
Tracheoesophagealgroove*,posteriormediastinum
Behindesophagus
*Mostcommonectopicsite
PTHproducedbyChiefcellsincreasesCa++viabonebreakdown,GIabsorption,increasedkidneyre
absorption,excretionofphosphatebykidney
Hyperparathyroidism
1. Primary:PTHsecretionbyparathyroid(highCa++,lowPO4;lookforCl/PO4>33,evenwith
normalCa++)
2. Secondary:PTHsecretionduetorenalfailureordecreasedGICa++abs(Ca++lowornormal)
3. Tertiary:PTHaftercorrectionof2hyperparathyroidism(highCa++)
4. FamilialHypercalcemiaHypocaluria(FHH):see serumCa++,PTH,buturineCa++(defectinset
pointfornormalCa++levels;patientsdonotexperiencethesequelaeofelevatedCa++);Nosurgery
ParathyroidImagining:
Sestamibiscan
U/S
201Technetiumthalliumsubtractionscan
CT/MRI
PrimaryHyperparathyroidism
Incidence:1/4000
Risks:MENI,IIa,irradiation,familyhistory(autosomaldominant)
Adenoma>85%[1],Hyperplasia10%[4],Carcinoma1%[1], [#glandstypicallyinvolved]
Typically:[Cl]/[PO4]>33
Initialmedicaltreatment:IVfluids,lasix,NOTthiazides
Treatment
1Adenoma:Surgicallyremoveadenoma(biopsyallenlargedglands)
1Hyperplasia:BilateralneckexplorationandintraoperativePTH.Subtotalparathyroidectomy
(leavelowerglandinsitu)ortotalparathyroidectomywithautotransplantation
1Carcinoma:WLEwithipsilateralthyroidectomyandlymphnodedissection
2:CorrectCa++andPO4,performrenaltransplant(noparathyroidsurgery)
3:CorrectCa++andPO4,performrenaltransplant,removeparathyroidglandsandreimplant30to
40mginforearm
15
ParathyroidCarcinoma
Signs/Sx:HyperCa++,elevatedPTH,palpablegland(50%),neckpain,recurrentlaryngealnerveparalysis
HCGisamarker
Treatment:Enblocresectionincludingipsilateralthyroidlobe+associatedlymphnodes
PostopComplications:
Recurrentlaryngealnerveinjury
Neckhematoma(openatbedsideifbreathingcompromised)
HypoCa++
ParathyroidPearls
90%ofprimaryhyperparathyroidismduetoasingleadenomaunilateralexposureisok(with
intraopPTH)
MUSTexcludefamilial/MENdisease(adifferententityaltogetherwhichrequiressubtotal
parathyroidectomyleaveofalowerglandinsitu)
Nuclearmedicineexpertiseiscrucial:ifpossible,subtractionofTc99mpertechnetate(potassium
analogspecificforthyroid)fromTc99mSestamibi(takenupbyboththyroidandparathyroid)
ForintraopPTHtobevalidmusthave>50%dropinbaselinePTHwithin10minutes
IntraopPTHmustbeusedifdoingsingleglandexploration(MIP),elsemustdo4gland
exploration
Ifdiseaserecurs,MUSTdistinguishbetweenpersistentandrecurrent:
Persistent:Onlytransientcure.Almostalwaysimpliesmissedadenoma.#1placeisTEgrooveon
rightside;alsoconsiderectopicglands
Recurrent(>6monthsnormocalcemia):Implieshyperplasiawithregrowth(e.g.familial,possibly
cancer)
10xincreaseinRLNinjuryduringredosurgery.Hence,firststepinredoisconfirmdiagnosis
with24hoururinaryCa++(ifnormalnodisease).Second,checkforfamilyhistoryofMENI
manifestations
LocalizationwithSestamibiandU/S.ConsiderCT/MRI(verybrightonT2todifferentiatefrom
LNs)
16
Ultimatepearls:
Superiorglandsisreallyamisnomer,theyshouldbecalledPosteriorglands,sincetheyarevirtually
alwaysposteriorandcephaladtotheRLN.EctopicsitesaregenerallyposteriorinTEgrove
InferiorglandsshouldbecalledAnteriorglandssincetheyarevirtuallyalwaysanteriorandcaudalto
theRLN.Ectopicglandsareusuallyanterior/mediastinal
Thefigurebelowshowsindottedlinesthepossiblelocationsfortheparathyroidglandsinrelationtothe
RLN.Thereissignificantverticaloverlap,suchthatsuperiorglandscanactuallybebelowinferiorglands,
andviceversa.
17
MultipleEndocrineNeoplasia(MEN)
*inheritedautosomaldominant(withvariablepenetrance)
MENTypeI
akaWermersSyndrome(PPP)
ParathyroidHyperplasia(90%)
HyperCa++usuallyfirst
Pancreaticisletcelltumors(67%)
Gastrinoma(ZES)(50%)
Insulinoma(20%)
PituitaryTumor(67%)mostoftenPLsecretingtumor
MENTypeIIA
akaSipplesSyndrome(MPP)
MedullaryThyroidCarcinoma(100%)2ndto3rddecade
calcitoninsecreting
usuallyquiteindolent
Pheochromocytoma(>33%)
catecholexcess
usuallybenign,bilateral,adrenal
ParathyroidHyperplasia(50%)
hyperCa++
MENTypeIIB
MMMP
MucosalNeuromas(100%)
naso,oropharynx,larynx,conjunctiva
MedullaryThyroidCarcinoma(85%)
moreaggressivethanIIA
Marfanoidbodyhabitus
Pheochromocytoma(50%)
oftenbilateral(70%)
MEN1ConsensusSummaryStatements(lossoffunction)
Diversearrayofdefects(missense,nonsense,frameshift,mRNAsplicing);hencedifficultto
screenbecauseofsomanypossiblemutations
1997:geneMeninfoundofCh11.Exactfunctionunknown,butitisatumorsuppressorgene
TheMEN1germlinemutationtestisrecommendedforMEN1carrieridentification.
AllkindredwithMEN1arelikelytohaveamutationintheMEN1gene.
However,MEN1germlinemutationtestsfailtodetect1020%ofmutations.Ifafamilylacksan
identifiableMEN1mutation,11q13haplotypetestingabouttheMEN1locusorgeneticlinkage
analysiscanidentifyMEN1carriers.PeriodicbiochemicaltestingisanalternativewhenDNAbased
testsarenotpossible.
18
ThemaincandidatesforMEN1mutationanalysisincludeindexcaseswithMEN1,theirunaffected
relatives,andsomecaseswithfeaturesatypicalforMEN1.
MEN1carrieranalysisshouldbeusedmainlyforinformation.Itshouldrarelydetermineamajor
intervention.
MEN1tumorpatternsinfamiliesdonothaveclearvariantsorspecificcorrelationswithanMEN1
germlinemutationpattern.Thus,theMEN1carriersinafamilywitheithertypicaloratypical
expressionofMEN1shouldbemonitoredsimilarlyfortypicalexpressionsofMEN1tumors.
MEN1tumorscausemorbiditythroughhormoneexcess(PTH,gastrin,PRL,etc.)andthrough
malignancies(gastrinoma/isletcellorforegutcarcinoid).
Medicationscontrolmostfeaturesofhormoneexcess(gastrin,PRL,etc.).Surgeryshouldcontrol
featuresofexcessofsomeotherhormones(PTHandinsulin).Surgeryhasnotbeenshownto
preventorcureMEN1relatedcancers.
Hyperparathyroidismdevelopsinover90%ofMEN1carriers.Thereiscontroversyoverindications
forparathyroidsurgeryinMEN1patients.
ThepreferredparathyroidoperationintheHPTofMEN1issubtotalparathyroidectomy(without
autograft);transcervicalneartotalthymectomyisalsosimultaneously.Parathyroidtissueshouldbe
cryopreserved.
CurativesurgeryforgastrinomainMEN1israre.Thereiscontroversyovertheindicationsfor
surgeryforgastrinomasinMEN1.
SurgeryinMEN1isindicatedandisusuallysuccessfulforinsulinoma.Formostotherpancreatic
islettumors,exceptgastrinomas,surgeryisalsoindicated;however,thereisnoconsensusover
tumorcriteriaforthelatteroperations.
ThemanagementofpituitarytumorinMEN1shouldbesimilartothatinsporadiccases.
MEN2ConsensusSummaryStatements(gainoffunction)
1995:RETprotooncogene(responsiblefortyrosinekinaseactivity)identifiedonCh10
Fewerpossiblemutations(codons609,611,618,620,634;involvereplacementofacystineresidue)
ThemainmorbidityfromMEN2isMTC.MEN2variantsdifferinaggressivenessofMTC,in
decreasingorderasfollows:MEN2B>MEN2A>FMTC.
MEN2carrierdetectionshouldbethebasisforrecommendingthyroidectomytopreventorcure
MTC.Thiscarriertestingismandatoryinallchildrenat50%risk.
ComparedwithRETmutationtesting,immunoassayofbasalorstimulatedCTresultsinmore
frequentfalsepositivediagnosesanddelaysofthetruepositivediagnosisoftheMEN2carrierstate.
However,theCTteststillshouldbeusedtomonitorthetumorstatusofMTC.
RETgermlinemutation(10q1112)testinghasreplacedCTtestingasthebasisforcarrierdiagnosis
inMEN2families.ItrevealsaRETmutationinover95%ofMEN2indexcases.
TheRETcodonmutationscanbestratifiedintothreelevelsofriskfromMTC.Thesethreecategories
predicttheMEN2syndromicvariant,theageofonsetofMTC,andtheaggressivenessofMTC.
19
Thyroidectomyshouldbeperformedbeforeage6monthsinMEN2B,perhapsmuchearlier,and
beforeage5yrinMEN2A.Policiesaboutcentrallymphnodedissectionatinitialthyroidectomyare
controversialandmaydifferamongtheMEN2variants.
MEN2hasdistinctivevariants.MEN2AandMEN2BaretheMEN2variantswiththegreatest
syndromicconsistency.
FMTCisthemildestvariantofMEN2.ToavoidmissingadiagnosisofMEN2Awithitsriskof
pheochromocytoma,physiciansshoulddiagnoseFMTConlyfromrigorouscriteria.
MorbidityfrompheochromocytomainMEN2hasbeenmarkedlydecreasedbyimproved
recognitionandmanagement.ThepreferredtreatmentforunilateralpheochromocytomainMEN2is
laparoscopicadrenalectomy.
HPTislessintenseinMEN2thaninMEN1.Parathyroidectomyshouldbethesameasinother
disorderswithmultipleparathyroidtumors.
20
Gastrinoma
50%ofpatientswithMENIhaveagastrinoma
33%ofpatientswithZEShaveMENI(ClinicalTriad:1.PUD2.gastricacidhypersecretion3.Islet
celltumor)
InMENIassociatedZES:Mostcommonsiteisduodenum(2ndispancreas)
aremalignant
25%ofpatientswithpheochromocytomahaveZES
Riskofmetastaticbehaviorfromgastrinomarisessharplyat3cm(<3cm<2%chanceofmets)
ThesporadicdiseaseisadifferentonefromtheMENassociatedone
SporadicZESoccursoutsideoftheduodenum3060%ofthetime;MENversionisvirtuallyalways
intheduodenum(withorwithoutpancreaticinvolvement)
SporadicZESismuchmorelikelytobemalignant(theextrapancreaticprimariesareless
biologicallyaggressiveinbothdiseases)
SporadicZESismoreoftensolitaryandlargeratthetimeofdetection,usually>2cm
MENZESisadiffusedisease,rarelyamenabletotruecure
GastrinomaTrianglejoins:
1.junctionofcysticduct&CBD
2.junctionof2ndand3rdportionduodenum
3.junctionofneck&bodyofpancreas
(90%foundinthistriangle)[AmJSurg1984147:25Stabile,Morrow,Passaro]
Ddxforincreasedgastrin:
Gastrinoma
Retainedexcludedantrum(asurgicalmistake)
Highacid
Gastricoutletobstruction
AntralGcellhyperplasia/hyperfunction
Postvagotomy
Perniciousanemia
Atrophicgastritis
Low/minimalacid
Shortgutsyndrome
Renalfailure
H2blocker,protonpumpinhibitor*
*pH<2inhibitsgastrinsecretioninnormalpatients
Checkgastrinlevelsinpatientswith:
1.recurrentulcers
2.ulcersinunusualplaces(e.g.jejunum),
3.refractorytomedicalmanagement
4.priortoanyelectiveoperationforanulcer
5.unexplainedorpersistentdiarrhea
6.pepticulcerandanyendocrinopathy
7.familyhistoryofPUD
8.familyhistoryofMENI
Check:1.fastinggastrinlevel
2.postsecretinchallengegastrinlevel(syntheticsecretin2units/kgIVbolus)
3.Ca++(MENIscreen)
4.Chemistrypanel
21
Lookfor:
ZESfasting:2001000pg/mL(normal<100pg/mL)
Basalacidsecretion:ZES>15mEq/hr(normal<10mEq/hr)
Note:generallywillseefailureoffeedback:fastinggastrin1000withgastricpH<2.5
SecretinStimulationTest:
IVsecretinadministered,gastrinmeasured
ZES:increasedgastrin(by>200pg/mL)within10to20minutes(normalresponseisdecreasein
gastrin)
Managementissues:
SomebelievedistalpancreatectomyshouldbedoneinanypatientwithMENIwitheitherhormonal
syndromeoraneuroendocrinetumorregardlessoflocationinpancreasorduodenum.Virtuallyall
patientswithMENIZEShaveconcomitantneuroendocrinetumorsinneck,body,ortail.
IfpatienthasgastrinomaandhyperparathyroidismremoveparathyroidfirsttonormalizeCa++
levels(sincehypercalcemiaismoredangerousthanhypergastrinemia)
HigherthannormaldosesofPPIareneededforachlorhydria
MinimalroleforCTscan/octreoscan
ImamuraTest:intraarterialsecretinintovisceralarteriestomeasurehepaticveingastrinlevels
(lookforstepup)isgoodforlocalization
Norolefordebulkingfunctionalgastrinomamets,sincepatientscanbemanagedmedicallyinthis
settingwithPPIs
PostOp
Muststayonacidsuppressionfor34monthsbecauseevenafterresectionacidsecretionhighforsome
time
Glucagonoma
The4DSyndrome:diabetes,diarrhea,dementia,dermatitis(patientslookcachectic)
Manypatientsalsohavenormochromicnormocyticanemia,hypoalbuminemia,weightloss,beefyred
tongue(glossitis),stomatitis,angularchelosis(i.e.signsofmalnutrition)
Usuallyfoundintailofpancreas,butcanbeanywhere.Usually>3cmattimeofdiagnosis;70%malignant
Diagnosissimplebymeasuringserumglucagonlevel,althoughmostpatientswithelevatedglucagonsdo
nothavegastrinoma[seereview:WermersRA,etal.Medicine(Baltimore).1996;75:53]
Sx:NecrotizingMigratoryErythemaNME(usuallybelowwaist),glossitis,stomatitis,diabetes
IVTolbutamideresultsinelevatedglucagon
MedicaltreatmentforNecrotizingmigratoryerythema:Somatostatin/octreotide,IVAminoacids
(TPN)
Aggressivesurgicalresectionsareindicated,evenifmetastatic
22
Insulinoma
Number1isletcellneoplasm;associatedwithMENI
8090%arebenignsolitaryadenomascuredbysurgicalresection
30%<1cm
10%multiple
1015%malignant
10%hyperplasiaornesidioblastosis
Presentswithsympatheticnervoussystemsymptomsduetohypoglycemia(patientslooklikePillsbury
DoughBoy)
WhipplesTriad:
1.Hypoglycemia<50mg/dl
2.CNSsymptoms.
3.ReversalofCNSsymptoms.withglucoseadmin.
Ddxforhyperinsulinemia:
Reactivehypoglycemia(verycommon),
Functionalhypoglycemiawithgastrectomy,
Adrenalinsufficiency,hypopituitarism,hepaticinsufficiency,
Munchausenssyndrome(selfinjection)
Tumorssecretinginsulinlikemolecule(sarcoma,mesothelioma,etc.)
First,checkforproinsulin,then:
Get72hourfastinglevelswithq6hourchecksuntilpatientbecomessymptomatic
Insulin:Glucoseratio=insulin(uU/ml)/glucose(mg/dl)>0.3foundinalmostallpatientswithinsulinoma.
AccuracyincreasedbyAmendedratio=insulin(uU/ml)/[glucose(mg/dl)30]>0.3
LocalizingTests:
CT,Agram,endoscopicultrasound,venouscatheterization(samplebloodalongportalandsplenic
veins)
Calciumangiogram:Ca++causesinsulinsecretionlocalizetoartery(e.g.splenicfortail)where
tumornearest
IntraoperativeU/Sisprobablythebesttestforlocalization
MedicalTreatment:
Diazoxidetosuppressinsulinlevels(untilresection).Diazoxideinhibitsthesulfonylureareceptor1
(SUR1)onthebetacell,whichisacomponentoftheK+ATPaseresponsibleforinsulinsecretion
Octreotide,IVglucose
23
AdrenalGland
Embryology:
Cortex:mesoderm(4thto6thweek)
Medulla:ectoderm/neuralcrest(sympatheticNSandganglion);migratesalongsympatheticchain
Ectopiclocation:IMA,OrganofZuckerkandl
Rightgland:drainsintoIVC;Leftgland:drainsintorenalvein
[FigureadaptedfromRUSHreviewmanual,2000]
AldosteroneisproducedexclusivelyintheZGbecauseofthepresenceofcorticosterone
methyloxidase(anatomicallyspecificenzymelocation)
PNMTconvertsnorepinephrineepinephrine.Foundonlyinadrenalmedulla.
RatelimitingstepisTyrosineDOPAviaTyrosinasehydroxylase
11hydroxysteroiddehydrogenasetypeIisrequiredtoconvertinactiveprednisonetoactive
prednisolone;itsactivityvariesmarkedlyfrompersontoperson
Cortisolisnotastoragehormone;however,itdoespromotegluconeogenesistopreservehepatic
reserve
Regardlessofsize,anadrenalmassshouldberemovedifitis:
1.Growing,
2.Functioning,or
3.SuspiciousonT2MRI(thebrighteritis,themoresuspiciousitis)
Ifnoneoftheabove,removelesionsgreaterthan46cm(since15%chanceofmalignancyifgreaterthan6
cmriskincreaseswithsize)
Ask:isitFunctional?Malignanttumorofadrenalgland?Likelymetastatictoadrenalgland?
24
Syndromes:
I.
Conns( aldosterone):75%unilateraladenomaRx:withresection
25%bilateralhyperplasiaRx:spironolactone+C++channelblocker
II.
Addisons( aldosteroneandcortisol):lowNa+,highK+,hypoglycemia;canpresentincrisiswith
hypotension
III. WaterhouseFriedrickson:adrenalhemorrhagewithmeningococcalsepsis
IV. Nelson:postadrenalectomy(10%)ACTH,pigmentation,changeinvisionfrompituitary
response
V. CushingsDisease(pituitary):80%ofnoniatrogeniccauses;pituitarymicroadenomaACTH
(willalsosee urine17OHprogesterone)
AdrenalCushingsSyndrome:(akaACTHindependentCushings)15%ofnoniatrogeniccauses
10%adrenaladenoma,5%adrenalcarcinoma;bilateralhyperplasiaisveryrare;willseeACTH
EctopicCushingsSyndrome:20%ofACTHdependent;sourcesofectopicACTHincluding:
Pulmonary(SCLC,bronchial,thymiccarcinoids),Neuroendocrinetumors,Pheochromocytoma,
MTC
Diagnosis:
1. Startwith24hoururinefreecortisolandplasmaACTH
2. Lowdosedexamethasonesuppressionwillsuppresscausesofhypercortisolismsuchasobesity
andexcessethanolingestion,butnotothers(confirmsdx)
3. Highdosedexamethasonesuppressionwillsuppresspituitaryadenoma,butnotectopicsources
(locatescause)
4. MRI,CT,and/orpetrosalvenoussampling
Treatment:
MedicalAdrenalectomy=metyraponeandaminoglutethimide
Surgicalremovalofallfunctionaladrenalmassesisindicated,includingbilateraladrenalectomyfor
diffusediseaseinpatientsrecalcitranttomedicalmanagement
StressDoseSteroids
[Chernowetal.AnnSurg1994,219:416]
Undernormalconditions,bodyproduces30mghydrocortisoneequivalent(solucortef)/day
Underextremestressupto300mg/day
Prednisoneis4:1(tosolucortef)
SoluMedrolis5:1
Decadronis25:1
Normaladrenalsecretionis2530mgcortisol/24h
Appropriatestresstest:250mcgcosyntropin
1.inplasmacortisolby7mcg/dL,or
2.Absolutelevel>20mcg/dL
25
Foradrenalcrisis:200mghydrocortisoneimmediately100mgq8hoursx48hoursthentaperby50%
reductionq2daysuntil25mgreached
Above50mghydrocortisone/dayyouaregettingenoughmineralocorticoidactivity(except
dexamethasone),BUTbelow50mg/daymustreplacealdosteronewithFlorinefAcetate
ProvenAdrenalInsufficiency/ChronicSteroids[givefollowinginadditiontomaintenancedoses]:
I.Mildillness/nonfebrile
noreplacement
II.Modillness(fever,minortraumaorsurgery)
15mgprednisoloneqduntil24hpostresolution
III.Severeillnessormajortraumaorsurgery
50mghydrocortisoneq6htapertonormalby50%/day
IV.SepticShock
50mghydrocortisoneq6h50mcgflorinefqdx7days
26
Pheochromocytoma
Tumorofadrenalmedullaandsympatheticganglion(fromchromaffincelllines)producingcatecolamines
(NE>Epi)
Incidence:0.2%(1/500hypertensives)
Ruleof10s
10%malignant
10%bilateral
10%inkids
10%multipletumors
10%extraadrenal
FoundinMENII(AandB)alwaysruleoutMENwithdxofpheochromocytoma
ClassicTriad
1.Palpitations
2.Headache
3.Episodicdiaphoresis
(also,50%hypertensive)
Ddx:
RenovascularHTN,menopause,migraines,carcinoidsyndrome,preeclampsia,neuroblastoma,anxiety
disorder,hyperthyroidism,insulinoma
Locations:
Adrenal(90%)
OrganofZuckerkandl(embryonicchromaffincellsaroundtheabdominalaortanearIMA;normally
atrophiesinchildhood)
Thorax
Bladder
Scrotum
(Note:ifepihigh,mustbeatornearadrenals,sincenonadrenalsiteslackabilitytomethylateNEtoepi)
Locators:
CT,MRI,131IMIBG(anNEanalogthatcollectsinadrenergicvesicles)
Note:Histologycantdeterminemalignancy;onlyspreadcan
PreopTreatment:
Increaseintravascularvolume
Mustgiveblockers(phenoxybenzamineorprazosin)for57dayspriortosurgerytocontrol
HTN.If,afterBPcontrolled,stilltachycardicaddonblockerfor2to4days.
Catastrophicerrortobeginwithblockerbecausethiswillleadtounopposedvasoconstriction
whichcancauseacuteheartfailure.
27
PituitaryGland
Bitemporalhemianopsiaisclassicvisualchangewithpituitarymasseffect
Prolactinoma:#1pituitaryadenoma
Sheehansyndrome:postpartumlackoflactation,persistentamenorrhea
28
ThoracicSurgery
LungCancer
170,000cases/yrinUS
#1cancerkillerinUS
5yearsurvival<15%
NSCLC[80%;adenocarcinomaseenwithincreasingfrequency(55%);doesworsethansquamous
cell(45%)],
SCLC[20%]
SquamouscellassociatedwithPTHrP;SmallcellassociatedwithACTH,ADH
Staging:
T1:3cm
T2:>3cm
T3:invasionofchestwall,pericardium,diaphragm,<2cmfromcarina
T4:unresectable;intomediastinum,heart,greatvessels;effusion
N1:ipsihilar N2:ipsimediastinal N3:contralateral,scalene,orsubclavian
M:2separatelesionsinsamelungM1diseaseundernewstagingsystem
StageI:T12
StageIIIb:unresectableT4orN3
StageII:T2N1,T3N0
StageIV:anyM
StageIIIa:uptoT3orN2
DdxforlungmassonCT:
29
Associationofsmokingandlungcancer
90%oflungcanceroccursinsmokers
1420foldhigherriskinsmokers;25foldhigher(neverzero)informersmokers
Showntobeamultistepprocess[NEJM265:253]offieldcancerization;moresmokingmoreCIS
onautopsy
3p14lossofheterozygosity88%smokers;45%formers;0%nonsmokers
Riskofsurgery:
PrethoracotomyPFTs:needFEV1>2L,1Lforpneumonectomy/lobectmy
WantPostopFEV1>8001000mL(40%predicted)
DLCO<60%significantrisk;MVO2<10mL/kg/minsignificantrisk
StageIIIdisease:
1.ConfirmN2status(FNA,mediastinoscopy,VATS)
2.CDDP/EtoposideorTaxol/CDDP+surgery+XRT
Severalstudies[RosellNEJM94,RothJNCI94+followups]couldendtheroleofsurgeryinIIIAdisease.Showed
thatwithinductionchemo+XRTsurgeryhadequalsurvivalwithsignificantlymoredeathsinsurgery
arm,butcurrentlystageIIIApatientsundergosurgicalresection
LymphNodeStations[MountainCF,etal.Chest,1997]:
Mediastinoscopycansamplestations1,2,4,and7(R10ifaggressive)
30
PancoastTumor:involvessympatheticchain(Hornerssyndrome);shoulder/medialscapulapainismost
commonpresentation;MediastinoscopyinductionchemoradicalresectionXRT
Significantlyhigherincidenceofrightsidednodeinvolvementwithleftsidedlungtumorsbecauseof
lymphaticpathwayswhichtravelfromleftright;thereverseinnotobserved
Metastatictumors(lung,breast)topleura>>primarypleuraltumor(mesothelioma)
InSummary:
1.SurgeryisstillstandardofcareforI,II,selectedIIIA,andselectedIIIBNSCLC(andveryrareIVdisease,
e.g.isolatedbrainoradrenalN0disease)
2.XRTimproveslocalcontrol,butnotsurvival
3.AdjuvantRTfor>T2,N12disease
4.InductionchemoisprovenforstageIIIdisease,butisuntestedforearlydisease.
Seeexcellentreview:MultidisciplinaryManagementofLungCancer[Spiraetal.NEJM350;379,2004]
Factorsthatairleakafterresection:
1.Neoadjuvantchemo/radiation
2.Deepdissection
3.Blebs/emphysema
Massivehemoptysis:>600mLin24hours
Spontaneouspneumothorax:usuallyresultofrupturedsmallbleb;1520%ofrecurrenceafterinitialevent
(muchgreaterafter2ndevent)
ChyleLeak:
Thoracicductenterschestonright(withaorta)crossestoleftatT4/5joinsatIJ/subclavian
junctiononleft
Mostofteniatrogenic
Normalchyleflowvariesbetween1.5and2.5L/dayaccordingtodiet
Highlymphocytes(makingitresistanttoinfection)and10xTGofserum
Treatwith2weektrialofNPOanddrainage(5070%success);ifstill>500mL/daytoORfor
ductligation
Empyema:exudative(thin,freeflowingfluid)fibrinopurulent(fibrindeposition,beginningtoloculate)
organizing(ingrowthoffibroblasts,peel)
ExudativeStage:mayrespondtoantibiotics
drainage
Thin
WBC<1000/mm3
LDH<5001000IU(pleuralfluid/serum>0.6)
Pleuralfluid/serumprotein>0.5
pH>7.30
Glucose>60mg/dL
FibrinopurulentStage:requireschesttube
surgery
Turbid,bacterialcellulardebris
Glucose<40mg/dL
LDU>1000IU
WBC>5000/mm3
pH<7.10
31
MediastinalDisease
Division
Anterior(and
Superior)
Middle
Posterior
Contents
1. Aorticarchandthoracicportionsofits
branches(brachiocephalic,leftcommon
carotid,leftsubclavian)
2. Brachiocephalicveins,upperhalfofSVC
3. Vagusnerves,leftrecurrentlaryngeal
nerve,phrenicnerves
4. Superioresophagus
5. Uppertrachea
6. Thymus
7. Upperportionofthoracicduct
8. Lymphnodes
1. Pericardium
2. Heart
3. Trachealbifurcationandmainstembronchi
4. Subcarinalandperibronchialnodes
5. Ascendingaorta
1. Thoracicportionofdescendingaorta
2. Azygos,hemiazygos,accessory
hemiazygosveins
3. Sympatheticchains
4. Thoracicduct
5. Esophagus
Tumors
Thymoma
Germcelltumor
Lymphoma
Thyroidadenoma
Parathyroidadenoma
Lipoma
Carcinoma
Hemangioma
Bronchogeniccysts
Pericardialcysts
Lymphoma
Neurogenictumors
Lymphoma
Entericcysts
Mostcommoninbold
32
RoleofthymomaandMyastheniaGravis:
ResectingthymusinMG,eveninabsenceofthymoma,improvessymptomsin90%,asthymushas
beenimplicatedinproducingpostsynapticantiAchantibodies
Completeremissionmostlikelyif:age<60andoperationperformed<8monthsfromdiagnosis
Radiatethymomaafterexcisiononlyifmarginspositiveandconsiderplatinumbased
chemotherapy.
Invasivenessattimeofresectionbestpredictsoutcome
Otherdiseasesassociatedwiththymoma:
EatonLambertsyndrome
Sjgrenssyndrome
Redcellhypoplasiaandaplasia
DiagnosticworkupofMediastinalMasses
Location
Mass
Test
Superior
Thyroid
ThyroidScan
Thymoma
Germcell
Lymphoma
Resection
HCG,AFT
Openbiopsy
Neurogenic
MRI
Anterior
Posterior
33
CardiacSurgery:CongenitalDefects
Echo,SaO2andCath
todistinguish
between:
Acyanosis
Central
Cyanosis
NormaltoPulmonary
BloodFlow
1. TetralogyofFallot
2. Tricuspidatresia
3. Pulmonicatresia
4. Ebsteinsanomaly
Normalto Pulmonary
BloodFlow
1. TranspositionofGA
2. Hypoplasticleftheart
syndrome
3. Singleventricle
4. Truncusarteriosis
5. Totalanomalous
pulmonaryvenous
return
PulmonaryBloodFlow
1. VSD
2. ASD
3. PDA
4. Aortopulmonarywindow
5. Endocardialcushiondefect(AV
canal)
6. Cortriatriatum
NormaltoPulmonaryBloodFlow
1. Coarctationofaorta
2. Pulmonicstenosis
3. Aorticstenosis
4. Anomalousoriginofleft
coronaryarteryfromPA
(ALCPA)
[FigureadaptedfromGeneralSurgeryBoardReview,Goldetal,1999]
VentricularSeptalDefect(VSD)
MostcommonCHD(25%,1/1000livebirths)
Multipletypes:perimembranousismostcommon
Upto50%haveassociatedanomaly(PDA,coarctation,AS)
PVRovertimebecauseofpulmonaryovercirculation,andmybeirreversibleat2years
MaygoondevelopEisenmengerssyndromewithshuntreversalacrosstheVSD
Fixifshuntfraction(Qp/Qs)>2(twicebloodflowtolungs)
RepairunrestrictiveVSDpriorto1yearofage(preventfailuretothrive)
PatentDuctusAteriosis(PDA)
Communicationbetweenupperdescendingaortaandleft/mainPA
Presentationdependantondegreeofleftrightshunt(pulmonaryovercirculationandstealfrom
systemicperfusion)
PersistentPDAismorecommoninprematureinfants
Medicalclosure:indomethacin(uptothreedoses)
Longtermcomplicationofpulmonaryovercirculationinclude:pulmonaryHTN,CHF,increased
respiratoryinfections
Earlysurgicalclosureindicatedforsymptomaticpatientswhoarerecalcitranttomedicaltherapy,or
arenotsuitablecandidatesformedicaltherapy
Useprostaglandintokeepopenincyanoticinfants;canalsocloseincathlab
34
CoarctationoftheAorta
Accountsfor68%ofCHD(25xmorecommoninmales)
Theusuallocationofthediscretecoarctationisjuxtaductal(justdistaltotheleftsubclavianartery)
Lessoften,thecoarctationisjustproximaltotheleftsubclavianartery;canalsobediffuse
Twotheories:
1.Reducedantegradeintrauterinebloodflow,whichcausesunderdevelopmentoftheaortic
arch
2.Extensionoftheductaltissueintothethoracicaortawhich,whenitconstricts,causes
coarctationoftheaorta
Themostcommonclinicalmanifestationisadifferenceinsystolicpressurebetweentheupperand
lowerextremities(diastolicpressuresareusuallysimilar),manifestedby:
1.Upperextremityhypertension
2.Absent/delayedfemoralpulses
3.Low/unobtainablebloodpressureinthelowerextremities
Treatmentoptionsincludeangioplastystenting(if>25kg)orsurgicalrepair(resection+endto
endspatulatedanastomosis,bypassifsegmenttoolongforprimaryrepair)
AtrialSeptalDefect(ASD)
Strictlyspeaking,aPatentForamenOvale(PFO)onlyshuts:rightleft
UsuallyanASDshunts:leftright
Accountsfor1015%ofCHD(mostcommononeinadults)
SecundumdefectismostcommonASD(PFOismorecommon)
Spontaneousclosurerare>2yearsofage
Typicallyasymptomaticwithmurmur;5060%haveeasyfatigability
FixalmostallpersistentASDs
Canbeclosedviacatheterization
TetralogyofFallot
Fouranatomicfeatures(keyisRVOTobstruction):
1. StenosisofPA
2. RVhypertrophy
3. VSD(usuallysingle,large,andunrestricted;intheperimembranousregionoftheseptum)
4. AortaoverridingtheVSD
Accountsfor710%ofallcongenitalheartdisease(3.3per10,000livebirths)
Approximately15%ofchildrenhaveextracardiacanomalies(e.g.trisomy21)
PhysiologyandclinicalpresentationoftetralogyisdeterminedprimarilybytheextentofRV
outflowobstruction.Mostchildrenarecyanoticandsymptomatic.
Severeobstructionwithpoorpulmonaryflow:profoundcyanosisduringnewbornperiod
Moderateobstructionwithbalancedpulmonaryandsystemicflow:maybeidentifiedduring
electiveworkupforamurmur
Minimalobstruction:pulmonaryovercirculationandlateheartfailure
Optionsforrepairinclude:
PatchrepairoftheRVOT,possiblyrenderingthepulmonaryvalveincompetent,which,ifsevere,
mayhavesignificantlongtermhemodynamicandelectrophysiologicconsequences.
AnalternateprocedureistheinsertionofavalvedconduitfromtheRVtothedistalmain
pulmonaryarteryifthereispulmonaryatresiaoracoronaryanomalyprecludingatransanular
incision
35
CardiacSurgery:AcquiredDefects
4buzzwordstodescribecardiacphysiology
Inotropy:forceofcontraction(systolic)
Chronotropy:rateofcontraction
Lusitropy:rateofrelaxation(diastolic)
Dromotropy:conduction
CoronaryArteryBypassisassociatedwithimprovedsurvivalinpatientswith
triplevesseldisease
leftmaindisease
patientswithEF
i.e.themoreextensivediseasethegreaterthebenefit
Indications:
Intractablesymptoms,medicallyrefractory
>50%leftmaindisease
TriplevesseldiseasewithdepressedEF
LeftdominantcirculationwithhighgradeLADstenosis
Dominance:85%arerightdominant,whichmeansRCAsupplies:
1. PDA
2. AVnode
3. Posteriorcruxofheart(nearIVC)
Branchesofmaincardiacvessels
1. Leftcircumflex:obtusemarginals
2. Leftanteriordescending:diagonalsandseptals
3. Rightcoronary:acutemarginalbranches;ifrightdominant:PDA,AVnodal;septals
Saphenousveinpatency5060%at10years
IMApatency95%at10years
RateofrecurrenceofanginafollowingCABis57%peryear
IABP
Positionedjustdistaltoleftsubclavianartery(aorticknobonCXR)
Inflatesduringdiastole(40msecbeforeTwave;afterload)anddeflateswithpwave(coronary
perfusion);AIisacontraindication
AcuteMIComplications
1.Arrhythmias:PVC,ventricularectopy,
VT/VF,PEA(pulselesselectricalactivity)(048hours)
ReperfusioncancausePVCs
2.Recurrence:(07days)
3.PericardialDisease*:pericarditis;Dresslerssyndrome(pericarditis+effusion)(6hours14days);likely
autoimmune inflammationofpericardium;pleuriticchestpain,lowgradefever,malaise;treatwith
steroidsorNSAIDs;
*keyistodifferentiatefrommediastinitis
36
4.Mediastinitis:follows13%ofcardiacsurgery;risksinclude:DM,age>60,reexplorationforbleeding,
steroids,obesitywithbilateralIMAharvest;needreoperativedrainageandflap(advancementpec,or
transfer)
5.StructuralCatastrophes(35days)
a)papillarymuscletear;usuallyfollowsposteriorMI:acuteMRpulmonaryedema
b)septalrupture:VSD(SOB)
c)freewallrupture:rapiddeath
6.Aneurysmformation(weeks);10%ofpatientspostMI;usuallyafteranterolateralinfarctcausedby
proximalLADocclusion(anteriorandapical);candevelopprogressiveLVfailurewithCHF;nidusfor
emboliandarrhythmia;surgicalinterventionifsymptomatic
7.CHF+Recurrence:ANYTIME
Mitralstenosis
Symptoms:CHF,pulmonaryedema,rightsidedheartfailure,AFib,embolization
Etiology:RF
Normalmitralarea=45cm2;usuallysymptomsdevelopwhenareafallsbelow1.4cm2
Physiology:LApressureCOPVR
Surgeryindicatedfor:Area<1cm2,CHF,pulmonaryHTN,embolization,gradient>5mmHg
Mitralregurgitation
Symptoms:CHF
Etiology:myocardialischemia/infarct,endocarditis(acute);MVP,RF,myxomatousdegeneration(chronic)
Physiology:abnormalityofannulus(dilatation),leaflets(redundancy[prolapse],defect[endocarditis],
shrinkage[RF]),chordaetendineaerupture,papillarymusclerupture
Surgeryindicatedfor:acuteMRcomplicatedbyCHForshock,endocarditisassociatedwithshockor
persistentsepsis/embolization,EF<55%,EDdimensions75mm,ESdimensions45mm
MitralStenosis
AlmostexclusivelycausedbyRF
PulmHTNandRHfailureseen
Afibandembolizationcommon
MitralRegurgitation
RFiscommoncause,butalsoendocarditis,MVP,ruptured
chordaetendineae,myxomatousdegeneration
PulmHTNandRHfailurealsoseen
Embolizationlesscommon;LVfailuremorecommon
OperateforLVchambersize(LVESV>55),heartfailure,
newAfib.
Earlieroperation=chanceforsuccessfulrepair
Aorticstenosis
Symptoms:Angina,SOB,syncope
Etiology:RF,bicuspidvalve,degenerative(ingeneral:<50congenital,5070bicuspid,>70
calcific)
Avoidpreloadreduction,avoidhypotensionandACEinhibitors
Slowcarotidupstroke,softS2
Criticalstenosis<0.8cm2
TypicallyCXRshowsnormalsizeheart(ruleofthumb:stenosisnormalsizeheart;regurgitation:
dilation)
37
Prognosisdependsonsymptoms:
1.CHFworstprognosis(1.5years*);occursatapproximately0.70.8cm2
2.Syncopepostexertional(3years*)
3.Angina(5years*)
*Meansurvivalfrominitiationofsymptoms
needantibioticprophylaxis
criticalASdiagnosedbysymptoms,notarea
symptomsneedsurgery,goodoutcomeevenin80s
averageprogression0.12cm2/year
Surgeryindicatedfor:Area<0.81.0cm2,gradient>50mmHg,symptoms,evidenceofrapidcardiac
enlargement
Aorticregurgitation(AR/AI)
3Fs:Fast(mustbekepttachy),Forward(reduceAL),Full(preloaddependent)
Symptoms:Fatigue,angina,progressivedyspnea,palpitations,peripheralvasomotorchanges;bounding
peripheralpulses(widepulsepressure)
ESLVdiametergreaterthan5cmhasincreaseddeathrate(19%vs.5%peryear)
AcuteRx:afterloadreduction,diureticsforCHF
Surgery:symptoms,evidenceofventricularenlargement
PerioperativeMI
Mostlikely23dayspostop
DifferentiateAcuteMIfromAcuteCoronarySyndrome
A. AcuteMI:CP,STelevations,+enzymes
Goalsare:1.Reperfusion(fibrinolytic06hours;cath),and2.DecreaseO2demand
B. AcuteCoronarySyndromeissubdividedintoNonQwaveMIandUnstableAngina(CP,withno
EKGchangesorenzymes)
NonQwaveMI:CP,EKGchangeswithoutSTelevation,+enzymes;giveMONA(MSO4,O2,nitrate,
ASA)+blockerthenIIb/IIIa+heparin
*Note:InferiorinfarctRCA90%chanceofAVnodalinvolvement2:1blockmorelikelytobeMobitz
I>IIgiveatropine
38
CXRappearancewithcardiachypertrophy/enlargement
(Blackoutlineisnormalcardiacsilhouette)
LVH
RVEnlargement
RAEnlargement
LAEnlargement
Arrhythmias
ThreeRulesofThumb:
1.Ifpatientishemodynamicallyunstableasaresultofdysrhythmiaproceeddirectlytocardioversion
(300J)
2.Ifpatienthasawidecomplextachycardiaproceeddirectlytocardioversion(300J)
3.Ifthepatienthasanarrowcomplextachycardiainfuseadenosine(orverapamil)fordiagnosis
(Amiodaroneisbecomingdrugofchoicefortreatment)
Adenosineisanendogenousnucleosidewithdifferentialantidysrhythmiceffectsonbothsupraand
ventriculartissue;alsodepressestheautomaticityofboththeSAandAVnode.
Twotypesofadenosinereceptorsinheart:
A1(onAVnodeandmyocytespromotingAVblockandbradycardic),and
A2(onvascularendothelialsmoothmusclemediatescoronaryvasodilation)
EaglesCriteria:Riskofsurgery(Morethan2warrantcardiologyworkuppriortosurgery)
I.Symptomatic
CHF
Angina
II.Demographic
DM
male
age>70
III.EKG
Qwavespresent
ventarrhythmia
Preopexercisetoleranceisthemostsensitiveindicatorofabilitytowithstandsurgery.Ifpatientunableto
walk2flightsofstairsproblemslikely
39
Criteriaforuseofperioperataive
blockade
Age>65*
Hypertension
Currentsmoker
Cholesterol>240mg/dL
NIDDM
RevisedCardiacRiskIndexCriteria
(3preopworkup)
Highriskprocedure(intraperitoneal,
intrathoracic,suprainguinalvascular)
Ischemicheartdisease
HistoryofMI
Historyofangina
UseofSLnitroglycerin
Positiveexercisetest
QwavesonEKG
PreviousPTCA/CABwithischemicchestpain
Cerebrovasculardisease
HistoryofTIA/CVA
IDDM
CRI(Cr>2mg/dL)
*Manywoulduseblockadeforpatients>40
AtrialFibrillation
RateControlvs.RhythmControl:2largestudies[NEJM2002,347:18251833,18341840]evaluatedpatients
withatrialfibrillationforlessthan1yeardeemedtobeathighriskforrecurrence.Thesestudies
concluded:
1. Ratecontrolwasnotinferiortorhythmcontrolforthepreventionofdeathandmorbidityfrom
cardiovascularcausesandmaybeappropriatetherapyinpatientswithrecurrenceofpersistentAfib
afterelectricalcardioversion.
2. ManagementofAfibwithrhythmcontroloffersnosurvivaladvantageovertheratecontrol
strategy.Anticoagulationshouldbecontinuedinthesepatients.
Hence,bothrateandrhythmcontrolledpatientsneedanticoagulationastheirstrokerateis1%peryear.
40
SurgicalApproaches:
[NittaT,etal.AnnThorSurg199967:27]
Radiofrequencyablation,cryoablationpossibleinterventionsforchronicAfib(RFAisbecoming
popularbecauseofthecomplexityoftheMazeprocedure).
ElectricalcardioversionisrarelysuccessfulinconvertingchronicAfib.
90%ofparoxysmalAfibcuredwithpulmonaryveinisolationalone
PersistentAfibgenerallyneedfullCoxMazeIII;RFA6070%cure;Maze90%cure
41
VascularSurgery
NitricOxide:derivedfromLarginine;reducesfreeradicals(byscavenging)andpreventsatherosclerosis;
cGMPactsasthe2ndmessenger
Cerebralischemiamostoftencausedbyatheroembolization(50%ofstrokesduetoHTN,25%duetocarotid
disease,25%duetobleedorothercause).
ClinicalClassification
1. Asymptomatic:bruits(+bruit3050%havesignificantstenosis;+significantstenosis2050%
bruit;Bruitareactuallyasignificantpredictorofcardiacdisease)
2. TIA:<24hourresolution(90%resolvewithin2hours)
3. RIND(ReversibleIschemicNeurologicDeficit):2448hourresolution
4. Fixeddeficit:stroke
RisksofStroke:
700,000peryear
160,000deaths/year
1yearpoststroke 2/3ofsurvivorshavedisability
TIA:15%strokeinfirstyear,thenabout6%peryearthereafter(40%chanceofstrokein5yearswithout
ASA)
CorticalTIA
VertebralTIA
Unilateral
Dizzy
Armweakness
Bilateralwoozy
Decreasedvision
Dropattack(transientlossofmotortone)
Asymptomatic:
CarotidStenosis
Stenosis>50%:about4%peryear
Stenosis>80%:35%riskover2years
2%peryearriskofstrokeforpatients>60
Lowresistancearterialsystems(suchasICA):totalbloodflowdoesnotdecreaseuntilstenosis>
50%.Hence,noneedtorepairstenosis<50%
Upto50%ofpatientswhosufferstrokehavehadpreviousTIA
AsymptomaticCarotidArteryStenosisTrial(ACAS)demonstratedthatpatientswithanasymptomatic
stenosisof60%orgreaterhada53%relativeriskreductionofstrokeafterundergoingCEA+ASA
comparedtoASAalone[115%].Thebenefitwasmuchgreaterinmenthanwomen.
NorthAmericanSymptomaticCarotidEndarterectomyTrial(NASCETI)demonstratedthatCEAis
highlybeneficialinpatientswithrecenthemisphericorretinalTIAornondisabalingstrokeandan
ipsilateralhighgradestenosis(7099%).Thebenefitofsurgerywasseenwithin3monthsofoperation.
Theincidenceofstrokewasdecreasedinallsubgroupsbutwaslargestinpatientswhoexperiencedmajor
ipsilateralstrokewithan81%riskreduction.Overall,26%ofpatientswithhighgrade(7099%)stenosis
sustainedastrokewithin18monthswithmedicalmanagementvs.9%withsurgeryat2years[269%]
NASCETII:lookedatsymptomaticpatientswith5069%stenosisandfoundareductionfrom2216%
(p<0.045).Morehospitalsparticipated,henceincreasedmorbidity.
42
Diagnosis:Ask3questions(ICAdisease?%stenosis?Characteristicsofplaque?)
Neckduplexconsistsof2parts:BmodeU/Simageandspectralvelocityanalysis
IC/CCsystolicratiogives%stenosis:
<2
<50%
23.9
5069%
>4
7099%
FollowingCEA:
Ifipsilateralpreorbitalheadachethinkhyperperfusion(sincestenosisremoved);usually35
dayspostsurgery.
MostcommonCNinjuryvagusnerve(clamp)hoarseness
CNXIItonguedeviationtosideofinjury;marginalmandibularlipdroop
CADismaincauseofpostopmortality
Restenosisrate510%(>50%stenosiswithin2years:myointimalhyperplasia,notatherosclerosis;
F>M)
UpperlimitguidelinesforacceptableM&MratesforCEA:
Asymptomatic:3% Symptomatic:5%
Symptomatic/CVA:7%
RecurrentStenosis:10%
ToparticipateinACASandNASCETtrialscentershadtohave<5%overallmortalityforCEA
CarotidAnatomy
th,1993]
[AtlasofSurgicalOperations,Zollinger&Zollinger,7
43
AbdominalAorticAneurysm
95%infrarenal
approximately75%asymptomaticanddiscoveredincidentally
growthrate0.4cm/yearindiameter
riskofruptureforsmall(<5.5cm)aneurysms:0.61%peryear[NEJM2002,346:14371444,14451452]
Pathology:matrixmetalloproteaseactivity(MMP1,2,3;MMP9)
riskofrupturerelatedtosize:
<5cm:20%5yearrisk
57cm:33%
>7cm:95%
1020%involveiliacs
whenremovingdistalclamps,removeINTERNALiliacfirst,thenEXTERNALiliactoavoiddistal
embolizationtolowerextremities
followingrupturewithoperativerepair:cardiaccomplicationsaremostcommoncauseofearly
death;renalcomplicationsforlatedeath
CADismostcommoncauseofdeathforpatientswithsmallAAA(<6cm);
Rupture(7590%mortality)ismostcommoncauseofdeathforpatientswithlargeAAA(>6cm)
[unlesstheyhavemetastaticcancerordebilitatingCHF]
IndicationsforRepair:
Goodriskpatients: 1.AAA>5.5cm+lifeexpectancy>2years
2.AAA<5.5cmwithCOPD,expansion>0.5cm/6months
Highriskpatients: 1.AAA>6cm,orsymptomatic
TheUKSmallAneurysmTrial:[NEJM346(19):1445,2002]Randomlyassignedover1000patientswith
aneurysmsrangingfrom4.0to5.5cmtoeitherundergoearlyelectiverepairorobservationwithU/S
surveillance.Meanfollowupwas8years.Themeansurvivalwas6.5yearsinthesurveillancegroupvs.
6.7yearsinthetreatmentgroup(p=0.29).Earlymortalitywasgreaterinthesurgerygroup,buttotal
mortalitywasgreaterinthesurveillancegroupat8years.
IndicationsforRetroperitonealApproach:
hostileabdomen
InflammatoryAAA
juxtarenalAAA
Rightiliacdiseaseisarelativecontraindication
Benefits(vs.anteriorapproach)include:respiratoryproblems,LOS,minimalileus
44
Optionsforocclusiveaortoiliacdisease:
[RUSHReviewofSurgery,2000]
40%ofaneurysmalinfectionscausedbysalmonella
Staphaureusandgramnegativebacteriaaremostcommonorganismsinearlygraftinfection;staph
epidermidisismorechronic(presents>4months;at2yearsonaverage)
AortoentericFistula(AEF):Primary(nograft)vs.Secondary(graft)
80%distalduodenum(aorticpathology>75%;GIpath15%)
causes:graftinfection,duodenaltrauma(ischemia)duringoriginaloperation,inadequategraft
coverage
SecondaryAEF:
90%aregraftentericfistula(anastomotic)vs.10%graftentericerosion(paraprosthetic)
6080%presentinitiallywithselflimitedsentinelbleed
OfallpatientswithGIbleed+historyofaorticreconstruction2%haveAEF(hence,doendoscopy
1sttoruleoutothercausesofUGIB)
Mortality35%
Documentfemoralpulses
CTwithIVcontrast(minimumof3mmcuts)[CT>angio:showsmorethanlumen]
Angiographyif:(i)symptomaticmesentericdisease,(ii)questionofrenaldisease,(iii)nofemoral
pulses(needtoknowtargets),(iv)significantPVD/claudication
GoldStandardrepair:graftexcision,closureofaorticstump,extraanatomicrevascularization(close
duodenumprimarily)
45
EndovascularStenting:
Endovascularstentgraftplacementiswidelyperformedforthetreatmentofinfrarenalabdominalaortic
aneurysms.Althoughadvancesingraftdesignhavegreatlyexpandedthepopulationofpatientswho
wouldbeconsideredcandidatesforendograftplacement,therearecertainanatomiclimitationsthatplace
thepatientathighriskforatypeIendoleak(alackof,orsuboptimalfixationin,theproximalordistal
attachmentsite).Criticalinformationthatthevascularsurgeon/interventionalistneedstoknowpriorto
embarkingonanendograftplacementprocedureincludes:
1.
2.
3.
4.
5.
6.
7.
8.
Isthereasufficientlengthofneck(15mm)ofnormalaortaabovetheaneurysm?
Isthewidthoftheneck<2026mm?
Whatisthedegreeofangulationoftheneck(needstobe<60o,seefigure)?
Istheinferiormesentericarterypatent?
Arethecommoniliacarteriesaneurysmal?
Arethecommoniliacarteriesaneurysmalwithrespecttothedistalaorta?
Arethehypogastricarteriespatent?
Aretheexternaliliacarteriespatent?
[FiguretakenfromtalkgivenbyLesCunningham,2005]
97%successinstallation
Nostudyshowsdecreasemortality(onlydecreasedmorbidity)
Actuallyincreasedcostwithfollowup
1%/yearrupture/explantrate
Upto50%ofpatientswilldevelopanendoleak
2030%needreinterventionwithin2years
5yearsurvival:75%(sameasopen)
Leaks(I,IIIareworst)
I. Presumedanastomosissite(fixedsiteleak)mustbefixedwhendiagnosed
II. Graftleakviacollaterals(branchvesselleak;backbleeding,usuallylumbars)mustbefixed
orconvertedtoopenifcontinuestoexpand*
III. Tearingraft(graftdefect)
IV. Transgraftegression(needleholes/porosity):selflimiting
V. Endotension(controversial):saidtooccurwhenthereisintrasacpressurewithoutevidence
ofendoleak.Unsureofcause.
*TypeIImyclosespontaneouslywithinfirst12months;hence,ifaneurysmsacnotexpandingwarrants
observationfor12months.Repairifsacpersists>12monthsORsacinsize.
PresentlyOVER(OpenVs.EndovascularRepairofAAA)Trialhasrandomized>400patients
46
PeripheralVascularDisease
Claudication:
Historyiskey:Reproduciblepainofbuttock,thighand/orcalfassociatedwithambulationand
relievedbyrest.
Initialtreatmentissmokingcessation,exercise;Pletal>Trental(butcost);notsurgery
Thesepatientshavethesameriskofdeathfromcardiovasculardiseaseaspatientswithknown
cardiacdisease(50%diewithin5years)
Progressestogangrene23%annually(only10%everloseleg)
Restpain/ulcersindicationforbypass
Clinicalmanifestationsofcriticallimbischemia(accordingtoEuropeanConsensusConference):
1.Restpainrequiringanalgesiaforatleast2weeks
2.Anklesystolicpressure<50mmHg(withorwithouttissueloss/gangrene)
ExerciseTestpositiveif>20%fallinanklesystolicpressurerequiring>3mintorecover
ArterialFlowistriphasic:1.Forward,2.Reverse,3.Lateforward(Note:willbenormallymonophasicin
lowresistancesystem,likeICA)
ABIValues:
Calcified(diabetic)>1.2;normal>1;Claudication0.50.99;Restpain0.3
*RequireABI>0.5tohealalowerextremityamputation
1yearsurvivalafteramputationforischemicdiseaseis75%
50%ofpatientsloseotherlegwithin5yearsof1stamputation
*Mostcommonsiteoflowerlimbatherosclerosis:SFAinregionoftheadductorcanal(Hunterscanal)
*CardioatrialembolimostfrequentlyoccludeCFA
Reversedsaphenousveinpatency(goldstandardbelowinguinalligament):8090%at1year;75%at5
years;persistentsmokingis#1reasonforlategraftfailure(valveleafletremnantsis#1reasonduring1sttwo
years)
Fempopbypass:
#Vesselrunoff5yearpatency
370%
235%
11520%
PoplitealArteryAneurysm
Mostcommonperipheralaneurysm(70%ofall)
50%arebilateraland30%alsohaveAAA
2030%oflimblosswithdistalembolielectiverepairofall,regardlessofsize
Managementoptions:medialexploration:proximal/distalligation&bypass
acutethrombosispreopthrombolytics
endovascularrepair(notyetaccepted)
47
TibperonealDisease(infrapop)*
insituSVvein:
armvein
PTFE
PTFE+coum(2.0)
PTFE+veinpat
1year4yearpatency
82% 68%
73% 58%(3year)
46% 21%
50%
74% 54%(5year)
*Peronealarteryisleastlikelyvesseloflowerextremitytobeoccludedbyatherosclerosis
Patch/collarreduceturbulenceincreasecomplianceatdistalanastomosisminimizetraumatoarterial
endotheliumdecreaseproliferativeresponse(intimalhyperplasia)
Belowkneerevascularizationshouldonlybeperformedforlimbsalvage(includingrestpain)
Contraindicationstothrombolytictherapy:recenthistory(6months)ofTIAorCVA;recent(10days)
operationorGIbleed;presenceofintracranialmalignancyorvascularmalformation;uncontrolled
hypertension
LowerExtremityVascularAnatomy
Anteriorview
PosteriorView
[VascularSurgery,HouseOfficerSeries,3rdFaustandCohen,1998]
48
EvaluatingLowerExtremityUlcers
Firstdiagnosethecause(diabetic,venousinsufficiency,arterialinsufficiency,vasculitis,IBD,etc.)
Themostcommonarediabetic,arterial,andvenousinsufficiency:
I.Diabetic:typicallyoccuronpressurepointsonthefootandarepainlesssecondarytotheacquired
neuropathy
II.ArterialInsufficiency:extremelypainful,associatedwithrestpainindistalfoot,havegrayishgranulation
tissue,surroundedbyblueandmottledskin,anddonotbleedwhendebrided.Painismostcommonover
metatarsalheads,nottoes(usuallyoccuratpressurepoints).
III.Venousinsufficiency:large,irregular,shallow,haveredgranulationtissue,occuraroundmedialand
lateralmaleoli,andaresurroundedbybrawnyedemaandstasispigmentation.Leukocytesarethoughtto
playanimportantroleinthepathophysiologybecausetheyhavebeenfoundtobesequesteredintheankle
regionofpatientswithelevatedvenouspressures,especiallyinthedependentposition.Theyplug
capillariesandbecomeactivatedandreleasetheirenzymesandsuperoxideradicals,decreasingflow,
leadingtoischemiaandulceration
Phlegmasiaalbadolens:venousclotresultsinsuchincreaseinvenouspressureedematous,swollen,
pale,cyanoticextremity;blanchedappearanceresultofedema;canimpairarterialinflow;asurgical
emergencyrequiringthrombectomycreationofAVfistula(canuseTPA)
EvaluatingLimbIschemia
Thepresentationofperipherallimbischemiadeterminesthechronicity
Acutelimbischemiais60%thromboticand40%embolic
Alwayscheckinflow(femoralpulses)
AbsentpoplitealpulsesimplySFAocclusionormultipleproximalocclusions
Whendescribingangiographiclesions/stenosesusetermslike:none,mild,moderate,severe,and
distinguishbetweendiffuseandfocal
SVSClinicalClassificationofLimbIschemia
Sensory
Motor
Doppler
Arterial
Normal
Abnormal
Doppler
Venous
Normal
Normal
Viable
Normal
Normal
Threatened
+/toes
Normal
Marginal
Threatened
Beyondtoes
Mildmoderate
Abnormal
Normal
Immediate
deficit
Irreversible
Profound
Paralysis
Abnormal
Abnormal
Ifyouhearamonophasicdopplersignaldistinguishbetweenarterialandvenous(venouswillchangewith
sequentialcalfcompression)
Treatment
Viable:
heparinfurtherworkup
heparinfurtherworkup
Threatened(Marginal):
Threatened(Immediate):
heparintoORforintraopangiogram+/intervention
Irreversible:
toORamputation
dose:bolus80units/kgfollowedbydripof18units/kg
49
ThoracoabdominalAneurysms
Themostcommoncauseofascendinganeurysmaldiseaseiscysticmedialnecrosis(seeninMarfans
syndrome);allotherareasofaneurysm(includingtransversearch)aremostassociatedwithatherosclerotic
disease.
Operateifsymptomaticor>6cm
[AnnThorSurg2001;71:1233]
[AnnSurg2004;240:677]
Riskofparaplegia:greatestriskTypeII;I50%risk;StagedRepairtoTAAwithelephanttrunk
III25%risk;IV10%risk
AorticDissection
StanfordA:involvesaorticarch[includedDeBakeyI(ascendinganddescending)andDeBakeyII
(ascendingonly)].Asurgicalemergency,1%mortalityperhour.
StanfordB:involvesdescendingaortaonly[sameasDeBakeyIII].Medicalmanagement(i.e.controlHTN).
Operateonlyforrupture,occlusion
50
SplancnicArteryAneurysms
Site
Incidence
Pathology
Splenic
Mostcommon;
1/1000
Atherosclerosis
F>M
60%occur
during
pregnancy
Hepatic
2ndmost
common
splancnic
Infectiousmost
common;
Mycotic
following
sepsis(e.g.
bacterial
endocarditis);
Approx80%
outsideofliver
Most
symptomatic;
PersistentRUQ
pain
SMA
3rdmost
common
splancnic
Rarely
atherosclerotic;
>50%mycotic
(2otoSBE)
Celiac
Rare;1/8000
Atherosclerosis;
Infectious,also
Almostalways
cause
symptoms;
Intermittentor
constant
epigastric/back
pain
Usually
asymptomatic
Clinical
Presentation
Most
asymptomatic
20%with
variable
symptoms
Diagnosis
NaturalHistory
Often
incidental
CalcsinLUQ
CT
Arteriography
isgoldstd
Unclear;if
symptomatic,
enlargingfix
Pregnantfix
>23cmfix
Somesayokto
watchif
1.Asympt+>60
2.calc+<1.5cm
Rarepreop;
Unknown,but
Selective
rupture
celiac
devastating,so
Arteriography fixallunless
serious
isgoldstd
contraindication
Epigastric
pain,tender
NONFIXED
pulsitilemass
Spontaneous
ruptureoccursin
over50%;
Operation
always
warranted
Usually
incidental
Unknown;
probablyhigh
riskofrupture
Treatment
Ifdistal
splenectomy
Ifproximal
ligateatboth
ends(noneedto
reconstruct
becauseofshort
gastrics)
ProximaltoGDA
aneurysmectomy
andligate
(retrogradeGDA
flow)
Maydosamefor
PHA,LHA,or
RHA,butrecon
withsaphenous
veinisbest
Aneursymectomy
+bypass(vein
preferredbecause
ofinfection);
Dacron
acceptable
Aneurysmectomy
witharterial
reconstructionis
desired;
Greatestriskis
intestinal
ischemia
51
ThoracicOutletSyndrome:anatomiccompressionofbrachialplexus,subclavian/axillaryartery,and/or
vein.
Mostpatients(95%)havepainorparesthesias
MostcommonlyintheC8toT1(ulnar)distribution[nerveconductiontestsdemonstrateslower
conductionvelocityacrossthoracicoutlet:meanof>80m/sinnormalsvs.<60m/sinaffected]
Canalsocauseatrophyofinterosseousmuscles
Arterialinvolvement:canseedistalischemia(similartoRaynaudsyndrome),1%
Venousinvolvement:extremityedema,effortthrombosisorPagetSchroettersyndrome,4%
Inexaminingthepatienttrytoreproducethesymptomswitharmelevation(EASTElevate
Arm,StressTest:putbotharmsupandpinchfingersshouldbeabletofor3minutes).
Conservativemanagementappropriateformost
Generally,thetransaxillaryapproachisbestforoperativecorrection
Fornervecompression:1stribresection,anteriorscalenectomy,resectionofcostoclavicular
ligament,andneurolysisofC7,C8,T1
Forarterialcompression(producingthrombosis):1stribresection,thrombectomy,embolectomy,
arterialrepairorreplacement
Forvenouscompression(producingthrombosis):viaantecubitalcatheterobtainvenogram,
performthrombolytictherapy;afterclotlysis1stribresection+othercompressiveelements.Do
venogram2weekslateras50%willrequireballoondilatationofstenosisinvein
Subclavianstenosis:
Canresultinsubclaviansteal,whereuseofarmstealsbloodfromcerebralcirculationvia
vertebralarteryorarmclaudication
Bestpatencyresultsseenwithcarotidsubclavianbypassorballoondilatation
Fascialcompartmentsoflowerleg(right):
Fasciotomyshouldbeperformedconcomitantlyonthelimbifithasbeensubjectedto>48hoursof
ischemia(includingheparinizedpatients),and/orinpatientswithsymptoms
52
VisceralIschemia
Celiac&SMAcollateralizeviaGDA,PDA
SMA&IMAcollateralizeviamarginalarteryofDrummond(arcofRiolan)
[GeneralSurgeryBoardReview,1998]
ArterialEmboli
Incidence(%)
50
Age
Elderly
ArterialThrombosis
25
Elderly
Nonocclusive(low
flow)
20
Elderly
VenousThrombosis
Younger
Priorsymptoms
Possibly
intestinalangina
Usuallynone
Riskfactors
Systemicatherosclerosisandthe
risksthataccompanyit;Afib
RecentMI,CHF,arrhythmias,Rh
fever
Usuallynone
Shock,CPB,vasopressors,sepsis,
burn,pancreatitis;digoxincan
exacerbate;treatunderlying
condition;ORforgangrenous
bowel
Possibleprevious Hypercoagulablestate,portal
thrombosis;
HTN,inflammatorystates,prior
DxbyCT
surgery,trauma;treatwith
immediateanticoagulation
Mortality
VeryHigh
High
Highest
Lowest
mostcommonlylodgeatmajorbranchpointsalongSMA,distaltomiddlecolic
mostcommonlyoccludeproximalSMA
tendstobemoreperipheralthanarterialocclusionshortersegmentsinvolved
*Bariumstudiesarecontraindicatedbecauseoftheintraluminalpressuregeneratedandthepotentialofthebariumto
obscurefutureangiographicstudies
ChronicMesentericIschemia:typicallyneed2/3vesselsoccluded.Preferredrepairisantegrade(aorto
mesenteric)bypasswithveinorprosthetic,typicallytoasinglevessel(SMA).Candilateandstent
(especiallyifolderand/ormalnourished)
53
Urology
1.BladderBody:cholinergiccontractsempties
2.BladderNeck:adrenergiccontractsinternalsphincterretains
Testicularmass:biopsyisorchiectomyviainguinalincision(nevertransscrotal)
Testiculartorsionbilateralorchiopexy
Ureteralinjury:useabsorbablesuture,stent,anddrain(debrideandspatulateendsoverstent)
Treatmentbasedonlocation(upper,middle,lower);middlehasworstbloodsupplyhardesttoheal
[FiguretakenfromatalkbyPeterPinto,2004]
Varicoceleseenmoreoftenonleftside:leftgonadalveinleftrenalvein;rightgonadalveinIVC
Rightvaricocoelepresent,ruleoutrightrenalmasswithIVCthrombus
Seminoma
2035yearsold;Anaplasticsubtypeismostmalignant;hCGin5to10%ofpureseminoma
patients
25%haveoccultmetsinstageI
Veryradiosensitive(allstagesgetRT)
Node+disease(N1andN2)getsRT
Bulkynode+disease>5cm(N3)getsplatinumchemo(BEP)ifresidualnodes,thensurgery,if
residualnodes+fortumor,salvagechemowithVIP(vinblastine,ifosfamide,cisplatinum)
Nonseminomagermcelltumors(choricocarcinoma,embryonalcell,yolksac,teratocarcinoma)
MayhavehCGANDAFP
AFPnotelevatedinpurechoriocarcinomaorseminoma
GetLNdissection;chemoifadvanced;NOTradiation
ChemoisBEP:bleomycin,etoposide,cisplatin;pulmonaryfibrosisismostfearedcomplicationdue
tobleomycin
Lymphaticdrainageoftestes(ifcrossoverdrainageoccurs,itisrighttoleft):
Right:interaortocavalnodes&rightrenalhilum
Left:paraaortic&leftrenalhilum
54
Prostatecancermostoftenarisesinperipheryofgland(peripheralzone);BPHarisesincenterofgland
(transitionalzone);Prostatemetstoboneareosteoblastic(50%),osteolytic(10%)mixed(40%)and
radiodense
95%ofEPOmadebykidney;stimulatedbyhypoxia
OrthopedicSurgery
Discherniationandassociatednerverootcompression:
Disc
L3L4
L4L5
L5S1
Nerveroot
compression
L4
L5
S1
Symptoms
Weakkneejerk;medialfootsensation
Weakdorsiflexion;weakbigtoe;sensationbetween1stand2ndwebspace
Weakplantarflexion;weakanklejerk;sensationtolateralcalf/foot
HipDislocation
90%posteriorinternalrotation+flexed+adductedthigh
Riskofsciaticnerveinjury,AVNoffemoralhead
TibialandCalcaneousfracture:pronetocompartmentsyndrome
HumerusFracture:mayseeradialnerveinjury(weakwristextension;insensationoverlateral/dorsal
hand)
ShoulderDislocation:90%anterior;riskofaxillarynerveinjury;posteriordislocationseenwithextremely
violentmovement(seizures,electrocution)
NavicularFracture:tendersnuffboxevenwithnegativexray,requirescasttoelbow
(Closed)PosteriorKneeDislocation:Reduce1st,thenarteriogram;3045%incidenceofpoplitealartery
injury(intimalteardisruption)
Femurfracture
Adults:earlyORIFallowsearlymobilization,fatemboli/complications
Children:closedreductionandtoavoidinterferencewithgrowthplate
Anteriordrawersign:tearofanteriorcruciateligament(ACL)
ChanceFracture:horizontalfracturethruvertebra(body,pedicles,laminae).Seenwithsudden
decelerationwithlaponlyseatbelts;usuallyL1orL2;>50%chanceofunderlyinghollowviscousinjury
(smallbowelismostcommon)
[www.auntminne.com]
55
GynecologicPathology
OvarianCancer
5majorclasses(basedonhistologyandembryologicetiology):
1. neoplasmsderivedfromcelomicepithelium
2. neoplasmsderivedfromgermcells
3. neoplasmsderivedfromgonadalstroma
4. neoplasmsderivedfromnonspecificmesenchyme
5. metastaticlesionstotheovary(usuallyGI,breast,oruterine)
Responsibleforhalfofallgynecologicdeathseachyear;25,000cases/yearinUS(33%5year
survival)
Allcomers:20%ofovarianneoplasmsaremalignant(withage)
Womanaged2030:10%chanceofmalignancy;50:50%chanceofmalignancy
Usuallydiagnosedinadvancedstage(2/3presentasstageIIIorIV)
CA125oflimiteduseforscreening,especiallyinpremenopausalwomen
Cytoreductivesurgeryismosteffectivetreatment(TAH+BSO;mustincludeomentum,peritoneal
washings;noneedforlymphadenectomysincetumorsspreadsbyexfoliationofcells)
UterineCancer
EndometrialcanceristhemostcommongynecologicmalignancyinUS(40,000cases/year)
75%arediagnosedasstageI,5yearsurvival>75%
Riskfactorsareassociatedwithestrogenexposure
80%ofcasesareinpostmenopausalwomen(5%inwomen<40)
Abnormalbleedingis#1presentation;histologyisadenocarcinoma>90%
TreatmentisTAH+BSO,peritonealwashings,LNsampling
Postoperativeradiation(5000radover5weeks)reservedfor:+pelvicnodes,poordifferentiation,
invasionintomyometrium,occultcervicalinvolvement
Uterinesarcomahaspoorprognosis
CervicalCancer
Most(>80%)aresquamouscell
Primarilyaffectswomenaged3545
Painlessbleedingis#1presentation(painoftensignalsadvanceddisease)
Papsmearallowsmosttobediagnosedaspremalignantlesions
HighlyassociatedwithHPVinfection(serotypes16and18virtuallyalwaysinvolved)
Treatmentforearlystage:radicalhysterectomy(noneedforoophorectomyunless>45orhas
ovarianpathology)
Chemoradiationifpoorsurgicalcandidateoradvanceddisease
56
PostmenopausalHRTisassociatedwith:
Increasein:
Decreasein:
Endometrialcancer
Breastcancer
Venousthrombosis
Stroke
Coronaryartery
disease
Gallbladderdisease
Vasomotorsymptomsof
postmenopause
Vertebral/hip/pelvic
fractures
Osteoperosis
ColorectalCancer
Surgeryduringpregnancy:
Secondtrimesterispreferred
Bothlaparoscopicandopenproceduresduringfirsttrimesterareassociatedwithriskof
spontaneousabortionandpossibleriskofteratogenicity
Duringthethirdtrimestersurgeryisassociatedwithriskofprematurelaboranddamagetothe
uterus
Neurosurgery
DiabetesInsipiduscentralorrenal
(ADHinhibited)
urineoutput
LowurineOsm,specificgravity
HighserumOsm,hypernatremic
SIADH
urineoutput
HighurineOsm,specificgravity
LowSerumOsm,hyponatremic
PeripheralNerveInjuries
Neuropraxia:focaldemyelinationimproves
Axonotmesis:lossofaxoncontinuity(nerveandsheathintact)regeneratesat1mm/day
Neurotmesis:lossofnervecontinuitysurgeryrequiredtorepair
57
CancerEpidemiology
58
EsophagealDisease
4Segments:
Noserosa;mucosaisstrongestlayer
Sphinctersarecontractedatrest;NormalLEStone1525mmHg
Orderofeventsinswallowing:softpalateclosesnasopharynxlarynxuplarynxclosesUESrelaxes
pharyngealcontraction
HiatalHernia
TypeI:sliding;mostpatientswithrefluxhave,butmostpatientswithitdonthavereflux
TypeII:paraesophagealrepairevenifasymptomaticbecauseofriskofinfarction
(Also:TypeIII:esophagogastricjunctioninmediastinum,andTypeIV:entirestomachinmediastinum)
BenignEsophagealDisorders
I.Primary
Achalasia:ganglioncellsinAuerbachsplexus,absenceofperistalsis;esophagealdilation(birdsbeak
onswallow);manometryshowsnoperistalsis,highLESpressure,&failuretorelax;Rx:Botox,pneumatic
dilation,Hellermyotomy
DiffuseEsophagealSpasm:chestpain;manometryshowshighamplitudecontractions,normalLES
relaxation;Rx:Ca++channelblockers;iffailmedicalmanagementthoracicesophagomyotomy
NutcrackerSyndrome(not=DES):chestpain;extremelyhighamplitudeperistalticwaves(upto400
mmHg);needlongmyotomy,occasionallyesophagectomy
HypertensiveLES
Nonspecificesophagealmotilitydisorder
59
II.Secondary
Collagenvascular(SLE,systemicsclerosis,polymyositis,dermatomyositis)
Chronicidiopathicintestinalpseudoobstruction
Neuromusculardisease
Endocrinedisorder
ZenkersDiverticulum
Lossofcomplianceinthepharyngoesophagealsegment;manifestedbyincreaseboluspressure
Musclebiopsieshaveshownhistologicevidenceofrestrictivemyopathycorrelatingwithdecreased
complianceofupperesophagus
RepetitivestressofbolusthroughnoncompliantmusclediverticulumthroughKillianstriangle
(betweencricopharyngeusandthyropharyngeusmuscles)
Primaryreason:dyscoordinationofthesphincterrelaxationwithpharyngealcontractiontogetherwith
impairedsphincteropening
Dx:withbariumswallow;notEGD
Rx:myotomyanddiverticulectomy(orpexyifunfitforresection)vialeftcervicalapproach
Zenkersandepiphrenicarebothfalsediverticuli(mucosaonly);epiphrenicrequireslongmyotomyat
1800
TractiondiverticuliareTrue:locatedmidesophagus;associatedwithTB/inflammatorydiseases
EsophagealClaudication:chestpaincausedbyaburstofuncoordinatedesophagealmotoractivityunder
ischemicconditions(i.e.esophagealbloodsupplyisinterruptedduringtheseburstsinsituationswhere
bloodflowmayalreadybecompromised)
Esophagealforeignbody:usuallyatpointsofnaturalnarrowing:belowcricopharyngeus,neararchof
aorta,behindrightmainstem;95%areimmediatelybelowcricopharyngeusmusclerigidscopeunderGA
istreatmentofchoice
Esophagealrupture(Boerhaaves):fullthicknessinjury(vs.partialthicknessinjuryofMalloryWeiss);often
leftposterior/lateral;85%dieifdiagnosisdelayed>36hours(Rx:earlyrepair,latediversion)
MalloryWeissTear:repeatedemesis;about10%presentwithmassivehemorrhagegastricbleeding
(usuallylessercurvature);sincearterialbleed,pressuretamponadeoflittlehelpusuallystops
spontaneously;Dxwithendoscopygastrotomy&oversewifdoesntstop
EsophagealPerforation
50%instrumentation,20%trauma,15%spontaneous
3/10kEGD,11/10krigid
Presentationdependson
1.Location,2.Size,3.Elapsedtime,and4.Underlyingpathology/etiology
Cervical:neckpain(especiallywithflexion),crepitus,rightpleuraleffusion
Spontaneous:usuallydistalleft
60
NonoperativeCriteria(i.e.containedleak)
1.IntramuralPerforation
2.Transmural,notinabdomendrainswellbackintoesophagus
3.Notassociatedwithobstruction/malignancy
4.Mildsymptoms;noevidenceofsepsis
Treatment:NPO,antibiotics
Diagnosis:
Alwaysget:CXR,EKG,gastroswallow
Poortissueresect
Goodtissue(early)1repair
ReinforcedwithGambistitch&tongueofstomachorparietalpleuralpatch
Cervicalperforations:usuallymanagedwithtranscervicaldrainage;repairiftechnicallyfeasible
Thoracicperforations:iffoundearlycanprimaryrepair(inlayerswithbuttressandthoracicdrainage)
Septic/Lateperforations:ifassociatedwithcancerresection;somefavoresophagealexclusion
Followingcorrosiveingestion:
EGDonlytoproximalmargin(notatallifsuspectperforation)
Emergentthoracotomyindicatedforevidenceofmediastinitisorperforation:severechestpain,
cervicalsubcutaneouscrepitus,widenedmediastinum,PTX,pleuraleffusion
Emergentlaparotomyindicatedfor:signsofperforationorwhennasogastricalkalicontentsfrom
thestomachhavebeenaspirated(directvisualizationofstomachnecessarytoruleoutliquefaction)
Benignesophagealtumors:farlesscommonthanmalignanttumors;leiomyomaismostcommon
usuallyfoundinlower;DONOTbiopsy;resectbyenucleation
BarrettsEsophagus
Semantics
Metaplasia:Achangeofcellstoaformthatdoesnotnormallyoccurinthetissueinwhichitis
found
Dysplasia:Anabnormaldevelopmentofcells,whichisnotcancerous,butcouldbecomecancerous
BarrettsEsophagus(classic):Thepresenceofacircumferentiallengthofatleast3cmofintestinal
metaplasiainloweresophagusabovetheGEJ
BarrettsEsophagus(current):Intestinalmetaplasiaanywhereinthetubularesophagus
ShortSegmentBE:AnysegmentofBE<3cm
Barrettswilldevelopin1015%ofpatientswithsymptomaticGERD
Patientswithhighgradedysplasia(akaCIS),willdevelopadenocarcinomain3050%ofcasesneed
esophagectomy(nodebate)
3040%increasedincidenceofadenocarcinomawithBarretts(comparedtogeneralpopulation);
RiskofcancerprogressioninBarrettsis0.22.1%peryear
Progressiontoadenocarcinomaassociatedwithlossofp53heterogenicityonch17
ControversyexistsforthemanagementofthelargerpopulationofpatientswithBarrettsesophagusbut
nodysplasia,lowgradedysplasia,orindeterminatedysplasia,althoughtheyclearlyrequireclose
surveillance
61
EsophagealCancer
Top10cancerworldwide
Geographicvariation17/100kU.S.(Adenocarcinoma,Barretts)100/100kAsia(SCC)
Lymphaticsrunlongitudinallyinesophagusstraighttothoracicduct;hencesmallprimarycanstill
spreadaggressivelyvialymphatics
T1:tolaminapropria(doesnotbreachsubmucosa)
T2:tomuscularispropria(doesnotbreachmuscularispropria)
T3:Adventitia
T4:Adjacentstructures
Noroleforadjuvantchemo/XRT(exceptadjuvantXRTformargin+todecreaselocalrecurrence)
RoleofNeoadjuvantTreatment[4studies]
2025%PRtoinductionchemo/XRTonfinalpath(50%ofthoseCR)
Survivalbenefit(includingLN+)withmoreaggressivelymphadenectomyandresection
1. [KelsonNEJM1998]:5FU+CDDP+surgeryvs.surgery(Prospectiverandomized):nosurvival
differenceat2years35%vs.37%
2. [HerskovicNEJM1999]:Nonsurgicalpatients:5FU+CDDP+XRT(50Gr)vs.XRT(6400Gr)
[differenceisbecausethesechemoagentsmaketissuemoreradiosensitive]12.9monthsvs.
8.9months(significantsurvival,local,distaldisease)
3. [*WalshNEJM1996]:5FU+CDDP+XRT+surgeryvs.surgeryalone(10protocolviolationsvs.1);16
vs.11months(p<0.01);1&3yearsurvivals:52/32%vs.44/6%(p<0.01)
*Controversy:(i)Protocolviolations(ii)Poorsurgicalsurvivalcomparedtopreviousstudies(iii)U/S
andCXRforstaging(noCT)(iv)ProportionofstageIII(13vs.38)
4. [MeluchCancerJ2003]:PhaseIItrialofTaxol/Carbo/5FU/XRT/Surg:mediansurvival22months
Whataboutradicalresection?
StageIII5yearsurvival
US:1017%(standardresection)
Japan:2734%(radicalresection)
[Altorki/SkinnerAnnSurg2001andAltorkiAnnSurg2002]
EUS:valuabletoolforstaging(betterthanCTforTstage;goodforNstaging)
SurgicalApproaches
Cervicalesophagusbestapproachedvialeftneck(cervicalesophagusisleftofmidline)
Thoracicesophagusbestapproachedviarightthoracotomy(IvorLewis)
Loweresophagusbestapproachedvialeftthoracotomyceliotomy
Optionsforresectioninclude:
3hole(leftneck,rightthoracotomy,celiotomy)offerscompleteexposure,butgreatestmorbidity
(ifintrathoracicanastomosis)
Transhiatal:nothoracotomy,cervicalanastomosis(verylowmorbidity,buthigherleakrate)
62
Stomach&GutPhysiologyandDisease
Parietalcells:produceH+andIF
Somatostatin:InhibitsreleaseofessentiallyallGIpeptides,includinggastrin,insulin,secretin,Ach,and
pancreatic/biliaryoutput;stimulatedbyH+induodenum
CCK:fromintestinalmucosacontractsgallbladder,relaxessphincterofOddi,pancreaticenzyme
secretion
Secretin:primarystimulusforpancreaticHCO3secretion
Enterokinase:activatestrypsinogentrypsinactivatestheotherdigestiveenzymes
PeptideYY:releasedfromTIinhibitsH+secretion(ilealbrake)
Proximalvagotomy:abolishesreceptiverelaxation,soliquidemptying,butinsolidemptying
Truncalvagotomy:alsosolidemptying(whenpyloroplastydone)andbasalacidoutputby80%
#1symptompostvagotomyisdiarrhea(1/3);Dumpingis10%almostalwaysrespondstodietchanges
Tc:solidemptyingstudy
99m
I:liquidemptyingstudy
111
Leftvagusnerveanteriorhepaticbranch;
Rightvagusnerveposteriorceliacbranch&CriminalnerveofGrassi(cankeepH+levelsif
leftundividedpostgastrectomy)
63
[FigurestakenfromtalkgivenbyJTLenert,2005]
Pacemakerinproximalstomachongreatercurve:generates23MMC/minute:
Wavegetsstrongerasitapproachesthepylorus
Diabetesis#1causeofgastroparesis
PUD:Gastricvs.DuodenalUlcers
Gastric:
painGreaterwithmeals
H.pylori70%
BloodtypeA
M=F
13%malignantpotential
Duodenal:
painDecreaseswithmeals
H.pylori100%
duetoincreasedacidsecretionordecreasedmucosalprotection
hemorrhage>perforation
BloodtypeO
NOmalignantpotential
M>F
64
Followingrepairofperforatedduodenalulcer,naturalhistoryissuchthatapproximatelyofpatients
havenofurtherproblems,havefurtherulcersamenabletomedicalmanagement,andultimately
requireoperation;
Followingrepairofbleedingduodenalulcer,becauseofhigherriskofrecurrence,adefinitiveantiulcer
operationshouldaccompanytherepair(ifsickTVandantrectomy;otherwisemoreselective)
ElevatedFastingGastrin
I.Elevatedacid
ZES
GCellhyperplasia
retainedantrum
renalfailure
gastricoutletobstruction
shortbowel
II.Low/Normalacid
perniciousanemia
chronicgastritis
gastricCA
postvagotomy
onacidsuppression
TypeIgastriculcerassociatedwithTypeAblood;otherswithTypeO;
II(25%),III(15%):Toomuchacid
I(5060%),IV,V:Toolittlemucosalprotection
SurgicalTherapyforPUD:
Nonhealingdespitemedicaltherapyisanindication(especiallytoruleoutcancer)
[algorithm:6weeksmedicaltreatmentEGDrepeat6weeksmedicaltreatmentEGDsurgeryif
nothealed]
Withprolongedvomiting:seeCl,H+(pH),andK+(becausekidneyisdumpingK+toholdH+)
65
DistributionofUpperGIBleeding
PUD
55%
Esophagogastricvarices
14%
Arteriovenousmalformations
6%
MalloryWeisstears
5%
Tumors/erosions
4%each
Otherlesions
12%
Includes:DieulafoysLesion:dilatedaberrantsubmucosalvessel(usuallyarterial)usuallyhighinthe
gastricfundus;canleadtosignificantbleeding.
Gastricantralvascularectasia(GAVE):AlsoknownasWatermelonStomachisgenerallyidiopathic,but
maybeassociatedwithautoimmunedisease
GastricVolvulus:2types:
Organoaxial(morecommon):rotationaroundtheaxisoflineconnectingcardiatopylorus
Mesenterioaxial:axisisorthogonaltoabove
GastricDilation:causeshypotension,bradycardia,abdominalpain
Obesity
ClassI:BMI>30
ClassII:BMI>35*surgeryifdevelopcomplicationsofobesity;
*IfBMI>35+significantGERDGastricBypassismuchpreferredoveranantirefluxprocedure
ClassIII:BMI>40surgery
(Note:previousjejunoilealbypassesledtorenalfailurebecauseofdevelopmentofCaOxalatestones)
GastricCancer
GastrointestinalStromalTumor(GIST)
ArisesfrominterstitialcellofCajal(intestinalpacemaker);Ckitmutation/CD117+
Gainoffunctiontyrosinekinase
Resectifpossible;Gleevacformets;roleofGleevacinadjuvantbeingcurrentlyevaluated
Adenocarcinoma:
Resectwith6cmmargins+draininglymphnodes+omentum;noobviousroleforextended
lymphadenectomy
Chronicatrophicgastritisunderliesmostgastriccancer;
otherrisks:adenoma>2cm,TypeAblood,nitrosamines,perniciousanemia
Lymphoma:distinguishbetweenTcell,NHL(nonMALT),andMALT
ExtranodalmarginalZoneBCelllymphoma(lowgradeBcelllymphomaofMucosaAssociatedLymphoid
Tissue,MALT):
50%ofpatientswithgastricNHLhavetheindolentMALTtype
gastricMALTisfrequentlyassociatedwithchronicgastritisandH.pyloriinfection
*thestandardtreatmentforMALTpatients(whoareH.pylori+)isantibioticsandfollowupEGD3and6
monthslater:
ifCRdone
ifPRcontinueantibioticsbeforeXRT(notsurgery)
Surgeryreservedforcomplications
Note:thethickerthelesionthelesslikelyitwillregresswitheradicationofH.pylorialone
66
SmallBowelPhysiologyandDisease
MMC:interdigestivemotility;90minutescycles;startsinstomachgoestoTI
PhaseI:quiescence
PhaseII:gallbladdercontraction
PhaseIII:peristalsis
PhaseIV:subsidingelectricactivity
MMCreturntonormal624hoursafterlaparotomy;stomachandcolontakelongertoreturntonormal
tone
SBtransitisapproximately1inchperminute
JejunumabsorbsmoreNa+andH2O(paracellular)thanileum
80100cm(30%)ofthesmallbowelisrequiredforabsorption,unlesstheICjunctionisabsent,in
whichcaseapproximately150cmisrequired.
DerangementsseenwithSBresectionleadingtomalabsorption/shortgutinclude:
1.Fat
2.B12
3.Electrolytes
4.H2O
FollowingbowelresectionCa++/Mg++soapformcationstocomplexwithoxalateincolonoxalate
absorption(worsenedbyVitCconsumption).TreatdeficiencieswithCa++,Mg++,potassiumcitrate,VitB6,
andavoidVitC
SmallBowelNeoplasms
Representonly5%ofGIneoplasms(12%ofallneoplasms)
Mostcommonbenign:
1.Adenoma(2535%)
2.GIST
3.Lipoma
Mostcommonmalignant:
1.Adenocarcinoma(50%)
2.Carcinoid
3.Lymphoma
4.GIST
Allshouldberesected,evenifasymptomatic(needpathtoconfirmlackofmalignantbehavior)
alsoperformregionallymphadenectomywithresection
Adenocarcinomasaremostcommonintheduodenum,theremainingmalignanttumorsaremore
commondistally,withfrequencyproportionaltolengthofsegment(ileum>jejunum>duodenum)
PeriampullaryWhipple
D3/D4segmentalresection+duodenojejunostomy
GISTarisefrommultiplemesodermalcomponents(muscle,nervoustissue,connectivetissue,vascular
elements,fat)
67
CarcinoidsarisefromtheKulchitskycellandarefoundintheappendix85%oftime
Mets2%iflessthan1cm;8090%if>2cm
MostcommonlocationsforGIcarcinoids:1.Appendix,2.Ileum,3.Rectum4.Stomach
Smallbowelcarcinoidsaremultiple30%;appendicealusuallysolitary
Urinary5HIAAonlyelevatedifabletobypassfirstpass(extensivelivermets,drainsdirectlyinto
systemiccirculation)
Metabolizestryptophanserotonin5HIAA(measuredinurine);carcinoidsutilize60%of
bodystryptophan,hencesideeffectsoftryptophandeficiency(3Ds:dermatitis,dementia,
diarrhea)
ClinicalManifestations
Dependsonlocation:
i)Foregut:stomachpain,bleeding;bronchushemoptysis,pneumonitis,wheezing
ii)Midgut:appendixobstructiveappendicitis;jejunoiliumobstruction,intusessuption
Localization
CXR,ChestCT,Bariumenema,colonoscopy,superiormesentericangiographyinadvancedtumors
Biopsy:+argyrophilstainissuggestive,butEMofneurosecretorygranulesisgoldstandard
Ifonefound,especiallyincolon,3640%incidenceofsynchronouslesionlookeverywhere
MetastaticdiseasediagnosedONLYbymets,nothistology
Treatment
Appendix:If>1.5cm,involvingbaseofappendix,orregionallymphadenopathypresentright
hemicolectomyindicated
Gastroduodenal:If<1cmendoscopicresection;>1cmormetssubtotalgastrectomyandomentectomy
Rectal:If<1cmendoscopicexcision;12cmresectionwithnegativemargins(23cm);>2cm
lowanteriorresection(LAR)orabdominalperinealresection(APR)iflow
Anytumorwithmetsenblocresection
Outcome>2cmportendsapoorerprognosis
Noninvasiveappendicealandrectal<2cm100%5yearsurvival
If>2cm40%;withlivermets:2040%
Approximately10%ofpatientswithcarcinoidtumordeveloptheCarcinoidSyndromeofflushing,
sweating,diarrhea,wheezing,abdominalpain,rightsidedcardiacvalvularfibrosis,andpellagra
dermatosis
Tumorneedsaccesstovenousdrainagethatescapesportalcirculation,suchaswhen:
1.Hepaticmetsarepresent
2.Venousbloodfromextensiveretroperitonealmetsdrainsintoparavertebralveins
3.PrimarytumorisoutsidetheGItract(bronchial,ovarian,testicular)
CarcinoidCrisis:resultsfromoverwhelmingreleaseofserotonin(liverunabletobreakdown)
CanoccurinORduringmanipulationoftumor
Resultsinhypoorhypertension
Hypertensionshouldbetreatedwithvolumeexpansion,octreotide,andketanserin(somostatin
analog)
68
Lymphoma:inadultsusuallyNHLBcell;stageIandIIrequireresection
inchildrenusuallyBurkittsbettersurvivalthanadults
Meckelsdiverticulumis#1causeofsmallbowelbleedinginthose<30yrs.
Oftencontainsgastricmucosa(75%)secretesHClpepticulceration
MeckelsscanTc99pertechnetatetakenupbyparietalcells
Mostcommoncauseofobstructionisvolvulusaroundpersistentfibrousbandfromtiptoumbilicus
Angiodysplasia(VascularEctasia):#2causeofsmallbowelbleedinginyoungerpatients;#1causeinthose
>50yrs.
Intussusception(inadults):upto90%resultfromunderlyingpathology(mostoftenatumor;abouthalfare
benign).NoroleforconservativemanagementtoOR
Ileus:lookforcolonicandrectalairtodifferentiatefromamechanicalobstruction
4Categories:
1.Postoperative
2.Paralytic
3.Intestinalpseudoobstruction
4.Colonicpseudoobstruction(Ogilvies)
DiverticulaofGItract:causedbypropulsionforces;10%symptomatic;510%developcomplications
(bleeding,perforation,obstruction,diverticulitisRPabscess);surgeryisonlyindicatedfor
complications/symptoms.
MostCommon:
1. Colon
2. Meckels
3. Duodenum*(seefigure)
4. Pharynx&esophagus
5. Stomach
6. Jejunum
7. Appendix
8. Ileum(excludingMeckels)
*Ifarisesinperiampullaryregionmustprotectduringsurgery
ForMeckelsresectasymptomaticpatientif:
1.youngerthan40,
2.longerthan2cm,
3.fibrousbandpersists,or
4.grossevidenceofheterotopicmucosa
69
Mostcommonreasonsforsurgery(i.e.surgeryisreservedforselectcases)inpatientswithCrohnsdisease
1.Failureofmedicalmanagement
2.Obstruction
3.Inflammatorymassorabscess
4.Fistula
Note:IfappendicitissuspectedfindCrohnsdoappendectomyprovidedthebaseofappendixnot
involved
SmallBowelFistula:
Highoutput(500mL/24hours)are3xlesslikelytoclosethanlowoutput
Overallmortality:20%(higherforjejunal;lowerforileal)
InpatientswithCrohnsdisease+highoutputfistulaTPNdoespromotefistulaclosure
SchillingtestforVitaminB12deficiency:revealsatypeofurinaryexcretionofB12similarlytothatseen
withperniciousanemia,exceptnotcorrectedwiththeadditionofIF,butiscorrectedwiththeuseoforal
tetracycline(nonabsorbable)
Appendix
Acomponentofthesecretoryimmunesystem
Appendicitisisinitiatedbyobstructionofthelumen.Inadultsfecalith;inchildrenlymphoid
hyperplasia
Continuedsecretionofmucusleadstopressure(upto126cmH2Owithin14hours)gangrene&
perforation
Theareaoftheappendixwiththepoorestbloodsupplyismidportionofantimesentericside,hence
locationofmostfrequentgangreneandperforation
PresentationofAppendicitis:
Classically,abdominalpainbeginsinperiumbilicalregion(somaticpainfromappendiceal
distention)thenlocalizestositeofappendix(e.g.RLQ)asvisceralpainoncetheserosais
involved.
Anorexiaprecedespain
Vomitingoccursinabout75%ofpatientsandtypicallyfollowstheonsetofpain
Hence:anorexiapainvomitingisobserved95%oftime
Acuteappendicitisisthemostcommoncauseofanacuteabdomeninwomenafterthefirsttrimesterof
pregnancy;theymaypresentwithRUQpain,especiallyduringthelasttrimester;however,pregnancydoes
notriskperse.Immediateoperationiswarranted.ACTscanissafeduringpregnancy.
70
ColorectalDisease
Colon:
activelysecretesK+andHCO3
absorbsNa+againstbothconcentrationandelectricalgradientstoavoidhyponatremia
normallyabsorbs12LofH2O/day;canabsorbupto56L/day
LowerGIbleeding:diverticulosis+angiodysplasia=90%ofcauses(forthose>50)
Diverticulosis
VascularEctasia
50%rightsided
virtuallyallrightsided
venousbleeding
rupturedvasarectaatneckof
diverticulaarterialbleeding;
85%rebleedrate
severe
only810%extravasationon
angiography
2550%rebleedrate
mostvisualizeonangiography
Angiographycandetectbleedingratesaslowas15mL/min(insomeseriesaslowas0.5mL/min)
TagRBCcandetectbleedingratesaslowas0.51mL/min(insomeseriesaslowas0.1mL/min)
1sttesttoperformonLGIB(i.e.NGaspirateisbilious),afterstartingresuscitation,isrigidproctoscopy
Volvulus
Cecal(rare);alsoknownascecalbascule
Sigmoid
presentswithSBO
young(2535)
OR(only25%successwithscope)most
doRhemi;butsomeattemptcecopexy
presentwithcolonicobstruction
old,debilitatedpatients(nursinghomes)
70%successwithscopetube
decompressionbowelprep
sigmoidcolectomyduringthat
admission
UlcerativeColitis:
Limitedtomucosaandsubmucosa
56%developcolorectalcancer;riskwithdiseaseduration,pancolitis,PSC
Proctocolectomydoesnothelpsclerosingcholangitisorarthritis,butmayhelpskinmanifestations
20%willrequireproctocolectomy
Ischemiccolitis:
Adiseaseofsmallarterioles
Canoccurinanysegmentofcolon,butmostcommoninwatershedareas,whichrelyon
Meanderingarteries,suchassplenicflexure(Griffithspoint)anddistalsigmoidcolon(Sudecks
point)
Seethumbprintingonbowelwall
Darkdiscolorationoncolonoscopy(black/green)isindicationforsurgicalresection
71
ColorectalCancer
120,000140,000newcases/year;60,000deaths/yearinU.S.
3rdmostcommoncancerinwesternsociety
2ndindeaths(tolung)
50%mortality
80%ofpatientspresenteligibleforresection(i.e.20%stageIV);67%ofthesewillrecur;80%ofthese
recurrenceswillbeintraabdominal(liver#1)
5cmgrossmarginforresectionincolon;1cmdistalmucosalmargin(UNfixed)isadequatebecause
rectalcancersrecurbasedonradialspread,ratherthanlongitudinalspread;need35cmofdistal
mesorectalmargin,ifpossible
Staging
Tis:mucosaonly
N0:nonodes
T1:intosubmucosa
N1:13regional
T2:intomuscularispropria
N2:>3regional
T3:intosubserosa
T4:intoadjacentstructure(throughserosa)
StageI:T1,T2,N0,M0
Survival
StageIIA/B:T3(A),T4(B),N0,M0
1year(all):83%
StageIIIA:T12,N1,M0
10year(all):55%
StageIIIB:T34,N1,M0
StageIIIC:anyT,N2,M0
StageIV:anyT,anyN,M1
5yearsurvival:I,II:90%;III:65%;IV:9%
Treatment
StageI,IIcolon:Surgeryalone(currenttrialslookingintoadjuvantchemoforII)
StageIIIcolon:Surgery+Chemo(FLwhatothertrialsthrowin)
StageII,IIIrectal:Surgery+Chemo/XRT(adjuvant)
Withrespecttoadjuvantvs.neoadjuvantXRT,goodevidenceofdownstaging(e.g.tosphincter
preservingoperation)anddecreasedlocalrecurrencerates,butnoevidenceofsurvivaladvantage,
particularlyineraofTME
StageIV:5FU/Leukovorin(FL),Oxaliplatin,CPT11(Irinotechan),Avastin;allcombinations
In2004:IFL(Saltzregimen)+Avastinincreasedmediansurvivalto20.3monthsfrom15.6months(IFL
alone);BUTNOINCREASEIN5YEARSURVIVAL(noregimenhasimpactedthisinnearly20years)
PostResectionFollowUp(Debatable)
*CEA
*colonoscopy
SerialCT
Liverenzymes
CXR
*mostagreeon
q3months
q13years
q6months
q23months(LDHismostimportant)
q6months
72
RisingCEA(happensin70%ofrecurrences)
CTwillmissnearly40%ofrecurrences,and6090%ofthesemissedlesionswillbeintraabdominal
FDGPETis89%sensitivewhenothermodalitiesarenegative,soalgorithmis:
RisingCEAnegativeCTPET;ifnegative,follow;ifpositivetreataccordingly(80%ofthesewillbe
operablelesions)[LibuttiSK,etal.AnnSurgOncol.20018:779]
PETfollow
CEACTPET
+PETtreat(80%willbeoperablelesions)
LiverResectionForColorectalMetastases[Fongscore]:
PrognosticFactor
pvalue(forpredictorofsurvival)
Dxfreeinterval
0.002
Tumors>3
0.01
CEA>200
0.05
Size>5cm
0.01
Node+primary
0.05
[FongY,etal.AnnSurg.1999;230:309]
Survivalbasedoncriteria
#factors5yearsurvival(%)
OS(months)
0
57
74
1
57
73
2
47
50
3
16
30
4
8
15
ColorectalPolyps
ClassifiedasNeoplastic(adenoma)orNonneoplastic(hyperplastic,hamartomatous,inflammatory)
(Adenoma)Classifiedhistologicallyastubular(6580%),villous(510%),ortubulovillous(10
25%).AspolysizeINCREASES,sotoodoesfrequencyofVILLOUShistology.
Approximately58%ofadenomashaveseveredysplasia,and35%haveinvasivecanceratthe
timeofdiagnosis
Riskofcancerattimeofdiagnosis:tubular(5%),tubulovillous(22%),villous(40%).
For<1cm,riskverylow,for>2cmapproaches50%
Allpolypsdetectedshouldberemovedendoscopically,althoughthisiscontroversialforpolyps<5
mm,whichshould,attheleast,bebiopsied.
Pedunculatedpolypsshouldberemovedviacolonoscopy,butthisisdifficultforlargesessilepolyps
(>2cm),whichharborhighmalignantpotential.Alternatively,multiplebiopsiestaken,andthe
areaismarkedwithinktattoo.
73
Formalignantpedunculatedpolyps,ifthereislymphovascularinvasion,poordifferentiation,or
cancerwithin2mmofresectionmargin,colonresectionisindicated.Sessilepolypswithinvasive
cancerrequireformalcolonresection.
HaggittLevel
Welldifferentiatedadenocarcinomainzone1,2,or3polypectomy;zone4formalresection
Poorlydifferentiatedinzone1polypectomy;zone2,3,or4formalresection
Gardnerssyndrome:(FAP)polyposis,desmoidtumors,osteomas
Turcotssyndrome:polyposisandbraintumors
PeutzJegherssyndrome:polyposisandmucocutaneouspigmentation
MuirTorresyndrome:polyposisandskincancer
*Note:theabovedonothavetobecolorectalcancer
HNPCC(HereditaryNonpolyposisColorectalCancer)
ADinheritance
Accountsfor26%ofallcolorectalcancer
AverageageofCRCdevelopment4045
Begincolonoscopyat25
60%by60yearsold;lifetimerisk80%
Germlinemutationinmismatchrepair(MMR)genes+somaticmutationinwildtypeallele
producesaMicroSatelliteInstability(MSI)
2genesaccountfor90%ofmutations(hMSH2andhMLH1)
PredominanceofRsidedcancer(6070%inright/transversecolon)
IncreasedsynchronousandmetachronousCRC
LynchSyndromeICRConly
LynchSyndromeIICRC+othercancer(endometrial,ovarian,stomach,smallbowel,UGI)
Followstheadenomacarcinomasequence,justdoessoquicker
FarebetterthanstagedmatchednonHNPCCwithCRC(i.e.thecancerislessaggressive)
SurgicalTreatment
TotalabdominalcolectomywithileorectalanastomosisrecommendedforAmsterdam+patients
withCRCorMMRcarriers
ProphylacticTAC+IRAasalternativeforMMRcarrieswithadenomasorpatientswithdifficultto
followcolons
74
RevisedAmsterdamCriteria(II)
1.HNPCCassociatedcanerin3relatives,oneafirstdegreeoftheothertwo
2.Atleast2successivegenerationsaffected
3.Atleast1diagnosed<50
4.FAPexcluded
FAP(FamilialAdenomatousPolyposis)
AD,100%penetrant
MutationisinAdenomatousPolyposisColi(APC)gene,localizedto5q21
NormalAPCproteinislocalizedtobasolateralmembrane
Truncated,inactiveAPCappearstoallowbetacateninaccumulationinthecellandnucleus,where
itturnsongenesandstimulatescellgrowth
80%familial,but1030%casesarenewmutations
Accountsfor<1%ofcolorectalcancer
Extraintestinalmanifestations:desmoidtumors,osteomas,sebaceouscysts(Gardners);withbrain
tumors(Turcots),CHRPE(hyperplasticretinalcomplicationblindness)
*Mostcommonextracolonicmanifestationisperiampullaryduodenalmalignancy(alsopancreatic,biliary,
gastric,smallintestinal,thyroid)
Desmoidtumorsappearin10%ofcarriesbyage30
Mostcommongeneticalterations:
p53:ch17;mostcommon(85%),tumorsuppressor
APCgene:ch5;sporadic&familial(35&75%,respectively);tumorsuppressor
DCC:ch18;70%cancers/10%adenoma,tumorsuppressor
Kras:ch12;50%cancers;oncogene
75
Summary:
GeneticPattern
LOH(lossofheterozygosity)
1. Sporadic
2. Familial
3. Inherited(polyposis)
FAP
Gardners
Turcots
RER(replicationerrorpathway
DNArepairmismatch)
1. Sporadic
2. Familial
3. Inherited
LynchI
LynchII
%ofColorectal
Cancer
6085%
35%
25%
13%
2035%
20%
6%
10%
ClinicalFeatures
Distaltumors(70%);noFHofpolyps/CRC;aneuploid
DNA;age>60
Distaltumors;FHofpolyps/CRCinseveralrelatives;
aneuploidDNA;age5060
>100polyps;earlyonsetdisease;mutationofAPC
UpperGIpolypsandCRC;retinalfindings
Desmoidtumorsandboneabnormalities
Medulloblastoma
Proximaltumors(70%);diploidDNA;better
prognosisthanLOH;age>60
Proximaltumors;diploidDNA;FHofpolyps/CRC;
age5060
CRConly;proximaltumors(70%);40%with
synchronous/metachronousCRC;age4045
LynchI+cancersofendometrium,ovaries,pancreas,
stomach,smallbowel,urinarytract,bileducts
76
RectalCancer
3approachesforlocalexcision:
1.Transanal
2.Transsacral(Kraskesprocedure)
3.Transsphincteric*
Unacceptableratesofperinealfistula,notpreferred
*Transsphinctericleadstounacceptablyhighratesoffecalincontinence,notpreferred
Transanalexcisionisreservedfortumorslessthan8cmanteriorand10cmposteriorfromtheanalverge,
notinvolvingsphincters(alsolessthan4cmindiameterandoccupyinglessthan40%ofrectal
circumference)
Preoperativestagingisimportant:patientswithevidenceoftransmural(e.g.tetheredlesiononphysical
exam)orregionalLNinvolvementarenotcandidatesforlocalexcision(unlessconsideredmedicallyunfit
formajorresection)
EvaluationofrectalcancerwithEndorectalU/S:
[FigurestakenfromtalkgivenbyJDouglas,2005]
Mucosa
Submucosa
Muscularis propria
Serosa
Rectal Cancer T3
Rectal Cancer T1
Threeprospectivestudies[Ota1992,Bleday1997,Steele1999]askedquestionsofadequacyoflocalexcision
adjuvanttreatment.
Conclusions:
1.PatientswithnodalinvolvementneedTME
2.T1lesionsarebestcandidatesforlocalresection
3.T3andT4havehighprobabilityofnodalinvolvementandshouldhaveTME
4.T2lesioncanbemanagedwithTME(goldstandard),butlocalexcision+adjuvantchemoradiation
achievessimilarsurvivalrates,butmayhavehigherlocalrecurrencerates(however,canoftenbesalvaged
byTME)
PostopXRTalonelocoregionalrecurrence,butnoimpactonsurvival
PostopXRT+chemolocoregionalrecurrenceANDsurvival
PreopXRTalone locoregionalrecurrence
PreopXRT+chemodownstagesandimprovesrespectabilityandlocoregionalrecurrence
77
[PatyPB,etal.AnnSurg.2002;236:522]
Aswithcoloncancermustdofullcolonoscopy,priortosurgery,tolookforsynchronouslesion(4%chance)
Squamouscellcancerofanalcanal:
TreatwithmodifiedNigroprotocol:5FU+mitomycin&XRT(50.4Gr),includingpatientswith
positiveinguinalnodes;notsurgery(8085%curerate)APRforrecurrentdisease(althoughup
to50%responsetocisplatininthissettingofrecurrence)
Riskofmetastaticdiseaserises,andsurvivalratesfallastumorsize>2cm
Pouchitis:Nonspecificinflammationofilealreservoirfollowingilealpouch/analanastomosis;occursin5
40%;usuallyrespondtooralflagyl;chronicproblemin15%ofpatients
FissureinAno:10%anteriorinwomen;nearlyallposteriormidline(90%belowdentateline)
*iffissurenotinmidlinethinkofIBD,TB,syphilis,HIV,Herpes,cancer
Goodsallsrule:iftheexternalopeningofthefistulaisanteriortoanimaginarylinedrawnbetweenthe
ischialtuberositiesthefistulausuallyrunsdirectlyintotheanalcanal;ifitisposteriorthetractcurves
totheposteriormidline;if>3cmfromanuscangoeitherway
[SurgeryoftheAlimentaryTract,VolIV,2001]
Hemorrhoids
External:dilatedveinsofinferiorhemorrhoidalplexus;coveredwithanoderm(belowdentateline);donot
band
Internal:exaggeratedsubmucosalvascularcushions,normallylocatedabovedentateline,hencecoveredin
mucousmembraneofanalcanal,notanoderm;canband
Whenthrombosedbesttreatedbyincisingtheoverlyinganoderminanellipticalfashionandevacuating
thethrombus
MedicalTreatment:bulkagents,stoolsofteners,localagents(e.g.NTG)
78
PediatricSurgery
Gastroschisis
Incidence:1:10,000to1:15,000(andincreasing)
Embryology:Mesodermalandectodermaldefectscausedbyischemiaresultingfromprematureinvolution
oftherightumbilicalvein(thisissupposedtohappen67weekspostconception)oravascularaccident
involvingtherightomphalomesentericartery.
Anatomy:
Fullthicknessdefectofabdominalwalltotherightoftheumbilicalcord;umbilicalcordhasa
normalinsertion
Herniationofbowelloops(uncommonlyliver):organsarenotcoveredbyamembrane
Meconiumstainedamnioticfluidcommon,andmaybesecondarytointestinalirritation
Associatedanomalies(510%):Notassociatedwithchromosomalabnormalities.Ileal/jejunalatresiais
mostcommonassociateddefect;cardiacanomaliesarerare
Outcomes:Mortalityrangesfrom725%;ifliverherniatesmortalityincreasesto50%:
Management:Vaginaldeliveryatterm,attertiarycarefacility.Caesareanmaybeindicatedifliver
herniationispresent.Primaryclosureisobtainablein90%ofcases;siloplacementandstagedreduction
necessaryintheremaining10%
Omphalocele
Incidence:1:5000to1:6000(anddecreasing)
Embryology:Impropermigrationandfusionoflateralembryonicfolds.Canbecephalic,caudal,orlateral.
Failureoflateralfoldstofuseresultsinisolatedomphalocele;failureofcephalicfoldsresultsindefects
seeninPentalogyofCantrell.
Anatomy:
Herniationoftheintraabdominalcontentsintothebaseoftheumbilicalcord.
Contentsarecoveredwithanamnioperitonealmembrane.Defectismidline.
Bowel,stomach,andlivermostfrequentlyherniated;amembranemadeupofperitoneumand
amnioncoverstheherniatedorgans.
Theumbilicalcordinsertsintothesac.
AssociatedAnomalies(4060%):Canbeseenwithchromosomalabnormalities(includingtrisomy18,
trisomy13).AlsoseenaspartofPentalogyofCantrellandBeckwithWeidemannsyndrome(seebelow).Other
anomaliesseenoccurwiththefollowingfrequencies:
Cardiacdefects:50%(Overall,VSDismostcommondefectseenwithomphalocele)
GUanomalies:40%
IUGRreportedin20%ofcases
BeckwithWeidemann:macroglossia,viceromegaly,hypoglycemia,macrosomia
PentalogyofCantrell:1.Cardiacdefects,2.Diaphragmaticdefects(2specific),3.Sternaldefect,
4.Abdominalwall(midline,supraumbilical)defect,and5.Ectopiccordis
Outcome:overallmortality4080%(variesdependingonpresenceofassociatedanomalies;cardiac
abnormalitiesdeterminemortalitytoalargeextent)
Management:Cardiacechoandkaryotypeindicated,aswellassearchforotheranomalies.Consideration
ofanomalieshaspriorityunlesssachasruptured.
79
Vaginalvs.C/Sdeliverycontroversial:importanttodiagnosepotentialanomaliesthatareincompatible
withlife.C/Sforlargelesionsorlesionscontaininglargeportionsoftheliverseemsprudent.Deliveryata
tertiarycarecenterneeded.
Omphalocele
Gastroschisis
midlinedefect
hasaperitonealsac
coveredabdominalcontentswithin
umbilicalcord
60%cardiacabnormalities
pulmonaryhypoplasia
repaircanbedelayed
defecttorightofumbilicalcord
nosac
fewassociatedabnormalities
10%associatedatresias
immediateinterventionrequired
(closurecanbedelayed,but
interventionmustbeimmediate;Silo
vs.closure)
IntestinalAtresia
Thoughttoresultfrominuterovascularaccidents;associatedwithmaternalcocaineuse
10%aremultiple
Frequency:generallyproximaldistal,althoughmostcommonisasinglejejunoilealatresia
Shortbowelmostlikelytoresultfromjejunalatresia(TypeIII)
Trisomy21mostlikelyassociatedwithduodenalatresia,usuallyin2ndportiondistaltoampulla(treatwith
duodenoduodenostomy,notduodenojejunostomy)
Congenitalcysticadenomatoidmalformationofthelung(CCAM)
Lobarhamartoma;overgrowthofterminalbronchioles
Rare;Nosexpredilection,usuallyunilateral.Notassociatedwithotheranomalies.
Types:Macrocystic:>5mmcyst
Microcystic:<5mmcystorsolid;poorerprognosis,morelikelytobecomplicatedbyhydrops.
TypeI macrocystic,generally>2cm
TypeII microcystic,areasofuninvolvedlung
TypeIII involvesentirelobe,nocysticspaces(allsolid)
Complications:
Hydrops:vascularcompressionbytumordecreasesvenousreturnandmyocardialcontractility
Polyhydramnios:causedbyesophagealcompression
Pulmonaryhypoplasiaandpulmonaryhypertension:compressionofotherwisenormallungtissue
bytumor(canresultinacuterespiratoryfailure)
DiagnosisismadebyU/Sfindingsofnonpulsatileintrathoraciclungmass;resectiontiming
dependsonsymptoms
15%willregressspontaneously
PulmonarySequestration
Distinguishbetweenintraandextralobar(samearteriesin,differentveinsout):
Intralobar:aortain,pulmonaryveinsout;muchmorecommonthanextralobar
segmentectomy/lobectomy
Extralobar:aortain,systemicveins(azygous,hemiazygous)out;nobronchialconnection;distinctand
separatepleuralinvestment(oftenasymptomatic);resectifsymptomatic
Bothpresentwithrespiratoryinfection,notdistress;clueislowpositionofabscesses(vs.uppersegmentsof
lowerlobes)
80
CongenitalLobarEmphysema
Massivehyperinflationofasinglelobeoflung;usuallyupper/middle(LUL>RML>>RUL>lowerlobes)
haverespiratorydistressatbirth;rarepresentationafter6monthsofage
M:Fratiois2:1
10%haveseveresymptomslobectomy
Malrotation:LigTreitzistorightofvertebralcolumn;duodenumhasacorkscrewconfiguration(onUGI)
Laddsbands(adhesionsfromRcolontoRpericolicgutter)contributetoduodenalobstruction.
TheyareremnantsoftheRPattachmentsthatwouldnormallysecureRcolon.
Mostchildrenwithmalrotationpresentwithinfirstyearoflife
Suddenappearanceofbiliousvomitingismalrotationuntilprovenotherwise
Mayormaynothaveabdominalpain/tenderness
GoldstandardfordiagnosisisUGI
IfmalrotationwithvolvulusorifsicktoOR
IfasymptomaticandnovolvuluselectiveLaddsprocedure
Operation:counterclockwiserotationofvolvulus;mobilizeduodenumlyseLaddsbandswiden
mesentericbaseruleoutobstructionappendectomy(sincececumnolongerinRLQ)smallbowelto
right/colontoleft(createnonrotation)
NEC:MostcommonsurgicalemergencyinNICU(17%ofNICUadmissions)
Those<2kgmakeup80%ofcases;primarilyadiseaseofprematurenewborns(3032weeks)
caninvolveanypart;mostcommonisSMAwatershedarea(distalileum/cecum)
Riskfactors:lowbirthweight;prematurity;maternalcocaine;indomethacin(forPDA);enteral
feeding(formulavs.breast),asphyxia,exchangetransfusions,anemia,umbilicalarterial/venous
catheterization
Presentation:toxicplateletcount;pneumatosisonAXR(absentin20%)
*AVOIDcontraststudies
Surgeryindicatedforperforation,+paracentesis,clinicaldeterioration,persistentloop(somehavealso
advocatedforPVgas)
Intussusception:frequentcauseofbowelobstruction
90%in3months3yearsold
10%haveanatomicleadpoint(hypertrophiedlymphoidtissue,polyp,Meckels,submucosal
hemorrhage)
U/Sinnoninvasiveprocedureofchoice;canshowpseudokidney=targetsign
Successofaircontrastenemainuncomplicatedcases5090%;canreducewithcolumnupto80
cmH2O
OR:righttransversesupraumbilicalincision
Reduce:proximalmilking(NEVERpullintussuceptumout)
81
ImperforateAnus(AnorectalMalformationARM)
LowARM:maypresentlate;donotrequirecolostomy;dilationsfirstthenanoplastyorlimitedposterior
sagittalanorectoplasty(PSARP)
HighARM:fistulatourethra,bladderneck,vagina,orcloaca(commonopening)
Requirecolostomy(usuallya2stageprocedure)
PSARP
Renalabnormalitiesmostcommon
MaybepartoftheVACTERLsyndrome:Vertebralanomalies,imperforateAnus,Cardiac
abnormalities,TEfistula,Esophagealatresia,Renalanomalies,andLimbabnormalities)
MeckelsDiverticulum:truediverticula;outpouchingonantimesentericsideofsmallbowel
Ruleof2s:
2%ofpopulation
2%symptomatic
<2feetfromileocecalvalve
2incheslong
2presentations(bleedingandobstruction)
2typesof(heterotopic)mucosa:gastric&pancreatic
Mostcommonlypresentsin<2yearsolds
BiliaryAtresia
hepaticU/SandHIDAtodiagnoseearly
ruleoutcholedochalcyst,giantcellhepatitis,ducthypoplasia
initialgoalofsurgeryistoconfirmdiagnosis;ifGBidentifiedperformcholangiogram
hepatoportoenterostomy(Kasaiprocedure)forbiledrainagemostsuccessfulifdonebefore2
monthsofage(successmuchlessifchild>3monthsold;drainwell,drainok,nodrainage)
ifKasaifailed(poorbiliarydrainage),latediagnosis,progressiveliverfailurerequiretransplant
TracheoesophagealFistula(haveassociatedVACTERLsyndrome)
Incidence:1:30004000;30%havecardiacabnormalitiesECHOfirst
TypeA:Gastrostomytubeandgrowthbeforerepair;NGTtodrainproximally
TypeC:Repairisdependantonhealthandsizeofinfant;ifhealthy+>2500gmprimaryrepair;
Ifnotligatefistula,gastrostomy,drainageofblindpouch,delayedrepair
TypeD:Bronchoscopytoconfirmpresenceof1or2fistula;repairviarightthoracotomy
TypeE:Presentslater(weeks)Hisusuallyhighrepairthroughneckincision
Placeupright,placeNGTforsuction,NPO,avoidvigorousbagging,checkCXRfortubecurl,ECHO
82
PyloricStenosis
Presentin3/1000livebirths
Mostcommoncauseofsurgicallycorrectablevomitinginnewborn
Presentswithnonbilious,oftenprojectile,vomiting,usuallyby36weeksofage;4:1M:F
Physicalexamrevealsoliveabout90%ofthetime
Examissufficienttodiagnose;UGIifnopalpableolive
TreatmentisRamstedtpyloromyotomy,butnotemergently(fixelectrolytesfirst,fluidbalance)
Associatedmalformations:malrotation,hepaticglucuronyltransferaseability(jaundice)
CongenitalDiaphragmaticHernia
Bochdaleck(posterolateralusuallyleft)andMorgagni(anteriomedial)
presentshortlyafterbirth(mayhavefewnormalhours)
CXRshowsloopsofboweland/orstomachinchest
Resuscitation/stabilizationispriorityovertimingofsurgery(includingECMO)
asinadults,repairisviaabdomen
HirschsprungsDisease
Morecommoninmales(7080%)
Lackofganglioncellsfromrectumtostomach(althoughrareproximaltocolon)
Rectosigmoidismostcommonlocation
DiagnosewithBE(lookforsigmoid/rectumratio>1),suctionrectalbiopsy(definitive)
Treatwithresectionandpullthrough(1stagevs.2stage);1stageassociatedwithanastomotic
disruption
Managementofundescendedtesticle:mayoccurspontaneouslyduringfirstyearoflife;ifnot
orchiopexyby1yearofage(riskofinfertility,butnotriskofcancer:risk1/4000,i.e.40foldincrease)
Umbilicalhernia:nourgentneedforrepair,unlessverylarge;ifnotspontaneouslyclosedwhenschoolage
electiverepair
Inguinalhernia:repairismostcommongeneralsurgicalprocedureperformedoninfants;M>F(3:1),R>L;
allshouldberepairedatthetimeofdiagnosis;bilateralrepairisperformedbysomeuptoage5
Pediatricmalignancy
#1overallisleukemia,#2isCNS(=#1solidtumor),#3isneuroblastoma
#1solidorgantumor(excludingintracranial)isneuroblastoma;90%have VMA; HVAworse
prognosis;cellsderivedfromneuralcrestandmayariseanywherealongsympatheticganglia
(adrenalmedullaismostcommonlocation);30%cure;associatedwithNmyc
Location:75%adrenal,20%posteriormediastinum,4%organofZuckerkandel,1%cervical
Favorableprognosis:age<1year;stage1,2,or4S,lowtumormarkers,normalNmyc,DNAindex>
1.0
Wilmstumornephroblastoma(mostcommoninchildren>2yearsold)80%curedwith
nephrectomy;chemoregimenisvincristine,Dactinomycinanddoxorubicin(stageIII)
Hepatoblastomaismostcommonlivertumorinchildren;AFPoften;ifHCGcanresultin
precociouspuberty;surgicalresectionistreatment
83
SpleenandSplenectomy
Functions:
FilterabnormalRBCs,storeplatelets,produceTuftsinandProperdin(opsins),produceAb(esp.
IgM),siteofphagocytosis(DoesnotstoreRBCs)
Whitepulp:lymphatic
Redpulp:phagocytic
BloodSupply:splenicarteryandshortgastricveins(gastroepiploic)
Drainage:splenicveinandshortgastricveins(gastroepiploic)
1520%ofpeoplehaveaccessoryspleens
Spleenisapproximately1%oftotalbodyweightreceives510%ofcardiacoutput
Mostcommoncauseofsplenicveinthrombosis:Pancreatitis
PatientswithUlcerativeColitisdevelophyposplenism
DefinitionofHypersplenism:
Hyperfunctioningspleen,lossofbloodelements,largespleen(splenomegaly),hyperactivebonemarrow
tryingtokeepupwithlossofbloodelements;spleniccellularsequestration
Primary:Adiagnosisofexclusionwillrespondtosplenectomy
Secondary:e.g.Resultofhepaticdiseasenosplenectomy
oftotalbodyplateletsarestoredinspleen
DelayedSplenicRupture:Asubcapsularhematomamayruptureatalatertimeafterblunttraumaupto
2weekslater.Presentwithshockabdominalpain
Signs/SxofRupture:
HemoperitoneumandKehrsSign(referredpaintotipofleftshoulder),LUQpainandmass(Ballances
Sign)
Diagnosis:
AbdominalCTifstable;
U/Sexlapifunstable
Treatment:
Nonoperativeif:stable,isolatedinjurywithouthilarinvolvementorcompleterupture
Ifunstable:splenectomyorsplenorrhaphy(salvageoperationwithwrappingvicralmeshandtopical
hemostatagents/partialsplenectomy)
84
Indicationsforsplenectomy:
Hyperslenism,Gauchersdisease,splenicveinthrombosis,sicklecelldisease,thrombocytopeniaviadrug
abuse,sphereocytosis,lymphoma(esp.Hodgkins),ITP,TTP,splenictumors/trauma,Feltyssyndrome,
lymphroproliferativedisorders(NHL,CLL),HairyCellleukemia,Thalmajor,notG6PDDeficiency
ITP:(Immune)
Autoimmune(usuallyantiplateletAb)plateletdestructionleadingtobleedingand
purpura
Spontaneousremissionoccursinmostchildren;only25%ofadults
Splenomegalyisrare
#1causeoffailedprocedureismissedaccessoryspleen
ErythrocytesMembraneAbnormalities
Hereditaryspherocytosis:abnormalityofspectrinosmoticfragilitysplenectomyis
onlyeffectivetherapy.MostcommonindicationforsplenectomyinUS(nontrauma)
RedCellEnzymeDefects
G6PDdeficiency:mostcommonenzymaticabnormalityofRBC;mostpatientsrequireno
treatment,butsomevariantsimprovewithsplenectomy
AutoimmuneHemolyticAnemia(AIHA):
IfsecondarytoIgGantibodies(warmantibodytype)mayrespondtosplenectomy;
ButifIgMmediated(coldagglutinindisease)liverissightofRBCsequestrationnosplenectomy
TreatmentofchoiceforTTP(Thrombotic):Plasmapheresis,steroids(splenectomyaslastresort);
TTPisadiseasecharacterizedbyocclusionofarteriolesandcapillariesbyhyalinedepositscomposedof
aggregatedplateletsandfibrin
Labtestsfollowingsplenectomy:50%increaseinWBC,markedthrombocytosis,HowellJollybodiesin
peripheralsmear(failuretoseeHJbodiesfollowingsplenectomymissedaccessoryspleen)
Possiblecomplications:
Thrombocytosis(treatwithASAifplatelets>1million),subphrenicabscess,gastricdilation,
OverwhelmingPostSplenectomySepsis(OPSS)
OPSS:
<1%inadults,morecommoninchildren(bothincidenceandmortality)
Morecommonfollowingsplenectomyforhematologicdisease(vs.trauma)
Streppneumo,Meningococcus,HIB,E.coli
Vaccinatepreopifpossible(Pneumcoccus,Meningococcus,HIB)
AggressivetreatmentwithPCNforallminorinfections
85
HepatobiliaryAnatomy,Physiology,andDisease
Mostcommonarterialvariations:
1.Lefthepaticarteryarisesinpartorcompletelyfromleftgastricartery(23%)
2.RighthepaticarteryarisesinpartorcompletelyfromSMAandpassesbehindheadofpancreas(25%)
Practicalpoint:TheRHA(oraccessoryRHA)istheonlystructuretotherightoftheCBD
Anatomically,theliverisdividedintosectorsbytheRHV,MHV(80%joinsLHV;20%intoIVC
directly),andFalciformligament
Eachsectorissubdividedintosegmentsbytheportaltriad(abovevs.below);eachsegmenthasits
ownportalpedicle
Rightportalveinbranchesbeforetheleft;andleftPVrises(i.e.seenonhighercutsonCT)
OnU/S,portalveinshaveprominenthyperechoicwallsbecauseoftheaccompanyingintrahepatic
Glissoniansheath
Hepaticveinsappearwallless
[FiguretakenfromWebMD,2000]
Flowtowardsliveristermedhepatopedal;Flowawayfromtheliveristermedhepatofugal
HepaticAbscess
usuallyinrightlobe
Pyogenic
entryviabiliarytreeorportal
vein
Rx:drainage
growsE.coli,bacteroides,strep
Amebic
entryviaportalvein
Abxonly(flagyl)
cultureusuallysterile
HydatidcystEchinococcalcyst:+casoniskintest,+indirecthemaglutination;appearsascalcifiedcystic
lesioncontainingmanycystsresect(pericystectomy)
86
BenignLiverTumors
History
CTfindings
Hemangioma
Oftenasymptomatic,
symptomsiflarge*;most
common
HepaticAdenoma
OCuse;oftensymptomatic;
bleedingorrupture
FocalNodularHyperplasia
OCuse(lessassociationthan
adenoma);usuallyasymptomatic;
2ndmostcommon
Peripheralenhancementand
delayedcentralpooling
Hypodense,heterogeneous
mass;arterialenhancement
MRIfindings
T1:hypointense
T2:extremelyhyperintense
T1:hypointense
T2:hyperintense
T1:isointense
T2:hyperintense+centralscar
RBCscanfindings
LiverScan
Poolingondelayedimages
colddefect
Nochange
colddefect
Nochange
Nodefect;sulfurcolloidtaken
upbyKupfferscellslesion
blendswithsurrounding
parenchyma
Management
Asymptomaticconservative Resect;ruptureorhemorrhage
+followup;
riskrelatedtosize;malignant
Symptomaticresectby
potential
enucleation
*KasabachMerritsyndrome:consumptivecoagulopathyorCHFduetohemangioma
Centralscar,whichenhances
Conservative;Resectonlyif
symptomaticoruncleardiagnosis
HepatocellularCancer
3rdhighestcancermortalityworldwide(lungis1st,stomach2ndasof2004)
Risks:HepB,HepC,cirrhosis(ethanol,hemochromatosis,PSC,1antitrypsindeficiency),
aflatoxins,clonorchissinensis(flukes)
SerumAFPin5595%
Size,stage,andhistologicgradeareimportantprognosticfactors
Bloodsupplymostlyfromhepaticarteryenhancesarterialphase;iso/hypodenseportalphase
(canhavecentralscar)
Resectionif:
Singlelesion<5cm;upto3lesionseach<3cm
OkudaI,CLIP01,BCLC0orA
ChildsAandB(notC)
Noportalhypertension(clinicallyorPVP>10mmHg)
Tumorrecurrenceoccursin70%ofcasesat5years
Transplantif:
Singlelesion<5cm;upto3lesionseach<3cm(Milancriteria)
OkudaI,CLIP01,BCLC0orA
ChildsBorC(notA)
Fibrolamellarvariantmayhavebetterprognosis
87
DdxforLiverMassonCT:
BiliarySystem:
BloodsupplytosupraduodenalbileductarisesfromRHAandbranchesofGDA(retroduodenalartery)
andlielongitudinallyatthe3and9oclockpositions
Bileisrequiredfor:
vitaminDabsorption
bilirubinexcretion
cholesterolexcretion(solublizedinphospholipidsvesicles)
Stonesassociatedwithilealdisease/resectionandTPNusearepigmentedstones,notcholesterol
stones(arecomposedofcalciumbilirubinate)
Primarycommonductstones(thoseinduct>2yearsaftercholecystectomy)arepigmentedand
relatedtobiliarystasisandinfection,notcholesterol
NaturalHistoryofAsymptomaticGallstones:Symptomsdevelopinabout13%ofpatientsper
year.Hence,observeasymptomaticstones.
Complicatedgallstonediseasedevelopsinabout35%ofsymptomaticpatientsperyear.
88
Bilecirculation:
[FiguretakenfromRUSHreviewofsurgery,2000]
Hepaticsynthesis=fecallosses=300600mg/day
Inthepresenceofacutecholecystitis(calculousoracalculous)allgallbladdersfailtovisualize
followingtechnetium99mpertechnetateiminodiaceticacid(99mTc)administration,becauseofcystic
ductobstruction(actualorfunctional)
Between8and18%ofpatientswithsymptomaticgallstoneshavecholedocholithiasis
SmallCBDstonescanbeclearedbyflushingtheductfollowingglucagonadministration(torelax
sphincter)
Acalculouscholecystitisresultsfromgallbladderstasisdistentionischemia
Cholangitis:requiresbothbacteriainbileandstasis;commonductpressure>20cmH2O
PreopERCPshouldbeperformedifanyofthefollowingarepresent:
1. cholangitis
2. jaundice
3. stonesseenonU/S
4. dilatedCBD
IOCisnotconsideredadequateunlessthefollowingarevisualized:
1. Bothrightandlefthepaticducts(ifnotbeconcernedaboutducttransaction)
2. CBDwithoutfillingdefect
3. Freeflowofcontrastintoduodenum(tryglucagonifnotseeing)
89
Gallbladder
ConcentratesbilebyactiveabsorptionofNa+,Cl(H2Ofollows);cholecystectomyworksby
eliminatingreservoirforcesamorecontinuoussourceofbileandeliminateschanceforsludge
andstoneformation.
70%ofpatientswithEF<30%(normalis>35%)onCCKHIDAbenefitfromcholecystectomy,
althoughthismaystillbecontroversial
1020%ofpatientswithsymptomaticgallstoneshavecholedocholithiasis
Bydefinitions:stonesinCBD>2yearsaftercholecystectomyareprimaryCBDstones(pigmented,
relatedtobiliarystasisandinfection),ratherthancholesterolstones;needsphincterotomyand
extraction
Porcelaingallbladderhas3065%riskofcancercholecystectomyindicated
Gallbladderadenocarcinoma:90%havestones.Cholecystectomyadequateifconfinedtomucosa;if
grosslyvisibletumorregionallymphadenectomy,wedgesegmentV,skeletonizeportaltriad
Gallbladderpolypscanbemalignant;riskisrelatedtosize;hence,shouldremoveGBforpolypis
symptomaticor>10mm;sessilemorelikelytobemalignant;pedunculatedmorelikelybenign
DiagnosisofCholecystitis
Threemostsensitivesignsofcholecystitis:
1.SonographicMurphyssign
2.Wallthickening>4mm
3.Pericholecysticfluid
Postoplapcholepatientnotdoingwell,think:
Viscousinjury(e.g.duodenum)
Ductinjury
Bileleak
RetainedCBDstone
Cysticductstumpleak
Managementofgallstoneileus:
1.Removestone(viaenterotomyproximalatsiteofobstruction)
2.Runentirebowel
3.Inacutesetting,especiallyelderly,reservecholecystectomyforlater(riskofrecurrence510%)&
repairbiliaryentericfistula
RatesofPositiveBileCultures
Bileculturesarepositiveinapproximately:
1.540%ofchroniccholecystitis
2.3070%acutecholecystitis
3.6080%ofcholedocholithiasis
4.2530%ofmalignantobstruction
5.100%ofbileductstrictures
Acalculuscholecystitis(pathophysiologyinvolvesischemia)mostcommonin:cocaineuseandHIV
Sclerosingcholangitis:ERCPtodiagnose;multiplestrictures/dilations(beadedappearance)
90
Bismuthclassificationsystemofbileductinjury:
Note:Type5injuryinvolvesaseparateinsertingsectoralductwithorwithoutinjuryofthecommonduct
CholedochalCystsTodaniClass
*20foldincreaseinbileductmalignancyifleftuntreated;F:M4:1
I
II
III
IVA
IVB
V
Solitaryfusiformextrahepaticcyst(82%)
Extrahepaticsupraduodenaldiverticulumsecondgallbladder(3%)
Intraduodenaldiverticulum,(choledochocele)(5%)
Fusiformextrahepatic&intrahepaticcysts
Multipleextrahepaticcysts(A+B=9%)
Multipleintrahepaticcysts,(CarolisDisease)(<1%)
*Currenttheoryisthatcystsoccurbecauseofbilereflux,whichresultsfromanabnormaljunctionofthe
biliaryandpancreaticducts;inotherwords,thecongenitalaspectofthediseaseistheductalabnormality
thecystsareaconsequenceofthis
[Figuretakenfromwww.uptodate.com]
Management:
I
Completecystexcisionwithhepaticojejunostomy
II
Excisionofcystwithprimarycholedochorrhaphy
III
Largesphincteroplasty
IV&VSelectivemanagementwithhepaticresectioniflocalizedbileductcyst,extrahepaticcystresection,
hepaticojejunostomywithlargestents,advancedbiliarycirrhosismayrequirehepatictransplantation
91
TransportofBilirubin
BilirubinissynthesizedintheRESfrombiliverdin.Insolubleunconjugatedbilirubin,reversiblyboundto
albumin,istransportedtotheliver,andintocytoplasmofhepatocytes.Theenzymeuridinediphosphate
glucuronyltransferaseconjugatesthebiliwitheitheroneortwomoleculesofglucuronicacidtoform
watersolublebilirubinmonoanddiglucuronide.Thisissecretedintothebilecanaliculus.
Intheterminalileum&colon,bilirubinisconvertedtourobilinogen,1020%ofwhichisreabsorbedback
intoportalcirculation
Bileis80%bilesalts,15%lecithin,5%cholesterol.Gallstonescanbeclassifiedascholesterolstones,black
stones,andbrownstones:
Cholesterolstonesformwhenbilebecomessupersaturatedwithcholesterol
Blackstonesformwhenbilebecomessupersaturatedwithcalciumsalts(primarilycalcium
bilirubinate)
Brownstonesfromwhenbileacquiresstasisinducedbacterialcontamination
GBconcentratesbilebyactivereabsorptionofNa+,Cl;H2Othenfollows
Bilepoolof5gisrecirculatedq4hourslose0.5g(10%)daily
AssessmentofJaundice
Askwhy?
Excessbiliproduction?
Deficienthepatocyteuptake?
Deficientconjugation?
Deficienthepatocytesecretion?
Deficientbilisecretion?
Groupedasprehepatic,hepatic,andposthepaticcauses
Checkfractionatedbililevels
1. Predominanceofunconjugated(indirect)suggestsprehepaticetiology(hemolysis)orhepatic
deficienciesofuptakeorconjugation
2. Predominanceofconjugated(direct)suggestsdefectsinhepatocytesecretionintobileductsorbile
ductsecretionintoGItract
3. Combinedelevationsuggestscomplexproblem,usuallyacquiredliverdamage
92
LaboratoryInvestigationofHyperbilirubinemia
Jaundicemayresultfromoverproductionofbilirubin(hemolysis),impairedconjugation(Gilberts
syndrome),impairedintracellularmetabolismorexcretion(drugeffect),hepatocyteinjury(hepatitis),bile
ductinjury(primarybiliaryandsclerosingcholangitis),andlargeductobstruction(stone,tumor,sclerosing
cholangitis)
Firstinvestigatebyfractionation:
Unconjugatedhyperbilirubinemia(hemolysis,Gilberts)isusuallydefinedaslevelsgreaterthan
80%oftotalbilirubin,whichshouldRARELYexceed5mg/dL
Conjugatedhyperbilirubinemia(hepatocellularorbileductdisease)existswhentheconjugated
fractionexceeds50%ofthetotallevel
bilirubinisanirreversibly(covalently)albuminboundformofbilirubinfoundinthesettingof
longstandingconjugatedhyperbilirubinemia;notfilteredthroughkidneys;T1/2=18daysreason
forslowdeclineofTBfollowinglongstandinghyperbilirubinemia,especiallyinpatientswithrenal
failure
Ingeneral,abilirubinof25mg/dl,ofwhichmostisunconjugated,inanotherwisehealthyadultis
Gilberts(25%ofpopulation),hemolysis,orboth.Thehemolyticcomponentwillbemorelikely
LDHandAST(bothinRBCs)arealsomildlyelevated
Alkalinephosphatasecomesfromliverandbone.MeasurementofGGT(gammaglutamyltranspeptidase)
isoftenusedtoindicatethesourceoftheAP.NormalGGTsuggestsnonhepaticsource,suchas
osteoblasticbonelesions,orcertainothertumors.SpuriouselevationsinAPmayalsobeseenafteralbumin
infusionifthealbuminisderivedfromplacentalblood,whichisrichinAP
SphincterofOddi
Regulatesflowofbileintoduodenum
Composedof4sphincterscontainingbothcircularandlongitudinalsmoothmuscle
Lengthisabout46mm
Basal(resting)pressureaverages13mmHg(515)
Undergoesphasiccontractionswithafrequencyof4/min;eachwithdurationof8seconds
Pressureincreasesto13015mmHg(50150)
RelaxationoccurswithCCKstimulationandparasympatheticstimulation;glucagons(tryIV
glucagonstopasssmallstones)
MSO4,sympatheticstimulationincreasessphinctertone
93
PortalHypertension
DefinedasPVPthatexceedsnormalvalueof36mmHg;eitherresistancetoflow(common)orportal
bloodflow(uncommon);bleedingrequiresapressure>12mmHg
Bleedingfromrupturedgastroesophagealvaricesisresponsibleforgreatestmortalityandmorbidity
Maybeclassifiedaspresinusoidal,sinusoidal,orpostsinusoidal:
Presinusoidal
Sinusoidal
Postsinusoidal
Extrahepatic
Portalveinthrombosis(congenital
atresia,pylephlebitis,
hypercoagulablestate,trauma,
adjacentinflammation,mechanical
obstructiontumors/nodes)
Intrahepatic
Schistosomiasis
congenitalhepaticfibrosis
myeloprolifertiivedisorders
PBC
fattymetamorphosis
toxichepatitis
Wilsonsdisease
*Cirrhosis
Extrahepatic
BuddChiari(extrahepatic):
congenitalwebs,compressive
neoplasms,trauma
cardiaccauses(constrictive
pericarditis,CHF)
Intrahepatic
BuddChiari(intrahepatic):veno
occlusivedisease,hypercoagulable
state
Betterprognosisthansinusoidal,postsinusoidal
*Overallmostcommoncause
Also,highflowportalhypertensionresultingfrom:
AVfistula(HAPV,splenic,mesenteric)
massivesplenomegaly
NaturalHistory
ofpatientswithcirrhosiswilldevelopvarices2033%willbleed
withsupportivemanagementalone30%willrebleedwithin6weeksand70%within1year
initialbleedisfatalin3050%ofcirrhoticpatients
factorsassociatedwithbleeding:large(>small),tortuosity,cherryredspot,presenceofgastric
varices,ChildsclassC(vs.A,B)
varicesbleedbyruptureratherthanerosion
portalsystemicshuntshavebeenshowntohavenoroleinprophylacticmanagementonesophageal
varices(butblockersdo)
Vasopressin+NTG>>Vasopressinalone[vasopressincausessplanchnicarteriolarvasoconstriction]
Octreotide[50mcgbolusfollowedby50mcg/hrx4872hours]isbest1sttreatmentforbleeding
varicesandisaseffectiveassclerotherapy[PlanasR,etal1994Hepatology20:370]
94
MassiveUpperGIBleed:
Allcomers:40%PUD,18%gastritis,13%esophagealvarices,9%MalloryWeisstear,9%other
Knowncirrhotic:53%esophagealvarices,22%gastritis,20%PUD
4Maincomplicationsofcirrhosis
1. portalhypertension
2. ascites
3. hepaticencephalopathy
4. malignancy(primaryhepatic)
SAAG(SerumAscitesAlbuminGradient)
If>1.1gm/dLindicatesportalhypertension.Shouldberesponsivetomedicalmanagementconsistingof
sodiumrestriction(2000mg/day)+oraldiuretics(spironolactone+lasix)
FluidrestrictwhenNa+fallsbelow120mmol/L
TIPSIndications
AcutevaricealhemorrhageisthemostcommonindicationforTIPS,followedbyrefractoryascitesand
hepatichydrothorax.
TIPScontrolsbleedingin75%to100%ofpatients;theefficacyissimilarforbothesophagealandgastric
varices,andrebleedingdoesnotusuallyrecurunlessthereisshuntdysfunction.TIPS,however,may
noteliminateisolatedgastricvaricesinupto50%ofpatients.Whenrebleedingoccursinspiteofan
openshunt,angiographicobliterationofthevaricesmayarrestbleeding.Despitegoodresultsfor
controlofbleeding,shorttermmortalityremainshighinpatientswhohaveTIPSforvaricealbleeding.
Asaresult,bettercriteriaforselectionofpatientshavebeensought.
Arecentstudyshowedthatpatientscouldbestratifiedby4clinicalvariablesbeforeTIPSinorderto
predictsurvivalafterTIPSplacement.Overall,allpatientsundergoingTIPShada19%1monthanda
48%1yearmortality.OfallvariablesavailablebeforeTIPSthefollowing:
1. varicealhemorrhagerequiringemergentTIPS,
2. bilirubin>3.0mg/dL,
3. alaninetransaminase>100IU/L,and
4. encephalopathy
wereassociatedwitha90%mortalityat1month.VaricealhemorrhagerequiringTIPSwasthe
strongestindependentpredictorofmortality.
WhenapatientwithTIPSpresentswithrecurrentbleeding/ascites1sttesttoperformisDopplerU/S
toruleoutshuntthrombosis
95
SurgicalShunts:
Inpresenceofsevereascitessidetosideportocavalshunt(ormesocavalshunt)ispreferable
Fewindicationsfordirectportalveinanastomosis(ratherthansplenic/SMVanastomosis)
Smalldiameterinterpositionalshunt
WarrenShunt(distalsplenorenal)
(Sarfeh)
[Surgery:ScientificPrinciplesandPractice3rd,2001]
96
Pancreas
pan(all)+creas(meat)theonlyorganthatcaneatthebody
Ventralbuduncinateprocessandinferiorportionofhead
Dorsalbudremainderofgland
Isletcellsare12%ofpancreaticmass,butreceive1025%ofarterialbloodsupply
Oftheisletcells,cellscompriseabout70%andarelocatedatthecenteroftheislet
Annularpancreas:doublebubbleonAXR;treatobstructionwithduodenojejunostomy(noresectionof
gland)
PancreaticEnzymesandFunction
1.Alphaamylase:starchdigestion,secretedinactiveform
2.Lipase,phospholipaseA,colipase:fatdigestion(removes#1,3carbon)
3.Proteases(trypsin,chymotrypsin,elastase,carboxypeptidases):proteindigestion,secretedasproenzymes
4.Trypsinogen*isconvertedtoactiveenzymetrypsinbyenteropeptidase,aduodenalbrushborder
enzyme.Trypsinthenactivatestheotherproenzymesandtrypsinogen(positivefeedback)
*PRSS1mutationsarerelatedtohereditarypancreatitis
StimulationofPancreaticFunctions:
1.Secretin*:stimulatesflowofbicarbonatecontainingfluid
2.Cholecystokinin(CCK)*:majorstimulusforzymogenrelease;weakstimulusforalkalinefluidflow
3.Acetylcholine:majorstimulusforzymogenrelease,poorstimulusforbicarbsecretion
4.Somatostatin:inhibitsreleaseofgastrinandsecretin
*secretedfromduodenum
SecretionRates
Pancreas:
Basalexocrine:0.20.3mL/minupto5mL/minwithmaximumsecretion(i.e.morethangastricH+)
Na+,K+alwaysplasma;
Atlowrates,HCO3,Clcompositionplasma;
AthighratesHCO3,Clreverse
Bile:
10001500mL/day(0.41mL/min);gallbladdercanonlystore60mLoffluid,butcanconcentrate
upto10fold*
*Keepthesenumbersinmindforpatientswithbileleakstoassessnatureofductalinjury,i.e.howmajoran
injury?
Howethanolcausespancreatitis:
1. Pancreaticducthypertrophyampullaryresistance
2. Stimulationofgastricacidsecretionsecretinexocrinesecretion
1+2enzymeextravasation;exacerbatedby
acetaldehyde(byproductofethanol)membranepermeability,and
TGsourceofcytotoxicfreefattyacids
97
RansonsCriteriaEthanolassociatedPancreatitis
Duringfirst48hours:
Initial:
Age>55
Hctfalls>10%points
3
WBC>16,000permm
BUNincreases>5mg/dL
Bloodglucose>200mg/dL
Serumcalcium<8mg/dL
AST>250mg/dL
ArterialPaO2<60mmHg
SerumLDH>350mg/dL
Basedeficit>4mEq/L
Fluidsequestration>6L
Mortality:
If02signs,then2%
If34signs,then15%
If56signs,then40%
If78signs,then100%
Note:allyoucanreallyconcludeis>3signspoorprognosis(inactuality,prognosisisslightlybetter
todaybecauseofgreatlyimprovedcriticalcare)
Distinguishbetweenedematouspancreatitis(resolves)andnecrotizingpancreatitis(progresses).
Pathogenesis:1ocelldeathlocalinflammatoryresponsesystemicinflammatoryresponseviaportal
circulationtoentirebody.
CTishelpfulfordiagnosisbecausedualphaseCTallowscomparisonofnoncontrastandarterialphaseto
delineatetheischemicextentoftheprocessand/ortoappreciateextralumenalgas
Antibioticsshouldonlybeusedforsevereepisodes(i.e.>3ofRansonscriteria)
1stlineagentisimipenem(crossesblood/pancreasbarrierbest)
2ndlineagentisciprofloxin
Operativedebridementif:
1. clinicaldeterioration,despitemaximalmedicaltreatment
2. infectionofnecroticpancreas(airinRP,+pancreaticculture)
3. failuretoimproveafter34weeks
IfgallstonepancreatitisperformcholecystectomywithIOC:
QuickimprovementlapcholeIOCduringindexadmission
Severediseaselapcholeatinterval
Pancreaticascites:
followsductaldisruption;oftencausedbyblunttrauma/pancreatitis
abdominaldistentionwithhighamylasefluid
Rx:nonoperative(NPO,TPN,octreotide)
ifpersists>3weeksERCP+sphincterotomytodelineateanatomyandconsidertranspapillary
stenting;iffailsplanRouxYvs.distalpancreatectomy
Siteofductaldisruptionrelatedtocollection:
DorsalruptureRPcollectioncanbesuckedintochest(=pancreaticpleuraleffusion)
Ventralruptureinsidelessersac,ifnotwalledoffpancreaticascites
98
PancreaticPseudocyst
Encapsulatedcollectionofpancreaticfluidformedbyinflammatoryfibrosis(NOTepitheliallining)
1in10afteralcoholicpancreatitis;chronicalcoholicpancreatitisis#1causeinU.S.
Sx:epigastricpain,emesis,fever,weightloss
Signs:palpableepigastricmass;tenderepigastrium;ileus
U/S,CT(goodformultiple)showfluidcollection;MRI/MRCP;ERCP(fortreatment):contrastwill
fillcystifcommunicationwithduct
Ddx:cystadenocarcinoma,cystadenoma,IPMN,solidpseudopapillarytumor,mesentericcyst,
adrenalcyst
Complications:infection,bleedingintocyst(mostcommoncauseofdeath),fistula,pancreatic
ascites,gastricoutletobstruction
Treatment:ittakes6weeks(bydefinition)tomatureandwalloffsoitcanholdsutures;ifitsgoing
toresolvespontaneously(50%will),itwilldosoduringthistime
Mostagreethatifpseudocystis>5cmitshouldbedrained(especiallyifsymptomatic)
SizeISanimportantpredictorofresolution
Internal(surgical)drainageissuccessfulin90%ofcases
External(surgical)drainageisreservedforthinwalledand/orinfectedcysts
Externaldrainageshouldbeusedonlyincasesofsepsis
Endoscopicdrainagemaybeappropriateinthesettingofchronicpancreatitis
SurgicalDrainage:
1.Ifadherenttoposteriorwallofstomach:cystogastrostomy
2.Ifadherenttoduodenum:cystoduodenostomy(rare)
3.Ifnotadherenttoeither:RouxenYcystojejunostomy(drainintoRouxlimbofjejunum)
4.Ifintail:resecttailwithcyst
*ALWAYSbiopsycystwalltoruleoutcysticneoplasia
CysticNeoplasmsofthePancreas
Accountfor<15%ofpancreaticcysticlesions(butincidenceincreasing)

IPMN*
MCN Serous
Gender
M=F
2:1
0.8:1
Age
70
50
6070
Location
Head
Tail
Uniform
Ductalcomponent Yes
Rare
No
Malignant
35%
30%
Rare
*Associatedwithchronicpancreatitis(andoftenmistakenfor)
Bydefinitionmusthaveunderlyingovarianstroma
EUA+FNAforCEAisprobablymostaccurate(optimizedsensitivity+specificity)measureof
malignancy,BUTresectionalmostalwaysindicatedasitisdifficulttoexcludemalignancyonthe
basisofbiopsies[BruggeWR,etal.Gastroenterology,2004;126:1330]
DonotperformCTguidedpercutaneousbiopsy(oftenundiagnostic,potentialtocausepancreatitis,
bleeding,ruptureofcapsule)
99
EndocrineNeoplasmofthePancreas
Seeprevioussectionsongastrinoma,insulinoma,glucagonoma.Ingeneral,pancreatictumorsproducing
ectopichormones(e.g.ACTHproducingtumor)areveryaggressive.
ExocrineNeoplasmofthePancreas
Fourperiampullarymalignantneoplasms:
1. pancreaticductaladenocarcinomaofthehead,neck,anduncinateprocess
2. ampullaryadenocarcinoma
3. periVaterianduodenaladenocarcinoma
4. distalcholangiocarcinoma
Ofthese,pancreaticductaladenocarcinomaaccountsforthemost(7585%)andhasthepoorest
prognosis(seefigurebelow)
[YeoCJ,etal.AnnSurg227:821,1998]
Lethality(death/incidenceratio)ofpancreaticadenocarcinomaisapproximately0.99
1520%ofpatientspresentingwithpancreaticcanceraresurgicalcandidates,theremainderhave
metastaticdiseaseorlocallyadvanced(unresectable)disease
Ofpatientswithpancreaticadenocarcinoma,thesurgicalcandidateshave1020%5yearssurvival
VisualizationoffatplanesaroundSMV/PVarepredictiveofresectability
ThrombosisofSMV/PVisacontraindicationforresection
100
Resectable
Unresectable
[FiguretakenfromtalkbyR.Royal,2004]
Outcomesforpancreaticcancer
Mediansurvivalfollowingresectionwithpositiveretroperitonealmargin:612months(with
chemoradiation)
Mediansurvivalfollowingstandardpancreaticoduodenectomyforadenocarcinomaofpancreas:
2022months(13.5monthswithoutchemoradiation)
MediansurvivalfollowingreconstructionofPV/SMV:2022months
MediansurvivalfollowingreconstructionofSMA/celiac:610months
Suggestsvenousinvolvementafunctionoflocation,notbiology
Predictorsofoutcomefollowingresection
1. ResectabilityR0,R1,R2(i.e.marginstatus)
2. LNinvolvement
3. Tumorsize
4. Adjuvanttherapy
5. Moleculargenetics(particularlymedullaryvariantwithMSIdobetter)
101
Sarcoma
8000cases/yearinUS;1%ofadultcancers
Mesodermorigin
Nopredilectionforsex,age,race
Overall5yearsurvivalapprox50%
MostCommon:Liposarcoma,fibrosarcoma,leimyosarcoma(MFHissortofawastebasketterm),
essentiallynochangeintreatmentorsurvival
Staging(grade,size/depth,metasteses;nothistology):
StageI:lowgrade,<5cmdeepor>5cmsuper,nomets99%OS
StageII:lowgrade,>5cmdeepORhigh<5cmdeep/>5cmsuper,nomets82%OS
StageIII:highgrade,>5cmdeep,nomets/nodes52%OS
StageIV:metasteses(includingnodes)20%OS
Sites:
Lowerextremity32%
Upperextremity14%
Retroperitoneal15%
Viscera16%
Trunk11%
H&N12%
Biopsy:
<3cm,uncomplicatedExcisionalbiopsy
Ifincisionallongitudinal
Coreneedle>>>FNA(notrecommended)
Prognosis:
Grade:low>high
Depth:superficial>deep
Location:distal>proximal;extremity>>RP/visceral
Treatment:
LowGrade
1. NCISurgeryBranchProspectiveRandomizedTrial(excludingRP/viscera):surgery+(XRT6800rad
vs.observation)XRTeffectiveinpreventingrecurrence,butnoeffectonsurvival
2. MSKProspectiveRandomizedTrial:surgery+(brachyvs.observe)nodifferenceinlocalcontrol
orsurvival
HighGrade
Narrow(<1cm)margin5090%recurrence
Wide(>1cm)margin3050%recurrence
Radicalresection(entiretissuecompartment)<20%recurrence
RoleofXRT:
1. NCISBPRT:Wideresection+adjuvantchemo(adria+cytoxan)(XRTvs.observe)p=0.003(0%vs.
22%recurrence),butnosurvivaldifference(p=0.64)
2. MSKPRT:consistentwithabove
102
Roleofsystemicadjuvantchemo:SMACMetaanalysis[Lancet1997350:1647]
Adriamycinvs.others
Found:decreasedriskofmets/distantdisease,localrecurrence
BUTnoincreaseinsurvival
OverallHR=0.89(0.761.0395%CI),p=0.12,increasedsurvivalfrom50to54%
Hence,nosupportofadjuvantchemotherapy.
Currenttrendfavorsinductionchemoradiationtoshrinklesionspreoperativelylessaggressive
resections
IncreaseRiskofRecurrence:+margin,previousrecurrence,noXRT;Localrecurrenceisstrongestpredictor
ofsurvival
Predictorsofsuccessformetastesectomy(lung):
1.Numberoflesions(5)
2.Diseasefreeinterval(>1year)
Melanoma
Thicknessofprimarytumor
insitu
<1mm
12mm
24mm
4mm
Marginofresection
5mm
1cm
12cmdependingonlocation(2ispreferred)
2cm
2cm
Lesionsofintermediatedepth(14mm)andlesions1mmthatareulceratingorClarkslevelIVorV
shouldreceivesentinelnodebiopsyintheabsenceofclinicallypalpablenodes
[summaryoftrialsinReintgenD,etal.SeminOncol.2004;31:363]
RevisedAJCCStagingforMelanoma:
103

[BalchCM,etal.JCO2001,19:3635]
Forpatientswithmelanomaofdepth14mmandpatientswithulceratedmelanomathereisasurvival
benefitassociatedwithelectivelymphnodedissectionvs.observation.[BalchCM,etal.AnnSurgOnc2000,7:87]
Merkelcellcarcinoma:rareskintumorofneuroendocrineorigin.Similartomelanomainthatittypically
appearsinsunexposedareas,andlymphnode(1030%)anddistantsites(2540%)ofmetastesesare
oftenpresent
104
Hernia&AbdominalWall
Approximately75%ofabdominalwallherniasoccurintheinguinalregionofwhicharedirect
Malesexperience5xmorethanfemales;inbothgendersdirectaremorecommon
Femoralcanalisboundedby:Coopersligamentinferiorly,theileopubictract(inferiormarginof
transversalisfascia)superiorlyandmedially,andthefemoralveinlaterally
Posteriorviewofinguinalanatomy:
IfstrangulationissuspectedtoOR(donotattemptreduction);opensacpriortoORreductiontoassess
viabilityofsaccontents
Spigelianhernia:inferiortolineasemicircularis(thepointatwhichtheinferiorepigastricarteryenterstherectus
sheath),throughlineasemilunaris;deeptoexternalobliquehencehardtodiagnose;repairall
Petitshernia:inferiorlumbartriangle:iliaccrest,externaloblique,latissimusdorsi
Grynfeltthernia:superiorlumbartriangle:12thrib,internaloblique,lumbosacralaponeurosis
[NettersAnatomy,1996]
105
TraumaPrinciples
Top3causesofprehospitalmortality
1.Headinjury
2.Hemorrhage
3.Airwayobstruction
Withmassivehemorrhage,themostimportantfactorinpredictingoutcomeisdurationofhypotension
Criticaldecisionforpatientwithheadinjuryiswhetherornotmasslesionispresent
Multipleinjuries,pluswidenedmediastinumdecompressionofmasslesioninheadisstillfirst
priority.
Ifpatientarrivesinshock,withwidenedmediastinumbleedingmostlikelyinabdomen(gothere
first)
IfpatientstablewithwidenedmediastinumCTchest/arterigraphyfirst,butmustRULEOUT
abdominalbleedingpriortothoracotomy
Thetwomajorinjuriesassociateswithwidenedmediastinum(typically>8cm):containedaorticrupture
andvertebralbodyfracturewithassociatedhematoma
Whenassessingcirculationmustdiscriminatebetweenpumpandvolumeproblems:
Pumpproblemsdistendedneckveins(tamponade,tensionpneumothorax,myocardialcontusion,air
embolus)
Finitenumberofsitesofsignificantinternalbleeding:Chest,thigh,abdomen,pelvis,RP
Ribfractures,includingthoseof1stand2ndribs,arerelatedtotheMAGNITUDEofdeformation;
ThoracicaortainjuryisrelatedtotheinitialSPEEDofdeformation;hence,notdirectlyrelatedtoeachother
Amnioticfluidonpelvicexamwillbealkaline(deepblueonnitrazinepaper);KleihauerBetke(KB)blood
testdetectsevensmallamountsofmaternalfetaltransfusion
LowCVPisnotagoodindicatorofhypovolemia,ratheritsuseishelpfulwhenhigh(tamponade,tension
pneumothorax)
ZoneI:clavicletocricoid;ZoneII:cricoidtoangleofmandible;ZoneIII:angleofmandibletobaseofskull
Ingeneral:ZoneIIunstablesecureairwaytoOR;ifstablecandosameorconservativeapproach:
carotidarteriogram,bariumswallow,rigidesophagoscopy,bronchoscopy
Brachiocephalictrauma:ZoneIItoORwithoutarteriography;Zone1&3frequentlytreated
conservatively
Patientswithexsanguinatingexternalhemorrhage,expandinghematomas,orneurologicdeficitsairway
OR(nodiagnosticprocedures)
106
Bluntcarotidarterytrauma:fewsignspriortoneurologicalchanges;mortalityhigh(25%)andof
survivorshavepermanentneurologicaldeficit.Thelesionsarerarelyamenabletosurgicalrepair
anticoagulationappearstobethemainstayoftreatment
[CurrentTherapyofTrauma,4th,1999]
Ingeneral,trytoavoidoperatingonthevertebralartery,evenproximally.Angiography+embolizationis
alwaysthebetteroption.
Carotidarteryligationresultsinneurologicdeficitinonly20%ofadults
UseofrecombinantFactorVIIainbleedingtraumapatients[Boffardetal.JTrauma59;8:2005]
Randomizednearly300patientswitheitherblunt(143eligible)orpenetrating(134eligible)traumato
receiveeither3xplaceboinjectionsor3xrFVIIa(200,100,and100g/kg)inadditiontostandardtreatment
withthefirstdosefollowingthe8thunitoftransfusedRBCandsubsequentdosesadministered1and3
hourslater.InblunttraumathetreatmentgrouphadasignificantreductioninRBCrequirementand
massive(>20)transfusionrequirements.Inthepenetratingtraumaarm,treatmentresultedintrends
towardsfewertransfusions,buttheresultsdidnotreachstatisticalsignificance.Bothgroupsexperienceda
trendtowardsreducedmortality.Adverseevents(e.g.thromboembolism)weredistributedequally
betweenallgroups.
107
Incisions
Suspectedinjuryto
Incisionforbestexposure
Innominateartery
Rightsubclavianartery
Leftsubclavianartery
Carotidartery
Axillaryartery
Mediansternotomyextensionintocervicalorrightsupraclavicular
incision
Mediansternotomyforproximalvesselinjury;distalsupraclavicular
incisionfordistalinjury
Mediansternotomy+extensionintosupraclavicularincision
Cervicalincision
Innerarmwithpatientsarmawayfromside;infraclavicularincisionmay
benecessaryproximally
Ingeneral:mediansternotomyisalwayssafestbecauseofbetterproximalcontrol;neverhesitatetoresect
theclavicle
PelvicFractures:
Mostcommonassociatedwithhemorrhageare:
1.Butterfly/Straddle:all4pubicrami
2.Openbook:diastasesof>2.5cm
3.Verticalshear:bothanteriorandposteriorelementswithverticaldisplacement>1cm
Ifunstablemustruleoutintraabodominalhemorrhage
Pelvicfractureassociatedwithurethralinjuryin15%ofmales(veryrareinfemales)andbladder
rupturein7%ofpatients
AbsoluteindicationsforurgentoperativerepairinGUtrauma:
1.Avulsionofrenalpedicle
2.Acuteischemiaresultingfromarterialintimalflap
Bloodatmeatus,highridingprostate,anteriorpelvicfracture,orpenetratinginjuryproximaltourethra
requireretrogradeurethrographybeforeFoley(12Frcathwithoutlube1to2cmin2040mLcontrast
in).Inhemodynamicallystablepatientswithoutgrosshematuriaincidenceofrenalinjuryis<1%
PeripheralVascularTrauma
20%ofpatientswithseriousarterialinjurieshavenormalpulsesdistaltoinjuryhenceany
penetratinginjuryinpathofmajorarteryshouldbeinvestigated;ABI<0.9shouldraisesuspicion
Posteriorkneedislocationshouldundergopoplitealarteriographyafterreduction,unlessABI>
0.9
Hardsignsofvascularinjury(pulsedefect,pulsatilebleeding,thrill,bruit,expandinghematoma)
GodirectlytoOR(noangiography);administerheparinimmediately;reversedsaphenousvein
graftisinterpositionalgraftofchoice,butPTFEok
108
NeurologicTrauma
GlasgowComaScale(motorisbestprognosticindicatorofoverallneurologicoutcome)
EyeOpening
Verbal
Motor
6:obeyscommands
4:spontaneous
5:oriented
5:localizespain
3:topain
4:disoriented
4:withdrawsfrompain
2:toverbalstimuli
3:inappropriatewords
3:decorticateposturing
1:none
2:incomprehensiblesounds
2:decerebrateposturing
1:none
1:none
Lesionsclassifiedasfocalandnonfocal:
Focal
epidural/subdural,intraparenchymalhematomas(requireurgentsurgicaldecompressionfor
masseffect)
IndicationsforOR:midlineshift>5cm,ICP>20mmHg,deteriorationinneurofindings
Subdural>>Epidural(3%ofpatientswithsevereheadinjury);subarachnoidrarelycauses
masseffect,butvasospasmisbiggestconcern
Nonfocal
3categories(mildconcussion,classiccerebralconcussion,DAI)
Hypotension(prehospitalandhospital)issinglebiggestpredictorofpoorneurooutcome
anddeath
Tools:CT,ICP,JugularbulbO2saturation(<50%believedtorepresentcerebralischemia),TCD
1995AitkenBrainTraumaFoundationGuidelinesforTreatmentofHeadInjury
(Only3levelonestandardsforpatientsGCS38)
1. NOprolongedhyperventilation[Note:respiratoryalkalosiscausesareflexvasoconstrictionofthe
cerebralbloodvesselsdecreasingintracerebralbloodvolumeandpressure;butbestusedinacute
management]
2. NOprophylacticsteroids
3. NOprophylacticantiseizuremedsbeyond7days
WhogetsICPmonitoring?
1. GCS8+abnormalCT,or
2. GCS8+twoofthefollowingthree:(age>40,MAP<90mmHg,clinicalsignsofelevatedICP),or
3. ANYTBIpatienthavinganinvasiveoperation/intervention
SkullFractures
Inandofthemselvesdonotcauseinjuryorwarrantintervention,butmarkersofdamage
Operateifdepressedand:CSFleak,underlyingtissueinjury,significantdeformity
109
CSpineFracture
C1burstfracture(Jeffersons):causedbyaxialloadingstable(ifisolated)treatwithcollar
C2posteriorelementfracture(Hangmans):causedbyextensionanddistractionunstable3monthsin
halo
Odontoidfracture:
TypeI:abovebasestable;
TypeII:atthebaseunstable;<5mmdisplacement3monthshalo;>5mmC1/2fusionor
screwfixation
TypeIII:extendintovertebralbodyhalo
3Columnsdeterminethestabilityofthespine:
1. Anterior:anteriorspinousligament
2. Middle:vertebralbody,posteriorspinousligament
3. Posterior:facet/laminainterface
Instabilityresultswhenatleastareinterrupted.Penetratinginjuryrarelyresultsininstability.
TandLspinefractures(occurbetweenT11andL3):
Fracturesthatinvolvethemiddleorposteriorcolumnsarebydefinitionunstableand,becauseofthe
narrowspinalcanalinthisregion,cancausesevereneurologicinjury
Iffingerspreadingcanbeaccomplishedwithsymmetryandstrength,thereisnocordinjuryabove
C8
CordInjury
MostcommonC6toT1
Iftipofodontiod(dens)is>4.5mmaboveMcGregorsline(hardpalatetolowestpointonoccipital
bone)basilarimpressionlikely
ORforcompression>50%heightofvertebralbodyor>30%narrowingofcanal
NASCIS2Trialdemonstratedthatinpatientswithblunttraumatothespinalcordhighdose
methylprednisolone(30mg/kgbolusfollowedby5.4mg/kg/hourfor23hours),ifinitiatedwithin8hoursof
injury,resultedingreaterneurologicrecovery,whichremainedatoneyear[NEJM322;20,1990]
Afollowupstudyfurtherdemonstratedthat24hourtreatmentwassufficientforpatientsinitiatedon
treatmentwithin3hours,but48hoursteroidtreatmentwasnecessaryforpatientsinitiated38hoursafter
injury[JAMA277;20,1997].
NeurogenicShock
Nottobeconfusedwithflaccidspinalshock
Lossofvasomotortoneinvisceraandlowerextremities;needvolumefirst,peripheral
vasoconstriction(e.g.neo)second.Hypotensionshouldfirstpromptsearchofothercausesofshock
(suchashypovolemia)
Mayseebradycardiaandwarm,perfusedextremities
NexusCriteria
Nofilmsif:
Nointoxication,alert,awake,noMS
Noneurodeficit
Noneckpain
Nodistractinginjury
Normalneckexam
110
FocusedAbdominalSonogramforTrauma(FAST)Exam:
Ultrasoundcandetectaslittleas100mLoffreefluidintheperitoneum.Withholdfoleyplacementuntil
FASTisdonetofacilitatebladderview
1stView:Subxiphoid,demonstratesalongitudinalcrosssectionoftheheartandpericardialsac
2ndView:RUQ,demonstratesasagitalviewoftheliverandright
kidney
rd
3 View:LUQ,demonstratesasagitalviewofthediaphragm,spleen,andleftkidney
(Note:2locationsforfluidaccumulation)
4thview:Pelvis,demonstratesatransverseviewofthepelvis
111
ChestWallInjuries
Sentinelinjuries:
Firstribfracturecanindicateunderlyingheadandneckinjuryorgreatvesselinjury
ScapularfractureCNSinjuries,pulmonarycontusion
Sternalfracturecardiaccontusion,greatvesselinjury
Bilateralribfracture,lowerribfractureliver,spleen
Flailchest:adjacentribs,eachintwoormoreplacesparadoxicalmovementonrespiration(canbe
overlookedinpositivepressureventilation).Threecomponents:
1.Alteredchestwallmechanics,
2.Underlyingpulmonarycontusion(*mostsignificant),
3.Painreducedtidalvolume
Ifawake,alert,deservetrialofnonintubation,butadequateIVpaincontrol(considerepidural);if
respiratorydistressvolumecontrolledventilation
OpenPneumothorax:Ifthedefectismorethanthediameterofthetracheaoninspirationairwill
preferentiallypassthroughchestwallratherthanairway;initialmanagementiscreatingafluttervalvetype
dressing+chesttubeatsiteremotefromdefect
TrachealInjury:
IfpenetratingexploreviaSCMincision
Patientspresentingwithmassivesubqormediastinalemphysemashouldbesuspectedofhaving
distaltrachealorbronchusinjury;Also,constantbubblingafterchesttubeplacement;Perform
bronchoscopyASAPtoruleouttracheal/bronchialtear
80%oftraumatictearsoccurwithin2.5cmofcarina;AirwayrepairdoneviarightPLthoracotomy
PulmonaryContusion:donotmanifestonCXRuntil>24hours;hypoxiamaybefirstsign;consider
intubationifPaO2<60mmHgon>40%O2orifPaCO2>50mmHgwithnormalHCO3
PulmonaryLaceration*:Thoracotomyindicatedfor:
1.Entirehemithoraxopacified,
2.Shockthatispersistentordevelopsorispersistentashemothoraxisevacuated,
3.Rapidremovalof>1500mLblood,
4.>250mL/hourx46hours,
5.Significanthemoptysis
*ConsidertractotomywithGIAstaplerovertraumapneumonectomy(morepapersthansurvivors)
AirEmbolism:
Asdistributedtoendorgans,smallbubblescauseischemicdamageastheyoccludevesselsofthe
microcirculation;Brainandmyocardiumaremostsensitive;
RCAisanteriorinsupinepatient,hence,receivessubstantialproportionofAEastheyexitaortic
root
PenetratingthoracictraumacausesoftraumaticAE
Cluestoinjury:Chestinjury,withoutheadinjuryyetfocalneurosigns
Treatment:cessationofcontinuedAE;headdown,thoracotomyonsuspectedsidewithhilarcross
clamping;InterventionsthatincreasePaO2,CO,BPenhanceairbubbledissolution
112

Fatemboli:longbonefracture;petechia,hypoxia,confusion/agitation;Sudanurinestainforfat
CardiacTrauma:
Penetratinghearttraumahave75%prehospitalmortality(higherforblunttrauma)
RV>LV>RA>LA
Majormorbidityiscoronaryarteryinjury
Presentationoftamponade:extremeanxiety,hypotension,distendedneckveins
Followingthoracotomyandaorticcrossclampingopenpericardium(longitudinallyfrominferior
tosuperior)
FinefibrillationisabadsignandwontconverttocoursefibrillationuntilthepHreaches7.20
s/pbluntcardiactrauma:newmurmurshouldraisesuspicionofvalvularprolapse(mitral,
tricuspid)ortraumaticVSD
EsophagealTrauma:mostcommonsiteiscervical(>80%)
Shouldbesuspectedwhen:
posteriorchestwound,
transmediastinalinjuries,
penetrationsofplatysma,and/or
tracheobronchialtrauma;
Gastrograffincanmissupto15%ofinjuriesandshouldbefollowedwithdilutebarium
Management:
<24hours,stablepatient:primaryclosure,buttressedwithtissueanddrained
>24hours;unstablepatient:Cervicalsimpledrainage;iflargespitfistula;ThoracicclosewithGrillo
(pleural)patch,extensivedebridement,widedrainage
CausticInjuries:scopeonlytofirstareaofburn,notbeyond
FirstDegree(hyperemiaandedema):IVuntilabletohandleownsalivabariumswallowadvancediet
astolerated
SecondDegree(hemorrhage,exudates,ulcerations):asabove,repeatendoscopyin3weekstoruleout
stricture
ThirdDegree(completeobliterationofmucosa,circumulceration,eschar):controversial;consider
esophagectomy
113
RetroperitonealInjuryExploration:
114
GreatVesselInjury:acutehypotension,suddenCVcollapse,unusualshadowonCXR
Suggestivephysicalsigns:unequalperipheralpulses,steeringwheelcontusiononchest,palpablesternal
fracture
ORindications:initialbloodfromchesttube>1500mL;>200mL/hourx4hours;hemopericardium;
tamponade;expandinghematomaatthoracicinlet;hemorrhagefromsupraclavicularwound
Exposure:ifunstable:leftALthoracotomywithtranssternalextensionintorightchest;
Ifconfirmedthoracicvenacava,ascendingaorta,arch,thoracicinnominate,carotidmediansternotomy
ofbluntaorticinjuriesarrivingtothehospital(20%oftotal80%dieatscene)willhaveanormal
arrivalCXR
DiaphragmaticInjury:occursin15%and45%ofpatientswithstabandGSWinvolvingupperabdomen
andlowerthorax,respectively.
Forpenetratinginjuries:L=Rsidedinjuries(usuallysmalltears),BUTforbluntinjuries:L>5xRsided
lesions(usuallylargertears)
SplenicInjury:mostcommonlyinjuredabdominalorganinblunttraumathatrequirestreatmentduring
celiotomy
RiskofOPSIisgreatestafter1styear,butappearslifelong;greaterinchildren
Nonoperativeapproachbetterif:<55,nosubstantialhemoperitoneum,nocoagulopathy,novascularblush
oncontrastCT;Canmanagenonoperativelyifvascularblushpresentifnoextravasationofcontrastand
stablehemodynamics.
LiverInjury:mostcommonlyinjuredorganinpatientswithbluntabdominaltrauma(3040%)
IfdeepvenousbleedingfromoverthedomeoftheliverencounteredgradeVorVIinjurylikely
extendincisionintochestwithoutapplyingtractiononliver;UseHeaneysmaneuver(clampingsupraand
infrahepaticIVC),venovenobypass,oratriocavalshunting
IVcontrastinthegallbladderindicates(abnormal)connectionbetweenbiliaryandvascularsystems
(severalweeksoutfromlivertraumaindicateshemobilia)
Canmanagebothliverandspleenwithangiographyifblushpresentinstablepatient
PancreaticandDuodenalInjury:
0.23%ofblunttrauma,slightlymorewithpenetratingtrauma
90%haveatleastoneotherintraabdominalinjury,withanaverageofthree
Duodenummostcommonsiteofintramuralhematomafollowingblunttraumacanpresentas
highgradeproximalobstruction1272hoursaftertrauma;(assumingstable)obtaingastrograffin
SBFTfollowedbybariumswallow;afterrulingoutotherinjurycanmanagewithNGT/TPN,butif
noresolutionin1014daystoORtoevacuate
OrganInjuryScale:
IHematomaminorcontusionwithoutductinjury
Lacerationsuperficialwithoutductinjury
IIHematomamajorwithoutductinjuryortissueloss
Lacerationmajorwithoutductinjuryortissueloss
IIILacerationdistaltransactionorparenchymalinjurywithductinjury
IVLacerationproximaltransactionorparenchymalinjuryinvolvingampulla
VLacerationmassivedisruptionofpancreatichead
115

SelectiveTreatment:
IExternaldrainage
IIExternaldrainage;distalpancreatectomyifdistal
IIIDistalpancreatectomy
IVExtendeddistalpancreatectomy
VResect(ordrain)pancreas,excludeduodenum;considerWhipple
Colon/Mesocolon:
Atlaparotomyexploreallhematomasorcolonwallormesocolontoidentifyoccultperforations
Primaryrepairofcolonicinjuriescanbeperformedunlessfollowing:
>50%circumferentialinjury(i.e.destructiveinjury)
significantassociatedinjuries,ISS>25(i.e.unstable)
peritonitis
significantfecalspillage
hemodynamicinstability
RectalInjuries:3Principles:
1.Formationofaproximal,completelydivertingcolostomy
2.Insertionofpresacraldrainsbetweenanalvergeandthecoccyx
3.Debridementandprimaryrepairoftheinjuryitself,ifitisaccessible
116
CriticalCare
SIRS(SystemicInflammatoryResponseSyndrome):atlease2ofthefollowing4(intheabsenceofother
explanation):
1. Hyperthermia(>380Cor100.40F)ofhypothermia(<360Cor940F)
2. Tachycardia(>90bpm)
3. Tachypnea(>20/minorPaCO2<32)
4. WBC>12,000or<4,000permm3(or>10%bands)
Sepsis:Knownorsuspectedpresenceofinfection(bacteremia,toxemia,fungemia,viremia)plus2ormore
SIRScriteria
SevereSepsis:Sepsisplusevidenceoforgandysfunction,hypotension,orevidenceofhypoperfusion
Shock:Endorganhypoperfusion.Period.Oftenmanifestedbylacticacidosis,oliguria,mentalstatus
changes,andhypotensionrefractorytofluidadministration.
SepticShock:Severesepsisleadingtoshock
Pathophysiologyofthiscascadeleadingtoshock:
Itreallybeginswithapanendothelialorganfailureasaconsequenceofaninflammatorycascade.
MacrophagesreleaseTNF(itselfadirectmyocardialdepressant)andIL1,whichresultsintwodetriments:
1. IncreasedexpressionoftheadhesionmoleculesCD11,CD18,ICAM1,andICAM2onendothelial
cellsandWBCs,resultinginleukoaggregation.
2. PromotionofNOSynthaseactivity,increasingcirculatinglevelsofNO,whichdoestwothings:
directmyocardialdepression,andvasodilation
Theendotheliumitselfbecomesthetargetorganasbloodflowisshuntedaroundcapillaries(becauseof
obstruction),leadingtopoortissueoxygenation
Otheretiologiesofshock:
1.Cardiogenic
2.Neurogenic
3.Hypovolemic
4.Obstructive
5.Distributive(anaphylaxis)
Catecholamineresponsetoinjuryismaximalat2448hours
CO=HR*(EDVESV)
Generally,COasHR(sinus)upto160/min
Atrialkickprovides1520%ofEDV
AreductioninHctby50%producesan8foldreductioninbloodviscositymechanismwhereby
COinnormovolemicanemia
Asthearterialwaveformpropagatesdistallythesystolicpressureincreasesanddiastolicpressurefalls
slightlysothattheMAPremainsconstantexceptincertaincircumstanceslikerewarmingfromCPBor
duringvasopressoradministrationinsepsis
AorticMAPanddiastolicpressuresareslightlyhigherthandistalpressure;BUTsystolicpressurerises
withdistalpropagation
117
PADPreflectsleftatrialpressurewhennopulmonaryvascularhypertensionexists.PADPisusually12
mmHghigherthanPCWPandLApressure;PAOPisnotcommonlysuperiortoPADPforestimatingLAP;
AdifferencebetweenPADPandPAOPof>45mmHgisindicativeofPVR,assumingtovalvular
diseaseexists
CarbonMonoxidePoisoning:fewsymptomsiflevel<10%;mostdeathsassociatedwithlevel>60%
AffinityofCOforHbis240xthatofO2withslowdissociation;T1/2is250mininroomair;with100%O2
T1/2reducedto40minutes
OxygenDelivery,Uptake,andExtraction
I.OxygenDelivery(DO2)
DO2=CO*CaO2, [whereCaO2=Hg(g/dl)*1.34(mlO2/gHg)*SaO2+0.003*PaO2(torr=mmHg)]
=CO*[Bound+Dissolved]
takehomemessage:boundO2iseverything when
=CO*[1.34*Hg*SaO2+0.003*PaO2]
consideringdelivery,butitisthedissolved
componentthatisnecessaryfordiffusionto
thetissues
II.OxygenUptake(VO2)
VO2 =CO*(CaO2CvO2)
CO*13.4*Hg*(SaO2SvO2)*10
III.OxygenExtractionRatio
O2ER=(VO2/DO2)*100
[Normally:2030%]
ControlofO2Uptake
VO2 =DO2*O2ER
BelowCriticalDO2(300mL/min/m2or4mL/kg/min,butvaryingfrom150to1000inthecriticallyill),VO2
becomesDEPENDENTonsupply,andenergyproductionbecomesoxygenlimited(dysoxia)
AboveCriticalDO2,VO2doesnotvarywithDO2,andisessentiallyconstant
RelationshipbetweenO2saturationandpartialpressure:
whereN=Hillcoefficient2.42.6;P50=PaO2atwhichpointSaO2=50%2426mmHg
118
VasoactiveDrugs
Drug
Mechanism
Action
Indication
Amrinone
Phosphodiesteraseinhibitor
withpositiveinotropic
effects+vasodilatoractions
Dobutamine
Syntheticcatecholamine
consideredinotropicDOC
foracutemanagementof
severesystolicheartfailure.
Mostly1
effectivesingletherapyof
lowoutputstatescausedby
systolicfailure.
vasodilatormustbe
adequatelypreloaded
goodforlowoutputstates
(rightorleftfailure)
NOTsuitableasmonoagent
forcardiogenicshock
mustbeadequatelypre
loaded
Dopamine
Endogenouscatecholamine
servingasa
neurotransmitter
Effectsdependonpatternof
receptoractivation
increasestrokeoutputwithoutanincrease
instrokework.
similartodobutamine,BUTdoesnot
stimulateadrenergicreceptors(hence,not
attenuatedbyantagonists)
dosedependentincreaseinstrokevolume
accompaniedbyadecreaseincardiacfilling
pressure(measuredbywedgepressure)
thesechangesarematchedbyadecreasein
SVR,hence,arterialpressureremains
virtuallyunchanged,buthypotensioncan
occurespeciallywhenloworborderline
volumestatus
Receptorprofilechangeswithdose:
Splanchnic
(25g/kg/min)(58)(>10)
Epinephrine
Endogenouscatecholamine.
likeDA,atlowdoes(0.0050.02
g/kg/min);
athighdoes(0.010.1g/kg/min)
severevasoconstriction:>0.1g/kg/min
Blockshistaminerelease
Vasopressin
Endogenoushormone
(ADH)
DirectlystimulatessmoothmuscleV1
receptors,resultinginvasoconstriction
hormonallevels(0.010.03U/min)can
helpweanoffothervasopressors
>agonistoftenresultsinreflex
bradycardia
Norepinephrine Endogenouscatecholamine
Phenylephrine
Endogenouscatecholamine
Selectiveagonist
cardiogenicshock,and
circulatoryshocksyndrome
associatedwithsystemic
vasodilation(e.g.septic
shock)
Highneurogenicshock
(aboveT3/T4,hypoand
bradycardic)
cardiacarrest,pulseless
VT/VF,AS,PEA
severeanaphylacticreaction
goodinchildren
FirstLinein:
1.anaphylaxis
2.RHfailure(massivePE)
3.HeartfailurewithlowBP
(toolowforinotrope)
sepsisrefractoryto
norepinephrine,
phenylephrine.
lowSVR,inneedof
inotropicsupport
drugofchoiceinsevere
septicshock
improvesrenalbloodflow
lowSVR(providedadequate
preload);donotusefor
pumpfailure
WhenyouseelowSVRandnormal/highfillingpressuresthink:
1. Sepsis
2. Adrenalinsufficiency
3. Anaphylaxis
4. Neurogenicshock(ifhighfluidsanddopamine;iflowfluidsandphenylepherine)
5. AVfistula(large,central)
119
MechanicalVentilation
Distinguishbetweenproblemsofventilationandoxygenation:
VentilationProblems
OxygenationProblems
Apnea:headtrauma,meds(narcotics),spinalcordinjury,OD
Hypoventilation:narcotics,headtrauma,spinalcordinjury,
neuromusculardisease,electrolyteabnormality(PO4),in
adequatepainrelief
AirwayDisease:obstruction(foreignbody,aspiration),COPD
MechanicalProblems:ribfracture(splinting),diaphragmatic
rupture,increasedabdominalpressure
Shunt:atelectasisandcollapse,HTX/PTX,pulmonary
contusion,ARDS,cardiogenicpulmonaryedema
DecreasedInspiredO2:highaltitude,smokefilledrooms,
malfunctioningO2deliverydevices
DiffusionLimitations:sarcoidosis,alveolarproteinosis,
extremehyperdynamicstates
V/QMismatches(mostcommoncauseofhypoxia):PE,
pneumonia,asthma/COPD
Conventionalventilation:I:E(inspiratory:expiratoryratio)of1:2(orupto1:1);
Inverseratioventilation(IRV)spendsmoretimeoninspiration(upto4:1)canfurtheroxygenationby
totalPEEP
PhysiologicPEEPislowlevelPEEP(5cm)tostimulateglotticclosuremechanism(whichiseliminated
byETT)showntoFRC,shuntfraction,andimproveoxygenation
autoPEEPisdefinedasPEEPoccurringatthealveolarlevel,whichisgreaterthanthePEEPgeneratedby
theventilator
Theworkofbreathingatrestconsumes2%oftotalbodyVO2;canincreaseupto50%
ShuntFraction=pulmonaryvenousadmixture=amountofbloodshuntedaroundthelungasafractionof
theCO(measuredattheinspiredO2concentrationrequiredtomaintainoxygenation)
VentilatorInducedLungInjury
Notcausedbyhighpeakairwaypressures,butratherbyalveolaroverdistension,whichstretches
thealveolusbeyonditsmaximumvolumeanddisruptsthealveolarcapillarymembrane,and/orby
openingandclosingofthealveoliwithshearstresscausingendothelialinjury.Peakpressureisa
markerofthis,butapoorone.
Bestmeasureoftransmuralpressureactingtodistendthealveoliduringinspirationistheplateau
pressuremeasuredduringa1secondendinspiratorypause(mustbelessthan40cmH2Otoavoid
lunginjury;andmustbeamodeofventilationthatallowsthismeasurement:IMV,supportmode;
notPS).ARDStrialsshowoutcomebestwhenplateaupressure<30cmH2O,withafewtrials
implying25isbest.
VentilatorAssociatedPneumonia(VAP)
2ndmostcommonnosocomialinfection(afterUTI);1stinmorbidityandmortality
Within48hourscolonizationwiththeprevalent(usuallygramnegative)organisms;ETTallows
themin,butimpairsthenormalmucociliaryclearancemechanisms
Highestriskduringfirst57days(3%perday),thendays710(2%perday),then1%perday
thereafter[CookDJ,etal.AnnInternMed,129:1998]
BALandquantitativecultureisgoldstandard(colonycount>104cfu/mLindicatesbacterial
pneumonia).[SeeexcellentreviewinDodekP,etal.AnnInternMed,141:2004]
120
ARDS:
1.PaO2/FiO2<200
2.PCWP<18 ornoassumptionofCHF
3.Diffuseinterstitialinfiltratesinatleast2quadrants
4.Decreasedcompliance(TV/[PIPPEEP];normal6080cmH2O)
LungVolumes:
Tobin(andYang)Index:Bestobjectivedatatoaidinweaningoffvent:
RSBI=RR/VTwhereVTisinliters
RapidShallowBreathingIndex(RSBI):InTpiecetrial:RR/VT(inLiters)if<80thenlikelihoodof
remainingextubatedat24hoursisabout90%.IfRSBI>105breaths/min/Llikelihoodofremaining
extubatedat24hourswasabout10%.NoneedtoweanifRSBI<80CPAPorTpiece[YangKL,TobinM.
NEJM1991,324:1445]
DeadSpace:
121
3reasonsforPaCO2
1. CO2production
2. Expiredvolume(hypoventilation)
3. DeadspaceMostcommonreasonsforthisinclude:

1.PE

2.Rightheartfailure

3.PEEP/autoPEEP

4.Hypotensiveshock(perfusion/ventilation)
IfDeadspace/TidalVolume(VD/VT)>0.6usuallynotweanable;
Anatomicdeadspace(airwaybronchiole)150mL;(inanormaladult2mL/kg)
PhysiologicVD=anatomicVD+anywellventilated/poorlyperfusedalveoli
Duringapnea:PaCO26mmHgduringthefirstminuteand3mmHgperminutethereafter(ifCO2
productionnormalandconstant)
Systematicwaytoidentifyetiologyoflowbloodpressure(considerallvariablesintheequation):
6problemsinthetorsothatmustberuledoutquicklyinanacutelyillpatient
1.
2.
3.
4.
5.
6.
Tensionpneumothorax
Rupturedaneurysm
Cardiactamponade
Aorticdissection
Myocardialinfarction
Pulmonaryembolism
122
MostInfluentialRecentTrials/PapersinCriticalCareMedicine(reversechronological):
EvidenceBasedClinicalPracticalGuidelineforthePreventionofVentilatorAssociatedPneumonia
[AnnIntMed141:305,2004]
Theseguidelinesprovideexcellentevidencebasedrecommendationsforthepreventionandtreatmentof
VAP.Recommendationsincluded:orotrachealintubation,useofclosedsuctionsystem,heatandmoisture
exchangers,andsemirecumbentpositioning.Treatmentsnotrecommendedincluded:useofsucralfate,
useoftopicalantibiotics.Becauseofconflictingand/orinsufficientdatanorecommendationsweremade
about:chestPT,timingoftracheostomy,pronepositioning,prophylacticIVantibiotics.
EliminatingCatheterRelatedBloodstreamInfectionsintheIntensiveCareUnit
[CritCareMed32;10:2014,2004]
AprospectivecohortcontroltrialinasingleinstitutionICUaimedateliminatingCRBSIbyimplementing
multifacetedinterventionsincluding:handwashingbeforegloving,usingoffullsteriletechnique,and
chlorhexidaneprep.ThisstudyshowedadecreaseinCRBSIratefrom11.3/1000catheterdaysto0/1000
days,whichwasextrapolatedtoprevent43CRBSIs,8deaths,andover$1.9million
AComparisonofAlbuminandSalineforFluidResuscitationintheIntensiveCareUnit
[NEJM350;22:2247,2004]
Amulticenter,randomized,doubleblindedtrialwhichcompared28dayoutcomesofpatientintheICU
whowereadministerednormalsalineor4%albuminforresuscitation.3500patientswererandomizedinto
eacharmandtherewerenodifferencesfoundindeaths,organfailure,numberofdaysspentinICU,
numberofdaysinhospital,requirementsformechanicalventilation,ordaysofrenalreplacement.
Comparisonof8vs.15DaysofAntibioticTherapyforVentilatorAssociatedPneumoniainAdults
[JAMA290;19:2588,2003]
Aprospective,randomized,multicenter,doubleblindedstudytodetermineif8daysofantibiotictherapy
isaseffectiveas15daysinpatientswithmicrobiologicallyprovenVAP.Thepatientstreatedfor8dayshad
similarratesofmortalityandrecurrentinfections.However,inpatientswithnonfermentinggram
negativebacilli,includingPseudomonasaeruginosa,higherratesofrecurrentpulmonaryinfection(40.6%vs.
25.4%)wereseen.
EffectofTreatmentwithLowDoseofHydrocortisoneandFludrocortisoneonMortalityinPatientswith
SepticShock
[JAMA288;7:862,2002]
Aplacebocontrolled,randomized,doubleblind,multicentertrialtoassesstheroleoflowdose
corticosteroidsinthemanagementofpatientsinsepticshockwithrelativeadrenalinsufficiency.Over300
patientswerestimulatedwithcorticotripinandresponders(appropriatestimulation)andnonresponders
(inappropriatestimulation)wererandomizedtoreceiveeithersteroids(hydrocortisone50mgq6+
fludrocortisone50gqd)orplacebo.Amongstnonresponderstherewerestatisticallyfewerdeaths(53%
vs.63%)andstatisticallylesstimespentonvasopressorsinthesteroidtreatmentgroup.Amongst
responderstherewerenodifferencesbetweensteroidandplacebotreatments.
123
IntensiveInsulinTherapyinCriticallyIllPatients
[NEJM345;19:1359,2001]
Aprospective,randomized,controlledstudyinvolvingmechanicallyventilatedpatientstoevaluatethe
impactoftightglucosecontrolincriticallyillpatients.Over1500patientswererandomizedreceiveeither
tightglucosecontrol(maintenanceofbloodglucosebetween80and110mg/dL)orconventionalglucose
control(insulinonlywhenbloodglucose>215mg/dL;maintenancebetween180and200mg/dL).At12
monthsintensiveinsulintherapyreducedoverallmortalityfrom8%to4.6%(p<0.04).Inadditionto12
monthmortality,intensiveinsulintherapyalsoledtodecreasedinhospitalmortality,bloodstream
infection,acuterenalfailure,andredcelltransfusionrequirements.
EfficacyandSafetyofRecombinantHumanActivatedProteinCforSevereSepsis
[NEJM344;10:699,2001]
Arandomized,doubleblinded,placebocontrolled,multicentertrialevaluatingtheuseofrecombinant
activatedhumanproteinCinthetreatmentofseveresepsis.Nearly1700patientswithSIRSandorgan
failureduetoacuteinfectionwererandomizedtoeithertreatment(24g/kg/hrrecombinantactivated
proteinCfor96hours)orplacebo.Themortalityintheplacebogroupwas30.8%vs.24.7%inthetreatment
group.Therewasanabsolutereductionintheriskofdeathof6.1%(p=0.005).Theincidenceofserious
bleedingwashigherinthetreatmentgroup(3.5%vs.2.0%,p=0.06).Thisstudyisnoteworthyinthatitisthe
firstagent(ofcountlessagents)toshowadecreasedmortalityinsepticpatients.
DailyInterruptionofSedativeInfusionsinCriticallyIllPatientsUndergoingMechanicalVentilation
[NEJM342;20:1471,2000]
Arandomized,controlledtrialinamedicalintensivecareunitinvolving128patientsreceivingmechanical
ventilationandcontinuousinfusionsofsedatingdrugs.Inthetreatmentgroupthepatientswereawaken
dailybytemporarydiscontinuationofthesedatives.Inthecontrolgroupthesedationwasonly
discontinuedatthediscretionofthetreatingphysician.Themediandurationofmechanicalventilationin
thetreatmentgroupwas4.9daysvs.7.3daysinthecontrolgroup(p=0.004)andthemedianlengthofstay
intheICUwas6.4daysvs.9.9days(p=0.02).Therewerealsofewerdiagnosticstudiestoassesschangesin
mentalstatusinthetreatmentgroup(9%vs.27%,p=0.02).
LowDoseDopamineinPatientswithEarlyRenalDysfunction:APlaceboControlledRandomisedTrial
[TheLancet356:2139,2000]
Over300patientswererandomizedinaplacebocontrolled,doubleblindedstudytoreceiveeitherplacebo
orrenaldosedopamine(2g/kg/min)viacontinuousinfusionuponadmissiontoanICU.Patientswith
preexistingrenaldysfunctionwereexcluded.Useofdopaminedidnotconferanadvantageinpeakserum
creatinine,needforrenalreplacement,lengthofstayinICU,oroverallhospitalstay.Thisstudywas
essentiallythefinalnailinthecoffinofthedebateoverthemythofrenaldosedopamine.
VentilationwithLowerTidalVolumesasComparedwithTraditionalTidalVolumesforAcuteLung
InjuryandtheAcuteRespiratoryDistressSyndrome
[NEJM342;18:1301,2000]
ThistrialrandomizedpatientsacrossmultiplecenterswithacutelunginjuryandARDStoreceiveeither
traditionalventilatorytidalvolumesof12mL/kg(withplateaupressuresupto50cmH2O)orlowtidal
volumesof6mL/kg(withplateaupressuresupto30cmH2O).Thetrialwasstoppedafter861patients
wereenrolledbecausemortalitywaslowerinthelowtidalvolumegroup(31.0%vs.39.8%,p=0.007)andthe
numberofdayswithoutventilatoryusewasalsolower.
124
AMulticenter,Randomized,ControlledClinicalTrialofTransfusionRequirementsinCriticalCare
[NEJM340;6:409,1999]
Thismulticenterstudyrandomizednonbleeding,euvolemic,criticallyillpatientswhohadaHb
concentrationof9.0g/dLwithin72hoursofadmissiontotheICUtooneoftwotransfusionstrategies:
Liberaltransfusions:transfusionwasinitiatedwhenHbconcentrationfellbelow10.0g/dLandwas
subsequentlymaintainedbetween10.0and12.0g/dL
Restrictivetransfusion:transfusionwasonlyinitiatedwhenHbconcentrationfellbelow7.0g/dL
andwassubsequentlymaintainedbetween7.0and9.0g/dL
Overall,the30daymortalitywassimilarbetweenthetwogroups.However,amongstpatientswith
APACHEIIscore20(i.e.lessill)mortalitywaslowerintherestrictivegroup(8.7%vs.16.1%,p=0.03),as
wasthecaseinpatientsyoungerthan55(5.7%vs.13.0%,p=0.02).Therewasnodifferenceamongstpatients
withclinicallysignificantcardiacdisease(20.5%vs.22.9%).
AProspectiveStudyofIndexesPredictingtheOutcomeofTrialsofWeaningFromMechanical
Ventilation
[NEJM324;21:6170,1991]
Thisstudyevaluatedanumberofindexesdeterminedfrom36patientssuccessfulorunsuccessful
extubationsandprospectivelyappliedthemtoacohortof64patientsinanefforttopredictsuccessful
extubation.Ofalltheparametersstudied,therapidshallowbreathingindex(RSBI,affectionatelyreferred
toastheTobindespitethefactthatKarlYangsharedauthorshipwithMartinTobinonthislandmark
paper)definedastheratioofrespiratoryfrequency,f,totidalvolumeinliters,Tv,wasthemostaccurate
predictorofsuccess(RSBI<80)orfailure(RSBI>105)ofextubation,wheresuccesswasdefinedasnot
requiringintubationat24hours.
125
Hemostasis&Transfusion
Threereactionsmediatetheinitialhemostasisresponsefollowingvascularinjury:
1. Vascularresponsetoinjury(injuryexposessubendothelialcomponentsandinduces
vasoconstrictionindependentofplateletfunction)
2. Plateletadherenceandaggregation
3. Generationofthrombin
Aspirin,indomethacin,andmostotherNSAIDsblockformationofPGG2andPGH2resultingindecreased
plateletaggregation
Normalbleedingtimeis57minutes.Thevalueofthebleedingtimeinclinicalevaluationisvery
limited.Itcanbenormalinpatientswithplateletdisorders,eventhosewhohavetakenaspirin,andcanbe
prolongedinsubjectswithnormalhemostasis.Therefore,itcannotbetrusted.Muchofthelimitationis
probablyrelatedtotechnicalissues,suchasthedepthofthecut,thevascularityofthecuttissue,etc.Also,
thenormalrangeislogarithmicallydistributed,makinginterpretationof712minuteBTsimpossible.
PTandPTTonlyelevatewhenfactorsreducebelowapproximately20to40%ofnormal(varieswith
theindividualfactorandwiththeindividuallaboratorymethods/reagents.Generallythetestsare
adjustedtobecomeabnormalwhenanyofthefactorsisinarangethatmightnotsupportnormal
hemostasis.AverycommoncauseofaprolongedaPTTinapatientwithanegativebleedinghistory
isalupusanticoagulant,alaboratoryartifactnotassociatedwithableedingtendency.)
20%ofnormalisusuallysatisfactoryforgeneralhemostasis,but>50%formajorsurgery
Preoperativeevaluation:
Ifapatienthasapositivebleedinghistoryandrequiresminorsurgery:PT,PTT,BT,fibrinclot
solubility
Ifapatienthasapositivebleedinghistoryandrequiresmajorsurgery:PT,PTT,BT,fibrinclot
solubility,plateletfunctionstudies,FVIIIlevels,FIXlevel,alpha2antiplasminlevel
Asarule:
1unitplateletsfor2unitsRBC.Foratotalbloodvolumereplacement,expectplateletcountof250,000to
dropto80,000.
1mgprotaminerequiredforevery100Uofheparin(upto100mgtotal,or50mgover10min).IftheaPTT
ismeasurable(i.e.,lessthan2minutes),theplasmaconcentrationofheparinshouldbelowenough(i.e.,<1
U/mL)that2030mgprotaminewillbeveryeffective.However,theprotaminemaybeclearedbeforethe
hepariniscompletelygone.Soanotherdosemayberequiredinanhourortwo.
ClottingFactors(seefigurebelow):
Intrinsic(PTT):exposedcollagen+XIIXIIXX,whichactivatesthrombinfibrin
Extrinsic(PT):TF+VIIactivatedXthrombinfibrin
Note:Xiscommontoboth
VIIIisonlyfactornotsolelymadeinliver(madebyendothelialcells)
126
BleedingDisorder
VonWillebranddiseaseisthemostcommoninheritedbleedingdisorder(1%ofpopulation;AD)
symptomaticbleedingin1/1000
longPTTandbleedingtime(usually)
associatedwithvariabledeficienciesinbothvWFandfactorVIII;plateletdefectisalsopresent
(althoughthisiscalledplatelettypevWd,itisdifferentfromtheothertypesbecausethedefectis
intheplateletmembrane,notinthevWf).
+Ristocetintest(Ristocetincofactor[i.e.,vWf]activityisthelaboratorytestforvWfactivity,as
opposedtoantigenlevel.)
giveDDAVP(releasesintracellularstoresofvWF)forTypeI(lowvWF)(Theeffectonlylastsfor<
12hours.Repeatdosesmaybelesseffective.)(vWfconcentratesareavailablewhenextended
replacementisneeded.ThesearenotthesameasstandardfVIIIconcentrates,whichcontainvery
little,ifany,vWf.)
givecryoforTypeII(qualitativelypoorvWF)andIII(lowvWF)
HemophiliaA(factorVIIIdeficiency)Xlinkedrecessive;5%normallevelsfVIIIconsideredmild
DONTaspiratehemarthrosis
TxwithfactorVIIIconcentrates(to100%preoplevels)
PTT;normalPT
HemophiliaB(factorIXdeficiency)Xlinkedrecessive
TxwithfactorIXconcentrates
PTT;normalPT(to50%preoplevels)
Glanzmansthrombasthenia:PlateletshaveIIb/IIIadeficiencyaggregation abnormalitiesdueto
decreasedfibrinogenbinding.Extremelyrare.
BernardSoulier:PlateletshaveIbdeficiencyadherencetoexposedcollagenvonWillebrandfactor.
Extremelyrare
HypercoagulableStates
APCResistance:mostcommoninheritedhypercoagulablestate;AD;90%associatedwithFV(Leiden)
mutation5%prevalenceinCaucasianpopulations,muchlessinothers.SpontaneousDVTtypically
onlyoccurinthrombophilicfamilies,whoprobablycarryotherprothromboticgenesinadditiontoFVL.In
thegeneralpopulation(whereFVLislikelytobetheonlyprothromboticgeneinmostindividuals)FVLis
rarelyassociatedwiththrombosis.
ATIIIDeficiency:rare,1/5000;dontrespondtoheparinunlessgivenFFP(toreplaceATIII);canttreat
DVTwithoutgivingFFPThemostcommonformsofATdeficiencyareidentifiedbecausetheAT
moleculedoesnotbindheparinnormally.Theseactuallyarenotassociatedwithanincreasedriskof
thrombosis.SpecializedtestsarenecessarytoidentifytheindividualswiththedangerousformofAT
deficiency.
127
LupusAnticoagulant:antiphopholipidAbs;dx:longRussellsvipervenomtime;longPTT;confirmedby
assaysthatdemonstratethedependenceoftheanticoagulantactivityupontheconcentrationof
phospholipidpresent.
HIT:Heparininducedthrombocytopenia,duetoanantibodytothecomplexofheparinandplateletfactor
4,whichissecretedbystimulatedplatelets.Typicalonsetafter510daysofheparin,earlierifrecentprior
heparinexposure.HalfofHITpatientswilldevelopthrombosiswithin30daysunlesstheyaretreatedwith
nonheparinanticoagulants.Whiteclottreatwithhirudinorargatroban(directthrombininhibitor)or
danapariod(indirectthrombininhibitor);dextranisnotsufficientfortreatingclotsresultingfromHIT
Foreachincorebodytemperatureby10Cbloodviscosityby23%
Transfusions:
Bankedbloodhas2,3DPGleftshift(holdsO2tightly)
Risks:CMVhighest;HIV:1:500,000;HepatitisC:1:30,000150,000
HeparinbeforeCoumadin
Heparinmustbegivenfor3to4daysbeforecoumadinwhenanticoagulatingpatientstoprotectagainst
coumadinskinnecrosisiftheyhaveATIII,ProteinC,orProteinSdeficiency.
ForyearscardiologistshavestartedCoumadinwithoutheparinandnotrecognizedanyproblem,
presumablybecausesignificantproteinCandSdeficiencyaresorare.However,Coumadinaloneis
definitelyinadequate/deleteriousforthetreatmentofacutethrombosis.Coumadinandheparincanbe
startedtogether,sincetheeffectofCoumadindoesnotappeartill24dayslater,afterthepatientshould
havebeentheratpeuticallyanticoagulatedwithheparinforseveraldays.Itisespeciallyimportantthat
patientswithHITnotstartCoumadinuntiltheyhavebeentreatedwithanonheparinparenteral
anticoagulant.
ALLpatientswiththrombosistoreceivecoumadinshouldreceiveheparinfor34daysbecausethehalf
lifeoftheanticoagulationfactor,proteinC,ismuchshorterthanthevitKprocoagulantfactors(II,IX,X).
[GeertsWH,etal.,2001Chest119:132S]
128
129
Metabolism
Anumberofvitalareasofthebody(brain,renalmedulla,RBC,WBC,peripheralnerves)areglycolytic
tissues(requireaglucosesourceofenergyformetabolism)andareunabletoutilizefattyacids.
Whenthelimitedglycogenstoresaredepleted,thisisaccomplishedbygluconeogenesisandrecycling
incompletelymetabolizedglucose.Primarysourcesofgluconeogenesisare:
1. Aminoacids,derivedfromthebreakdownofmuscleproteins,
2. Glycerol,derivedfromthebreakdownoftriglyceridesinadiposestores
Intraumathehormonalmilieuresultsincatabolismofproteinstoresbeyondthatnecessaryforenergy
needsalone
Instarvationbodyattemptstoconserveproteinwastingbyadaptingtoallowutilizationoffattyacids
andketonesforfuelbynonglycolytictissues
Inprolongedfastingbraincanactuallyuseacetoacetateandhydroxybutyrateinplaceofglucose
Lactateandpyruvate(derivedfromincompleteglucoseutilization)canberecycledintoglucoseviaenergy
providedbyfattyacidoxidation(theCoricycle)
Latestarvationshiftfromlivertokidneyastheprimarysourceofgluconeogenesis(sincealanineis
depletedfromtheliver)
Hemochromatosis:
ExcessiveFeabsorptionfromgutafflictsheart,liver,pancreas,pituitary
EarliesttesttobecomeabnormalisFesaturationtest
WilsonsDisease:
AR
defectincoppermetabolism
mostimportantlabfindingiscerulosplasminlevel(<20mg/dL)
livercopperstoreselevatedonbiopsy
130
TransplantSurgery
I.TypesofRejection:
1.Hyperacute:preformedantidonorAb.Destructionin2448hours.Rarelyoccurswithpresentday
crossmatchingtechniques.
2.Accelerated:asabove+memoryTcellsinhost.Rejectionwithin5days
3.Acute:Tcellmediated.Mostcommon.Weekstomonths
4.Chronic:usuallyhumoralresponse.Monthstoyears.Currentlynocure.
II.RejectionProphylaxis,prevention,treatment:
Corticosteriods(Prednisone):blockcytokineproduction(IL1,2,3,6,TNF)
Cyclosporin(Neoral):selectivelyinhibitsIL2secretionandproliferationofTcells(calcineurin
inhibitor)
MycophenolateMofeil(Cellcept):inhibitinosinemonophosphatedehydrogenase,(denovopurine
synthesis)causingselectiveantiproliferativeeffectofTandBcells
Tacrolimus,FK506(Prograf):inhibitionofcalcineurindependentsignaltransductioninTcells,
inhibitingcytokineproduction
Sirolimus,(Rapamycin):blocksCa++dependentcytokinemediatedsignaltransduction(blocksthe
TORprotein,whicharrestscellinG1)preventingproliferationofTcells
Azathioprine(Imuran):inhibitsDNAsynthesisandconsequentTcellactivation
IL2Inhibitors(Zenapax,Simulect):monoclonalAbsagainstIL2receptors;usedasinduction
therapy
CD3Inhibitors(OKT3):murinemonoclonalAbstoCD3receptoronTcells
Thymoglobuline:rabbitpolyclonalAbtomultipleTcellreceptors.Usedforbothinductionand
rejectiontreatment
Longtermeffectsofsuccessfulsimultaneouskidney/pancreastransplantare:
1.Stabilizationofretinopathy
2.Reducedriskofdiabeticnephropathy
3.Improvementinnerveconductionvelocity
4.NoreversalofCADorPVD
PosttransplantDMisseenin520%ofrenaltransplantrecipients.Steroids,cyclosporine,FK506areall
diabetogenic
131
CompletelymismatchedHLA(0/6)LRRTdoesbetterthancompleteHLAmatch(6/6)cadavericischemic
timeandqualityoforganaremostimportantdeterminantsofgraftsurvival
BKVirusisanimportantfactorassociatedwithgraftnephropathy.Prevalentin90%ofpopulationand
resultsinnephropathyin18%oftransplantrecipients(byboutsofrejection,needforrejection
treatment(vs.IS),+donortorecipient);noadequateantiviraltreatment;insteadmustimmune
suppression,inparticularMMF
PostTransplantLymphoma
Lymphomais10100xmorecommonintransplantpatientsthangeneralpopulation(Rangesfrom
1%incidenceinkidney;45%inheart/lungpatients);especiallyseeninCNS
UsuallyNHLBcelllymphomarelatedtomalignanttransformationofEBV
Reduceorwithdrawimmunosuppression(lifebeforegraft)
Highdoseacyclovirmaybeeffective;conventionalchemotherapygenerallynoteffective
MELD(ModelforEndstageLiverDisease)Criteriaforliverfailure*
Score=3.8*ln[bilirubin(mg/dL)]+9.6*ln[Cr(mg/dL)]+11.2*ln[INR]
[Hepatology2001;33:464470]
*Formulapredictstheriskofdeathin3months;averagescoreformostpatientsbeingtransplanted
currentlyis15;additionalpointsgivenfortumorssuspectedorconfirmedtobeHCC
AcuteFulminantHepaticFailure:theappearanceofacuteliverdiseasewithhepaticencephalopathyinless
than8weeksinanindividualwithoutpreviouslyknownliverdisease.
StageI:Prodrome
StageII:Impendingcoma(5070%spontaneousrecovery)
StageIII:Stupor(4050%survival)*
StageIV:Deepcoma(<20%survival)*
*lactuloseoflittlebenefit
KingsCollegeCriteriaforacutefulminantliverfailurerequiringtransplant
AcetaminophenToxicity
Nonacetaminophentoxicity
pH<7.30afterresuscitation,or
INR>6.5,or3/5below:
INR>6.5,
Creatinine>3mg/dL,and
EncephalopathyIIIIV
Age<10or>40
Druginducedorcryptogenic
etiology
Jaundice>7daysbefore
encephalopathy
INR>3.5
Serumbilirubin>17.5mg/dL
132
Upperlimitsofacceptablecoldischemictimes:
Heart:
Lung:
Liver:
Kidney:
Pancreas:
6hours
46hours
24hours
48hours
2448hours
Warmischemictimemustbelessthan60minutes
Hepaticarterialthrombosisismaincauseofimmediategraftlossfollowinglivertransplant:
35%inadults
58%inchildren
HCCpatientsarecandidatesforlivertransplantprovided:
1.Asingletumor<5cm,or
2.Uptothreetumorsindividually<3cm
Milancriteria
HepatorenalSyndrome
10%ofhospitalizedpatientswithcirrhosisandascitesdevelop
progressiveoliguriaCr,CO,BP
similarlaboratoryfindingstoprerenalazotemia(UOP<500mL/24hours,UNa<10mEq/L,Uosm>
Posm)
physiology:splanchnicvasodilation(associatedwithNO)SVRrenalperfusion
onlyeffectivetreatmentishepatictransplantationrenalfunctionusuallyreturnstonormal
133
Nutrition
EnergyCapacity:(1calorie=energytotake1mLwaterfrom14.515.50Cat1atm)
Fat:9kcal/g
Protein:4kcal/g(butaqueous,soonly12kcal/gwhenutilized)
Carb:3.4kcal/g
RQ=ratioofCO2producedtoO2consumed=1.0forcarbs;0.7forfats;>1forproteins
EssentialAminoAcids:2L,2T,VIP&Me(Leucine,Lysine,Threonine,Tryptophan,Valine,Isoleucine,
Phenylalanine,&Methionine)
=[N]In[N]Out,where
[N]Balance
=[gprotein/6.25gproteinpergN]
[N]In
=[UUN(mgN/100mLurine)*1000mL/L*24hoururinevolume*gN/1000mgN+3]
[N]Out
BranchedChainAminoAcids:leucine,isoleucine,valine(metabolizedinmuscle;allessential)
AromaticAminoAcids:tyrosine,tryptophan,phenylalanine(essential)
Glutamineis#1AAinbody;mostrapidlyusedinstress;fueloftheenterocytes(whendepletedbrush
borderbreakdown);theadditionofglutaminetoenteralorparenteralfeedsmaysepsis[HoudijkAP,etal.
Lancet1998;352:772]
Hydroxybutarate:fuelofcolonocyte
Arginine:mostimportantforimmunefunction
InhepaticfailureMinimizearomaticAA;givebranchedchainonly
InrenalfailuregiveessentialAAonly
FattyAcidMetabolism:
mediumchainFAcanbeabsorbeddirectlyviaportalblood,hencebypassingthelymphaticsystem
longchainFApoorlytoleratedbypatientswithcompromisedgutfunction;mediumchainbetter,since
absorbeddirectly
ThreeMainformsofFatarefoundinthebody:
1. Glycerides(9598%ofbodystores),essential(seebelow)ornonessential;mostdietarysourcesare
medium(6C)andlong(>11C)
2. Phospholipids(mainlyincellmembranesandmyelinsheaths)
3. Sterols,comprisedprimarilyofcholesterol
EssentialFattyAcids:(unsaturatedbondwithinthelast7carbonsoftheFAchainatthemethylend)
linoleic(TPNmostlyconsistsofthis),linolenic,arachidonic;canNOTbesynthesizedbyhumans
6polyunsaturatedfats(linoleic)precursorsforPGsandleukotrienes
Fatdigestion:micellestoenterocyteschylomicronstolymphatics(tojunctionLIJ/subclavian)
134
EnergyStorage:
Fats:25%BW=fat;soif70kg17kgfat160,000kcal
Carbs:circulating80kcal;Liverglycogen300kcal;
Muscleglycogen600kcal(exhaustedin24hours)
Proteins:12kg48,000kcal;butnoaccessunlesslatestarvation
(MainadvantageofdextroseinIVFistoobviatetheneedforproteincatabolism)
glucose+(fructose+galactose)40%Liverglycogen+60%Muscleglycogen
NonproteincalorietogmNitrogenratioof150:1generallyappropriate(bothadultsandchildren)
*Patientswithmajorburn(>25%TBSA)havegreatestcaloricrequirements
AssessingNutritionalStatus:
Albumin:18dayT
Prealbumin:24hourT
Retinolbindingprotein:12hourT(mostsensitive)
Injuredpatientscanmaximallyoxidizeglucoseat56mg/kg/min(abovethisosmoticdiuresis,
respiratoryquotient)
Remember:MetabolicAlkalosisrequireK+
Marasmus=depletionofbodyfat;relativesparingofvisceralprotein(simplestarvation)
Kwashiorkor=acutevisceralproteindepletion(sparingoffat;acutelyillpatients)
Deficiencies:
Phosphorus:weakness,paresthesias
Zinc:perioralrash,alopecia,poorwoundhealing,impairedimmunity,changeintaste
Copper:anemia,neutropenia,pancytopenia
Iron:anemia
Linoleicacid:dermatitis,alopecia,blurredvision,paresthesias
Selenium:cardiomyopathy,weakness,alopecia
VitaminA:nightblindness,skinkeratosis
Chromium:glucoseintolerance(relativediabetes),peripheralneuropathy
Biotin:alopecia,neuritis
135
Fluids&Electrolytes
Sodiumconcentrationmustbecorrectedby23mEqper100mg/100mLelevationinbloodglucoseabove
100[i.e.asBGNa+]
Gastriclosses(vomiting)usuallyrequirehypercholoremicreplacement
Postpyloriclossesrequirebalancedsaltsolution(exceptpancreaticfistula,whichrequirehigh
HCO3replacement)
PatientswithGIlossesinitiallyloseisotonicfluidbutthebodyalwaystriestoprotectvolume
status(evenattheexpenseoftonicity)
InsensibleLosses:
Skin>Lung:total600900mL/day
0.9%NaCl=9gmNaClperL
HYPOMg++andCa++bothhaveHYPERexcitability:reflexes,tetany
CannotcorrectCa++withMg++sinceMg++inducesskeletalresistancetoPTHandmayimpairPTH
synthesis
Prolongedvomiting:resultsinhypokalemia,hypochloremia,metabolicalkalosis;earlyurineis
alkalineBUTasNa+isconservedH+/K+arelostwithHCO3resultinginparadoxicalaciduria
Note:ThemostimportanttreatmentforhyperkalemiaisCa++(vs.insulin,HCO3,etc.)becauseitistheonly
agentthatactuallystabilizesthemyocardium
MechanismsofDiarrhea:
OsmoticDiarrhea:accumulationofpoorlyabsorbedsolutesinlumensecretionofH2Ointolumen
SecretoryDiarrhea:excessiveelectrolytesecretion(toxins,neuroendocrinetumors)stimulatecAMP
production
InhibitionofAbsorption:unabsorbedfreefattyacidsorbilesaltsdecreasedH2Oabsorption
Sweat:normallyhypotonic,butcanapproachisotonicityduringperiodsofhighsecretion;Na+secretion
parallelsCl(both<plasma);K+approachesplasmaconcentration;ureaandNH3>>plasmaconcentrations
136
RenalPhysiology
Kidneycantolerateischemiaupto15minuteswithoutadverseevent
1590minutesproducesvaryingdegreesofchronicdamage
>90minutesusuallyirreversibledamage
Inresponsetorenalbloodfloworpressurejuxtaglomerularapparatusreleasesrenin,whichinteracts
withthe2globulineangiotensinogen(synthesizedintheliver)toproduceangiotensinI.
Inthelung,angiotensinIangiotensinII(halflife:4minutes)increasesBPbytwomethods:
1. directvasoconstrictorproperties
2. stimulatingthereleaseofaldosteronefromtheZGoftheadrenalcortex(Na+andH2O
absorptionindistaltubules)
3reasonsforcontraction(metabolic)alkalosis:
+
+
1.HypoK (K leavescelltocompensate,HCO3followstomaintainelectricalneutrality
2.Volumedepletion
3.Hyperaldosteronism(diuretics)
Na+ Unresponsive(UCl >20)
mineralocorticoidexcess
MetabolicAlkalosis
Na+ Responsive(UCl <10)
vomiting
NGsuction
RenalFailureIndex=UNa*PCr/UCrif<1prerenaloliguria
70%ofnephronmassisdamagedbeforeBUNandCrlevelsrise
FENa>3andUosm<350mOsm/LrepresentinabilityofrenaltubuletoreabsorbNa+andconcentrateurine
FENa=[UNa/UCr]/[PNa/PCr]<1%,BUN/Cr>30,UNa<20allindicatelowvolume
Ifpatienthasreceivedlasixand/orhypertonicNaClduringprevious48hoursFENamaybeoflimited
value.InsteaduseFractionalExcretionofUrea(FEUN):
FEUN=[UUREA/UCr]/[PUREA/PCr]<35%suggestiveofprerenalazotemia
Definitionsoflowurineoutputstate:
Polyuric:>1000mL/24hours
Oliguric:100400mL
Nonoliguric:4001000mL
Anuric:<100mL
InHighOutputRenalFailure[BUN,u/o>1500/24h]mildmetabolicacidosis:giveNa+withlactate,since
Clwillworsenacidosis
137
DifferentialDxofelevatedBUNorCr(oneoutofproportiontotheother):
Cr/BUN
BUN/Cr
Renalfailure
Dehydration
Musclebreakdown
+Nbalance
GIbleed
Hepaticfailure
TranstubularK+Gradient(TTKG)
[UrineK/PlasmaK,mEq/L]dividedby[Urineosm/Plamaosm,mosm/kg]
Normalis89;maybeupto1withpotassiumloading
IfK+ishighandTTKG<7implieshypoaldostoronism
Appropriateresponses
Hypokalemia <3
Hyperkalemia>10
Ifthespecificgravityofurineisnormalkidneyisworking,UNLESSartificialosmolesarepresent
including:
Mannitol
IVcontrast
Highglucoseload
Methanol
138
Immunology/Infections
IgG:opsonin(alongwithIgM)tofixcomplement(2IgGsor1IgM),#1inserum;crossesplacenta
IgM:madefirst;levelsaftersplenectomy
IgA:insecretions
IgE:allergicreactions,typeIhypersensitivity
IgD:largelyunknown
Complement:
C3a,C5aandanaphylatocins;C59:MAC(membraneattackcomplex)
Hypersensitivity
TypeI:immediate;IgEmediated;e.g.anaphylaxis
TypeII:cytotoxicreactions;IgGorIgM;e.g.ABO/Rhincompatibility
TypeIII:immunecomplexmediated;depositionofcomplex;e.g.serumsickness,rheumatoidarthritis
TypeIV:delayedtype:TCells(CD4+);e.g.contactdermatitis
HIVPatients
haveincreasedriskofdevelopingNHL(highgradeBcell)andKaposissarcoma
AdvantagesofZosyn
I.vs.3rdgenerationcephalosporins
enterococci,MSSA
pseudomonas,klebsiela
4+anaerobes
II.vs.quinolones
enterococci,MSSA
pseudomonas
4+anaerobes
III.vs.Unasyn
MSSA
E.coli,pseudomonas,otherG
4+anaerobes
IV.Timentin(betterforstenotrophomonas)
enterococci,MSSA
E.coli,pseudomonas,otherG
4+anaerobes
Remoteinfection(e.g.UTI)theriskofsurgicalsiteinfectionbyatleast7%
139
Burns
1.Silvernitrate:Broadspectrum,painless,cheap,poorescharpenetration,maycauseelectrolyteimbalance
2.Silversulfadiazine(Silvadine):Painless,noelectrolyteabnormalities,noocclusivedressingrequired,
littleescharpenetration;missesPseudomonas,idiosyncraticneutropenia;goodforsmallburns
3.Mafenide:Penetrateseschars,broadspectrum(butmissesstaph);painandburningonapplication;7%
haveallergicreactions;maycauseacidbasedisturb(metabolicacidosis);agentofchoiceinalready
contaminatedburns;watersoluble
ParklandFormulaforBurns
*AddMaintenanceFluidstobelow:*
1. First24hours:4mL/kg/%BSA.Halfover8hours,thenrestover16hours.
2. Second24hours:Fluidrequirementsare5075%ofthefirstdays.Useweight,electrolytes,UOP&
NGTtodetermineconcentrationandrate.
3. WithholdK+forfirst48hoursbecauseoflargetissuerelease.
4. KeepUOP@0.5mL/kg/hour
BurnpatientsinitiallyhavedropinCOthenareHYPERdynamic
BurnWoundInfection
Reducedby:
1.Aggressiveresuscitation
2.Earlydebridement
3.Topicalantibiotictherapy
Toconfirminfectionneedbiopsywithquantitativeculture(105):mustincludenormalandburnedskin
(2x2cmwithnormalunderlyingskin)
140
Skin&WoundHealing
Threemajorstagesofwoundhealing:
1.InflammatoryPhase(10minutes2weeks)
2.ProliferativePhase(36weeks)
3.RemodelingPhase(upto1year)
InflammatoryPhase:Hemostasis&Clotformation
PlateletplugmediatedbythromboxaneA2,thrombin,PF4,C5a(mostimportantcomplement)
Monocytesmustbepresentfornormalwoundhealing
Collagenandbasementmembraneproteinsclottingfactoractivation
Vasoconstrictiondecreasebloodlossandallowclotformation(<24hours)
Plateletdegranulation:PDGFandTGF;chemotaxisandproliferationofinflammatorycells
Vasodilation(>2448hours)suppliescellsandsubstratesforwoundrepair
ProliferativePhase:
Formationofmatrixoffibrinandfibronectin
Initiationofcollagenformation
Proliferationoffibroblasts
Growthfactorsfrommacrophagesinitiateangiogenesis(especiallyFGF)
CrosslinkingofcollagenrequiresVitC
Woundisnowascar
RemodelingPhase:
Collagenequilibrium
Increasetensilestrength(abundanceofTypeIcrosslinking)
Diminishingcapillarydensityandfibroblasts
TensileStrengthofWound*:
Early:fibrin
Late:collagencrosslinking
*Tensilestrengthisneverequaltoprewound
105organisms/cm2isenoughtoretardwoundhealing
Astimeprogresses:TypeIII(proliferation)collagen andTypeI(mature)
UltimatelytheratioofI:IIIis8:1(i.e.thatofnormalskin)
I
II
III
IV
V
Mostabundant,foundinscar
Incartilage
Inwouldhealing(lowinEhlerDanlos)
Inbasementmembrane
Foundincornea
141
Pharmacology
Cluestodrugoverdose:
1.Eyes
i)Miosis:opiates,org.phos,barbs
ii)Mydriasis:amphetamines,cocaine,antichol,ethanol,mushrooms,LSD
iii)Nystagmus:PCP,phenytoin,ethanol,VPA
2.Mouth
i)Dry:antichol,opiates,SSRIs
ii)Verysalivary:org.phos
3.Skinlookforneedletracks
i)Hot,dry:antichol
ii)Verypink:CO
iii)Verysweaty:org.phos
Pharmacology
P450
Phenobarb
Rifampin
PTN
Carbamazepine
P450
INH
Cimetidine
Benzos
Phenothyazines
TMPSMX
Lidocainetoxicity:tinnitus,perioralnumbnessneurosymptomscardiovascularchanges
LocalAnesthetics(2classes)
AminoEsters
Tetracaine
Cocaine
Procaine
Chloroprocaine
AminoAmides*
Lidocaine
Mepivacaine
Bupivicaine
Etidocaine
*Allhaveanibeforecaine
MalignantHyperthermia:canbegeneticallytransferred;triggeredbyhalogenatedinhalationalagents(1in
250,000);canalsobetriggeredbysuccinylcholine(1in60,000);earliestsignisriseinCO2;hyperthermiaisa
relativelylatefinding;treatwithdantrolene.
Ketamine:doesnotBP,butdoesICP;goodinchildren;avoidinheadtrauma,cardiacdisease
Propofol:rapidonsetandshortduration;idealforpatientswithalteredneuroexamtoallowforfrequent
neuroexaminations;doesBP;doesnotprovideanalgesia
4Componentsof(Informed)Consent:
1. Disclosure
2. Comprehension
3. Competency
4. Voluntariness
142
Radiology
Basics
Eachmodalityemitsasourceofenergy.ForconventionalxrayandCTtheenergyemissionisa
photongeneratedbyanelectron(e)collisionwithitstarget.ForMRItheenergyemissionisa
spinningdipoleofaproton(H+)convertedintoradiofrequencycurrent.ForPETtheenergy
emissionisagammarayproducedbythecollisionofapositron(e+)andanelectron(e).
Distinguishbetweenimagingtests(e.g.conventionalCT,MRI,U/S)andfunctionaltests(e.g.PET,
HIDA,U/Sforgallbladderejectiontime,etc.)
IBasicRoentgenogram
DiscoveredbyWilliamRoentgenin1895
Highvoltagecurrent(50120kV)isrunthroughacathodecontainingwirecoil(filament)
providingaconstantstreamofhighspeedelectronstoatungstentargetonananode.
Mostoftheenergyisdissipatedasheat,but1%oftheelectronenergyisconvertedtoxrays,
whicharedeflectedtowardsafilterthatcollimatesthebeamstowardstheanatomicportionof
interestbeforetheypassthroughthebodyofthepatient.Collimatoralsofiltersoutveryhigh
energyandlowenergyxrays
Thedensityofthetissueencountereddeterminesthexrayabsorption:lessdensetissues(e.g.lung)
allowthebeamtotravelthroughwithminimaldeflection;moredensetissues(e.g.bone)causethe
xraytoscatter.
Agridwithleadbarsinitremovesthescatteredbeamsbyabsorbingtherays
Finally,thebeaminteractswithanxraycassettecontainingafluorescentplatewhichemitslight
whenstruckbythexrayontoalightsensitivefilmcoatedwithsilvernitrateoraphosphorscreen
thatisscannedwithalaseroradirectCCDarrayfordigitalradiographs
Hence,morexray(lessdensetissue)darkerimage
143
IIComputedTomography(CT)
Essentially,anadvancedformofconventionalxraywhereaseriesoftwodimensionalimages(or
slices)ofabodyareconstructedbyrotatingthexraysourceordetectoraroundthebody(thisgives
theinformationforagivenslice)andparalleltotheaxisofthebody(thisgivesinformationfrom
oneslicetoanother).Now,volumescansareobtainedasthepatientmovescontinuouslythrough
thescannerasthebeamrotatesaroundsubtendedahelixonthepatient.Thedataarecollectedas
avolumeandthencomputationallydividedintoslicesthataredisplayed.
Hounsfieldunits,namedafterSirGodfreyN.Hounsfield,theBritishengineerwhodevelopedthe
firstclinicallyusefulCTmachine(attheEMIcorporationwhichwasalsotherecordcompany
ownedbytheBeatlesatthetime.SirGodreywontheNobelPrize,unusualforanengineer),area
standardizedunitforreportinganddisplayingthereconstructedxraycomputedtomography
values.
Theyrangefrom1000forairto+3095forlead;wateris0;thisrepresents4096(or212)bitstoo
manyforoureyestodistinguish.Insteadweget28linearlydistributedbits
Twoparametersareselected:windowwidthandwindowlevel(i.e.whereitiscentered).For
example,awindowof(400,40)meansweseebetween160and+240;henceanything<160
blackandanything>+240white
Tissue
Air
Lung
Fat
Water
Kidney
Liver
Blood
Clottedblood
Corticalbone
H.U.
1000
600
10010
0
30
50
3080
6080
5002000
[JOMeinternetjournal,KimandJiaw,1998]
144

Usethegallbladderasaninternalstandardof0H.U.(i.e.water)
Ifthereiscontrastintheperitoneum,lookfor3things:
1.Rupturedviscous(generalrules)
Stomach:freeair,fluid
Smallbowel:freeair,fluid
Colon:freeair,fluid
2.Vesselextravasation:mustseeclotandcontrast(clottedbloodwillbebrighterthanliquidblood)onpre
contrast(butthereverseonpostcontrast)
3.Rupturedbladder(intraperitoneal):mustlookatdelayedviews
ThePouchofDouglasswillnormallyhold300400mLofbloodbeforeoverflowingusuallyto
MorrisonsPouchthentorightsubphrenicrecess
IIIMagneticResonanceImaging(MRI)
AnHatomcontainsasingleprotonandbehaveslikeaspinningbarmagnetthatwillalignwithamagnetic
fieldcreatedbythesolenoidoftheMRscanner.Beforearadiofrequency(RF)isappliedtheprotonsare
aligned.TheRFdeflectsthemsomenumberofdegreesfromtheZaxisofthemagnettheythenrelax
backtobeingaligned,although,theprotonsarespinningallthetimeattheLarmorfrequency.Thecoil
picksupthespinningmagneticcomponentthatisperpendiculartothemainmagneticfieldandinducesa
current(FaradaysLaw)thisisthesignalfromMRI.
TheRFfieldisappliedtothepatienttomakethebarmagnetstandupat90o(perpendicular)tothespine.A
wire(antenna)paralleltothespine,outsideofthepatientsbody,hasanalternatingcurrentformedinit,
whichdeterminesthesignalintensity.Themagnitudeofisproportionaltothenumberofprotonsandthe
extenttowhichtheirspinsareperpendiculartotheZaxis.Protonspredictablyrealignwiththespine,
whilecontinuingtopreceess.Sothereare2thingsatplayhere:
1.Theshorteninglengthofthespinningmagnet,and
2.Thelengtheningmagnetparalleltothespineasmoreandmoreprotonsrealign.
Thelongitudinal(orrestorationwiththemainmagneticfield)realignmentisknownasT1RELAXATION.
Itisaconstantforagiventissueand,bydefinition,itisthetimerequiredfor63%oftheprotonstorealign
withthemainmagneticfield.Itsexponential,soafter1T163%haverealigned,after2T1s86%have
realigned,after3T1s95%haverealigned,etc.[i.e.1(0.37)3]
Inreality,thespinningmagnetshrinksevenfasterthanpredictedbytheT1decaybecausethespinning
protonsactuallylosecoherenceandceasetospininunison.Thiscausessomeoftheremainingprotonsto
cancelouteachotherssignalandfurtherreducethesignalgeneratedintheantenna.Thisprocessof
protonsrandomlylosingcoherenceandcancelingouteachothersmagneticfieldsisknownasT2
RELAXATION.T1andT2areindependentofeachotherbutsimultaneousandT2relaxationisusually
muchfasterthanT1relaxation.Again,the63%decayischosentodescribetheconstantT2.Forexample,
after3T2shaveelapsedthenetstrengthofthemagneticfieldinthetransverseplanewillbe5%oforiginal
strength.
145
MRIexploitsthefactthatdifferenttissuesandstatesofpathologyhavedifferentT1andT2.Themost
commonwaytodothisistoacquireimagesusingaspinechopulsesequence,where2parametersare
utilized:TR(repetitiontime)andTE(echotime).TRisthetimebetweenRFpulses.Thisisthetime
duringwhichT1relaxationoccurs.AttheendofTR,anotherRFpulseisappliedandthoseprotonsthat
haverealignedwiththemagneticfieldwillbebroughtupagainandproducecurrentintheantenna.SoTR
adjuststheamountofsignalreceivedfromatissuedependingonitsT1value(e.g.ifTR=3T1,thesignal
willbe95%intensity).
TEisthetimebetweenthefirstRFpulseandtheobservationofsignal,thatis,thetimeforT2relaxationto
occur.Forexample,settingTE=2T2wouldresultin15%netremainingsignalintensityproducedbythe
componentoftheprotonsinthetransverseplane.
Contrastbetweenthetwotissuescanbeproducedbytheinteractionofthetwoparameters.AverylongTR
willeliminatedifferencebetweentissueswithdifferentT1(e.g.TR=2500mswillallow5T1stoelapse
whetherT1is250msor500ms).AveryshortTEwouldsimilarlyminimizethedifferenceinT2decayby
differenttissues.
T1WeightedImageutilizesashortTR(tomaximizeT1contrast)andashortTE(tominimizeT2
contrast).AnatomicdefinitionissuperiortoT2weightedimages.Fatisdarkandfluidisbright
T2WeightedImageutilizesalongTR(tominimizeT1contrast)andalongTE(tomaximizeT2
contrast).Fatisbright,fluidisdark
PD(ProtonDensity)issomewherebetweenT1andT2.ItutilizesshortTE(1420ms)andlongTR
(4000ms)toeliminatedifferencesinT1andT2i.e.differencesareonlyduetotheprotondensity
ofeachtissue.Fatandfluidarebright.
HASTE(HAlffourierSingleshotTurbospinEcho),FLAIR(FLuidAttenuationInversionRecovery),STIR
(ShortT1InversionRecovery),etc.arevariousalgorithmsbasedondifferentTR/TEtimesandmethodsof
dataacquisition.However,thebasicprinciplesdescribedaboveremainthesame.
146
IVPositronEmissionTomography(PET)
PETisafunctionalstudythatdetectsuptakeofvariousradioisotopes.Theisotopeusedmostcommonly
usedinclinical(surgical)applicationisF18,whichhasfavorablechemistry(similartoOH)andareasonable
halflife(2hours).18FDGor2fluoro2deoxyDglucoseistreatedbymetabolicallyactivecellslikeglucose,
exceptthatitcannotbemetabolized.WhentheFDGmoleculeentersacell,theextraproton,whichcauses
thenucleustobeunstable,degradesintoaneutronandreleasesapositron(samemassasanelectron,but
withapositivecharge).Thisveryunstablepositronleavestheatomandtravelssomedistance,depending
ontheenergyatrelease(usually23mm),untilitcollideswithanelectron,resultingintheirmutual
annihilation.Two(almost)antiparallelphotonsarereleasedfromthereactionandtraveltoadetector
outsideofthebody
[PhysicsofPET,Badawi,R,1999]
[ScientificServices,1998]
Nonpathologicalcellswithhighmetabolicrates(heart,brain,kidney,andliver)takeupFDGinadditionto
pathologiccells,suchastumorcells.HighFDGuptakeisnotalwayssynonymouswithmalignantdisease,
however,asothermetabolicallyactivecells,suchasthosefoundininfectionsandinflammatorylesions,
mayappearindistinguishablefromtumorlesionsbyPET.
147
VUltrasound
Ultrasoundworksbyemittingabriefpulseofsound(atahighfrequency)andlisteningforthereturning
echofromthesurfacewithinthebody.
Audiblesoundisintherange:2020,000Hz
Ultrasoundisdefinedas>20,000Hz
Medical(diagnostic)ultrasoundoperatesbetween120MHz(e.g.AbdominalU/S35MHz)
Higherfrequencysuperiorresolution,butdecreasedpenetration
Themonitordistinguishesbetween256(28)shadesofgrey:0(black)256(white)
Differenttissueswithinthebodyhavedifferentsoundtransmissioncharacteristics(acousticimpedances);
thedenserthetissuethefastersoundtravelsthrough
Material
Air
Fat
Water
Softtissue
Blood
Liver
Kidney
Bone
SoundVelocity(m/s)
340
1450
1480
1540
1570
1535
1560
21004080
Greaterdifferencesinacousticimpedancebetweenadjacentsurfaces(acousticmismatch)determines
thestrengthofthereturningecho
WhileU/Shasseveraladvantages(nodeleterioussideeffects,inexpensive,fast)thereareseveral
drawbacks:
1. Soundwavespropagateverypoorlythroughgashence,U/Smusthaveagaslesscontactwiththe
bodyandorgan(s)ofinterest
2. U/Simagesareverynoisycomparedtoxray/MRimagesandproducepoorerimages
3. Operatordependence
4. Difficulttoquantify
148
StatisticsinMedicine
TypeIError:Rejectthenullhypothesiswhenyoushouldnt(probability)
TypeIIError:Failingtorejectthenullhypothesiswhenyoushould(probability)
Power:TheprobabilityofavoidingTypeIIerror(1).Antherwayofsayingthis:Theabilityofyour
statisticaltesttodetectadifferencebetween2populationsshouldadifferenceexist.Seemoreonstatistical
powerbelow.
3BroadClassesofStatisticalPitfalls
ISourcesofBias
Includeerrorsofsamplingbias(studiedpopulationdosenotadequatelyrepresentpopulationofinterest)
anddatagathering(questionnaireswithleadingquestions).
IIErrorsinMethodology
Threemostcommoninclude:designingexperimentswithinsufficientpower(seebelow),failingtopay
attentiontoerrorsinmeasurement(understandthedifferencebetweenreliabilityandvalidity,seebelow),
andgoingonfishingexpeditions(makingmultiplecomparisons)withoutappropriatelycorrecting(seethe
Bonferronicorrection,below).
IIIInterpretationofResults(Misapplicationofstatisticalmethods)
Includeerrorsofstatisticalassumptions(e.g.usingamethodsuchasANOVAwhichreliesonassumptionsof
normalityandindependence,whensuchconditionsarenotmet),misunderstandingsofstatistical
significance,andassessingcausality(seebelow).
Reliability:theabilityofatesttomeasurethesamethingeachtimeitisused(Howclosearethedartsto
eachotherafterrepeatedlythrowingthematthedartboard?).Evenifthetestismeaningless,itshould
yieldthesameresultsovertimeifusedonsubjectswiththesamecharacteristics.
Validity:theextenttowhichatestmeasurestheoutcomeitwasdesignedtomeasure(Howclosearethe
dartstothecenterofthedartboard?).
Bonferronicorrection:astatisticaladjustmentforthemultiplecomparisonsoftenmadeduringstatistical
fishingexpeditions.Thiscorrectionraisesthestandardofproofneededtojustifythesignificanceofa
findingwhenevaluatingawiderangeofhypothesessimultaneously.Iftestingnoutcomes(insteadof1),
dividethebyn.Forexample,iftryingtofindtheassociationbetweenbodyweightand25differenttypes
ofcancer,dividedthetraditionalof0.05by25(0.05/25=0.002)toensureanoverallriskofTypeIerror
equaltoorlessthan0.05.Beaware,however,thatapplicationoftheBonferronicorrectioncanresultina
lossofsubstantialprecision.
Causality:Observationalstudiesareverylimitedintheirabilitytomakecausalinferences;doingso
requiresrandomassignment.Hence,correlationcanbeusedtoinfercausationiftheinterventionsare
randomlyassigned(e.g.doseofdrugvs.outcome).
149
ThebelowPowerTable(toquotemylabmentor,isthesinglemostimportanttableforsomeonedoing
clinicalresearch)providesthenumberofsubjectsneededtoadequatelydetectadifferencebetweentwo
populations,shouldoneexist.Powerisadirectfunctionofthedegreetowhichthenullandalternative
distributionsoverlap(lessoverlapmorepower)and
Forexample,ifwithoutinterventiontherateofaninfectionis30%,andyouexpectyourtreatmentto
reduceitto20%,youwillrequire411patientsperarm(822intotal)tohave90%power,or313perarm(626
intotal)tohave80%power.Toarriveatthesenumbersfromthetablebelowdothefollowing:subtractthe
smallersuccessrate(0.20)fromthelargersuccessrate(0.30),0.300.20=0.10.Alignthiscolumnwiththe
rowcorrespondingtothesmallerofthe2successrates(inthisexample0.20).Thisleadsyoutothe
numbers411and313.Theuppernumberisthenumberofsubjects,perarm,requiredfor90%power,and
thelowernumberthenumberofsubjects,perarm,requiredfor80%power,withasignificanceof95%.
Glancingatthistablefromlefttorightyouseethatmoresubjectswillberequiredwhentheexpected
differencebetweenthetreatedanduntreatedgroupsissmaller.Thatis,thelessofadifferencethe
treatmentisexpectedtohave,themoresubjectsyouwillneedtofindadifference,shouldoneexist.
[Cancer:Principles&PracticeofOncology5th,1999]
However,moreisnotalwaysbetter.Toomuchpowercanresultinstatisticalsignificancethatlacks
practicalsignificance.Inotherwords,ifthesamplesizebecomestoolarge,essentiallyanydifference
betweenthegroups,includingthosewithnopracticalsignificance,mayreachstatisticalsignificance.
150
Summaryofwaystoanalyzedata(i.e.WhichtestdoIuse?)
*ROC:ReceiverOperatorCharacteristiccurve(forthoseinterested,mathematicalexplanationoftheROC
curveisincludedbelow)
Withlogisticregression:values01negativeassociation;values>1positiveassociation
Withlinearregression:values<0negativeassociation;values>0positiveassociation
MultipleSamples
MeasuredData
RankedData
IndicationData
(e.g.counts)
Independent
Samples
Ttestifn30*
MannWhitneyUTest
(forsmallsamples)
Paired
Samples
Ttestifn30*
WilcoxanRank
(forsmallsamples)
SignsTest
*Forn<30toomuchvariancetousettestunlessyouknowthedistributionisnormalandtheselection
israndom
SummaryofClinicalTrials
PhaseI:Theirpurposeistodocumentthedoselevelatwhichsignsoftoxicityfirstappearinhumansto
determineasafe,tolerated,dose.Theendpointofsuchstudiesistoxicity.
PhaseII:Theirpurposeistodeterminetheoptimaldoseresponserangeforanewdrugandverifyits
efficacyfortheintendeddisorder.
PhaseIII:AfterphasesIandIIarecompleted,phaseIIItrialsareconductedandcontinueuntilthedrugis
releasedforgeneraluse.Theyfurtherverifytheefficacyofthedrug.
PhaseIV:FollowingFDAapproval,thesestudiesareoftenconductedinlargepopulationstofurtherdefine
theroleofthedrug/treatmentinspecialsubpopulations(e.g.children,elderly,pregnantwomen).
151
ReceiverOperatorCharacteristic(ROC)Curve
Recall:
Sensitivity=TP/D+=TruePositive/TotalDisease+=TruePositiveRate(TPR)
Specificity=TN/D=TrueNegative/TotalDisease
1Specificity=1TN/D=(DTN)/D =FP/D
=FalsePositive/TotalDisease
=FalsePositiveRate(FPR)
Sometimestheresultsofatestfallintooneoftwoobviouslydefinedcategorieshence:one
sensitivity/specificitypair
Whatifthetestismorecomplicated?Forexample,useofCEAlevelasaprognostictoolfordecidingif
pancreaticcystfluidisfromabenignormalignantpancreaticcysticlesion.IfyoudecidethatalowCEA
willbeyourcutoffforacceptingthelesionasmalignant,youwillprobablynotmissanylesions,butwill
unnecessarilyresectmanybenignlesions.Conversely,ifyoudecideonaveryhighCEAasthecutoff,you
willlikelyonlyresectmalignantlesions,butwillcertainlymissmalignantlesionswithlowerCEAlevels.
Hence:
Asthecutoffdecreases SensitivityandSpecificity
TheROCcurveisdefinedasaplotoftestsensitivity(truepositiverate)astheycoordinateversusitsfalse
positiverate(1sensitivity)asthexcoordinate
Thisisaveryeffectivemethodofevaluatingtheperformanceofadiagnostictest.Whatdoesthislooklike?
AUC=AreaunderCurve
TestA(bestpossible):AUC=1
TestD(chancediagonal):AUC=0.5
Hence,
TestA>TestB>TestC>TestD
[KorenJRadiol,5:11,2004]
152
AnalysisofSurvival
Thegoalofsurvivalanalysisistoestimatethesurvivalofapopulationbasedonasample.Thereare
severalmethodsfordoingthis,however,themostwidelyusedmethodisthatofKaplanMeier(infact,
theiroriginalarticle,JournaloftheAmericanStatisticalAssociation1958;53:457481,isoneofthetop5most
citedpapersinthefieldofscience).Thereasonthismethodissoimportant,inparticularforclinical
medicine,isbasedonthefactthatrarelyinanytrialarepatientsfollowedforthesamelengthoftime.
Patientaccrualtakesplaceovermonthstoyearsandpatientsleavethetrialforreasonsotherthestated
endpoints.However,theanalysisofsurvival(orsomeothermeasure,suchastimetodiseaserecurrence)
takesplaceatonepointintime,meaningthatnoteachpatienthasthesamelengthoffollowup.Hence,the
HolyGrailofsurvivalanalysisisonethatallowsustofollowapatientfortheentiretyoftheirtreatment
andfollowup,butremovethem(statistically)fromtheanalysiswhentheyleavethetrial.
Forexample,apatientparticipatesinatrialofananticanceragent,wheretheprimaryendpointofthetrial
issurvival,butislosttofollowup(i.e.leavesthetrial)at4years.Thefactthatthepatientlived4years
shouldcontributetothesurvivaldataforthefirst4years,butnotafterthat.However,youdontwantto
considerthepatientdeadat4years,sincetheymaystillbealiveandwell.Inclinicalpractice,mosttrials
haveaminimumfollowuptime,forexample,3years.Patientsleavingthetrialaliveinlesstimethanthis
willnotbeincludedintheanalysis.
Mathematicallyremovingapatientfromthesurvivalanalysisisreferredtoascensoringthepatient.When
patientsarecensoredfromthedata,thecurvedoesnottakeadownwardstepasitdoeswhenapatient
dies.Rather,ticks,onthehorizontallines,indicatewhencensoringoccurred.
Ateachtimeintervalthesurvivalprobabilityiscalculatedbydividingthenumberofpatientssurviving
bythenumberofpatientsatrisk.Patientswhohavedied,droppedout,ornotyetreachedthetimefor
minimumfollowuparenotconsideredtobeatrisk,andhence,arenotincludedinthedenominator.
Theprobabilityofsurvivingtoanypointisestimatedbytheproductofcumulativeprobabilitiesofeachof
thepreviousintervals.
[FiguretakenfromSTATA:StatisticalSoftwarefromProfessionals]
Comparingsurvivalcurvesisoneofthemostimportantaspectsofsurvivalanalysis.Ifnosubjectswere
censoredinanyofthetreatmentarms,theWilcoxonranksumtestcanbeusedtocomparemediansurvival
times.However,ifcensoreddataarepresent(mostsituations)othermethodsmustbeusedtodetermineif
survivaldifferencesexist.Onesuchmethodcommonlyusedisanonparametrictechniqueknownasthe
logranktest.
153
Notes
154
Notes
155
Notes
156
Notes
157
Notes
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