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11/12/17
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AReviewoftheLargeIntestine
PraveenMettu,MD10/30/2017
Contentsl Vasculature
l Functionl Absorptionl Motilityl NeuralreflexesandControl
l Colitis
l Malignancy
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Anatomy
Section1.Vasculature
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Vasculature
• SuperiorMesentericArtery• InferiorMesentericArtery
• InternalIliacArteries
Vasculaturel SuperiorMesentericArtery(SMA)
l Suppliesbloodflowfromthejejunumdistallytothesplenicflexurel Middlecolicarteryl Rightcolicarteryl Ileo-colicartery
l InferiorMesentericArteryl Suppliesbloodflowfromthesplenicflexuretotherectum
l Leftcolicarteryl Marginalarteryl Sigmoidarteryl Superiorrectalartery
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DualBloodSupplyoftheRectuml InferiorMesentericArtery
l SuperiorRectalArtery
l InternalIliacArteriesl MiddleRectall InferiorRectal
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IschemicColitisl MostcommonischemicinjurytotheGItract
l 1in1000hospitalizationsest.l Underestimated
l OcclusivevsNon-occlusive
l Variablepresentationl Transientl Gangrene
IschemicColitisl Perfusion
l Decreasedsystemiccirculationvschangestolocalmesentericvasculaturel OcclusivevsNon-occlusivel Hypoperfusion
l Shock/Sepsisl Peri-operativeperiodl StrenuousPhysicalExercisel Constipationl Medications
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IschemicColitisl Risks
l Age:90%casesoccurinpts>60yrsoldl Medicationsl HypercoagulableState
l FactorVLeidenl ProteinC/S
l Idiopathicl Youngerptsl Estrogens,cocaineandmeth,sicklecelldisease
EndoscopicClue:Anti-MesentericStripe
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IschemicColitisl Severity
l 80-85%classifiedasnon-gangrenousl Majorityresolves24-48hrs,endoscopicresolutionw/in2wksl Supportivecare,resuscitation,antibiotics
l Canbeacuteorchronicl Chronic->recurrentsegmentalcolitisorstricture
l Gangrenousl Peritonitis,septicshock,freeaironradiographicstudiesl Laparotomywithresectionofdiseasedcolon
IschemicColitisl Diagnosis
l HistoryandPhysical(diarrhea,pain,bleeding,fever)l Imaging
l XRabdomenl CTabdomen/pelvisl MesentericAngiography
l ReservedforRcoloninvolvementl Colonoscopy
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IschemicColitis
Section2.Function
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FunctionsoftheLargeIntestinel Absorbwaterandelectrolytes
l Proximalhalfofthecolonrespforabsorption
l 1.5-2Loffluidpassintothecolondailyl Canmaximallyabsorbupto5-8Lfluid
l Storeandconcentratefecesl Electrolytes/ionsabsorbedwithwater,
100mLlefttobeexcreted
l Roleofcolonicbacterial FormationofvitaminK,thiamin,
riboflavin
FunctionoftheLargeIntestine:Secretionl MucusSecetion
l CryptsofLieberkuhnarelinedwithmucusproducingcellsl Controlledby
l Direct,tactilestimulationonsurfaceofthemucosal Intenseirritantscanleadtoadditionalsecretionoffluidandelectrolytes(bacterialorviralenteritis),dilutingtheirritant
l Byneuralreflexesl Parasympatheticstimulationincreasesmucussecretion
l Alsoincreasesmotility,causingmucoiddiarrhea
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NeuralControloftheLargeIntestinel EntericNervousSystem
l Liesentirelywithinthewallofthegutl Twonerveplexuses
l Myentericplexus(btwthetwooutermusclelayers)l Gastrointestinalmovements(bothinhibitoryandexcitatoryneurons)
l Submucosalplexus l Sensorysignalsl Localbloodflowl Gastrointestinalsecretion
NeuralControloftheLargeIntestinel Neurotransmitters
l Acetylcholinel Norepinephrinel Serotoninl Dopaminel VIP
l SympatheticvsParasympatheticControl
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FunctionalGastrointestinalDisorder(FGID)l IrritableBowelSyndrome
l FunctionalDiarrhea
l ChronicIdiopathicConstipation
IrritableBowelSyndrome:RomeCriteria
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IrritableBowelSyndrome:RomeCriteriaIVl May2016
l ShiftfromFunctionaltoDisordersoftheBrain-GutInteractionl Avoidstigmal Focusonalterationsingutbacteria,alterationsingutpermeability,CNSrolel Diagnosis
l Abdominalpain(discomfortremoved)withtwoormorefeaturesof:l Relatedtodefecationl Assocw/changeinfrequencyofdefecationl Assocw/changeinappearanceofstool
l Symptomspresentatleast1dayperweekforthelastmonthl Symptomspresent>6monthstotal
IrritableBowelSyndromel Testing
l Labsandstoolstudiesl +/-ColonoscopyandEGDbasedonsymptomsl HydrogenGlucoseBreathTesting
l InflammatoryvsNon-inflammatory
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IrritableBowelSyndromel Disruptionofbi-directionalbrain-gutcommunication(neuralandhormonalmediated)l Visceralhypersensitivityl Altersdigestivesecretionandmotility
l Decreasedintegrityoftheoftheintestinalbarrierl Causedbychangestocompositionofgutmicrobiota,psychologicalstress
l Activatesmastcells->increasesintestinalpermeabilityl Antigenscrossepithelialbarrierandtriggerimmuneresponse,abnormalneuronalbehavior
IrritableBowelSyndromel Treatment
l Anti-spasmodicsl Dicyclomine(Bentyl)l Hyoscyamine(Levsin)
l Motilityl Loperamide
l Antidepressants(focustreatmentonneurotransmitters,visceralorneuropathic,pain,alterationofmotility) l SelectiveSerotoninReuptakeInhibitors(SSRI)l Serotonin-NorepinephrineReuptakeInhibitor(SNRI)l Tri-CyclicAntidepressants
l Hypnotherapy,Biofeedback
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ChronicIdiopathicConstipationl Nosingle“definition”,subjective
l Causesl Normal-transitl Slow-transitl Disordersofrectalevacuation
ChronicIdiopathicConstipationl Normaltransit
l Mostcommonl Perceiveddifficultyandhardstools,oftenwithbloating/discomfort
l Oftenimproveswithhydrationandfiberorotherosmoticlaxatives
l Lackofimprovementraisespossibilityofeitheroftheothertwocauses
l Slowtransitl Youngwomen,oftenstartsatpuberty
l Lackofdefecatoryurge,presenceofabdpain+bloating
l Oftenpoorresponsetoincreasedfiber
l Causedbydecreasedemptyingoftheproximalcolonanddecreaseinhighamplitudepost-prandialperistalsis
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ChronicIdiopathicConstipationl Slowtransitconstipationpathology
l Myentericplexusneuronsandneurotransmittersl Excitatory:SubstancePl Inhibitory:VasoactiveIntestinalPeptide(VIP)andnitricoxide
l InterstitialCellsofCajal(regularGImotility)
l Diseasesrelatedtoslowtransitl Hirschsprung’sdisease
l Ganglioncellsabsent(developmentalarrest)l Narrowingofaffectedsegmentsofbowell Mostoftendiagnosedininfancyorchildhood
l ColonicInertial Severeabsenceofmotoractivityaftermealsandnoresponsetomusclestimulants(bisacodyl,
anticholinesterasesuchasneostigmine)
ChronicIdiopathicConstipationl Continence
l Normalrectalsensationl Toniccontractionoftheinternalanalsphincterl Toniccontractionofthepuborectalismuscle(createstheano-rectalangleasitwrapsbehindtheano-rectum)
l Defecationl Thepelvicfloormusclesrelax,allowingdescentoftheperineum(1.0-3.5cm)l Puborectalismusclerelaxes,straighteningtheano-rectalanglel Relaxationoftheexternalanalsphincter
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ChronicIdiopathicConstipation
ChronicIdiopathicConstipationl DefecatoryDisorders
l Diagnosedwithdefecographyorano-rectalmotilityorballoonexpulsionl Reduceddescentoftheperineumand/orreducedchangeintheano-rectalangleduringstraining
l Causedby:l reducedrectalsensationl disorderoftheanalsphincterl injurytothepelvicfloorl paradoxicalcontractionsofthepelvicfloorduringdefecationl prolongedavoidanceofanalpainfromhard,largestools
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ChronicIdiopathicConstipationl Treatment
l Pharmacologic
l Biofeedbackwithphysicaltherapyl Strengthenpelvicfloormusclesl Retrainingofthepelvicfloorforptswithparadoxicalsphinctercontractionl SubjectiveImprovement
l Increasedfreq,reducedbloatingl Improvementinsymptomdrivenanxiety,hostility,depression
l ObjectiveImprovementl ARMvalues
Section3.Colitis
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InflammatoryBowelDiseasel Crohn’sdisease
l UlcerativeColitis
l IndeterminateColitis
InflammatoryBowelDiseasel Incidence
l HighestinNorthernEurope,U.K.,N.Americal UCratesstableordecreasing,CDcontinuestoincrease
l LesscommoninSoutheastandSouthAsia,butincidenceisincreasingl UCrisesfirst,thenCD
l Prevalence(N.America)l CDandUC:btw50-200per100,000l 1-2ofevery1,000indevelopedcountries
l Age(peak)l CD:20-30yrsofagel UC:30-40yrsofagel PediatricIBDacctsfor10-20%ofcases
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InflammatoryBowelDiseasel Crohn's,anatomical
l AnypartoftheGItractl Mostcommon:TI,colonl Only10-15%haveupperGIlesionsl 15-20%haveperi-analfistulaattimeofpresentation,upto45%willby20yrs
l Riskincreasedforpatientswithcolitisvsriskinileitis
InflammatoryBowelDiseasel CDphenotypes
l Inflammatoryl Penetratingl Stricturing
l Phenotypes=Spectrum
l Post-operativemodel,diseaseprogression
l RoleofSurgeryinCDandUC
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InflammatoryBowelDiseasel Treatment,UC
l Inductionl Mildtomoderate:5-ASAproductsl AcuteSevere:Steroids,Infliximab,Cyclosporine,Surgery
l Maintenancel Mildtomoderate,5-ASAproducts
l Dependsonlocationl Relapsesdespitetreatmentwith5-ASAproduct
l Biologics>Thiopurines
InflammatoryBowelDiseasel Treatment,CD
l Inductionl Mildtomoderate:5-ASAproductshavequestionableefficacy
l Steroids,Methotrexate,Budesonidel AcuteSevere:Steroids,Infliximab,Surgery
l Maintenancel Smokingcessationl Noroleformesalaminel Budesonidel Relapsesorseveredisease
l Biologics+Thiopurinesl Perianaldisease
l Antibiotics
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MicroscopicColitisl Commoncauseofwaterydiarrhea
l 4-13%ofcasesofdiarrheal Female,6th-7thdecade,Caucasianl IncreasedincidenceinpatientswithCeliacdisease
l Diagnosisl Endoscopicappearanceisnormall Pathology
l CollagenousandLymphocyticsubtypes
l Pathophysiology
MicroscopicColitis:Treatmentl Stopoffendingdrug
l NSAIDs
l Anti-diarrheals
l Bismuthsubsalicylate
l Steroids
l 5-ASAproducts
l Azathioprine/Mercaptopurine
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DiverticularDiseasel Diverticulosis
l Diverticulitis
l DiverticularHemorrhage
Diverticulosisl Pseudo-diverticulum,herniationofthemucosaandsubmucosaonly
l Distalcolon
l Truediverticula,allthreelayersl Proximalcolon
l Physiologyl Lowdietaryfiber->Smallervolumestools->Exaggeratedcontractionscreatinghighintra-luminalpressures
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Diverticulosis
Diverticulosisl AcuteDiverticulitis
l Fever,localizedpain,leukocytosisl Diagnosisandseverity:CTScan
l Bowelwallthickening,fatstranding,phlegmon,smallabscess,frankperforationl Treatmentwithantibiotics,bowelrest,managementofabscess,surgery
l AerobicandanaerobicGram-negativecoveragel InpatientvsOutpatientmanagement
l Presenceofcomplicationsl Abilitytotolerateoralmedsl Responsetooralmeds
l Pathophysiology:Obstruction+/-alterationislocalbacterialflora
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Diverticulosisl Chronicpainsecondarytodiverticulosis
l Cause l Visceralhypersensitivity
l Inflammation(chronic)altersnerveregenerationandtransmitterreleasel Alteredcolonicmotilityl Low-grademucosalinflammation
l MustdifferentiatefromIBS,assymptomsrespondtosurgicalresectionofdiseasedarea
l Treatwith5-ASAproducts,probiotics
Diverticulosisl Segmentalcolitisassociatedwithdiverticulosis(SCAD)
l Painandrectalbleedingl Friabilityinregionofdiverticuli(absenceofulcers)l Pathophysiologyunknown;linkedtoIBDl Treatment:5-ASAproductsandantibiotics
l RecurrentDiverticulitisl 25%ofpatientswithacutediverticulitiswillsufferarecurrencel Noincreaseinmorbidityormortalitywithrecurrentattacks
l Changessurgicalguidancel Considerageandutilizeprobiotics
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Section4:ColorectalCancer
ColorectalCancerl 3rdmostcommonlyDx’edcancerworldwide
l 3rdhighestincidenceinmales(lung,prostate)l 2ndhighestincidenceinfemales(breast)
l Globalvariationl Australia/NZ(m=45/100,000),Europe,N.Americal LowestincidenceinW.Africa(m=3/100,000)
l UStrendl Decreasingincidencesincemid80’s,whenCRCscreeningwidelyimplementedl Increasingincidenceinpatientsbtw40-45(!)
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ColorectalCancer:RiskFactorsl Increasedgeneticsusceptibility
l Hereditarycolorectalcancersyndromesl 10%ofCRCcasesl Hereditarynon-polyposiscoloncancermostcommon
l Familyhistoryofcoloncancerl Potentially2-3xgreaterlifetimeriskwhen1stdegreefamilymemberhasCRC
l Environmental/Acquiredl IBDl Cigarettesmokingl Obesityl “Western”diet
l Highinredmeatl Lowinfiber
l EtOH–moderatetoheavy
ColorectalCancer:ProgressionofAdenoma
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ColorectalCancer
ColorectalCancer:ScreeningToolsl StoolTesting
l Guaiac-basedFOBT:Hemecatalyzesreactionbtwhydrogenperoxideandguaiacl Subjectivel Falsepositives(highmeatcontentdiet->animalheme)l Falsenegatives(VitaminC,lackofsensitivityrequires3consecutivesamples)
l FecalImmunochemicalTestingl UsesspecificAbtohumanHgb(removessubjectivityanddietaryinfluence)l Stilllimitedtodetectingbleedingcancers(missesnon-bleedingpolyps)l Limitsonspecificity
l Molecularstooltestingl Cologuard(multi-targetstoolDNAtest)every3yrsl Commonmutationsfoundincoloncancerl Highlyspecific
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ColorectalCancer:ScreeningToolsl Imaging
l Double-ContrastBariumEnemal Sensitivityforlargepolyps>10mmis~50%l Requiresbowelprep
l CTColonographyl Sensitivityforcolorectalcancerapproachingrateswithcolonoscopyl Nosedation,butstillrequiresprepl Extra-colonicfindings(goodorbad?)
ColorectalCancer:Screeningl Colonoscopy
l Goldstandardl Rateofcomplication(major)0.1-0.2%l Bowelprepandsedation
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ColorectalCancerl Staging
l Surgicall Radiographicall TNM
l T:depthofinvasionwithinthewall,relationtostructuresbeyondthecolonl N:numberofnodesl M:presenceofmetss
ColorectalCancer:PrognosisStage TNM Survival
Stage0 Tisonly 100%
StageI T1-T2only 93%
StageII-A T3only 85%
StageIII-A T1-2withLNmets<7ordepositsintomesenteryorpericolictissuew/outLN
83%
StageII-A,B T4lesionw/outLNormets 72%
StageIII-B,C T4lesionwithLN,nomets 44-64%
StageIV Anymets 8%
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ColorectalCancerl TreatmentStrategies
l Chemotherapyl Radiationl SurgicalResection
Questions?
