Conclusions

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Ростовский Государственный Медицинский Университет

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Morerecently,aKoreantrialsoughttodelineateprognosticfactorsfor oncologicaloutcomesin163patientsundergoingintersphincteric resectionsfollowingneoadjuvantchemoradiationtherapy.Withamedian follow-upof53months,analysisoftheKaplan–Meiersurvivalcurves demonstratedadifferenceinboth3-yearoveralldisease-freesurvival (DFS)andlocoregionalrecurrence-freesurvival(LRFS)forpatientswith Stage-IIIdisease.Indeed,DFSwasreportedas96.2%,84.8%,72.9%,and 38%andLRFSwasreportedas100%,92.4%,91.1%,and70.9%,for Stages0–IIIdisease,respectively.Multivariateanalysissuggestedthat ypT(3/4vs.0/1/2)andypN(1/2vs.0)stageswereassociatedwith differencesinDFS.LRFSwassimilarlyassociatedwiththeypNstage,as wellastumorsize(≥3.5vs.>3.5cm),anddistancefromtheanalverge (≤2vs.>2cm).

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p.180

IRPforrectalcancerwasinitiallyproposedtoobtainanadequatedistal marginofresectionforultra-lowrectaltumorswhileavoidingpermanent colostomy.FollowinganinitialsuccesswithIRP,theenvelopewas pushedwherebyadistalmarginof2cmwasdeemedacceptable.The impetustoavoidapermanentostomyinoursocietyissuchthatefforts weremadetoreconnectthebowelsincontinuitywithdistalmarginsof lessthan1cminpatientswhohadundergoneneoadjuvant chemoradiation.Itisthroughtheevaluationofthedatacollectedfrom theseproceduresthatwecanconfidentlystatethatfollowingthe neoadjuvanttherapy,IRPwithdistalmarginsoflessthan1cmdoesnot appeartocompromisetheoncologicoutcomeofanR0resection.

Allpatients,whetherundergoingstandardLARwithstapledcoloanal anastomosis,LARwithintersphinctericproctectomy,andhandsewn coloanalanastomosis,orAPRshouldbefollowedforaminimumof5–8 yearsbasedonstandardpublishedguidelinestoevaluateforrecurrence andmetastasis.

FunctionalOutcomes

FollowingIRP,thefunctionalcomponentsofinterestincludestool incontinenceandfrequency.Itappearsreasonablethatresectingthe internalanalsphincterresultsinincreasedincontinence.Asexpected fromourunderstandingofphysiology,ISRresultedinastatistically significantreductioninanalsphincterrestingpressure.Thesqueeze pressures,however,werenotedtobeattheirpreoperativelevelsatthe

timeoftheirpostoperativeevaluation.Whencomparingcoloplastyand CJP,Furstwasabletodemonstratetheabsenceofanysignificant differenceinrestingandsqueezepressureandneorectalvolumebetween boththegroups,butobservedanincreasedneorectalsensitivityinthe coloplastygroup.

ThesamestudythatreportedontheKoreanexperienceof62patients alsoevaluatedfunctionaloutcomesofpatientsundergoingISR.Inthis study,patientswereevaluatedat1and2yearsfollowingstomareversal. BowelfrequencywasincreasedinpatientswhounderwentextendedISR ascomparedwithstandardISRat1year(P<0.05).However,by2years, thefrequenciesdecreasedinbothgroups,withnostatisticallysignificant differencebetweenthoseundergoingstandardorextendedISR.Any differencesinKirwanclassificationforcontinenceorWexnerscorefor fecalincontinencewerenegatedby2years.Theyconcludedthatextended ISRwithquadrantresectionoftheupperexternalsphincter(extended ISR)achievedappropriatepostoperativecontinencestatusandcanbe usedasanalternativetoAPRwithoutcompromisingcureorqualityof life.

AsecondsurveytoevaluateGIfunctioninpatientswhounderwentIRP revealedthatthemeanWexnerscoreat1yearfollowingstomaclosure was10.BecauseaWexnerscoreof16correlatedwithpatientswho experiencedmajorandfrequentsoiling,thisscorewasutilizedasacutoff forpooranalfunction.FollowinganIRP,patientscanexpect2–5bowel movementsdailyandapproximatelya20–60%chanceofexperiencing urgency.DaytimeandnocturnalleakagefollowingIRPispresentin15% and20%ofpatients,respectively.ComparisonofIRPwithsphincter sparingCAAfoundworseningofcontinenceasmeasuredbytheKirwan andWexnerScoresfollowinganIRP.Tocompensate,thesepatients requiredmoreutilizationofantidiarrhealmedications.Inaunivariate analysis,boththeneoadjuvanttherapyandtheextentofinternal sphincterresectionwereassociatedwithpooranalfunction,but multivariateanalysisrevealedthatonlyneoadjuvanttherapyis significantlycontributorywithanoddsratioofmorethan10.Overall, outcomeshavebeengenerallyacceptablewithminimalpatient dissatisfaction(Tables20-5and20-6).

TABLE20-5

FactorsAssociatedwithPostoperativeContinence/FunctionalOutcome

Age Gender

Tumor

location Diff/Grade

TNM

stage

Level

ofIRP

Preoperative

radiation

Yamada, 2009

0.008/0.013

0.082 0.006*/0.055

0.778 0.897 0.139

Tiret, 0.2 0.82 0.63 NS

2007

0.035/0.04

Ito,2009 0.5 0.1 0.04/0.8 <

0.01/

IRP,intersphinctericrestorativeproctocolectomy;PSWD,pelvicsidewalldissection.

TABLE20-6

One-YearFunctionalResultsafterIntersphinctericProctectomy

>5BM/24h

Nocturnal

defecation Urgency Padwearing

Flatus/Feces

discrimination

Chamlou,2007 3(4)  24(29) 16(19) 38(46) 21(25.3)

Ito,2009 27(36) 13(18) 9(12) 42(57) 8(11) 

Han,2009 11(31) 30(86)

Tilney,2008

Meta-analysis

20 (19–59%)

BM,Bowelmovements.

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AnItalianstudyaddressedroboticintersphinctericdissectionwith handsewnanastomoses.Intheirlimitedcohortof23patientsobserved over4years,fecalcontinencewasshowntobegoodin85.7%basedon theKirwanscore,andnopatientsrequiredcolostomy.Inthesamegroup,

57.1%showednoLowAnteriorResectionSyndrome(LARS)symptoms, 19%withaminorLARS,and23.8%withamajorLARS.

AJapanesestudyinvestigatedlong-termfunctionaloutcomesin patientsundergoingstapledversushandsewnISRsfordistalrectalcancer followingachemoradiationtherapy.Theyconcludedthattherewereno significantdifferencesintotalLARSscoresbetweenthetwocohorts.ISR washoweverassociatedwithpoorerincontinencescorescomparedwith thatincaseofdouble-stapledtechnique.Inamultivariateanalysis,only tumordistancefromtheanalvergeandpostoperativeperiodwere independentlyassociatedwithamajorLARS.

Multiplestudieshavelookedatthefunctionalbenefitsofpouch proceduresversuscoloanalanastomosis.Whencomparingtheshort-term functionaloutcomesbetweenCJPandCAAfollowinganISR,the frequency,urgency,WexnerscoreandFecalIncontinenceSeverityIndex wereshowntobesignificantlyinthefavoroftheCJP.Longer-term

studiesfailedtorevealthesebenefits.Itshouldbeobservedthata differenceinimprovedfunctionaloutcomesevenovertheshorttermmay beasignificantbenefit,giventhesometimeslowlifeexpectancyofthese individuals.

Ameta-analysisrevealedthat61%ofpatientsafterCPAand55%after CAAexperiencedgoodfunctionaloutcomesintermsofcontinence (KirwanIorII).CJPresultedingreaterdecreasedstoolfrequencythan CAA.Atalong-termfollow-up,studiesfailedtorevealanydifferencein maximumpouchvolumeasneorectalcapacitydecreasedequallyinboth thegroups.Thisfindinghasledsomeauthorstoproposethatthe advantageofpouchproceduresmaynotbederivedfromtheincreased volume,butratherfromdecreasedmotility.

p.181

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Studiescomparingthevarioustypesofpoucheshaveobserved advantagesoftheCJPovertheside-to-end-anastomosisintheearly postoperativeperiod.TheTCPwasobservedtobesimilarintermsof functionalresultstoCJP.Althoughnodefinitivereportshavebeen published,thereisageneralconsensusthataBaker/Side-to-End anastomosishassimilaroutcomestothoseoftheCJPandTCP.

SexualMorbidity

Sexualdysfunctionfollowingarectalresectionhasbeenstudiedby multipleauthors.Itismorereadilyobservedinmaleswhereitmanifests asaninabilitytoobtainanerectionorasretrogradeejaculation.In females,themanifestationisusuallyintermsofdyspareuniarelatedto vaginaldrynessfromdecreasedparasympatheticstimulationofexcretory glands.

Whenconsideringsexualfunctionordysfunctioninpatientsfollowing restorativeproctectomy,itisnecessarytocompareitwiththesexual morbidityrelatedtothealternative,anAPR.Inonesurvey,findings indicatedthatfollowingAPR,therewasnosignificantchangeinthe patient’ssexualactivity.Theonlyindexofsexualactivitythatfell postoperativelywasrelatedtomaritalinfidelity.AnAPRwitha permanentstomaaddstothesexualmorbiditybyaddingthe psychosocialbarriersrelatedtothepresenceofastoma,theperceived effectofastomaonthepartner,andthefearofleakagefromthestoma appliance.Thisimpactismorelikelytobeperceivedbywomenthanby menandbypatientsthanbytheirpartners.

Amorerecentprospectivestudylookingatthesexualdysfunctionof APRcomparedwithrestorativeproceduresin295womenrevealedthat

womenwhounderwentAPRwerehalfaslikelytobesexuallyactive1year postrectalresectionwhencomparedwiththeircounterparts.The frequencyofintercourseimprovedovertimethenext4years.APRwas alsoassociatedwithasixfoldhigherlikelihoodofdyspareuniaanda higherfrequencyofurologicdysfunctionsaswell.

Thelateralpelviclymphadenectomydescribedandpublishedby Japanesegroupsappearstoaddtothesexualmorbidityrelatedtorectal resectionbydamagingtheIHPoverlyingthepelvicvesselsandassociated lymphnodes.Thismanifestsasahigherrateofimpotenceandbladder dysfunction.Whenconventionalrectaldissectionispracticed,andlateral pelvicsidewalllymphadenectomyisnotundertaken,theratesof impotencereportedbythesameauthorsaresignificantlylower,and bladderdysfunctionisuncommon.

Stoma-FreeSurvival

Weiserpublishedthemostrecentandlargestseriesdocumentingthe ratesofstoma-freesurvivalinpatientswithdistalrectalcancer undergoingLAR.Asubgroupanalysiscomparingpatientsundergoing LARwitheitherstapledcoloanalanastomosisversusintersphincteric proctectomywithhandsewncoloanalanastomosiswasperformed.With anevendistributionbetweencohorts(41and44,respectively),therewas nostatisticallysignificantdifferenceinthenumberandpercentof patientsbeingstoma-freeatthelastfollow-up(98%and86%,P=0.06). Failuretorestoreintestinalcontinuity(2%and5%,respectively)was attributedtoanastomoticleakageandonedeathfromcardiovascular causes.StomaswererecreatedinfourpatientsintheIRPgroupdueto anastomoticleak(1),rectovaginalfistula(2),andstricture.Nostomas werecreatedforpoorbowelfunction.

EffectofNeoadjuvantChemoradiation

Chemoradiationintheadjuvantorneoadjuvantsettinghasadramatic effectontheoncologicalandfunctionaloutcomesinrelationto intersphinctericproctectomy.Italsohasasignificanteffectonother aspectsofapatient’slifeasrevealedinastudythatfoundwomenwho underwentradiotherapyinadditiontoIRPhadafivefoldincreasein dyspareunia.

Ameta-analysisrevealedalocalrecurrencein51of538patients(9.5%) followinganIRP.EarlyresultsrevealedasignificantlyhigherrateofLR recurrencefollowingISRwithout(46.5%)comparedwith(14.2%) adjuvantchemoradiotherapy.Inagroupof39patientswhoalso underwentlong-courseneoadjuvantradiotherapy,afollow-uprevealed localrecurrenceonlyinthreepatients(8%),allofwhomhadlymphnode

positivedisease.Otherreportsofresultsfollowingneoadjuvanttherapy havenotbeenasimpressivewithRouanetreportingalocalrecurrence rateof13%inasimilarcohortwhereasanotherstudyreporteda surprisinglyhighrecurrencerateof21%.Althoughtherehavebeensome reportsofanastomoticfistulasandpelvichematomasinthesepatients, noclearpatternofhighratesofanastomoticcomplicationsisevident fromanalyzingstudieswithhighproportionsofpatientsreceivinga neoadjuvanttherapy.Indeed,themostrecentstudyevaluatingLR recurrenceanddisease-specificsurvivaldemonstratedfavorablerates despiteneoadjuvantchemoradiationtherapyandhavebeendescribed hereinbefore.

p.182

p.183

StudiesofGIfunctioninpatientsfollowinganeoadjuvanttherapynote adecreaseinrestingandsqueezepressuresaswellasmaximumtolerable volumefollowingIRP.Multivariateanalysisrevealedonlymaximum tolerablevolumetobecorrelatingwiththeWexner/FecalIncontinence Scores.Thischangewasdecreasedwithapouchanastomosis. Interestingly,neorectalsensitivitywasincreasedwithcoloplasty.

Whenexaminingfactorsthoughttohavecontributedtopoorbowel function,preoperativeradiationtherapywasmostconsistentlyobserved tobethesoleprognosticfactor.Age,gender,andtypeofreconstruction techniquewerenotsignificant(Table20-7).

TABLE20-7

One-YearWexnerFecalIncontinenceScoreandKirwanClassMeasuresofFunction

Wexnerscore

Kirwanclassification

I—Perfect

II—Incontinence

toflatus

III—Occ.minor

soiling

IV—Freq.major

soiling

Ito,2009 10 18(25) 8(11) 27(37)

Han,2009 15(43) 10(29) 6(17)

CONCLUSIONS

IRP,beitsubtotalortotal,appearstobeaviablealternativetoabdominal perinealresectionintermsofoncologicoutcomeswhilemaximizingthe qualityoflifeincarefullyselectedcohortsofpatientswithmalignant disease.Indeed,inproperlyselectedandmotivatedpatientsableto undergoIRP,excellentandequivalentrecurrence-freesurvivaland disease-specificsurvivalsimilartothoseundergoingLARwithstapled anastomosishavebeenreported.Theseoncologicaloutcomesare significantlyimprovedcomparedwiththoserequiringAPR.While avoidingastomaandmaintainingintestinalcontinuitywithsphincter preservationisaprincipleconcern,patientsshouldbecounseledastothe expectedfunctionaloutcomeandtherealriskofincontinencefollowing anIRP.Thisisparticularlythecaseifneoadjuvanttherapyisutilizedfor malignantdisease.Theuseofchemoradiationtherapycanofferbenefits intermsofoncologicresultwithdecreasedLRrecurrence,improvements inresectability,andsphincterpreservation.However,thismaycomeat thecostofworse,yetacceptable,functionaloutcomes.Inthesepatients, eventhebestreportedresultsallowfor25%ofpatientswithoccasional andmajorincontinence,thoughrarelyprogresstorequiringpermanent stomas.Newtechniquesandinstrumentation,particularlycomputeraidedminimallyinvasivesurgery—orroboticsurgery,havefacilitated moredistaldissectionintheintersphinctericspaceandmayallowfor increasednumbersofdouble-stapledanastomoseswithimproved functionaloutcomes.

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