转移性结直肠癌

转移性结直肠癌Approximately20%ofpatientswithcolorectalcancerpresentwithestablisheddistantmetastases.Despiteconsiderable

progressStageIVpatientsare

notcurable.5-year

survivalrateforStageIVpatientsdiagnosedbetween1991

and2000was8%.Systemicchemotherapy,

endoscopictreatmentstopalliateobstruction,surgicaldiversion,andsurgicalresectionallhaveimportantrolesintreatmentofStageIVpatients.将近20%的结直肠癌患者都会发生远处转移尽管医疗技术有了很大进步，但IV期患者仍无法治愈1991-2000年IV期患者的5年生存率为8%系统的化疗，内镜治疗缓解梗阻，造瘘，手术切除都是治疗IV期患者的重要手段Forpatientswith

goodperformancestatusandminimalsymptomsfromtheir

primarycancers,standardtreatmentissystemicchemotherapy,whichiswelldocumentedtoincreasesurvivalandqualityoflife.

Surgicalresectionoftheprimarytumorand,

whenfeasible,ofthemetastaticlesionscanprovideexcellent

palliationandcan,insomecases,providelastingcure.

Inthepastdecade,therehasbeenremarkableimprovement

intheefficacyofchemotherapyforcolorectalcancer.FOLFOXorFOLFIRI.Mediansurvivalhas

improvedfrom12–14monthsto21months对于一般情况好，原发肿瘤症状轻的患者，标准的治疗应为系统的化疗，可以有效的提高生存率和生活质量对于有转移患者的原发肿瘤切除，如果可以切除的话，有些情况下对病情有良好的缓解作用在过去的10年里，化疗的疗效有了显著的提高，FOLFOX、FOLFIRI方案的应用使转移癌患者的中位生存时间从12-14月提升至21个月BiologyofMetastaticDiseaseTheclinicalpresentationofStageIVpatientsisvariable.Most

presentwithsymptomsreferabletotheprimarytumor.

Initialstagingevaluationshouldincludecolonoscopywith

biopsy,andimagingoftheprimarytumor,liver,andlungs.

EndorectalultrasoundorMRIisrecommendedforrectalcancerstodocument

theinitialTandNstage.CT

scanningofthechest/abdomen/pelvisisahighlyaccurateand

efficientmethodofdetectingmetastases.PETscanningdetectsoccultdiseasenotseenon

CTscanin20%ofStageIVpatients.

Diagnosis/StagingIV期肿瘤患者的临床表现是多种多样的。大部分与原发病灶有关。初始的评估手段应有：结肠镜（取活检），肿瘤、肝脏、肺部的影像学检查。经直肠腔内超声或MRI是指导临床TNM分期的重要手段。胸、腹、盆的CT检查是发现转移的准确有效的方法。PET可以发现CT发现不了的一些隐性疾病，检出率达20%。诊断/分期Oncetheextentofdiseaseworkupiscompleteanddistant

metastaseshavebeendocumented,thesurgeonmustmake

threeimportantjudgments.Firstiswhetherthepatientisfit

foraggressivetreatment.Secondiswhethertheprimarytumorpresents

aclinicallysignificantriskofbowelobstruction.The

thirddeterminationiswhetherthepatient’smetastasescanbe

surgicallyresected,andthereforetreatedwithcurativeintent当常规检查完善，并发现转移时，外科医生需要做3个判断。1患者是否适合接受手术治疗。2原发肿瘤是否有显著的梗阻风险。3转移灶是否可以手术切除。以达到治愈的目的Managementofpatientswithadvanceddiseaseisoftencomplex,andmultidisciplinaryevaluationcanbehelpfulindetermininginitialtherapy.Thesurgeonandmedicaloncologist

shouldevaluatethepatientinconsultationwitharadiologist

andgastroenterologist.Thegoals,priorities,andexpected

courseoftreatmentshouldbediscussed.Forrectalcancers

thatarebulkyorsymptomatic,theadviceofaradiationoncologistisoftenhelpful.MultidisciplinaryEvaluation晚期肿瘤病人的管理是复杂的。外科及肿瘤科医生应与放疗及消化科医生会诊。多学科评估Approximately8%–29%ofpatientswithcolorectalcancer

initiallypresentwithsymptomsofpartialorcompletebowel

obstruction.Forpatientswithadvancedobstruction,

nonresectivepalliativeoptionsincludelasertherapy,fulguration,colonicself-expandingmetalstents,andcreationofa

divertingstoma.

PalliativeManagementofthePrimary

Cancer—Stents,Laser

将近8-29%结直肠癌患者以全或不全性肠梗阻为首发表现。对于晚期肿瘤梗阻患者，不可切除的姑息治疗包括：激光、电灼、肠内自扩张支架、造瘘。原发肿瘤的姑息治疗-支架，激光Lasertherapyhasbeenusedforpalliationofobstructing

rectalcancersforthepasttwodecades.However,

lasertherapyisonlyfordistalcolonandrectum,andisrarelyusedtotreatproximal

lesions.Complications

suchasbleeding,perforation,andseverepainhavebeen

reportedin5%–15%ofpatients.过去20年，激光治疗用于缓解直肠癌所致的梗阻症状。激光治疗仅适用于末端结肠和直肠，几乎不用于近端结肠并发症主要有：出血、穿孔、剧痛。报道的发生率为5-15%。Surgicalfulgurationofrectalcancersisanothermethodof

openingtherectallumen.

Fulguration,incombination

withendoluminaldebulking,canremovealargevolumeof

tumor;however,unlikelasertherapy,thisprocedurerequires

hospitaladmissionandregionalorgeneralanesthesia.电灼疗法是另一种打通直肠腔的方法。电灼结合经直肠腔内减瘤，可以去除大块的肿瘤组织。需要住院，麻醉支持。In1991,colonicstentshave

becomeanimportantmethodofpalliationforobstructionin

colorectalcancerpatients,especiallythosewithunresectablemetastaticdisease.Theseself-expandingmetallic

stentscanpotentiallydilatethelumentoanear-normal

diameter,providingquickreliefofsymptomsand,insome

cases,allowingendoscopicassessmentoftheproximal

colon.Complicationsincludedstentmigrationresultinginexpulsion,

reobstruction,andintractabletenesmus.Stentingofcancersin

themidandlowrectummayresultin

incontinence.

Complicationsoncolonicstents

includestentmalpositioning,migration,tumoringrowth,tumorovergrowth,perforation,stoolimpaction,bleeding,tenesmus,andpostprocedurepain.

结肠支架自1991年出现以来，已成为晚期结直肠癌梗阻患者姑息治疗的重要方法，特别是那些转移灶无法切除的患者。自我扩张的金属支架可以扩张肠腔近乎正常直径，快速的缓解梗阻，甚至有些患者还可容结肠镜通过，以完善近端结肠的检查。并发症主要有移位、脱出、再次梗阻、里急后重感、肿瘤向支架网内生长、肿瘤生长超过了支架的覆盖、穿孔、出血、便嵌塞。Theroleofbowelresectioninpatientswithunresectable

metastasesiscontroversial.NorandomizeddatademonstratingasurvivalbenefitforbowelresectioninStageIVpatients.However,palliativeresectionoftheprimarytumordoesprovidedurablelocal

control,isgenerallywelltolerated,andcanbenefitmany

StageIVpatients.

It’sshownthatStageIV

patientsreceivingsystemicchemotherapyhaveincreased

lengthandqualityoflife.Withmodernmultidrug

regimens,thebeneficialimpactofchemotherapycontinuesto

increase.Thus,standardmanagementforpatientswith

unresectablemetastaticcolorectalcancerissystemic

chemotherapy.

SurgicalManagementofthePrimary

Cancer—Resection对转移灶无法切除的患者行肠切除的作用仍存争议没有数据表明手术对IV期患者的生存率有更多益处然而，切除原发肿瘤对局部控制的益处确实惠及很多IV期患者。有数据支持系统化疗可以延长生存期提高生活质量，而且现代药物的进步以及多药物联合化疗确实使疗效得到了提高。所以对于转移灶不可切除的结直肠癌标准的治疗方案应该选择系统化疗。原发肿瘤的外科治疗-切除术Theproperuseofelectivecolon/rectalresectioninnonobstructedpatientsisasourceofcontinuing

debate.Oncologistsproperlycitelossofperformancestatus,

riskofsurgicalcomplications,anddelayinchemotherapyas

majordownsidestopalliativeresection.Surgeons,however,

understandthatelectiveoperationshaveafarlowermorbidity

thanemergencysurgeryandfearhavingtooperateonpatients

whoobstructwhilereceivingchemotherapyorwhopresent

withmoreadvanceddiseaseaftermultiplecyclesofineffectivechemotherapy.对未梗阻的患者选择性的行结、直肠切除术是否恰当仍是争论的源泉。内科医生担心患者一般情况变糟、术后并发症的风险、以及因为手术所耽误的化疗时间。外科医生的理由是择期手术比急症手术解决梗阻的并发症发病率更低，尤其是经过数个周期化疗之后，以及肿瘤恶化使手术难度加大。Studiesdocumentthatsurgicalresectioncanachieveexcellent

palliationoflocalsymptoms.Forpatientswithnonobstructingprimarytumors,

upfronttreatmentwithchemotherapyisfavoredbecause,in

thiseraofincreasinglyeffectivechemotherapyItshouldberememberedthatthe

goaloftherapyiseffectivepalliation,andsurgicalresection

remainsthemosteffectiveanddurablelocaltreatment

option.

一些研究得出的结论手术干预可以很好的缓解局部症状。对于尚无梗阻迹象的原发肿瘤，化疗更受青睐，这也得益于化疗药物的发展和效果的提高。需要记得的是，对于晚期肿瘤患者的治疗目的是有效的缓解症状，所以手术切除仍是对局部症状最有效持久控制的选择。Ofthe150,000newcasesofprimarycolorectalcancerdiagnosedintheUnitedStateseachyear,approximately60%of

thesepatientswilldeveloplivermetastasesandaboutone-thirdwillhavediseaselimitedtotheliver.Ofthoseabletoundergocompletehepaticresection,25%–35%achievelong-termsurvival.

Therefore,only

asmallpercentageoftheoverallnumberofpatientswith

metastaticcolorectalcancerarecuredbyliversurgeryItshouldbenoted,however,thatwith

improvementsinchemotherapy,surgicaltechnique,andablativetechniques,thenumberofpatientseligibleforhepatic

surgeryisontherise.

LiverMetastasis美国每年新增原发结直肠癌约15万，将近60%的患者会发生肿瘤转移，其中大约1/3为肝转移。对于能够接受肝切除的患者，25-35%能延长生命。所以只有很少一部分人能够被肝手术治愈。值得注意的是，随着化疗药物、外科技术和消融技术的进步，越来越多的患者可以接受肝切除。肝转移Beforethe1980s,mosthepaticmetastaseswereleft

untreated.Severalinvestigatorshaveretrospectivelystudied

untreatedpatients,documentingmediansurvivalsof5–10

months;long-termsurvivalwasrarelyseen.Nonetheless,someinvestigatorsretrospectivelyidentifiedpatientswithisolated,potentially

resectablehepaticmetastaseswhowereleftuntreated.In

thesepatientswithlimitedmetastasesisolatedtotheliver,

whowouldotherwisebepotentialcandidatesforsurgery,

3-yearsurvivalwas14%–23%and5-yearsurvivalwas

2%–8%.eveninthebestofcircumstances,5-yearsurvivalofpatientswithuntreatedliver

metastasesisdistinctlyuncommon.NaturalHistoryofUntreatedLiverMetastases在19世纪80年代之前，大部分肝转移是不治疗的。回顾性研究指出如果肝转移癌不予治疗，中位生存时间是5-10个月，长生存期极为罕见。一些研究回顾了转移灶孤立有切除可能却没有切除的患者，3年生存率14-23%，5年生存率2-8%即便在最佳的条件下，不治疗肝转移的话，患者活过5年的极为罕见。未治疗的肝转移癌的自然病程Acarefulextentofdiseaseworkupshouldbe

initiated.First,acompleteevaluationofthecolonvia

colonoscopyshouldbeperformedwithinayearofpresentation;thisaddressestheissueofsynchronousandmetachronouscolonicneoplasms,aswellastheissueoflocal

recurrence(especiallyinrectalcancers).Completecrosssectionalimagingoftheabdomenandpelviswithhigh-quality

CTisalsoessential,toruleoutextrahepaticdisease.PETscanningis

routinelyperformedbecauseofearlyprospectivedatadocumentingitsutility.TheinformationobtainedfromPETscanningchangesmanagementdecisionsinpatientswithrecurrent

colorectalcarcinoma20%–50%ofthetime.Themajor

strengthofPETscanningseemstobethedetectionofoccult

extrahepaticdisease.

DiagnosisandPatientEvaluation1.

1年内结肠镜检查，判断是否有同时或异时原发癌，以及是否有局部复发，尤其是直肠癌患者。2.腹+盆高分辨CT平扫，判断是否有肝外转移。3.PET应该作为常规。因为能发现20-50%的复发，从而影响治疗策略。PET的优势就在于能够发现隐匿的肝外病变。诊断及患者的评估CEAlevelshouldalsobedrawn,andservesasabaselineto

followaftertheconclusionoftherapeuticinterventions.

High-qualityimagingoftheliverisessentialindetermining

bulkofdiseaseandresectability.CTscan.RoutineCTscanscannowevaluate

theliverincombinationwithCTangiographyortriphasic

imagingoftheparenchymathroughvariousphasesofintravenouscontrastcirculation.ThemostsensitiveCTtechnique

isCTportography,whichisaCTscanperformedafterinjectionofcontrastintothesuperiormesentericartery.Wheninjectedcontrastenterstheportalcirculation,

metastasesappearlikefillingdefects.evaluatingthe

numberofhepatictumors,itoftenfailstodefinetheanatomic

relationshipsoftumortohepaticvasculature,itrequiresan

invasiveprocedure,anditiscostly.

4.检测CEA水平的变化。5.肝脏的高清影像，如CT。现在对肝脏的评估常采用常规CT联合CT血管造影以及注射对比剂之后的三相摄片。敏感度最高的是CT门静脉造影，向肠系膜上动脉内注射对比剂，当对比剂经过门脉循环时转移灶会呈现充盈缺损。缺点是难以分辨肿瘤与肝脏血管的解剖关系、有创、价格高昂。UltrasoundandMRIareadditionalimagingtechniquesthat

canbeusefulinspecificcircumstances.Ultrasoundisnotan

accuratemethodforaddressingextrahepaticdisease,oftencannotvisualizetheentireliver.Distinguishing

neoplastictumorsfrombenignlesionssuchascysts,focal

nodularhyperplasia,orhemangiomata.Additionally,ultrasoundcanspecificallyevaluatetherelationshipofspecific

lesionstomajorvascularstructuresandthebiliarytree.MRI

isanexcellentmethodforcharacterizingliverlesions.

Particularlyiftherearemultiplehepaticlesions.MRIisalsoanexcellentmodalityfor

evaluatingrelationshipsoftumortothebiliarytree(viamagneticresonancecholangiopancreatography—MRCP)andto

hepaticvasculature.High-qualityMRIandCTareprobably

equivalent.6.超声和MRI腹部超声对肝外病变的确定稍差，而且常常不能检查到整个肝脏。但是能用于鉴别肿瘤与良性疾病，如囊肿、局部增生结节、肝血管瘤等。另外还有助于确定肿瘤与肝血管及胆管结构的关系。MRI可以很好的明确肝转移。尤其是肝内多处转移灶，以及转移灶与血管、胆管的关系。Inanypatientbeingconsideredfor

hepaticresection,acompletemedicalworkupshouldbeperformedtoassessthepatient’sfitnessforundergoingamajor

abdominaloperation.Anypotentialforliverdysfunction;Pulmonaryfunction;Cardiacdisease.所有需要行开腹肝切除的患者都应完善上述检查，并评估是否适合手术。除此之外，还应考虑患者的全身情况，是否存在肝功能不全，肺功能障碍及心脏疾患。Untilrecently,chemotherapywasconsideredlargelyineffectiveastreatmentofunresectablemetastaticcolorectalcancer.

However,withthedevelopmentofirinotecan,oxaliplatin,

hepaticarterialinfusionalchemotherapywithfluorodeoxyuridine(FUDR),andnewermolecular-basedtherapies,thereare

nowmoreeffectivechemotherapeuticoptionsforthese

patients.Irinotecan(CPT-11)inconjunctionwith5-FU/LVhasbeen

recentlyshowntobemoreeffectivethan5-FU/LValonefor

treatmentofmetastaticcolorectalcancer.The

additionofoxaliplatinhasbeenparticularlyexcitingbecause

oftheinvitrosensitivityseenincisplatin-resistantcelllines,

aswellasitssynergywith5-FU.

TreatmentOptions

Chemotherapy

截至近期，对于不可切除的转移性结直肠癌，化疗是无效的。但是随着伊立替康、奥沙利铂、肝血管灌注脱氧氟脲苷化疗以及靶向治疗的发展，提供了更有效的化疗方案。伊立替康联合5-FU/LV比单纯5-FU/LV有更好的疗效。奥沙利铂对顺铂耐药的细胞有效，而且与5-FU有协同作用。治疗选择

化疗Asthesetrialsmature,andmodernsystemicchemotherapyregimensarerefined,wearenowseeing

mediansurvivalsinexcessof20months.随着现代化疗方案的改善，结直肠癌肝转移患者的中位生存时间已经超过20个月。Regionalhepatictherapyviahepaticarteryinfusional

(HAI)chemotherapyhasbeenstudiedsincethe1970s.This

treatmenttakesadvantageofthefactthathepaticmetastases

derivetheirbloodsupplyfromhepaticarterialbranches.

Additionally,onlyasmallproportionofsystemicallyadministeredchemotherapyreachestheliver.Themostfrequently

usedagentforHAIisFUDR,whichhasa90%hepaticextractionratio.Thispermitsmaximaltreatmentoflivermetastases

andminimizationofsystemicsideeffects.However,HAI

withFUDRlimitstreatmentofoccultextrahepaticdisease.

Thiscanbeaddressedbygivingadditionalsystemicagents,

orbyusing5-FUviathehepaticarterywithahigher”spillover”effectintothesystemiccirculation.

对于肝脏血管内灌注化疗的研究始于19世纪70年代。肝脏转移灶的血供来源于肝脏血管是该治疗手段的依据。另外，全身性化疗中只有一小部分化疗药物能够到达肝脏。HAI最常用的药物是FUDR脱氧氟脲苷，在肝脏中吸收率达90%，使对转移灶的治疗最大化，全身的副反应最小化。然而HAI对肝脏外病变作用有限，这可以通过额外的全身性化疗解决，或使用5-FU灌注，通过肝动脉与更多的“外溢”到全身血液循环的效果。Thedevelopmentoftargeted

molecular-basedtherapyprovidesevengreaterhopeformore

effectivesystemictreatments.Anti-angiogenictherapywith

anti-vascularendothelialgrowthfactorantibodies(bevacizumab)arealsocurrentlybeingevaluated.Inhibitorsofthe

receptorforepidermalgrowthfactor,atyrosinekinasereceptor,hasalsoshownpromisingresults,anddrugssuchas

cetuximab(C225),ZD1839(Iressa),andOSI774(Tarceva)

areactivelybeingstudied.Resultsofcurrentclinicaltrialsare

anxiouslyawaitedtoseewherethesemolecular-basedtargetedtherapieswillultimatelyfitinamongthearmamentariumofsystemictherapyforcolorectalcancer.

分子靶向治疗的发展提供了更有效的治疗手段，前景被业界看好。抗血管内皮生长因子抗体（贝伐单抗），酪氨酸激酶受体，表皮生长因子受体抑制剂，也有着可喜的进展，以及药物，如西妥昔单抗（C225），ZD1839（易瑞沙），OSI774（特罗凯）正在积极研究。大家都在焦急的等待这些临床研究的结果，期待最终能有效治疗大肠癌。Although

responseratestochemotherapeuticregimensareimproving,

theonlytherapyevershowntobepotentiallycurativefor

hepaticcolorectalmetastasesiscompleteresection.Liverresectionperformedinthe1970sand

1980swasassociatedwithhighmorbidityandmortality,makingitsroleinthetreatmentofadvancedcancersuspectatthat

time.

Overthelast20years,largeserieshave

demonstratedthatliversurgerycannowbepracticedwith

acceptablesafety,andthatpatientswithisolatedandresectable

hepaticmetastaseshavethepotentialforlong-termsurvival.

Inmodernseries,mortalityratesforhepatectomyfor

metastaticcolorectalcancerareuniformly5%orless.Resection虽然化疗的反应率在提高，但是对于结直肠癌肝转移的患者唯一可能达到治愈目的的手段就是手术切除。在19世纪70-80年代，肝切除有着高并发症率及死亡率，使其治疗作用遭到质疑。在过去的20年中，大宗的研究表明随着手术技术的进步肝脏手术已经安全许多，并使孤立的（转移灶）和可切除肝转移患者有了长期生存的可能性。研究显示肝转移癌肝叶切除术的死亡率为5%或更低。切除Morbidityfortheseoperationsremains

substantial,andisusuallyreportedbetween20%and50%.Themostominouscomplications,

suchasliverfailureandsignificanthemorrhage,arenowdistinctlyuncommon,thankstobettersurgicaltechniqueand

postoperativecare.inthe1970s,thefirsttime,

documented5-yearsurvivalratesof25%.Majorinstitutional

andmulti-institutionalreviewsofpatientsundergoinghepatectomyformetastaticcolorectalcancerhavenowclearlydocumentedthat,inwell-selectedpatients,5-yearsurvivalranges

from25%to40%,10-yearsurvivalrangesfrom20%to26%,

andmediansurvivalsrangefrom24to46months肝切除的并发症发病率在20-50%最恶性的并发症如肝衰竭及严重出血现在已非常罕见，这也得益于手术技术的进步和术后护理的发展。19世纪70年代研究中首次发表的5年生存率为25%。现如今，大量单中心及多中心研究，病例选择恰当的条件下，5年生存率在25-40%，10年生存率在20-26%，中位生存时间在24-46个月。Despite

recentimprovementsinchemotherapyresultinginmediansurvivalsashighas20months,completeresection

stillprovidesthebestoutcomes.Truelong-termcurefrom

chemotherapyisextraordinarilyrare,whereasatleasthalfof

thelong-termsurvivorsafterliverresectionaredisease-free

andpresumablycured.

Forthesereasons,notrialhasever

comparedhepatectomytonotreatmentorchemotherapy

alone.Liverresectionforresectablehepaticcolorectal

metastasesisthetreatmentofchoice.

Thetwomostconsistentnegativeprognosticfactorsarethe

presenceofextrahepaticdiseaseandtheinabilitytoresectall

tumor;thesetwofactorsremaincontraindicationstohepatectomy.虽然接受化疗中位生存时间达到20个月，但是要想达到最佳的预后还是需要完整的切除。经过化疗治愈的患者极为罕见，而接受肝切除术的患者中至少有一半能长期生存，并且无瘤生存。所以没有研究去对比肝切除和不治疗以及仅化疗的疗效。两个预后不良的因素：肝外病变和不能切除全部转移灶。这两点也是肝切除的禁忌症。

Althoughtherearemanyinconsistenciesinthemajor

reportedseries,alistofotherpoorprognosticfactorsexist;

theseincludelymphnodesinvolvedbytheprimarycolorectal

tumor,synchronouspresentation[orshorterdisease-free

interval(DFI)],largernumberoftumors,bilobarinvolvement,CEAelevationgreaterthan200ng/mL,andinvolvedhistologicmargins.

none

ofthesefindingsinandofthemselvesprecludethepotential

forlong-termsurvival.研究发现影响预后不良的因素还有：原发灶的淋巴结转移，同时性或异时性的多个肿瘤，肝脏多叶累犯，CEA高于200ng/mL。但这些研究结果本身并没有排除长期生存的可能性。Recurrenceafterhepatectomyforcolorectalmetastasesis

common,occurringinmorethantwo-thirdsofpatients.In

fact,long-termsurvivaldoesnotnecessarilyimplythatthere

hasbeennorecurrence.Inpatientswhodorecur,the

liveristhemostcommonsiteofrecurrenceandisinvolved

approximately45%ofthetime.Mostoftheserecurrencesare

isolatedtotheliver.Othercommonsitesarelung,bone,and

variousintra-abdominalsites.Repeathepatectomyfor

metastaticcolorectalcancerissafeandeffectiveinwell-selectedpatients.Mortalityislessthan5%,mediansurvival

fromthetimeofthesecondliverresectionrangesfrom23to

46months,and5-yearsurvivalrangesfrom30%to41%.

肝切除后的复发也很普遍，大约2/3.对于复发的患者，肝脏还是最常见的部位，45%。另外就是肺部、骨及腹腔内。再次肝切除是安全有效的，但是对适应症的选择是严格的。死亡率不足5%，二次手术后的中位生存时间在23-46个月，5年生存率在30-41%。Thefactorsmostoftenassociatedwithapooroutcomeafter

repeathepatectomyaresizeandnumberoftumors,aswellas

shortDFI.影响二次手术预后的因素有复发病灶的大小、数量、间隔时间。Withthe

adventofmoreeffectivesystemicchemotherapy,suchas

irinotecanandoxaliplatin,aswellasmoleculartargetedagents,

newtrialsareneededtoassessoptimaladjuvanttherapy.

Becausethemajorityofpatientswithhepaticcolorectal

metastasesaretechnicallyunresectable,thedevelopmentof

moreeffectivechemotherapyhasinspiredmanyoncologiststo

usea“neoadjuvant”chemotherapystrategyinanattemptto

renderpatientsresectable.Theseearlystudiessuggestthat

patientswithunresectablelivermetastasesshouldbetreated

aggressivelywithchemotherapyandreevaluatedatintervals

forthepossibilityofresection.大多数结直肠癌肝转移患者的肝转移灶都是不可切除的，这也促使肿瘤学家研究更为有效的新辅助化疗方法以期从不可切除转化为可切除。所以对于不能切除的肝转移癌应积极化疗并不断的评估是否存在切除的可能。Althoughresectionhasbecomethegoldstandardfortreatmentoflivermetastases,othermethodsoftumordestruction

usingthermalablationtechniqueshavealsobeendeveloped.Cryotherapyhasbeenusedfordecades,andutilizesprobesto

freezetumorsandsurroundingnormalhepaticparenchyma.complicationssuchasbleeding,livercracking,andacryoshockphenomenacharacterizedbythrombocytopeniaandDICcanoccur.Morerecently,radiofrequencyablation(RFA)probeshavebeendevelopedthatcan

heatlivertumorsandasurroundingmarginoftissuetocreate

coagulationnecrosis.RFAcanbeusedpercutaneously,laparoscopically,andatlaparotomyunderultrasound,CT,orMRI

guidance.尽管手术切除是治疗肝转移的金标准，但还有一些其他方法可以破坏肿瘤细胞，比如热烧蚀、冷冻疗法等。最近的，射频消融技术得到了发展，他可以烧灼肿瘤组织，使组织凝固性坏死。RFA技术可以在超声、CT、MRI指引下，经皮、经腹腔镜、经开腹施术。Furthermore,RFAhaslowmorbiditythatgenerally

rangesaround10%andisrarelyserious.AlthoughRFAcanbe

usednearbloodvessels,becausetheheat-sinkeffectofblood

flowprotectstheendothelium,majorbileductscanbeseriouslyinjured,limitingtheuseofRFAincentraltumorssituatednearmajorbileducts.LocalrecurrenceafterRFAisa

significantproblem,andseemstobestronglycorrelatedwith

tumorsize.recurrenceismorecommonintumors

greaterthan4or5cmindiameterandintumorsabutting

majorbloodvessels.而且RFA有着较低的并发症发病率，10%，而且通常不是很严重。尽管RFA可以在血管周边使用，热量经血液循环散去不至损伤血管，但是如果作用于胆管将会造成严重损伤。局部复发也是RFA术后比较棘手的问题，与肿瘤的大小相关。复发常见于肿瘤直径大于4或5cm，位置邻近大血管的患者。Ithasbeenestimatedthatapproximately10%ofpatientswith

colorectalcancerwilldeveloplungmetastasis.Ofthese,only

10%willhavemetastasesisolatedtothelung;andofthose

patientswithisolatedlungmetastases,onlyasmallproportion(probablyanother10%)willbeconsideredcandidatesfor

pulmonarymetastasectomy.themajorityofpatientswithmetastaticcolorectalcancer

tothelunghaveadvanceddisease,andarethustreatedwith

systemicchemotherapyorbestsupportivecare.LungMetastasis大约10%的大肠癌患者会发展为肺转移，这些患者中，又只有10%为单纯肺转移，这些人中又只有10%（大约）适合行肺转移灶切除。大部分发生肺转移的患者都是晚期，所以最佳的治疗方案是全身性化疗或良好的支持治疗。肺转移Modernseriesoflungresectionformetastaticcolorectal

canceruniformlyreportoperativemortalitiesoflessthan2%

.Five-yearsurvivalratesrangefrom16%to64%,

butgenerallyclusteraround30%to40%.现代的研究关于肺转移灶的切除显示，并发症发病率低于2%，5年生存率在16-64%，大部分集中在30-40%。Moststudiesevaluatefactorsassociatedwithoutcome;however,giventhelimitednumberofcases,thestatisticalpowerofthesestudiesto

detectsignificantfactorsislimited.Generally,thepathology

oftheprimarytumor(grade,location,stage)hasnotbeen

associatedwithoutcome.Themostfrequentlycitedsignificantfactorsassociatedwithadverseoutcomearenumberand

sizeoflungtumors,shortDFI,increasedCEA,andincompleteresection.

大部分研究都评估了影响预后的危险因素，但是受到临床样本少的限制，结果的统计学意义也有限。总的来说，原发肿瘤的病理分级、位置、分期与肺转移癌预后无关。肺部肿瘤的大小、数量、短的无瘤间隔、增高的CEA以及未完全切除等因素，提示预后不良。Withmodern-dayCT,themajorityofsurgeonsperformpulmonarymetastasectomythroughaunilateralstandardthoracotomy.Theuseofvideo-assistedthoracoscopicsurgery(VATS)

hasincreasedinrecentyears,andisoftenusedinmetastasectomywhenaminimalparenchymalresectionisnecessary.One

problemwithVATSisitsinabilitytopalpatethelung

parenchyma;aprospectivestudyevaluatingconfirmatorythoracotomyafterVATSshowedthat22%oflesionscanbe

missed.

手术方法多采用单侧开胸转移灶切除电子胸腔镜VATS在近年得到发展，常用于小块肺实质切除。缺点在于胸腔镜不能触诊，研究显示VATS漏诊率达到22%Theperitonealsurfaceisinvolvedinapproximately

10%–15%ofpatientswithcolorectalcancerattimeofinitial

presentation(synchronousmetastases)andin20%–50%of

patientswhodeveloprecurrence(metachronousmetastases).

Peritonealmetastasesareclinicallyimportantbecauseof

theirfrequentprogressiontomalignantascitesand/ormalignantbowelobstruction.Standardmanagementofpatientsknowntohaveperitoneal

metastasesatinitialpresentationissystemicchemotherapy.

AggressivesurgicalcytoreductionandIP

chemotherapywillbenefitpatientswithlimitedperitoneal

tumorburden.PeritonealMetastasis同时性腹膜转移发病率10-15%，异时性的为20-50%腹膜转移常发展为恶性腹水和（或）肠梗阻。标准的治疗手段是全身化疗。对于局限的腹膜肿瘤，手术减瘤及腹腔内化疗都能使患者受益。腹膜转移Approximately7%–30%ofovarianneoplasmsaremetastatic

cancers,themostcommonbeingcolorectalandbreastcancer.

Inapproximately1%–7%ofallwomenwithprimarycolorectalcancer,ovarianmetastasesarediscovered

eitheratthetimeofcolonsurgeryorduringfollow-up.

Inawomanwithrecentdiagnosisofadvanced

colorectalcancer,anyovarianmassshouldbeconsidereda

metastasisfromcolorectalcanceruntilprovenotherwise.

OvarianMetastasis卵巢恶性肿瘤中7-30%为转移癌，大部分来自结直肠和乳腺肿瘤。在女性大肠癌患者中发病率约1-7%对于近期被诊断为大肠癌的女性患者如果发现卵巢肿块都应考虑转移癌的可能，除非证明是其他疾病。卵巢转移Metastaticspreadoccursprimarilythroughtheperitoneum,butcanalsooccurviathebloodstream,throughlymphaticvessels,orbydirectextension.Carefulintraoperative

assessmentoftheovariesatthetimeofcoloncancersurgery

isessential.Synchronousmetastasesoccurin0%–8.