胃癌及其癌前变化的临床问题.docx
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胃癌及其癌前变化的临床问题
胃癌及其癌前变化的临床问题
目录CONTENTS
1.癌前病变的监测
2.随访和管理
3.胃癌的预防:
成熟和研究中的
1.癌前病变的监测
有关癌前病变的概念
●WHO胃癌的癌前变化分为癌前疾病(癌前状态)和癌前病变,前者是指与胃癌相关的胃良性疾病,有发生胃癌的危险性;后者是指较易转变为癌组织的病理学变化,主要系指异性增生。
●国外学者将上述的癌前疾病和癌前病变统归为广义的癌前病变(precancerouslesion,precursorlesion),萎缩,肠化和异型增生均属于此。
●国内消化病理学术界尚未应用此广义的癌前病变概念。
MaJL,etal.Fifteen-yeareffectsofHelicobacterpylori,garlic,andvitamintreatmentsongastriccancerincidenceandmortality.JNatlCancerInst.2012Mar21;104(6):
488-92.
WongBC,etal.EffectsofselectiveCOX-2inhibitorandHelicobacterpylorieradicationonprecancerousgastriclesions.Gut.2012Jun;61(6):
812-8.
Pimentel-NunesP,etal.Amulticentervalidationofanendoscopicclassificationwithnarrowbandimagingforgastricprecancerousandcancerouslesions.Endoscopy.2012Mar;44(3):
236-46.
Chronicatrophicgastritisisaprogressivedisease:
analysisofmedicalreportsfromShanghai(1985-2009)
ChooiEY,etal.Chronicatrophicgastritisisaprogressivedisease:
analysisofmedicalreportsfromShanghai(1985-2009).SingaporeMedJ.2012May;53(5):
318-24.
预测CAG数学模型及其多因素回归分析
Alltheparticipantsreceivedendoscopyandhistologicalexaminationaswellasastandardquestionnaire.MultivariateanalysiswasperformedbylogisticregressiontobuildtheCAG risk model. 63subjectsreceivedanotherendoscopyafter1-yearfollow-upanddividedintothreegroupsaccordingtothecomparisonofthehistologicalresults(improved,nochangeandworse).
The model showedrelativelygooddiscrimination,withanAUROCof0.888(95%CI0.852-0.925).Afinalprobabilitycut-offscoreof0.73wasusedto predict thepresence(>0.73)orabsenceofCAG(≤0.73).Sensitivity,specificity,PPVandNPVwere82.8%,74.7%,91.8%and56%,respectively.
扩大样本前瞻性研究
Thepredictedresultsof1418subjectscomparedwiththehistologicalresultswerequitesimilar.Therewasasignificantdifferenceofthescoresbetweenthreegroupswhowerefollowed-upfor1year(F=3.248,p=0.046).
模型:
CAG发生危险度=Y/(1+Y),其中
Y=exp(0.9829–0.7103*X1+0.8342*X2+1.3059*X3-1.1250*X4-1.1254*X5-1.4227*X6+1.7224*X7)
参数
X1性别(女1,男2)
X2一般健康情况(健康1,普通2,差3,很差4)
X3胃癌家族史(有1,无0)
X4除胃癌之外的其他肿瘤家族史(有1,无0)
X5进餐时饮用汤、水(是1,否0)
X6喜好口味比较清淡(是1,否0)
X7饮酒(是1,否0)
GaoQY,FangJY,etal.Anovelmodelmightpredicttheriskofchronicatrophicgastritis:
amulticenterprospectivestudyinChina.ScandJGastroenterol.2012May;47(5):
509-17.
胃龄StomachAge
●胃的生物学年龄
●真实反映胃衰老程度
●同一年龄者可有不同的胃龄
●胃龄的大小将依据端粒的长度进行测定,计算
精确胃龄数学模型
X(years)=(11.719-Y)/0.174
Y为FISH实验测定的荧光强度值
X则为精确胃龄
胃龄简易数字模型
胃龄(岁)=实际年龄+Δ年龄
StomachAge(years)=realage+Δage
Δage=1.87–0.45*X1–3.39*X2+1.72*X3+3.15*X4+13.99*X5+18.62*X6–16.96*X7+18.16*X8;
X1-X4均来自胃镜病理诊断(无0,轻度1,中度2,重度3)
X1炎症,X2活动性,X3萎缩,X4肠化
X5胃癌家族史(有1,无0)
X6有无合并心血管系统疾病(有1,无0)
X7有无合并胃食管反流性疾病(有1,无0)
X8每周进食垃圾食品/饮料的次数(有1,无0)
不同Δage值的推荐使用范围
胃癌高发地区患者:
Δage>0标准,随访人群范围扩大,减少漏诊率
胃癌一般发病率地区:
Δage>3.11标准,随访人群相对减少,节约医疗费用
GaoQY,FangJY,etal.Evaluationandclinicalsignificanceofthestomachagemodelforevaluatingagingofthestomach-amulticenterstudyinChina.BMCClinPathol,2014;28:
14-29.
关于萎缩----假性萎缩的情况
小凹上皮肠化
淋巴滤泡占位
溃疡/糜烂边缘粘膜不算萎缩性胃炎
萎缩是否可逆转的可能预测
可逆
难或不可逆
施尧.慢性胃炎的萎缩诊断标准和分期分级[J].胃肠病学,2006,11(4):
195-197.
AB-HID染色:
1、AB阳性为小肠型肠化
2、HID阳性为大肠型肠化
3、均阳性为混合型肠化
完全型肠化
HE染色
与小肠粘膜吸收细胞相似,有刷状缘,不分泌粘液,具有潘氏细胞、杯状细胞和吸收细胞
AB-PAS染色:
AB+PAS-
不完全型肠化
HE染色
无刷状缘,刷状缘不明显,微绒毛发育不全,胞浆内有粘液分泌颗粒
AB-PAS染色:
AB+PAS+
Fig.2.Morphologicchangesingastricmucosaduringgastriccarcinogenesis.c,dModerateatrophyofdeepantralglands(glandlossbetween30%and60%),withoutintestinalmetaplasia:
(c)H&Estaining,×40;(d)Periodicacid–Schiff(PAS)–alcianbluestaining,×40,highlightingglandlossandasinglefocusofintestinalmetaplasiainthesuperficialpartofthegastricmucosa.e,fSevereatrophyofantralmucosa,withlossofmorethan60%oforiginalmucous-secretingglands,replacedbyintestinalmetaplasia:
(e)H&E,×40;(f)PAS–alcianblue,×40.
Areviewoftheevidence
●对所有评估IM不同类型主体罹患胃癌的风险的横断面(n=14)研究和随访(n=10)研究进行了检索
●在14项横断面研究中,有13项研究表明:
相较于其他胃部病变,广泛的不完整型肠化生在胃癌中有统计意义的显著增高
●在10项随访研究中,6项研究发现不完全型肠化生与罹患胃癌的风险在统计学上有显著关联
●在报道风险高低的研究中,存在不完全型肠化生与完整型或不存在不完整型相比,罹患胃癌的风险升高4-11倍
●根据这一全面的综述,大部分科学证据支持IM分型对预测GC风险的价值
GonzalezCA,etal.Utilityofsubtypingintestinalmetaplasiaasmarkerofgastriccancerrisk.Areviewoftheevidence.IntJCancer,2013Sep1;133(5):
1023-32.
2.随访与管理
胃癌的早期筛查和检测:
常用标志物
标志物
灵敏度
临床应用
截断值
早期
进展期
筛查
进展判断
监测复发
肿瘤抗原
CEA
5.0ng/ml
<20%
40-50%
可以
可以
CA19-9
37.0U/ml
<20%
20-50%
可以
可以
CA72-4
6.0U/ml
<20%
30-50%
可以
可以
AFP
5.0ng/ml
可以
可以
激素
B-HCG
4pmol/l
20-53%
30-50%
可以
蛋白酶
PGI/II
PGI<70ng/ml
PGI/II<3.0
可以
CirculatingmiRNAsasdiagnosticbiomarkersinGC
Bodyfluid
microRNAs
Serum
miR-1,miR-20a,miR-27a,miR-34,miR-196a,miR-378,miR-221,miR-376c,miR-423-5p
Plasma
Let-7a,miR-17-5p,miR-21,miR-106a/b,miR-199a-3p,miR-218,miR-223,miR-370,miR-451,miR-486
Gastricjuice
miR-21,miR-106a,miR-129,miR-421
miRNAsasprognosticbiomarkersinGC
Clinicopathologicalcharacteristic
miRNAs
Overallsurvivalandrecurrence
OncomiRs:
miR-10b,miR-21,miR-214,miR-335,miR-375
Tumor-suppressor-miRs:
Let-7a,Let-7g,miR-125a,miR-126,miR-146a,miR-142-5p,miR-223,miR-338,miR-433
miRNAsarealsoreportedtobeaberrantlyexpressedinhumanovariancancer
WuHH,etal.Advancesinmolecularbiomarkersforgastriccancer:
miRNAsasemergingnovelcancermarkers.ExpertReviewinMolMed,2014;16:
e1.
癌前疾病的管理程序
GonzálezC,AgudoA.Carcinogenesis,preventionandearlydetectionofgastriccancer:
whereweareandwhereweshouldgo.IntJCancer.2012Feb15;130(4):
745-53.
欧洲胃肠内镜学会等胃癌癌前状态处理共识意见
Dinis-RibeiroM,etal.Managementofprecancerousconditionsandlesionsinthestomach(MAPS):
guidelinefromtheEuropeanSocietyofGastrointestinalEndoscopy(ESGE),EuropeanHelicobacterStudyGroup(EHSG),EuropeanSocietyofPathology(ESP),andtheSociedadePortuguesadeEndoscopiaDigestiva(SPED).Endoscopy2012;44:
74-94.
3.胃癌的预防:
成熟的和研究中的
Environmental,dietaryandlifestylefactorsassociatedwithgastriccancerrisk
GonzálezC,AgudoA.IntJCancer.2012Feb15;130(4):
745-53.
●在胃癌高发区的Hp根除治疗组(1130例)和安慰剂组(1128例)随访14.7年
●胃癌的发生率分别是3.0%和4.6%;根除Hp可降低胃癌发生率,但对胃癌的死亡率降低无统计学意义
●大蒜素(提取物或提取油)干预组与维生素干预组短期随访无降低胃癌作用,但长期随访则有降低胃癌发生倾向
不同组别和不同周期中胃癌的发生率
干预7.3年,停药后又随访7年余
Gastriccancerdeathsindifferentinterventions
Vitmintreatmentwasassociatedwithstatisticallysignificantlyfewerdeathsfromgastricoresophagealcancer,asecondaryendpoint
Abstract
IntheShandongInterventionTrial,2weeksofantibiotictreatmentforHelicobacterpylorireducedtheprevalenceofprecancerousgastriclesions,whereas7.3yearsoforalsupplementationwithgarlicextractandoil(garlictreatment)orvitaminC,vitaminE,andselenium(vitamintreatment)didnot.Herewereport14.7-yearfollow-upforgastriccancerincidenceandcause-specificmortalityamong3365randomlyassignedsubjectsinthismaskedfactorialplacebo-controlledtrial.Conditionallogisticregressionwasusedtoestimatetheoddsofgastriccancerincidence,andtheCoxproportionalhazardsmodelwasusedtoestimatetherelativehazardofcause-specificmortality.Allstatisticaltestsweretwo-sided.Gastriccancerwasdiagnosedin3.0%ofsubjectswhoreceivedHpyloritreatmentandin4.6%ofthosewhoreceivedplacebo(oddsratio=0.61,95%confidenceinterval=0.38to0.96,P=.032).Gastriccancerdeathsoccurredamong1.5%ofsubjectsassignedHpyloritreatmentandamong2.1%ofthoseassignedplacebo(hazardratio[HR]ofdeath=0.67,95%CI=0.36to1.28).Garlicandvitamintreatmentswereassociatedwithnon-statisticallysignificantreductionsingastriccancerincidenceandmortality.Vitamintreatmentwasassociatedwithstatisticallysignificantlyfewerdeathsfromgastricoresophagealcancer,asecondaryendpoint(HR=0.51,95%CI=0.30to0.87;P=.014).
MaJL,etal.Fifteen-yeareffectsofHelicobacterpylori,garlic,andvitamintreatmentsongastriccancerincidenceandmortality.JNatlCancerInst.2012Mar21;104(6):
488-92.
单一celecoxib干预(52.8%vs41.2%)或单独根除(59.3%vs41.2%)对于胃癌前疾病的好转有利
根除Hp后继之以celecoxib治疗,并无另外益处
WongBC,etal.Gut2012;61:
812-8.
根除与未根除组4年6个月随访后至少一次组织学积分:
萎缩和肠化的进展或逆转情况
伊朗德黑兰地区胃癌患者一级亲属人群根除Hp与胃粘膜组织学变化的临床试验
MassarratS,etal.PrecancerousconditionsafterH.pylorieradication:
arandomizeddoubleblindstudyinfirstdegreerelativesofgastriccancerpatients.ArchIranMed,2012;15:
664-69.
荟萃分析显示根除Hp可降低胃癌发生率
Fig2ForestplotofrandomisedcontrolledtrialsofHpylorieradicationtherapy:
effectonsubsequentoccurrenceofgastriccancer
由已发表论文资料分层分析,显示根除Hp时无论有无癌前病变,对于胃癌预防效果均无统计意义
Fig3ForestplotofrandomisedcontrolledtrialsofHpylorieradicationtherapy:
effectonsubsequentoccurrenceofgastriccanceraccordingtopresenceorabsenceofpre-neoplasticlesionsatbaseline.(You200632andMa201226studyhadmissingdataconcerningpresenceorabsenceofpre-neoplasticlesionsatbaselinefor16individuals,leadingtotheloss
ofonegastriccancerfromtheanalysis)
配合应用抗氧化剂或维生素可提高根除Hp预防胃癌的效果
Fig4ForestplotofrandomisedcontrolledtrialsofHpylorieradicationtherapy:
effectonsubsequentoccurrenceofgastriccanceraccordingtoanti-oxidantorvitaminuse
Fordac,etal.Helicobacterpylorieradicationtherapytopreventgastriccancerinhealthyasymptomaticinfectedindividuals:
systematicreviewandmeta-analysisofrandomised