12 Tumori

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TUMORI

DR. MARICA CONSTANTIN

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TUMORI CU MALIGNITATE

REDUSA

• EVOLUTIE LENTA

• RECIDIVE LOCALE

• FOARTE RAR METASTAZANTE

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• Carcinoidul bronsic (carcinoidele)

-1-2%din tumorile bronsice-sunt tumori secretoriiserotonina

Carcinoidul comun

-proximal:vizibil endoscopic

vegetant

-periferic:asimptomatic

radiologic=nodul izolat

Carcinoidul atipic – neuroendocrin diferentiat-metastaze osoase,hepatice

*Manifestari endocrine = metastaze

(tesutul pulmonar inactiveaza serotonina)

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-continuare-

Carcinoame ale glandelor bronsice

#carcinomul adenochistic (cilindrom)traheal

#carcinom mucoepidermoid

 bronhii mari

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TUMORI MALIGNE

BRONSICE PRIMITIVE

• Tumori bronhopulmonare care iau nastere

la nivelul mucoasei bronsice

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Cancer Clinical Trials

Staging of Lung Cancer

1993 World Health Statistics

33.04, 562651.190,130Female

72.09, 693783.7105,438MaleCanada

39.450, 194812.01,035,046Female

75.191, 091918.41,113,417MaleUnited States

Death

Incidence/10

0.000

Lung Cancer

Total Death

Incidence

Lung Cancer

Death

Incidence/10

0.000

All Causes

Total Death

Incidence

All Causes

SexCountry

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Frecventa cancerului br.pn.la barbat si

femeie

fata de alte localizari neoplazice

0

510

15

20

25

30

35

C.B.P. Barbat

C.B. Femeie

Alte cancere

22

11

33

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CANCER BRONSIC PRIMITIV

Epidemiologie –cel mai frecvent la om

(Franta)

La femei

200/000

La barbati

1982 – 710/000

80/000170/0001970 – 450/000

180/000210/0001950 – 180/000

300/000130/0001930 – 50/000

C.StomacC.ColonC.Bronsic

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Cancer Clinical Trials

Staging of Lung Cancer

Risk Factors• Smoking

• Secondary smoke exposure

• Asbestos

• Radon

• Bis(chloromethil) ether• Polycyclic aromatic hydrocarbons

• Chromium

• Nickel

• Inorganic arsenic compounds

• Genetic predisposition

Source:(Devita VT,Hellman S and Rosemberg SA. Cancer:

principles and practice of oncology ,4th edition Philadelphia;

J.B.Lippincott,1993

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CANCERUL PULMONAR 

• Din 10 bolnavi de cancer pulmonar 9 sunt

fumatori,iar dintre fumatori 11% fac cancer

pulmonar.

• O persoana care fumeaza 40 tigari/zi inhaleazape un an 140g de substante cancerigene.

• Marii fumatori au un risc de 15-25 ori mai

mare de a face cancer pulmonar decat

nefumatorii.

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• Fumul de tigarete ar actiona prin substantelecarcinogene pe care le contine , dar in acelasi timp siprin alterarea cleareanceului muco-ciliar.Secvential

s-ar produce o hiperplazie a celulelor bazale,o metaplaziemalpighiana,aparitia de atipii celulare si de carcinoame

in situ (fara invazia membranei bazale),urmate decarcinoame veritabile invazive.

• Aryl-hidrocarbon-hidroxilazei(AHH),se atribuie un rolprincipal in activarea hidrocarburilor policiclice,apte

de a induce transformari maligne.• AAH a fost gasita considerabil crescuta in macrofagele

alveolare si in limfocitele fumatorilor.

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• Fumatul si expunerea in mediul industrial poluantimpreuna multiplica riscul de a face cancerpulmonar.Fumatorul a 20 de tigarete/zi care nu esteexpus la poluarea industriala are un risc deaproximativ de 20 ori mai mare de a deceda prin

cancer pulmonar comparativ cu nefumatorul.Nefumatorul din mediul de azbest, neprotejat fata deaceasta noxa,are o probabilitate de 4 ori mai mare de amuri de azbestoza decat nefumatorul care isidesfasoara activitatea intr-un mediu inconjurator de

munca nepoluat.Daca muncitorul expus la azbest maifumeaza si 20 tigarete /zi , probabilitatea de a muri decancer pulmonar este de 80 de ori mai mare decat aaceluia care nu este expus la unul din cele doua riscuri.

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• A fost emisa si teoria patogenica in 2

trepte a cancerului fumatorilor (Two

Steps Process) dupa care, intr-o prima

etapa s-ar produce iritatia nespecifica a

epiteliului ciliat (datorita cianurei dehidrogen,acroleinei, formaldehidei,

acizilor de azot)

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CONSECINTELE FUMATULUI

ASUPRA PLAMANULUI • Inhibitia mobilitatii cililor bronsici si a

macrofagelor ,ceea ce provoaca staza secretiilor sisensibilitatea la infectii;

• Hiperplazia si hipertrofia glandelor mucoase cu

hipersecretie de mucus;• Stimularea receptorilor de iritatie vagala cu

 bronhospasm;

• Eliberarea enzimelor proteoliticede catre PMN;

• Alterarea calitatii surfactului.

La originea acestei patologii stau substantele iritantedin fumul de tigara ,gudronul si gazul

cianid,responsabile de dezvoltarea bronsitei siemfizemului.

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• Un studiu recent din Elvetia demonstreaza rata decrestere a incidentei adenocarcinoamelor la inceputulanilor `90 atat la barbati cat si la femeile tinere,valorilefiind de 3 ori mai mari decat pentru carcinoamelescuamoase din aceleasi grupuri.

• Carcinoamele scuamoase si cu celule mici care sedezvolta in bronsiile mari sunt traditional asociate cufumatul , dar cresterile relative si absolute in incidentaadenocarcinomului plamanului au fost recunoscute dince in ce mai mult.

• Partile periferice ale plamanului sunt in felul acestamai expuse la cantitati mai mari de substantecarcinogene asociate cu consumul tutunului,aici fiindsediul in care se dezvolta de electie adenocarcinomul.

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BIOLOGIA SI CRESTEREA TUMORALA

ONCOGENE SI FACTORI DE CRESTERE

TULORALA

• Deletia bratului scurt al cromozomului 3

• Amplificarea oncogenelor Cmyc si Nmyc

• Nr.insemnat de receptori pentru E.G.F.NSCLC

• Secretie si utilizarea hormonilor peptidiciSCLC

ca factori de crestere

(bombesina;calcitonina;ACTH;lipotrofina)

• Receptori pentru hormoni steroidieni

***Depistarea cancerului Br.Pn.se realizeaza dupa aproximativ 30

T.dublari

=1 cm(10 9 celule)

C.anaplazic

Cu celulemici

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30 timpi de dublare 10 timpi de dublare

Faza infraclinicaFaza clinica

1 cm

10 9 

celule

Debut

10 12 

celule

PERIOADA DE METASTAZARE

CRESTERE RAPIDA

TENDINTA MARE DE METASTAZARET.de dublare

-C.epidermoid 60 zile

ADENOCARCINOM 80 ZILE

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CARCINOMUL EPIDERMOID

FRECVENTA 40-45 %

SEDIU PROXIMAL• Microscopic +/- diferentiat (cheratinizare)

elemente epidermice

zone de necroza

stroma bogata

• Macroscopic: formatiuni burjorante endobronsic

Timp de dublare 60 zileEvolutie local + metastaze

CANCERUL CU CELULE MICI

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CANCERUL CU CELULE MICI

FRECVENTA 15-20%

SEDIU PROXIMAL

• Microscopic :celule mici 5% “bob de ovaz”(oat cell)

celule intermediare 15%

absenta arhitecturii

stroma discreta

necroza abundenta

Secretie argirofila(cel.KULTCHISCKY)neurosecretie

 Neurosecretie T.neuroendocrine (TNE)-C.cu celule mici

-Carcin.neuroendocrine (CNE) diferentiat (carcinoid)

CNE putin diferentiate (c.cu celule mici intermediare)

CANCERUL CU CELULE MARI

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CANCERUL CU CELULE MARI

FRECVENTA 15-20%

SEDIU PROXIMAL SI DISTAL

• Microscopic :celule mari nediferentiate

• Macroscopic:variabil

• Evolutie:local + metastaze

• Timp de dublare : scurt

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CLASIFICARE ANATOMICA

Struct.

papilara

Pneumocite

II

Celule Clara

distal3%c.bronhiolo-

alveolar

Chimio-radio-

chirurgie

Local +

meta

VariabilCelule mariProximal

si distal

15-20%c.cu celule mari

Chirurgie+ra

dio-

chimioterapie

Variabil

asem

c.secundare

VariabilCel.struct.

Glandulare

Proximal

si distal

15-20%Adenocarcinomul

Chimio+radio

terapie

Extensiv

Meta

bilateral

Infiltratie

peribronsic

a

Celule “bob

de ovaz”

Intermediar

Proximal15-20%c.cu celule mici

Chirurgie

Radioterapie

Local+metaBurjon

endobronsic

Elem.tesut

epiteliat;Necroza

Proximal

sau distal

40-45%c.epidermoid

TratamentEvolutieMacroMicroSediuFrecventa

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ADENOCARCINOMUL

FRECVENTA 15-20%

SEDIU FRECVENT PERIFERIC DAR SI CENTRAL (C.SECUNDAR?)

• Microscopic:30% dezvoltat pe cicatrice

aspect glandular –tubular -acinos

-papilar 

• Macroscopic:cu sau fara manifestari endoscopice

• Evolutie :variabila

• Timp de dublare: 80 zile

CANCERUL BRONHIOLO ALVEOLAR

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CANCERUL BRONHIOLO-ALVEOLAR 

FRECVENTA 3%

SEDIU PERIFERIC

• Microscopic:celule din bronsiolele terminale(Clara)

si invelisul alveolar (Pneumocite tip II)

-unifocal - difuz• Macroscopic:endoscopie adesea normala

secretie abundenta

• Evolutie: variabila

• 1.etapa trenanta

• 2.etapa cu evolutie mai rapida

C Cli i l T i l

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Cancer Clinical Trials

Staging of Lung CancerFrequency of Lung Cancer Symptoms in a Group

of 69 Patients with Inoperable Non-small Cell

Lung Cancer

25hemoptysis

48Pain

54Weight loss

57Decreased appetite

59Dyspneea

71Cough

81Decreased activity84Fatigue

PercentageSymptom

MANIFESTARI CLINICE

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MANIFESTARI CLINICE

• Perioada asimptomatica lunga

Simptome de “imprumut”dominante-iritatie

-obstructie

-infectie

Simptome “proprii”sarace

-hemoptizie

-modificari radiologice

• Debut

1.lent 70% 2.Acut 20% 3.Atipic 10%

MANIFESTARI CLINICE

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• LENT –tuse iritativa rebela – hemoptizii(x)-durere toracica – sd.de

obstr.bronsica partiala (xx) –astenie.anorexie – rar febra –pierdere

ponderala

x-mici ,matinale,repetate,rar “jeleu de coacaze”

xx –caracteristic parasternal in expir si inspir

• ACUT –pneumopatie acuta(1)

- sindrom supurativ retrosternotic

- sindrom pleuretic :infectios metastatic

• ATIPIC –sd.embolic –sd.neurologic(2) –sd.de vena cava superioara

-disfonie(paralizie recurentiala) –disfagie(invazie esofag)

-dispnee acuta (3) –adenopatie supraclaviculara

-dureri toracice intense (invazie pleurala;sd.Pancoast- Tobias)-sd.algic osos –sindroame paraneoplazice

(13) –prelungita ,subacuta,recidivanta “in situ”

(2)-metastaza de la c.pn.latent

(3) –atelectazie brusca, invazie frenic , c.traheal

MANIFESTARI CLINICE

ASPECTE RADIOLOGICE

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ASPECTE RADIOLOGICE• Condensare parenchimatoasa

Pneumonie

Atelectazie

Localizate preferential in :

segm.ventral superior varf la lob inferior

Piramida bazala culmen

• Hil tumoral

-arborescent –umbra nucleara –contur policiclic(adenopatie)

• Nodul pulmonar solitar

Rotund –ombilicat –cu/fara prelungiri• Cavitati

Frecvent in c.epidermoide, c.cu cel.mici

Rar la adenocarcinom

Marginale –pereti grosi neregulati (“in rama”)

ASPECTE RADIOLOGICE

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• Aspecte particulare

Liza costala pleurezii de insotire/ metastatice

Noduli multiplii + condensari intinse uni/bilat

Localizari

Preferential plaman drept si lobii superiori

C.epidermoid si microcelular=central si periferic

Adenocarcinom=periferic

ASPECTE RADIOLOGICE

BRONHOLOGIC

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BRONHOLOGIC

• Muguri neoplazici

 Netezi neuniformi vegetanti

Hemoragici necrozanti

• Infiltratie

 Neregulata stenozanta

Disparitie cartilagii rigiditate bronsica

Bronhografic

Obstructie bronsica distala-amputare partiala/totala

-stenoza progresiva

-stenoza limitata cu bronsectazii in aval

ALTE EXAMENE

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ALTE EXAMENE

PARACLINICE• Angiopneumografia

Amputari compresii

Deplasari abolire de perfuzie

• Scintigrafia pulmonara I31 Tc99 Indiu 113

Amputari vasculare perfuzie in mozaic

Zone reci egale cu opacitatile (metastaze)

• Tomografia computerizata

Metoda neinvaziva de evaluare a extinderii tumorale

Asociere cu B.A.F.

• Esofagografia

Invazia mediastinala

EXAMEN HISTOLOGIC SI CITOLOGIC

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EXAMEN HISTOLOGIC SI CITOLOGIC

CONFIRMAREA DIAGNOSTICULUI• VSH

Crescut peste 50mm/ora80% din cazuri

nespecific

• Anemie normo sau hipocroma

• Markeri biologici

Antigen carcino-embrionar (ACE)

30% +

Enolaza neuronal specifica (NSE)80% + SCLC

30% + NSLC

• Anticorpi monoclonali

SINDROAME PARANEOPLAZICE

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SINDROAME PARANEOPLAZICE

FRECVENTA 2-20%

PRECED SAU INSOTESC C.B.P.DOMINA TABLOUL

CLINIC

MANIFESTARI FARA IDENTITATE NEOPLAZICA

TIPURI:

•  Neurologice: neuropatia Denny-Brown

polinevrite senzitive/motoriisindroame cerebeloase

encefalomielopatii

• Musculare si cutanate

dermato si polimiozite

sd.psudomiastenice

acanthosis nigricans

SINDROAME PARANEOPLAZICE

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• Osteoarticulare

sd.Pierre –Marie-Bamberger 

sd.reumatoidehipocratism digital

• Endocrine

sd.Cushing

hiper-tiroidism /paratiroidismsd.Schwartz-Bartter 

ginecomastie

SINDROAME PARANEOPLAZICE

FRECVENTA 2-20%

PRECED SAU INSOTESC C.B.P.DOMINA TABLOUL

CLINIC

MANIFESTARI FARA IDENTITATE NEOPLAZICA

SINDROAME PARANEOPLAZICE

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• Hematologice

anemii

 poliglobulii

 purpura

reactii leucemoide etc.

• Vasculare

flebite superficiale recidivante

SINDROAME PARANEOPLAZICE

FRECVENTA 2-20%

PRECED SAU INSOTESC C.B.P.DOMINA TABLOUL

CLINIC

MANIFESTARI FARA IDENTITATE NEOPLAZICA

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Clasificarea T N M UICC 1988

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N-N0 =fara invazie ganglionara

-N1 =invazie ggl.homolaterali (hilari,peribronsici)-N2 =invazia ggl.carinali (anter.poster.)

mediastinali homolateral (frecv.paratraheali)

-N3 =ggl.mediastinali sau/si hilari controlateralisau ggl.supraclaviculari

Clasificarea T.N.M. UICC 1988

-pentru cancerele non small cells ,deoarece pentru cele cu celule mici

evolutia foarte rapida nu lasa timp de clasificare;

-permite stadializarea si abordarea relativ omogena a neoplasmelor

pulmonare

Clasificarea T.N.M. UICC 1988

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M

-M0 =metastazare absenta

-M1 =metastazare la distanta

Stadializare

Std. 0 –T1sNoMo

Std. I –T1NoMo;T2NoMoStd. II –T1N1Mo;T2N2Mo;T3No,1,2Mo

Std. III –A-T1N2Mo;T2N2Mo;T3No,1,2Mo

Std. IV –toate T toate N M1

C N U CC

-pentru cancerele non small cells ,deoarece pentru cele cu celule mici

evolutia foarte rapida nu lasa timp de clasificare;

-permite stadializarea si abordarea relativ omogena a neoplasmelor

pulmonare

DIAGNOSTICUL DIFERENTIAL

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DIAGNOSTICUL DIFERENTIAL

AL NB

•Cancerul periferic rotund

-metastaza unica pulmonara

-tuberculom

-granuloame infectioase (histoplasmoza,coccidiodomicoza,aspergilom)

-granuloame neinfectioase

-hematom-leziuni diverse(chist hidatic,pneumonie lipoida,

chist bronhogenic,infarct pulmonar rotund etc.)

continuare

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-continuare-• Cancerul centrohilar 

-tuberculoza primara a adultului

-boala Hodgkin

-limfom non-Hodgkin

-tumori mediastinale

-sarcoidoza-adenopatii silicotice

• Cancer cu opacitate segmentara lobara

-pneumopatie acuta (diverse etiologii)

-tuberculoza

-pneumonii cronice

-infarct pulmonar 

-atelectazii de diverse cauze

-continuare-

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• Cancer cavitar -abces pulmonar 

-tuberculoza cavitara

-chist hidatic pulmonar 

• Cancer bronsic cu pleurezie importanta

-toate tipurile etiologice de pleurezii

serofibrinoase,hemoragice sau chiloase

-continuare-

CONTRAINDICATII CHIRURGICALE

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CONTRAINDICATII CHIRURGICALE

IN NB.

• Semne de cancer nerezecabil

-metastaze la distanta ,inclusiv in plamanul controlateral-revarsat pleural persistent cu celule maligne +(sau-)

-afectare mediastinala (extensie directa sau metastaza limfatica)

Obstructia unei cave

Paralizia corzilor vocale prin afectarea nervului recurentCompresie sau invazie esofagiana

Paralizia hemidiafragmului

Adenopatie mediastinala controlaterala(cu histologie +)sau

supraclaviculara –laterocervicalaInfiltrarea peretelui traheal sau prinderea unei bronsii principale la

<2cm de carina (dupa unii,lez.rezecabila)

-neoplasm cu celule mici (scc)cu exceptia bolnavilor cu T1NoMo(posibil leziune chirurgicala)

CONTRAINDICATII CHIRURGICALE

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• Stare cardiaca

-insuficienta cardiaca necontrolata

-aritmii necontrolate

-infarct miocardic recent (3-6 luni)• Rezerva pulmonara mica

-PaO2<50mmHg sau PaCO2>50mmHg

CV<40%din valoarea anticipata

FEV1< 1l

-Pap < 35mmHg in repaus

CONTRAINDICATII CHIRURGICALE

IN NB.

ETIOLOGIA NPS

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ETIOLOGIA NPS

•   Nodul malign aprox.40%

-carcinom bronsic-adenom bronsic

-leziune metastatica unica

•  Nodul benign aprox.60%

-granuloame infectioase (tuberculom histoplasmoza,

coccidiodomicoza etc)

-granuloame neinfectioase (granulom reumatoid,

granulomatoza ,Wegener etc.)

-tumori benigne (hamartom etc)

-diverse (infarct pulmonar,fistula arterio-venoasa , leziuni de

amiloid ,pneumonie lipida ,chist bronhogenic etc)

METASTAZE

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METASTAZE• Ganglioni mediastinali 30-90%

• Ficat 30-50%• Ganglioni supraclaviculari 30-60%

• Pleurezii 5-30%

•Pulmonare 10-30%

• Cardio-pericardice 5-20%

• Cerebrale 20-30%

• Osoase 25-30%

• Renale 15-20%

• Subcutanate 1-5%

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PROGNOSTIC

NETRATAT 80-90% DECES SUB 1 AN

• Factori determinanti:

-tip histologic

-timp de dublare

-stadiul TNM

-stare clinico-biologica

-varsta/sex

• Microcelular –supravietuire 1-6 luni

• Nemicrocelular –dependent de stadiul TNM

• Epidermoid S II- III 10 % la 5 ani

• Indicele KARNOFSKY (1948)-capacitatea de activitate

-simptome

-nevoia de asistenta