ONCOLOGY Epidemiology

ONCOLOGY
Epidemiology
Leading cancers worldwide Total New Cases

Rank
1 2 3 4 5 6 7 8 9 10

Males
Lung Stomach Colon/rectum Prostate Liver Mouth/pharynx Esophagus Bladder Leukemia NHL*

Females
Breast Colon/rectum Cervix uteri Stomach Lung Ovary Corpus uteri Liver Mouth/pharynx Esophagus

Both Sexes

Lung 1,037,000 Stomach 798,000 Breast 796,000 Colon/rectum 783,000 Liver 437,000 Prostate 396,000 Cervix uteri 371,000 Mouth/pharynx 363,000 Esophagus 316,000 Bladder 261,000

*Non-Hodgkins lymphoma.

Adapted from Parkin DM, et al. CA Cancer J Clin. 1999;49:39.

ONCOLOGY
Epidemiology
Cancer incidence by world region Males Rank 1 2 3 4 5 6 7 8 9 10 Region N. America Australia/N.Z. W. Europe Japan N. Europe E. Europe S. Europe S. America* Southern Africa Eastern Asia Incidence/ 100,000 369.9 312.7 294.8 270.9 270.0 269.4 256.0 255.1 247.4 235.7 Region Females Incidence/ 100,000 277.5 254.0 234.5 230.1 210.4 205.2 187.8 185.6 185.0 180.1

N. America Australia/N.Z. N. Europe S. America* W. Europe Micronesia/ Polynesia Southern Africa Melanesia S. America Central America

*Temperate South America. Tropical South America. Other than Japan or China.

Adapted from Parkin DM, et al. CA Cancer J Clin. 1999;49:43.

ONCOLOGY
Epidemiology
Leading causes of death
Percentage of Total Deaths, US
Heart Diseases Cancer Cerebrovascular Diseases Chronic Obstructive Lung Diseases Accidents Pneumonia & Influenza Diabetes Mellitus Suicide Homicide

31.4 23.3 6.9 4.7 4.1 3.7 2.7 1.3 0.9 0.7

HIV Infection

Adapted from Greenlee RT, et al. CA Cancer J Clin. 2000:50;22.

ONCOLOGY
Epidemiology
Evolution of cancer death rates, males
Rate per 100,000 Male Population
70
Pancreas Liver Prostate Stomach Lung & bronchus Colon & rectum Leukemia

60

50
40

30 20

10

1930

1940

1950

1960

1970

1980

1990

Year
Adapted from Greenlee RT, et al. CA Cancer J Clin. 2000;50:27.

ONCOLOGY
Epidemiology
Evolution of cancer death rates, females
40
Uterus Breast Pancreas Ovary Stomach Lung & bronchus Colon & rectum

Rate per 100,000 Female Population

30

20

10

0 1930 1940 1950 1960 1970 1980 1990

Year
Adapted from Greenlee RT, et al. CA Cancer J Clin. 2000;50:26.

ONCOLOGY
Epidemiology
Mortality for leading cancers Males by Age (years), US
All Ages
Lung & bronchus 91,278 Prostate 32,891 Colon & rectum 28,075 Pancreas 13,470 NHL 12,286
*Non-Hodgkins lymphoma. Other nervous system.

20-39
NHL* 723 Leukemia 662 Brain & ONS 625 Lung & bronchus 512 Colon & rectum 412

40-59
Lung & bronchus 15,379 Colon & rectum 4,347 NHL 2,552 Pancreas 2,584 Esophagus 2,069

60-79
Lung & bronchus 59,558 Prostate 16,277 Colon & rectum 15,842 Pancreas 7,898 NHL 6,383

> 80
Lung & bronchus 15,823 Prostate 15,511 Colon & rectum 7,459 Bladder 2,900 Pancreas 2,843

Adapted from Greenlee RT, et al. CA Cancer J Clin. 2000;50:23.

ONCOLOGY
Epidemiology
Mortality for leading cancers Females by Age (years), US
All Ages
Lung & bronchus 61,922 Breast 41,943 Colon & rectum 28,621 Pancreas 14,205

20-39
Breast 1,629 Uterine cervix 629 Leukemia 462 Lung & bronchus 462

40-59
Breast 12,093 Lung & bronchus 10,088 Colon & rectum 3,426 Ovary 2,801

60-79
Lung & bronchus 38,488 Breast 18,385 Colon & rectum 12,799 Pancreas 7,437

> 80
Lung & bronchus 12,879 Colon & rectum 12,046 Breast 9,835 Pancreas 5,045

Ovary 13,507
*Other nervous system. Non-Hodgkins lymphoma.

Brain & ONS* 385

Uterine cervix 1,803

Ovary 7,207

NHL 3,859

Adapted from Greenlee RT, et al. CA Cancer J Clin. 2000;50:23.

ONCOLOGY
Epidemiology
Male cancer statistics
Estimated incidence
Melanoma of skin Oral cavity & pharynx 4% 3%

Estimated deaths
3% Esophagus
31% Lung & bronchus 5% Pancreas 3% Liver & intrahepatic bile duct

Lung & bronchus 14% Pancreas Kidney & renal pelvis 2% 3%

3% Stomach
10% Colon & rectum 11% Prostate 3% Urinary bladder

Colon & rectum 10% Prostate 29%

Urinary bladder
Leukemia Non-Hodgkins lymphoma

6% 3% 5%

4% Leukemia
5% Non-Hodgkins lymphoma 22% All others
Adapted from Greenlee RT, et al. CA Cancer J Clin. 2000;50:16.

All others 19%

ONCOLOGY
Epidemiology
Female cancer statistics
Estimated incidence
Melanoma of skin Thyroid Breast Lung & bronchus 3% 2% 30% 12% 2% 11% 4% 6% 2% 4% 22%

Estimated deaths
2% 15% 25% 5% 2% 11% 5% 2% 5% 4% 2% 21% Brain & other nervous system Breast Lung & bronchus Pancreas Stomach Colon & rectum Ovary Uterine corpus Non-Hodgkins lymphoma Leukemia

Pancreas
Colon & rectum Ovary Uterine corpus Urinary bladder Non-Hodgkins lymphoma All others

Multiple myeloma
All others

Adapted from Greenlee RT, et al. CA Cancer J Clin. 2000;50:16.

ONCOLOGY
Epidemiology
Known cancer causes

Occupational exposure Lifestyle factors Biologic agents Iatrogenic factors

Trichopoulos D, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;231-257.

ONCOLOGY
Epidemiology
Alcool

Esofag Cap si git colon

ficat
Pancreas Sin

Trichopoulos D, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;231-257.

ONCOLOGY
Epidemiology
Fumat

Cauze majore plamin Laringe Cavitate bucala Esofag

Asociat Pancreas Vezica urinara renal Stomac Col uterin

Blum A, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;545-557.

ONCOLOGY
Epidemiology
Virus-related cancers

Agents

Site of Cancer
Liver Liver

Hepatitis B Hepatitis C

HTLV-1
HPV Epstein-Barr

Adult T-cell leukemia or lymphoma

Uterine cervix Burkitts lymphoma, nasopharynx, Hodgkins disease

Adapted from Trichopoulos D, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;249.

ONCOLOGY
Epidemiology
Bacterial-related cancers

Agents Helicobacter pylori Schistosoma haematobium Opisthorchis viverrini

Site of Cancer Stomach Urinary bladder Liver

Adapted from Trichopoulos D, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;249.

ONCOLOGY
Epidemiology
Iatrogenic contributors

Agent Ionizing radiation

Type of Cancer Breast cancer Leukemia

Trichopoulos D, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;231-257.

ONCOLOGY
Epidemiology
Iatrogenic contributors (contd)

Pharmaceuticals
Agents Cancer chemotherapeutic drugs Site of Cancer Bone marrow

Immunosuppressive drugs
Exogenous hormones Menopausal estrogens Diethylstilbestrol Anabolic steroids Oral contraceptives Tamoxifen Phenacetin analgesics

Reticuloendothelial system

Endometrium, breast Vagina, cervix uteri Liver Liver Endometrium Kidney, pelvis

Adapted from Trichopoulos D, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;249.

ONCOLOGY
Epidemiology
Occupational-related cancers
Industries Associated with Exposure to Carcinogens Industry
Shipbuilding, demolition, insulation Varnish, glue Pesticides, smelting Mineral refining and manufacturing Furniture manufacturing Petroleum products

Carcinogen
Asbestos Benzene Arsenic Nickel, chromium Wood dusts Polycyclic hydrocarbons

Cancer
Lung, pleura, peritoneum Leukemia Lung, skin, liver Lung Nasal passages Lung

Rubber manufacturing/dye workers

Vinyl chloride Radium

Aromatic amines
Vinyl chloride Radium

Bladder
Liver Bone Skin

Petroleum refining/coal hydrogenation Coal tar products, mineral oils

Bal DG, et al. American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995;48.

ONCOLOGY
Epidemiology
Genetic risk factors: mechanisms of cancer predisposition

Germline tumor suppressor gene inactivation

Germline oncogene activation

DNA repair defects

Ecogenetic traits

Bale AE, Li FP. Cancer: Principles & Practice of Oncology. 5th ed. 1997;285-293.

ONCOLOGY
Epidemiology
Genetic risk factors: characteristics of cancer families

Family history of cancer

Cancer appears earlier in life Multiple and bilateral tumors May include rare tumor types (eg, retinoblastoma) Multisystem involvement

Bale AE, Li FP. Cancer: Principles & Practice of Oncology. 5th ed. 1997;285-293.

ONCOLOGY
Epidemiology
Genetic risk factors: Familial cancer syndromes Familial Cancer Syndrome
Neurofibromatosis type 1

Site of Cancer
CNS, neurofibrosarcomas, pheochromocytomas, leukemia CNS, spine CNS, renal cell, spine, pancreas, adrenal glands CNS, breast, head and neck, soft tissue, osteosarcoma, adrenal cortical carcinomas, leukemia Wilms tumor Skin, CNS, ovary

Neurofibromatosis type 2 von Hippel-Lindau disease

Li-Fraumeni syndrome

Wilms tumor gene Basal cell carcinoma syndrome

Bale AE, Li FP. Cancer: Principles & Practice of Oncology. 5th ed. 1997;285-293. Linehan WM, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;1253-1271.

ONCOLOGY
Epidemiology
Genetic risk factors: Familial cancer syndromes (contd)

Familial Cancer Syndrome

Site of Cancer

Familial adenomatous polyposis coli Colorectal, jaw, skull, skin, stomach, CNS Hereditary nonpolyposis colorectal cancer Cowdens syndrome BRCA-1 Colorectal Thyroid, stomach, breast, ovary Breast, ovary

BRCA-2

Breast (female and male)

Bale AE, Li FP. Cancer: Principles & Practice of Oncology. 5th ed. 1997;285-293. Safai B. Cancer: Principles & Practice of Oncology. 5th ed. 1997;1883-1933. Cohen AM, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;1144-1197. Dickson RB, Lippman ME. Cancer: Principles & Practice of Oncology. 5th ed. 1997;1541-1557.

ONCOLOGY
Epidemiology
Reducing mortality

The National Cancer Institute estimates that cancer mortality rates could be significantly reduced, as follows:

8% to 16% by a 15% decrease in tobacco use among adults 8% by dietary measures (ie, reduction of dietary fat to <25% and double dietary fiber) 3% by early screening and early detection 10% to 26% by the wider application of state-ofthe art treatments

Bal DG, et al. American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995;40-63.

ONCOLOGY
Epidemiology
Risk reduction

Relative risk = risk of developing a disease in the population exposed to a risk factor, divided by the risk of developing that same disease among those not exposed to that same risk factor Population attributable risk = the percentage by which the disease could be eliminated if exposure to the risk factor was eliminated

Bal DG, et al. American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995;40-63.

ONCOLOGY
Epidemiology
Modifiable risk factors
Site of Cancer
Lung

Risk Factor
Cigarette smoking Occupation

Relative Risk
Strong Strong

Attributable Risk
87% 13%

Residential radon exposure

Second-hand smoke Diet low in beta carotene Dietary fat/low-vegetable diet Urban air pollution Colorectal High-fat/low-vegetable diet Physical inactivity Occupation Obesity

Moderate
Weak Weak Possible Possible Weak Weak Weak Weak

10%
2% 5% 50% 20% -

Adapted from Bal DG, et al. American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995;44.

ONCOLOGY
Epidemiology
Modifiable risk factors (contd)
Site of Cancer
Breast

Risk Factor
First full-term pregnancy after age 30 Large doses of chest radiation Never married Never having children Post-menopausal obesity Alcohol consumption

Relative Risk
Moderate Moderate Weak Weak Weak Weak

Attributable Risk
7% 2% 5% 12% -

High fat
Low physical activity Use of diethylstilbestrol Use of oral contraceptives or ERT

Possible
Possible Possible Possible

Adapted from Bal DG, et al. American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995;45.

ONCOLOGY
Epidemiology
Modifiable risk factors (contd)
Site of Cancer
Cervix

Risk Factor
Multiple sex partners Early age at first intercourse History of STD Cigarette smoking Use of barrier contraceptives Low dietary intake of vitamin A, beta-carotene, and folate

Relative Risk
Moderate Moderate Moderate Weak Weak Weak

Attributable Risk
38% 25% 5% 32% -

Adapted from Bal DG, et al. American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995;45.

ONCOLOGY
Epidemiology
Early detection guidelines
ACS Screening Recommendations for Asymptomatic People (Average Risk)
Test/Procedure Sex Age
>50 >50 >40 >50 >18* 18-40 >40

Frequency
Every 3-5 yrs, based on advice of physician Every year Every year Every year Every year, if normal >3 times, Pap test may be performed less frequently at discretion of physician Every 1-3 years, with Pap test Every year At menopause and thereafter at discretion of physician Every month Every 3 years Every year Every 1-2 years (1st by age 40) Every year Every 3 years Every year

Sigmoidoscopy, preferably flexible M&F Fecal occult blood test M&F Digital rectal exam M&F Prostate exam M Pap test F Pelvic exam Endometrial tissue sample Breast self-exam Breast clinical exam Mammography Health counseling and cancer checkups F F F F F M&F

>20 20-40 >40 40-49 >50 >20 >40

* Or before if sexually active. At menopause, for women at high risk for endometrial cancer due to history of infertility, obesity, failure to ovulate, abnormal uterine bleeding, unopposed ERT or tamoxifen use.

Adapted from Fink DJ, Mettlin CJ. American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995;181.

ONCOLOGY Cancer Biology

ONCOLOGY
Cancer biology
Tumorigenesis

Normal cell

Initial genetic change

(eg, loss of function of pRb or overexpression of c-myc)

Secondary genetic change

(eg, dysfunction of p53 or overexpression of bcl-2)

Subsequent genetic change

Increase in cell proliferation and apoptosic cell death

Decrease in apoptosic cell death

Further alterations in phenotype

(eg, invasiveness and metastasis)

Kastan MB. Cancer: Principles & Practice of Oncology. 5th ed. 1997;121-134.

ONCOLOGY
Cancer biology
Emergence of tumor cell heterogeneity

Primary Neoplasm

Metastases

TRANSFORMATION

TUMOR EVOLUTION AND PROGRESSION

METASTASIS

TUMOR EVOLUTION AND PROGRESSION

ONCOLOGY
Cancer biology
Host influences on metastatic disease

Anatomical factors Organ microenvironment Angiogenic factors Immune response

Fidler IJ. Cancer: Principles & Practice of Oncology. 5th ed. 1997;135-147.

ONCOLOGY
Cancer biology
Cancer cells vs normal cells

CANCER CELLS
Frequent mitoses

NORMAL CELLS
Normal cell Nucleus

Blood vessel

Few mitoses

Abnormal heterogeneous cells

Loss of contact inhibition Increase in growth factor secretion Increase in oncogene expression Loss of tumor suppressor genes Neovascularization

Oncogene expression is rare

Intermittent or coordinated growth factor secretion Presence of tumor suppressor genes

ONCOLOGY
Cancer biology
The role of oncogenes
Paracrine (adjacent cells) Growth factor Growth factor receptor

Growth factor and receptor synthesis

Post receptor signal transduction pathways

Gene activation Oncogenes

ONCOLOGY
Cancer biology
Pathogenesis
TRANSFORMATION ANGIOGENESIS MOTILITY & INVASION

Capillaries, Venules, Lymnphatics

ADHERENCE

ARREST IN CAPILLARY BEDS

TRANSPORT

EMBOLISM & CIRCULATION

Multicell aggregates (Lymphocyte, platelets)

EXTRAVASATION INTO ORGAN PARENCHYMA

METASTASES

RESPONSE TO MICROENVIRONMENT
METASTASIS OF METASTASES

TUMOR CELL PROLIFERATION & ANGIOGENESIS

ONCOLOGY Cancer biology

Angiogenesis

Establishment of a capillary network from the surrounding host tissue A series of processes originating from microvascular endothelial cells Mediated by multiple molecules released by both tumor and host cells [eg, fibroblastic growth factor (FGF), vascular endothelial growth factor (VEGF), vascular permeability factor (VPF), angiogenin, epidermal growth factor (EGF)]

Fidler IJ. Cancer: Principles & Practice of Oncology. 5th ed. 1997;135-147.

ONCOLOGY
Cancer biology
Cell cycle
CELL DIVISION G1 PERIOD CELL DIFFERENTIATION

G2 PERIOD

CELL LIFE CYCLE

TIME

(CHROMOSOME REPLICATION) S-PHASE

ONCOLOGY
Cancer biology
The doubling process
Malignant transformation Dividing 2 cancer cells 8 cells Doubling Doubling 4 cells Doubling

Normal cell
1 million cells (20 doublings) undetectable

16 cells

1 trillion cells (40 doublings 2 lb/1kg)

1 billion cells (30 doublings) lump appears 41 43 doublings Death

ONCOLOGY
Cancer biology
Tumor growth and detection

1012

Number of cancer cells

109

Diagnostic threshold (1cm)

time
Undetectable cancer Detectable cancer

Limit of clinical detection

Host death

Fenotipul malign: implicaii clinice

I. Proliferarea tumoral

1. Parametrii creterii tumorale

2. Perioada de evoluie ocult 3. Relaia diagnostic clinic metastaze II. Transformarea migratorie

1. Invazia local: boala subclinic

2. Metastazarea: invazia la distan]

Proliferarea tumoral
1. Parametrii creterii tumorale
creterea T: diviziune celular = numrul celulelor care prolif cu volumului T, durata ciclului celular scderea activitii prolif: reducere nutrieni timp de dublare - TD: nr. zile n care T i dubleaz volumul

variabilitate es. normale vs T, vs histologie vs individ

Proliferarea tumoral:
Curbe de cretere:
specificitate: caracteristic pentru dif. tipuri T
regularitate: ritm ordonat de cretere

exponenial: ritm de cretere constant, indiferent de numrul total de celule

gompertzian: dup o prim perioad exponenial, creterea diminu progresiv

Proliferarea tumoral:
esuturile tumorale = esuturi cu turnover rapid; organizare:
compartimentul de pierderi celulare: moarte, eliberare din T (exfoliere, diseminare) Creterea tumoral = proporia GF, durata ciclului celular - Tc (Time cycle), pierderea de celule - (Cell loss): TD = (GF.Tc) -

Proliferarea tumoral
esuturile tumorale = esuturi cu turnover rapid; organizare:
compartiment proliferativ = growth fraction - GF variabilitate: 43%: leucemia mieloid cr 8%: carcinoame spinocelulare

4%: sarcoame
2%: cancere mamare

Proliferarea tumoral:
Cretere exponenial: GF 50%, Tc 24 h de la 1 celul la 100 celule (102) = 23 zile 1 celul 1 cm3 (109) = 100 zile

1 celul 7 cm diametru = 4 luni

Cretere gompertzian:

1 celul 1 cm3 (109) = 49 zile

Proliferarea tumoral:
Tumora
Plaman AK CC pav San: TP M pulmonare Testicol Limfoame AK colorectal TP M pulmonara ORL TP recidiva

TD-sapt
21 12 14 11 4 4 90 14 14- 28 4 zile

Relaia diagnostic clinic - iniiere metastaze

Proliferare: 3. Dg clinic - metastaza

Cunoaterea iniierii M: interes practic diseminare tardiv: dg precoce benefic

diseminare precoce: tratament sistemic necesar!

Corelaii:

ritmul de cretere
mrimea TP gradul de malignitate numr gglioni regionali invadai

Cancer mamar: model exponenial: iniierea M la cca 3 ani nainte de

dg. clinic gompertzian: 30% M iniiate la 16 luni, 13% - 6 luni aplicaii clinice: planificarea aciunilor de screening: 2 ani

Dg. Clinic - M (3)

Prag metastazare:

3.5 cm TP

II. Transformarea migratorie: Metastazare (2)

Caracteristicile metastazrii pe cale limfatic:

cale predilect pentru tumorile epiteliale

interesarea ggl limfatici respect drenajul limfatic normal al organului tumoral interesarea ggl. este progresiv, n sensul circulaiei limfatice

skip metastases: probabilitate redus, < 2%

invazie retrograd: prognostic rezervat

II. Transformarea migratorie: Metastazare (2)

Caracteristicile metastazrii pe cale hematogen

cale predilect pentru tumorile mezenchimale diseminarea sanguin: proces rapid, eficient dar citemia tumoral nu este sinonim cu formarea M celulele T n circulaie supravieuiesc < 0.1%

ptrunderea celulelor tumorale n casele sanguine: invazie direct, anastomozele veno-limfatice

CLASIFICAREA STADIALA

cancer localizat
cancer avansat locoregional cancer metastatic
Necesitate impartire

CLASIFICAREA STADIALA

OBIECTIVE
indicatiei terapeutice indicatii asupra prognosticului aprecierea unitara a rezultatelor diferitelor metode de tratament schimbul de informatii : limbaj comun

Reguli generale de clasificare

1.
2. 3. 4.

Confirmare HP . Cazurile fara separat TNM - Examene minime necesare ; X se tine cont de indicatiile privind definirea teritoriilor limfatice T indici in dreptul simbolului
1. 2. Masurare in 2 diametre (cel mai mare si perpendicular pe primul) Tumora nemasurabila = se folosesc criterii clinice specifice localizarii respective (ex. Col extensie parametre , vagin)

Trepte de T

Tis T0 nu e decelabila clinic T1,2,3, 4 trepte progresive Tx

daca sunt mai multe tumori : (2)T1, (5)T2 subcategorii a,b,c,d.

Trepte de N

Date clinice (palpare) , paraclinice (limfografie, CT, Eco) N0 N1- regionala mobila; < 2 cm ; consistenta dura, N2 bloc adenopatic ; > 2 cm ; fixare supra ; subjacent N3 treapta de gravitate mai mare : ex. Sin, plamin .. Nx

Trepte de M

M0 M1 Mx M1a : col (hidronefroza, rect, vezica) M1b : meta la distanta

Gruparea pe stadii clinice

Combinarea diferitelor trepte T, N, M I IV I si II considerate curabile III greu curabil IV incurabil nu se schimba niciodata indiferent de constatarile facute in evolutia ulterioara a bolnavului 3 medici oscilare intre 2 stadii se alege cel mai putin avansat (pentru a nu falsifica rezultatele terapeutice) NU stadiu I/II sau III/IV ..

Clasificarea postoperatorie

completare cea clinica; chir curativa informatii intraoperator in general pT = cT daca este pT = se alege pT, pN ,pM numarul de ganglioni invadati indicatie terapeutica ulterioara capsula intacta / nu ; grupare pe stadii

Clasificarea postop (cont.)

DEFINIREA : - formei HP - mono / pluricentric - dimensiunea exacta a piesei - descriere macro - tesut peritumoral - elemente specifice pentru fiecare localizare : tegument, IHC..

Mastita carcinomatoasa

Meta hepatice

Meta osoase

Cancer bronhopulmonar
Bronhoscopie

Cancer bronhopulmonar
Radiografie

Cancer bronhopulmonar
Tomografie computerizata

Cancer bronhopulmonar
Scintigrafie osoasa

NSCLC
Anatomie patologica

Cancer de san
stadiu I
T1 N0 M0
T1a: T 0.5 cm
T1b: 0.5 cm < T 1 cm T1c: 1 cm < T 2 cm T1 T 2 cm

N0 = no regional lymph node metastasis M0 = no distant metastasis

Cancer de san . Stadiu IIA

T0 T1

N1 M0

T2 N0 M0

T0 Fara tumora

T2
2 cm < T < 5 cm

N1 = mobili M0 = fara metastaze

Cancer de san
Stadiu IIB
T2 N1 M0
T3 N0 M0

T3

T > 5 cm

Cancer de san
Stadiu IIIA
T3 N1 M0 T0 T1 T2 T3 N2 M0

N1 = mobili N2 = fixati intre ei sau la alte structuri M0 = fara meta la distanta

Cancer de san
Stadiu IIIB
T4 orice N M0
orice T N3 M0

T4

Cancer de san
Stadiu IV
orice T orice N M1

M1 = metastaze la distanta (fara supraclaviculari ipsilaterali)

Formulare diagnostic

se incepe cu forma HP (adenocc, cc, sarcom ) localizare elemente suplimentare despre tumora stadiul clinic + TNM

Adenocarcinom mamar drept, CSE , T2N1Mo (IIB) - daca evolueaza . . . Metastaze hep. - daca se prezinta cu stadiu IV- localizarea metastazei

Grad de diferentiere

G1 = grad crescut de diferentiere G2 = moderat G3 = scazut G4 = nediferentiat Gx

SBR (Scale Bloom Richardson), scor Gleason

Diagnosticul de malignitate

Conditii esentiale

precoce :
recunoastere primele semne/simptome necaracteristice !!!! Si aceata posibilitate

complet :
cunoastere a istoriei naturale investigare anumite zone susceptbile de a fi interesate

Semne de suspiciune

directe

indirecte

Semne directe

expresia unei cresteri anormale :

tumora primara metastaze

adenopatia : 60-70%: motiv principal ORL, sin tu palpabila :

stadii avansate () localizari superficiale : sin, parti moi, tegumente

semn - :LIPSA DE SENSIBILITATE NU DOARE

Semne indirecte

scurgeri anormale
hemoragic, seros mamelon, vagin, fosa nazala

semne de compresiune
mediastin (VCS), HTic (tumori intracraniene)

semne neurologice
nevralgii rebele, paralizii, tulburari sfincteriene,

sindroame paraneoplazice
degete hipocratice (pulm), hipercalcemia (sin)

semne generale nespecifice

febra , transpiratii, prurit, anorexie, slabire in G

Semne indirecte (cont.)

efuziuni :
pleurezie : meta , ovar ascita : carcinomatoza peritoneala (ovar, colon) impune diag.diferential

altele :
hemoptizie (!!! Semn de alarma) rectoragii etc .

Diagnostic de malignitate

ORICE SUSPICIUNE DE MALIGNITATE

ELUCIDARE

examen clinic examinari paraclinice

Examinare clinica

Macro :
leziune persistenta, infiltrativa, indurata , ulceratie care nu se vindeca inspectie , palpare : leziune superficiala, accesibila examinari endoscopice : tumori profunde (?) nodul mamar cu caractere de malignitate :
duritate contur neregulat modificari tegumentare (aderenta, piele in coaja de portocala) adenopatie axilara : caractere

Examinari paraclinice:

Examinari neinvazive
teste biologice uzuale : HLG, VSH probe specifice tumorii respective : b-HCG, AFP (tumori germinale) , PSA examinari radiologice de rutina , specifice endoscopie si izotopice

Examinari invazive
material pentru examen HP (citologie, biopsie) citologie nu certitudine (numai cele +, tip, particularitati)

Diagnosticul de MALIGNITATE trebuie fondat pe argumente inconstestabile si certitudinea este data numai de

EXAMENUL HISTOLOGIC

PRECURSORI TUMORALI .

GRUPE DE RISC

Precursori tumorali
stari precanceroase = dezordini tisulare predispun OMS :
Conditii precanceroase Leziuni precanceroase (precursorii tumorali)

Conditii precanceroase = stare biologica , histologica sau clinica care

prezinta o tendinta anormal de ridicata de a evolua spre cancer FARA sa existe o relatie cunoscuta cu factori cancerigeni specifici

anomalii cromosomiale sau genetice : xeroderma, plipoza colica familiana, von Recklinghausen disgenezii (criptorhidia) distrofii

Precursori tumorali

Leziuni precanceroase = rezultatul actiunii unor factori

cancerigeni externi sau endogeni bine cunoscuti ; definitie histologica hiperplazii atipic metaplazii displazii : leziuni avansate ; celule cu morfologie si fenotip anormal (neregularitati ale nucleului, ) ; 3 grade usoare
intermediare severe : include carcinomul in situ (CIS)

macro:

normal : evidentiate prin ex.micro (frotiu , biopsie) zone suspecte leucoplazie, hiperkeratoza, papilomatoza, eritroplazie

Pielea si organele genitale externe

Conditii precanceroase
xeroderma pigmentosum procese iritative (cicatrici actinice, ulcerul cronic al gambei, radiodermite, kraurozisul vulvar)

Leziuni precanceroase
keratoze actinice, eritroplazii vulvare, boala Bowen (carcinom epidermoid al pielii sau mucoaselor OGE) boala Paget nevul displazic congenital sau dobindit

Colul uterin

conditii precanceroase:
cicatricile cervicale, infectii virale

leziuni precanceroase :
displazia (<35 ani) si carcinomul in situ (35-45 ani) carcinomul invaziv : 45-49 ani

Proces ce dureaza 15-20 ani => tratarea si eradicare

leziunilor precanceoase cc.invazive - fara tratament : 2/3 din CIS devin invazive in 1-10 ani

Cai aerodigestive superioare

conditii precanceroase
fibrozele submucoase, corelate cu mestecarea de betel, carenta de fier , lichenul plan

leziuni precanceroase = corelate cu tabagismul

leucoplaziile = proliferari benigne (exceptie : localizarile pe
planseul bucal, fata ventrala a limbii, palat moale risc )

eritroplazia (Queyart) buze , limba , plaseu bucal metaplazii pavimentoase (intilnit in inflamatii cronice, tabagism)

Sinul

conditii precanceroase
predispozitia famliala (genetica)

leziuni precanceroase : mastopatii fibrochistice (!! Cele proliferative)

hiperplazii atipice ductale si lobulare DCIS si LCIS leziuni multifocale ()

Tub digestiv

esofag :
conditii : megaesofag, cicatrici postcaustice leziuni : esofagita cr atrofie displazie carcinom in situ cancer invaziv

stomac :
conditii : aclorhidria gastrica, atroafia gastrica leziuni : metaplazia intestinala (8-10% evolutie)

rectocolice:
conditii : polipoza rectocolica , colita ulceroasa, boala Crohn leziuni : polipul adematos izolat / polipozic

Conduita

depinde de :
virsta pacientei / pacientului expectanta de viata tipul leziunii precanceroase perioada de cind evolueaza riscul statistic de evolutie spre un cancer tratamentul necesar pentru eradicare (riscuri vitale, consecinte functionale) posibilitatea urmaririi acceptarea de pacient a unui risc evolutiv potential

Grupe de populatie cu risc crescut

= grup de indivizi care au in comun unul/mai multi factori de risc FR = prezenta lor crestere posibilitatea a a face un cancer
mod de viata alimentatie mediu inconjurator ocupatii profesionale conditii hormonale teren genetic agenti terapeutici

Grupe de populatie cu risc crescut

importanta :
urmarire persoane cu risc + sfat genetic

profilaxie eliminarea factorilor favorizanti

selectionarea poplatiei pt. examinari periodice de depistare

Cancer mamar

virsta : > 45 ani factori hormonali :

activitate ovariana prelungita nuliparitatea, S1 > 25 ani

predispozitie : grad I mod de viata : standard socioeconomic factori igienico-dietetici : supraalimentatia si obezitate antecedente patologice : cc.sin contralateral, mastoza
fibrochistica, DCIS, LCIS

Col uterin

Virsta > 45 ani predispozitie familiala : NU mod de viata :

debut precoce activitate sexuala parteneri multipli multiparitatea standard socioeconomic scazut

antecedente patologice
cervicite cronice infectii ginecologice, in special virale leziuni precanceroase (CIN)

Endometru

virsta : postmenopauza factori hormonali :

nuliparitatea cicluri anovulatorii tratamentul estrogenic prelungit dupa instalarea menopauzei , fara asocierea progestativelor hiperplazia adenomatoasa

antecedente patologice
diabet obezitate HTA

Cai aerodigestive superioare

virsta > 40 ani sex > B: 9% factori igienico-dietetici

alcoolismul tabagismul igiena buco-dentara deficitara

antecedente patologice
alta localizare CRS : risc 10-15% eritroplazii, displazii microtraumatisme (proteze dentare)

mod de viata mestecare foi de betel factori profesionali - industria prelucrarii lemnului

Bronhopulmonar

virsta > 40 ani sex : 90% B factori igienicodietetici === tabagismul :

risc la 100.000 de tigarete fumate = 15 pachet/an debut virsta tinara

factori profesionali : industrie azbest, nichel, crom , uraniu,

mineri

mod de viata poluare antecedente patologice bronsita cronica cu metaplazie

pavimentoasa

Colorectal

virsta > 45 ani sex : egal AHC :

cancer colorectal polipoza rectocolica familiala

APP :
rectocolita ulcerohemoragica boala Crohn polipoza

factori igienico-dietetici
alimentatia saraca in fibre bogata in grasimi animale

Gastric

Virsta > 45 ani sex : egal factori igienico-dietetici

fibre (legume, fructe) alim.sarate, conservate prin fum

APP
gastrita atrofica anemie Biermer metaplazia intestinala

Cutanat

virsta > 60 ani sex : egal mod de viata : expunere prelungita si intensa la ultraviolete factori ereditari : xeroderma pigmentosum (AD) antecedente patologice si terapeutice
arsuri supuratii cronice ulcer de gamba radiodermite cronice

factori profesionali : expunere la gudron, arsenic, derivati de

nitrat

Aprecierea raspunsului

RC raspuns complet RP raspuns partial

> 50% apreciere in 2 examinari la interval de 4 saptamini (pt.confirmare)

BS boala stationara
< 50% - < 25%

BE boala evolutiva
> 25%