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Volledige samenvatting Thema 3 Nieuwvormingen 1 GNK jaar 2

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Dit is een complete samenvatting van de leerstof voor Thema 3 Nieuwvormingen 1 voor geneeskunde jaar 2! Alles staat er uitgebreid maar wel beknopt in, in duidelijke taal, op een overzichtelijke manier.

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  • August 16, 2021
  • August 17, 2021
  • 80
  • 2020/2021
  • Summary

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By: izadewilde • 2 year ago

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Thema 3 – Nieuwvormingen I
Geneeskunde jaar 2 semester 2.1

Inhoudsopgave

Week 9 – Basisprincipes van de oncologie en mammacarcinoom.................................................................... 3
De celcyclus......................................................................................................................................................... 3
Pathogenese van kanker..................................................................................................................................... 4
Hallmarks of cancer................................................................................................................................... 4
Diagnostiek van kanker ...................................................................................................................................... 6
Anamnese en lichamelijk onderzoek ........................................................................................................ 6
Beeldvorming ............................................................................................................................................ 6
Laboratorumdiagnostiek ........................................................................................................................... 6
Celdiagnostiek ........................................................................................................................................... 6
Behandelprincipes .............................................................................................................................................. 7
Behandeldoelen ........................................................................................................................................ 7
Scoring de fysieke conditie van de kankerpatiënt .................................................................................... 7
Behandelvoordelen beoordelen ............................................................................................................... 8
Behandeltypen .......................................................................................................................................... 8
Mogelijke behandelingen.......................................................................................................................... 9
Acute oncologie ................................................................................................................................................ 12
Borstkanker ...................................................................................................................................................... 13
Risicofactoren ......................................................................................................................................... 13
Erfelijke borstkanker ............................................................................................................................... 13
Mammacarcinoom .................................................................................................................................. 14
TNM-classificatie van borstkanker (carcinomen) .................................................................................... 14
Diagnostiek van borstkanker................................................................................................................... 16
Behandeling van borstkanker ................................................................................................................. 20
Behandelingsschema’s bij verschillende stadia ...................................................................................... 22
Follow-up ................................................................................................................................................ 22
Screening................................................................................................................................................. 23
Risicoanalyse en -communicatie ....................................................................................................................... 24
Waarschijnlijkheid (Probability) .............................................................................................................. 24
De evaluatie van diagnostische testen.................................................................................................... 25
Risico’s..................................................................................................................................................... 26
Risico’s communiceren ........................................................................................................................... 26

Week 10 – “koorts, bloedingen en vermoeidheid” ........................................................................................ 27
Leukemie........................................................................................................................................................... 27
Acute myeloïde leukemie (AML) ............................................................................................................. 29
Acute lymfatische leukemie (ALL) ........................................................................................................... 30
Chronische myeloïde leukemie (CML) .................................................................................................... 31
Chronische lymfatische leukemie (CLL)................................................................................................... 32
Diagnostiek leukemieën .......................................................................................................................... 33
Behandeling leukemieën......................................................................................................................... 34
Melanoom ........................................................................................................................................................ 37
Immunologie en immunotherapie .................................................................................................................... 39
Immuuncheckpoints................................................................................................................................ 39

, Immuunsynaps ........................................................................................................................................ 39
Technische procedures ........................................................................................................................... 40
Voorspellende en/of prognostische biomarkers van (mogelijke) klinische relevantie ........................... 40
Klinische resultaten ................................................................................................................................. 41
Toekomst ................................................................................................................................................ 41
Immunotherapie bijwerkingen ......................................................................................................................... 42
Het immuunsysteem en kanker .............................................................................................................. 42
Immuno-oncologie .................................................................................................................................. 43
Verschil tussen moderne immunotherapie en chemo- en tumor-gerichte therapie .............................. 43
Bijwerkingen van immunotherapie ......................................................................................................... 44
Management van de bijwerkingen van immunotherapie ....................................................................... 45
Andere vormen van immunotherapie..................................................................................................... 45

Week 11 – Jeuk, koorts en opgezette klieren ................................................................................................ 46
Bloedziekten ..................................................................................................................................................... 46
Typen bloedziekten (lymfoïde neoplasieën) ........................................................................................... 46
Belangrijke principes van lymfoïde neoplasieën ..................................................................................... 46
Symptomen van maligne bloedziekten ................................................................................................... 47
Differentiaaldiagnose .............................................................................................................................. 47
Hodgkin lymfoom ............................................................................................................................................. 48
Non-Hodgkin lymfomen .................................................................................................................................... 50
Folliculair lymfoom.................................................................................................................................. 50
Diffuse large B-cell lymphoma (DLBCL) ................................................................................................... 51
Burkitt’s lymfoom ................................................................................................................................... 52
Lymfoplasmacytisch lymfoom................................................................................................................. 52
Mantel cel lymfoom ................................................................................................................................ 53
Marginal zone lymfoom .......................................................................................................................... 53
Primaire extranodale lymfomen ............................................................................................................. 54
Primaire cutane (T- of B-cel) lymfoom .................................................................................................... 54
T-cel en NK-cel lymfomen ....................................................................................................................... 55
Plasmacel neoplasieën (=Dyscrasias) en gerelateerde aandoeningen ............................................................. 56
Monoclonale gammopathy van onbepaalde significantie (MGUS)......................................................... 56
Lymfoplasmacytisch lymfoom................................................................................................................. 56
Heavy-chain disease ................................................................................................................................ 56
Primaire of immunocyt-geassocieerde amyloïdose ................................................................................ 56
Multiple myeloom (=plasma cel myeloom) ............................................................................................ 57
Myelodysplastische syndromen (MDS) ............................................................................................................. 59
Versatest – structuur en cellulaire compositie van lymfeknopen ..................................................................... 60
Versatest – B-cel ontwikkeling .......................................................................................................................... 62
Versatest – B-cel lymfomen .............................................................................................................................. 69
Kankeroverlevenden ......................................................................................................................................... 73
Chronic comorbidities among surivors of adolescent and young adult cancer................................................. 77
Cardio-oncology: an overview on outpatient management and future developments .................................... 78

,Week 9 – Basisprincipes van de oncologie en mammacarcinoom
De celcyclus
G0-fase: (Gap-0) meest cellen in het lichaam (99%);
- Reeds gedifferentieerde cellen.
G1-fase: (Gap-1) groei in massa;
- G1/S-checkpoint: checkt voor DNA-schade; monitort
integriteit van het DNA.
o DNA-schade: P53 eiwit activeert CDKI -> remt
CDK -> remt RB.
o Geen DNA-schade: groeifactor activeert
cycline-CDK -> RB wordt gefosforyleerd ->
activatie transcriptiefactoren.
S-fase: chromosoom/DNA-duplicatie;
G2-fase: (Gap-2) voorbereiding voor mitose;
- G2/M-checkpoint: checkt voor schade / niet-
gedupliceerd DNA; monitort juiste genetische
replicatie.
o DNA-schade: P53 of andere eiwitten activeren CDKI -> remming celcyclus
(d.m.v. geen transcriptie) + activatie DNA-repair mechanismen.
Interfase = fase waarin geen microscopisch observeerbare veranderingen plaatsvinden.
Mitose: celdeling.




P53: detecteert cellulaire stress en houdt het genoom intact (= guardian of the genome)
- Verlies P53 (door mutatie TP53) -> ongevoelig voor radio-/chemotherapie (geen
apoptose meer).
APC-eiwit: breekt b-catenine af bij afwezigheid van groei-stimulatiefactoren, waardoor er
geen transcriptiefactoren worden geactiveerd en er dus heen groei plaatsvindt.
Deregulatie van de celcyclus is een eerste stap in de ontwikkeling tot kanker

, Pathogenese van kanker
Hallmarks of cancer

= Kenmerken die nodig zijn voor de ontwikkeling tot kanker
1. Self-sufficiëncy in growth
a. Celdeling gaat door, zonder de aanwezigheid van een groeistimulans.
i. D.m.v.: productie groeifactoren (autocrien of paracrien), mutaties
groeifactorreceptoren (TKR), mutaties in down-stream pathways.
b. Cyclins: leiden de cel door de gehele celcyclus.
i. RB regelt G1/S-transitie.
c. Mutatie in proto-oncogenen => oncogenen -> coderen voor onco-eiwitten.
i. Onco-eiwitten promoten de celgroei zonder externe stimuli.

2. Insensitivity to growth inhibition
a. Tumorsuppressorgenen remmen de cel; insensitiviteit voor tumor-
suppressorgenen zorgt voor geen remming.
i. APC = tumorsuppressorgen: breekt b-catenine af wanneer er geen
groeifactor aanwezig is -> zo wordt de cel niet gestimuleerd tot groei.
Groeifactoren remmen APC, zodat b-catenine aan kan zetten tot groei.
Bij afwezigheid van APC (door mutatie) wordt b-catenine niet
afgebroken -> groei zonder stimulans.
ii. TP53 = tumorsuppressorgen die codeert voor P53; vaakst aangedaan.
“Guardian of the Genome”: detecteert cellulaire stress -> reguleert de
celcyclusprogressie, DNA-herstel, cel-senescence en apoptose.
Verlies P53-functie -> geen DNA-herstel -> maligniteit
3. Evasion of apoptosis
a. Apoptose kan worden geïnitieerd door 2 pathways;
i. Intrinsieke pathway: DNA-schade -> P53 -> BAX/BAK -> mitochondria
-> cytochroomC APAF1 -> caspase 9 -> caspase 3 -> apoptose.
ii. Extrinsieke pathway: FasL bindt Fas (CD95) -> porcaspase 8 -> caspase
8 -> direct caspase 3 of via BAX/BAK -> apoptose.
b. Vooral abnormaliteiten in de intrinsieke pathway (P53)

4. Unlimited replication
a. Afwezigheid/mutatie P53: apoptose wordt niet geïnitieerd door verlies/
verkorting van telomeren.
b. Expressie van telomerase: herstel van de telomeren.

5. Angiogenesis
a. Angiogenese promoters > angiogenese inhibitors.
b. Nodig om >2 mm te groeien (i.v.m. O2 + nutriënten en afvoer afval)
c. Triggers: hypoxie (d.m.v. VEGF), P53 (induceert synthese inhibitors), RAS, MYC
en MAPK (­VEGF-expressie)

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