GI Cancer

Question 1

What tissue markers are expected on a GIST?

Answer 1

C kit, CD117

Question 2

What treatment for GIST?

Answer 2

Imatinib (C Kit TKI)

Question 3

What bad prognostic factors for GIST?

Answer 3

1. BIG (>5cm)
2. high mitotic count
3. non-gastric locations

Question 4

What is the molecular profile for gastric cancers?

Answer 4

Chromosomal instability: ERBB2, VEGF, TP53
EBV: PIK3CA, PDL1
MSI: Gastric CIMP, MLH1 Silencing

Question 5

What is the treatment for resectable Gastric cancer?

Answer 5

1. NEOADJ - FLOT4 (5FU + Leucovorin + Oxaliplatin + Docetaxel)
2. ADJ - CAPOX (Capecitabine + Oxaliplatin)

Question 6

What is the treatment for unresectable Gastric Ca?

Answer 6

HER2 -VE: Platinum + fluoropyrimidine

HER2 +VE: Platinum + Fluoropyrimidine + Traztuzumab

Question 7

What is dumping syndrome?

Answer 7

post gastrectomy - destruction/bypass of pyloric sphincter and rapid emptying of hyperosmolar chyme (Carbs) into SB
- draws fluid into intestine -> vasoactive hormones

Question 8

What genetic characteristics associated with hereditary diffuse gastric cancer?

Answer 8

Autosomal Dominant

CDH1 Mutation

Question 9

What is the treatment for Hereditary diffuse gastric cancer?

Answer 9

Prophylactic total gastrectomy (18-40yo)

note increased risk fo lobular breast ca

Question 10

What genetic characteristics are associated with LYNCH syndrome and what cancers?

Answer 10

Autosomal DOMINANT
MLH1: CRC, Endometrial, Ovarian, Gastric
MSH2: CRC, Endometrial, Ovarian, Urothelial
MSH6: Endometrial, CRC
PMS2: CRC, Endometrial 

Highest Risk for CRC: MSH2 > MLH1 > MSH6 > PMS2

Question 11

What tx/surveillance needed for lynch syndrome?

Answer 11

CRC - subtotal colectomy 
         - surveillance: annual scope 
Endometrial: hysterectomy after kids
Ovarian - risk reducing salpingo-oopherectomy with hysterectomy -> then HRT
Gastric - 2nd yearly scope

Question 12

What are the genetic characteristics of juvenile polyposis syndrome?

Answer 12

Autosomal DOMINANT

SMAD4, BMPR1A Mutation

Question 13

What surveillance for Juvenile Polyposis syndrome?

Answer 13

yearly scope if polyp, 2nd yearly if no polyp

Question 14

What are the genetic characteristics for Peutz Jeghers Syndrome?

Answer 14

Autosomal DOMINANT
STK11 Mutation
- Hamartous polyps in GIT/Skin

Question 15

What is the surveillance for Peutz Jeghers Syndrome?

Answer 15

2nd yearly scope

Question 16

What are the genetic characteristics of Familial Adenomatous Polyposis?

Answer 16

Autosomal DOMINANT

APC mutation on Chr 5

Question 17

What are the extra colonic manifestations of familial adenomatous polyposis?

Answer 17

Gardner Syndrome: GI + desmoid tumour, Sebaceous cyst, lipoma, CHRPE (Eye thing)
Turcot syndrome: GI + Brain Tumour

Question 18

What are the types of oesophageal Ca?

Answer 18

Squamous - Prox -mid

Adenocarcinoma - Dis - GEJ (white people)

Question 19

What is the tx for oesophageal ca?

Answer 19

T1/2 - Resect
T3 - Resect + NEOADJ - Carboplatin/Paclitaxel
Unresectable - Platinum + Fluorouracil

Question 20

Who to surveil for HCC and how?

Answer 20

1. Cirrhotics
2. Chronic Hep B no Cirrhosis
   - Asian Men 50+, Asian Women 40+
   - Subsaharan Africa 20+
   - ATSI 50 +

6 monthly USS +/- AFP

Question 21

How to Dx HCC?

Answer 21

CT Multiphase: Arterial hyperenhancement, wash out on portal+delayed
50% HCC PET Avid

Question 22

What is the general management for HCC in terms of stages?

Answer 22

Stage A (single tumour any size OR 3 nodules <3cm) - locoregional stuff
Stage B (multinodular) - locoregional, think about chemo
Stage C (portal invasion/extrahepatic) - Chemo
Stage D (end stage liver) - supportive care

Question 23

What are the locoregional Tx for HCC?

Answer 23

Local ablation with ETOH, Thermal RFA or thermal MWA
TACE - chemo/DC beads + occlusion of arterial supply
Stereotactic Radiosurgery
SIRT (selective internal radiation therapy) - delivery via hepatic artery using Yttrium

Question 24

What Chemotherapy is used in HCC?

Answer 24

1. Atezolizumab (PDL1) + Bevacizumab (VEGF)
2. Sorafenib (VEGF)
3. Lenvatinib (VEGF)
   Other: Regorafenib (VEGF), Carbozanitinib (C-MET, VEGF)

Question 25

What are the risk factors for pancreatic ca?

Answer 25

reversible: Smoking, ETOH, High BMI, DM
irreversible: Peutz Jegher, Lynch, BRCA 2

Question 26

What chemotherapy is used in pancreatic ca?

Answer 26

FOLFIRINOX: 5FU + Irinotecan + Oxaliplatin
Gemcitabine + paclitaxel
PARP if BRCA

Question 27

What is involved in colorectal carcinogenesis?

Answer 27

Chromosomal instability (distal disease): errors in mitosis
- APC, KRAS, TP53
CpG Island Methylator phenotype (CIMP) (proximal disease)
- MLD1 Promoter hypermethylation
Microsatellite instability
- loss of MMR

Question 28

What is Proximal (Right) CRC associated with

Answer 28

High MSI, High CIMP
BRAF mutation, KRAS, HNPCC
Old Women

• Bevacizumab (Cetuximab doesnt respond well to KRAS mutation)

Question 29

What is distal CRC associated with?

Answer 29

CIN +
Young Men
FAP
BRAF Wild Type

Cetuximab

Question 30

How to screen general population for CRC?

Answer 30

Near Normal risk - FOBT 2nd yearly 50-74 (1 old relo with CRC)
Moderate Risk - FOBT 2nd yearly earlier (40-49), Scope 5yrly (50-74)
- 1 younger relo CRC, or 2 old ones with CRC
Higher risk - FOBT 2nd yearly EVEN earlier (34-44), Scope 5yrly (45-74)
- 3 ppl in fam with CRC

Question 31

What is the treatment for CRC?

Answer 31

Resect + ADJ Chemo
Chemo: 5FU/Capecitabine (AKA fluoropyromidine) + Oxaliplatin
if MSI HIGH (5FU a bit useless)

Metastatic
Chemo + EGFRi (cetuximab) - KRAS mutation makes EGFR less effective
If BRAF + VE: BRAF + EGFR + MEK (encorafenib, cetuximab, binimetinib)
If MSI HIGH: Pembrolizumab

Question 32

What Mutations are associated with High MSI in CRC?

Answer 32

Lynch (85%)

BRAF (15%)