GI malignancy Flashcards

Question

HCC risk factors

Answer 1

HBV, HCV Chronic ETOH NAFLD, NASH Genetic haemochromatosis

Answer 2

All liver cirrhotic patients Abdo USS + AFP every 6/12

Answer 3

Arterial hypervascularity and 'wash out' on portal venous phases (multi-phase CT) Rising AFP Biopsy in selected cases - increasingly done now due to better techniques(due to risk of seeding)

Answer 4

Depends on resectability 1) BCLC A+B Resection, transplant = best cure - Resection is difficult in portal HTN. Transplant preferred. Locoregional therapies (TACE, ablation, RT) = not curative but can be a bridge to curative therapies 2) BCLC C Systemic therapy in advanced disease - Child pugh A (good liver function) only - PDL1 inhibitor (Atezolizumab) + Anti-VEGF (bevacizumab) 1st line 3) BCLC D Best supportive care

Answer 5

Milan criteria - Single tumour ≤5cm or ≤3 nodules ≤3cm Expanded criteria (UCSF criteria) - Single lesion ≤6.5cm - ≤3 nodules, each ≤4.5cm - Total tumour diameter ≤8cm

Answer 6

>90% adenocarcinoma Histologic variants include mucinous and signet ring cell carcinoma = inferior prognosis

Answer 7

3 main types - Sporadic 65% - FHx but no associated gene identified 25% - Hereditary 5% - HNPCC ie Lynch syndrome, FAP

Answer 8

Something wrong with the actual chromosome/gene APC gene - FAP KRAS gene TP53 gene Lt sided colon Younger male

Answer 9

MLH1 promoter hypermethylation Rt sided colon + transverse colon up to splenic flexure Can be associated with MSI high, BRAF mutation Older females

Answer 10

Loss of MMR protein (most due to MLH1 methylation) CIMP and MSI are correlated. 70% of MSI-high CRC are also CIMP-high Key differentiation is BRAF mutation which is strongly associated with sporadic origin i.e. CIMP

Answer 11

1) Adenoma-carcinoma sequence - Small adenoma --> large adenoma --> cancer - CIN-high - 90% of sporadic CRC 2) Serrated pathway - Hyperplastic polyp --> sessile serrated adenoma --> cancer - CIMP-high - 10% of sporadic CRC 3) Inflammatory pathway - <2% of all CRC

Answer 12

3% of CRC Genetic syndrome Autosomal dominant with high penetrance Rt sided colon cancer (early onset), endometrial ca, ovarian ca Mutation in mismatch repair genes (MMR): MLH1, MSH2, EPCAM, MSH6, PMS2 [From high to low risk] MMR usually goes and repair genes --> when it doesn't work, small genetic mutations accumulate --> 'microsatellite instability' Often poorly differentiated, mucinous and infiltrating lymphocytes

Answer 13

Amsterdam criteria "3-2-1' rule At least 3 relatives with associated lynch syndrome cancer (CRC, endometrial, small bowel, ureter, or renal pelvis) 2 successful generations should be affected 1 should be diagnosed before age 50

Answer 14

Surveillance colonmoscpy every 1-2 years Commence at age 25 or 5 years younger than the youngest affected family members if <30 years Extended resection generally favoured. Annual surveillance required for residual colon. High dose Aspirin prophylaxis 600mg daily for 2 years reduce Lynch-syndrome associated cancers

Answer 15

<1% Germline APC mutation Autosomal dominant with high penetrance Polyps ++++ Distal left sided colon, beginning from adolescence Risk of CRC 100% by age 40 Other associated ca: papillary thyroid, gastric ca, ileal carcinoid

Answer 16

Colonoscopy from age 10-15 In classical FAP, sigmoidoscopy is adequate since adenoma occur simultaneously throughout the colorectum Once an adenoma is identified, annual colonoscopy until colectomy Colectomy at age 15-25 NSAID chemoprophylaxis if surgery inappropriate

Answer 17

Immunochemical FOBT Age 50-74 Every 2 years Current screening participation 40% Cost effective Improve CRC mortality Diagnose at earlier stage

Answer 18

3 categories 1 - near average risk - iFOBT every 2 years from age 50-74 (same as general population) 2 - moderately increased risk - iFOBT every 2 years from age 40-49 - Colonoscopy every 5 years from age 50-74 3 - potentially high risk - iFOBT every 2 years from 35-44 - Colonoscopy every 5 years from age 45-74

Answer 19

Includes 5-FU infusion, oral capecitabine Diarrhoea, hand-foot syndrome, coronary artery spasm DPD enzyme - exaggerated toxicities which can be life threatening - diarrhoea, mucositis, myelosuppression

Answer 20

Diarrhoea, neutropenia, myelosuppression Acute cholinergic syndrome (early onset diarrhoea) Rx atropine UGT1A enzyme deficiency - toxicities

Answer 21

Diarrhoea, neutropenia Acute neurotoxicity - aggravated by exposure to cold, sensory and motor. Cold induced pharyngolaryngeal dysethesia 1-2% Chronic neurotoxicity mainly sensory, usually reversible

Answer 22

40% mCRC Ligand binds to EGFR receptor --> downstream signalling K-RAS --> RAF --> MEK --> ERK ---> DNA transcription --> cell proliferation, survival, cancer If you have a KRAS mutation, blocking EGFR (cetuximab/panitumumab) is not sufficient to block downstream pathways

Answer 23

Acneiform rash Diarrhoea Electrolyte derangement Skin and nail toxicities

Answer 24

Monoclonal ab against VEGF-A Inhibits new vessel growth, normalises tumour blood flow and allows chemo to be delivered to the tumour Used in conjunction with chemo Toxicities: HTN, proteinuria, GI perforation, VTE, delayed wound healing

Answer 25

Aggressive Poor prognosis Single BRAFi is not good enough Encorafenib (BRAFi) + cetuximab (EGFRi) + Binimetinib (MEK inhibitor) - not standard of care at the moment but great results in 2nd line and beyond

Answer 26

PD1 inhibitor with pembrolizumab | 1st line

Answer 27

Adenocarcinoma (95%) Neuroendocrine Lymphoma Sarcoma

Answer 28

Head of pancreas (70%) - Obstructive jaundice Others - Epigastric/back pain - LOW, LOA - Fatigue - Malabsorption Often vague sx leading to late presentation

Answer 29

CA19-9 (also for other GI ca)

Answer 30

Increased PFS but not overall survival Hence not currently PBS funded

Answer 31

Barcelona clinic liver cancer staging Combines tumour stage, liver function and ECOG

Answer 32

IBD - Especially those with PSC (UC) Previous abdominopelvic radiation Obesity Diabetes/insulin resistance Processed meats

Answer 33

Mismatch repair gene mutation --> deficient mismatch repair --> large increases in DNA sequences referred to as 'microsatellites' --> frameshift mutation --> CRC

Answer 34

Neoadjuvant chemotherapy (to reduce risk of recurrence given proximity to other organs) --> wait 10 weeks --> surgery --> adjuvant chemotherapy

Answer 35

Those who haven't had a full colonoscopy at diagnosis require one at the conclusion of treatment, then at 3 years, then 5 yearly Physical exam with CEA 3 monthly for 3 years, then 6 monthly CTCAP annually for 3 years

Answer 36

Right sided - More aggressive, worse prognosis - BRAF mutations - More active immune cells promoting immunogenicity Left sided - RAS/RAF mutations

Answer 37

Curative surgery +/- adjuvant chemotherapy (benefit is ~5% in stage 2 high risk patients) If MSI high, no need for adjuvant chemotherapy

Answer 38

Surgery + adjuvant chemotherapy (5FU/capecitabine + oxaliplatin) for 3-6/12

Answer 39

Surgery +/- adjuvant chemotherapy (5FU/capecitabine + oxaliplatin)

Answer 40

Neoadjuvant chemo --> surgery --> adjuvant chemo

Answer 41

Doublet chemotherapy (5FU/capecitabine PLUS oxaliplatin or irinotecan) If RAS/RAF wildtype: add EGFR inhibitor (panitumumab or cetuximab) If RAS/RAF mutation: add VEGF inhibitor (bevacizumab) If MSI high (not yet PBS approved): immunotherapy (pembrolizumab or nivolumab or ipilimumab with nivolumab)

Answer 42

1) All high grade serous ovarian ca (non-mucinous) <70 years 2) All triple neg breast ca <50 years 3) Breast ca with manchester score >15 (>10% pre test probability of BRCA1/2 mutation)