Colorectal cancer Flashcards
Arsenic is a carcinogen that increases the risk of developing which type of cancer?
Angiosarcoma of the liver
Squamous cell carcinoma of the skin
Lung cancer
Aspergillus (found on peanuts and maize) is a carcinogen that increases the risk of developing which type of cancer?
Hepatocellular carcinoma
Nitrosamines (present in smoked foods) are carcinogens that increases the risk of developing which type of cancer?
Stomach cancer
Vinyl chloride is a carcinogen that increases the risk of developing which type of cancer?
Angiosarcoma of the liver
What is alpha-fetoprotein a tumour marker for?
Hepatocellular carcinoma
Hepatoblastoma
Mixed germ cell tumour
Yolk sac tumour
Another cancer caused by APC variant of familial adenomatous polyposis coli?
Agressive fibromatosis
Desmoid tumours in abdominal and extrabdominal locations
Single gene causes of colorectal cancer?
Familial adenomatous polyposis coli (FAP) - autosomal dominant Lynch syndrome (hereditary non-polyposis colorectal cancer) - autosomal dominant
Risk factors for colorectal cancer?
Age >50
IBD
Polyposis syndromes - Peutz-Jehgers; Sessile serrated polyposis syndrome; MUTYH-associated polyposis syndrome
Peutz-Jehgers syndrome features:
Harmatomatous polyps (esp in small bowel) Pigmented lesions on lips, oral mucosa, face, palms and soles GI bleeding and obstruction Autosomal dominant, 50% of patients will have died from a different malignant cancer by the time they're 60
Dietary changes to decrease risk of colorectal cancer?
More fibre, Ca and garlic
Less red meat, animal fat and alcohol
Isothiocyanates from cruciferous vegetables increase apoptosis in neoplastic cells
Which oncogene allows the progression from hyper-proliferation to adenoma in CRC?
KRAS
Amsterdam II criteria for CRC:
3 or more relatives with histological verified CRC, endometrium, small bowel, ureter or renal pelvis cancer
Over 2 or more generations
1 has to be a 1st degree relative of another
CRC by age of 50
How do you diagnose Lynch syndrome?
Family history
Microsatellite instability (MSI) as screening for MMR genes
Mutational analysis of MMR genes
How do you manage confirmed Lynch syndrome?
Colonoscopy every 2 years from the age of 25
75mg aspirin daily as chemoprevention
Standard colonic resection +/- prophylactic resection to prevent metachronous cancer
Colonoscopy every 2 years unless panproctocolectomy and IPAA made
What is IPAA?
Ileo-pouch anal anastamosis
What is metachronous colon cancer?
A secondary CRC developing over 6 months after the index cancer - happens in 39% of cases
Features of FAP:
APC dominant gene mutation causing hundreds of CRC polyps
Malignant transformation occurs at around age 40
Congenital hypertrophy of retinal pigment epithelium (seen with ophthalmoscope)
Desmoid tumour, duodenal polyps/carcinoma
APC variant in 6% Ashkenazi Jews = x2 risk
FAP management:
Prophylactic colectomy between 16 and 20 years old
Later on proctocolectomy and IPAA
CT CAP
Worry with GI cancers?
Liver metastases through the portal vein
Purpose of MRI of the rectum?
Used to assess the necessity for pre-op chemo/RT
Need to see the status of the mesolectal fascia - if the tumour gets through this then it can access the LNs
Therefore may need to shrink the tumour away from the fascia with adjuvants before surgery
Symptoms of CRC?
Change in bowel habit - constipation/diarrhoea/straining/frequency
Abd. mass/pain from bowel obstruction
Rectal bleeding
Tiredness from anaemia
Weight loss
Obstructed ureters/fistula formation into stomach/bladder
Signs of left sided CRC?
Change in bowel habit Colicky abdominal pain Blood coating of the stool Straining Mucus PR
Signs of right sided CRC?
Less obstruction (more liquid and wider) Typically present with an iron deficiency anaemia - in this case the patient must have an upper and lower GI endoscopy to exclude gastric and colon cancer
What blood tests are ordered for suspected CRC?
FBC
U+E
LFTs - check for liver metastases
CEA - carcinoma-embryonic antigen
CRC T staging:
T1 = Submucosa T2 = Muscle layer T3 = Serosa T4 = Through serosa
CRC N staging:
N0 = No lymph nodes involved N1 = Involvement of 1-3 lymph nodes close to the bowel N2 = Involvement of 4 or more nearby lymph nodes
CRC M staging:
M0 = No spread to other organs M1 = Spread to other organs
Staging CRC: inner lining/muscle wall
Stage 1
Staging CRC: T1/2, N0, M0
Stage 1
Staging CRC: no lymph node involvement
Stage 1 or 2
Staging CRC: T1-3, N0, M0
Stage 2a
Staging CRC: T4, N0, M0
Stage 2b
Staging CRC: T1/2, N1, M0
Stage 3a
Staging CRC: T3/4, N1, M0
Stage 3b
Staging CRC: T1-4, N2, M0
Stage 3c
Staging CRC: T1-4, N1-2, M1
Stage 4
Duke’ stage A CRC:
Submucosa/slightly into the muscle layer
Duke’s stage B CRC:
Growth into the muscle layer
Duke’s stage C CRC:
Spread to at least 1 lymph node
Duke’s stage D CRC:
Distant metastasis e.g. liver/lungs
Management of high-risk locally advanced?
Pre-operative chemotherapy 6 weeks before
Stage 2 gets adjuvant therapy
Management of stage 3 (Duke’s C)?
Capecitabine as mono therapy
Oxaliplatin in combination with 5-fluorouracil and folinic acid
Which CRCs get adjuvant chemo?
All high-risk stage 2s and all stage 3 rectal cancers
Chemo therapy for advanced metastatic CRC:
FOLFOX then imnotecan
FOLFOX then FOLFIRI
XELOX then FOLFIRI
Which mutations are present in 35-40% of patients in colorectal carcinogenesis?
KRAS mutations
Monoclonal Abs to EGFR in CRC?
Cetuximab
Panitumumab
(they prevent signal transduction involving RAS, PI3K-AKT and SRC kinase)
Risk of chemotherapy?
Infection
Neutropenic sepsis
Post resection management?
First 2 years regular surveillance - minimum 2 CT scans CAP
Serum CEA 6 monthly
Screening programme for CRC:
FIT screening for men and women aged 60-74
Flexible sigmoidoscopy for people aged 55
Diagnosis of CRC:
Colonoscopy is gold standard
Double contrast barium enema
CT colonography
What is Gardner syndrome?
FAP with demoed tumours and osteomas
What is MYH associated polyposis?
Autosomal recessive condition with polyps in GI track with somatic KRAS mutations
