Small/ Large Bowel Cancer Flashcards
Most common small intestine tumours?
Adenocarcinoma - 50% (usually duodenal)
Lymphoma (non- Hodkin’s normally)
Carcinoid (10%)
Other: Lipomas, Stromal tumours
Risk factors for small bowel adenocarcinoma/ lymphoma?
Coeliac disease
Crohn’s disease
Immuno-proliferative small bowel disease (plasma cells in upper small bowel, in poor ppl with poor hygiene areas around Mediterranean and South America/ Asia, treat with tetracyclines)
Treatment of small bowl adenocarcinoma/ lymphoma
Surgery + ChemoRadio
What are carcinoid tumours?
- originate from enterochromaffin cells (APUD cells) of the intestine
- usually in terminal ileum or appendix (10% of these present with appendicitis)
- can cause carcinoid syndrome
What percent of carcinoid tumours cause carcinoid syndrome?
5%
And only when there are liver mets
Presentation of carcinoid syndrome?
bluish-red face/ neck flushing (can lead to permanent changes with telangiectases)
abdominal pain + watery diarrhoea.
Cardiac abnormalities (50%)
- pulmonary stenosis or tricuspid incompetence
Liver enlargement
Pathophys of carcinoid syndrome?
the tumours secrete a variety of biologically active amines and peptides:
- serotonin -> diarrhoea
- bradykinin, tachykinins -> one of these leads to flushing
- histamine
- prostaglandins
Tests for carcinoid syndrome?
• Ultrasound: liver mets
• Urine: 5-hydroxyindoleacetic acid (5-HIAA) - major metabolite of 5-HT
• Serum chromogranin A (not 100% of cases)
Management of carcinoid syndrome?
octreotide and lanreotide: somatostatin analogues that inhibit the release of gut hormones.
Peutz-Jeghers Syndrome
Autosomal dominant (STK11
mucocutaenous pigmentation
- circum-oral (95%)
- hands (70%) and feet (60%)
GI polyps
- generally in small bowel
- can bleed or cause obstruction or intussusception (50%)
Management for Peutz-Jeghers Syndrome?
polypectomy (endoscopically)
Try to avoid bowel resection if able.
Increased screening for non GI cancers (uterine, ovarian, cervical, breast, testicular cancer)
Risk factors for CRC?
IBD
Previous abdomino-pelvic radiation
Obesity
Diabetes/ insulin resistance
Meat consumption (processed meats and red meats in particular)
Low fibre
Who is eligible for CRC screening in Aus?
second yearly test for those 50-74 years of age
Paricipation 40%
Portion of CRC secondary to familial syndromes?
~ 5%
- Polyposis syndromes (FAP, MUTYH-associated polyposis) - each < 1% CRC
- Lynch syndrome (3% CRC)
Gener responsible for familial adenomatous polyposis?
Adenomatous Polyposis Coli (APC) gene
on chromasome 5
Gene(s) responsible for Lynch syndrome?
MLH1 (can be sporadic also due to promotor methylation – more common);
MSH2, MSH6
PMS2
I think MLH 3 also
Pathophys of Lynch syndrome, and treatment implications
Unable to form mismatch repair complexes -> lots of tandem repeats (microsatellite instability) -> abnormal promoter regions of DNA
Leads to neoantigens -> good for immunotherapy (checkpoint inhibitors)
More likely to have R sided CRC
What is Turcot’s syndrome?
FAP or Lynch syndrome with brain tumours
Diagnostic criteria for Lynch syndrome?
Modified Amsterdam criteria
• One individual diagnosed with CRC (or extracolonic Lynch tumours) before age 50 years
• Two affected generations
• Three affected relatives, one a first-degree relative of the other two
• FAP excluded
• Tumours verified by pathological examination
OR
Bethesda guidelines
• CRC diagnosed in patient who is younger than 50 years
• Presence of synchronous, metachronous CRC, or other Lynch tumours, irrespective of age
• CRC with the MSI-H histology diagnosed in a patient who is younger than 60 years
• CRC diagnosed in one or more first-degree relative with a Lynch-related tumour, with one of the cancers being diagnosed under the age 50 years
• CRC diagnosed in two or more first- or second-degree relatives with Lynch-related tumours, irrespective of age
Inherited syndrome(s) -> hamartomatous polyps?
- Juvenile Polyps: most in colon in kids/ teenager.
- Peutz-Jeghers syndrome
- PTEN hamartoma-tumour syndrome
- caused by germline Phosphatase and Tensin Homologue (PTEN) mutations
Pathophys of FAP (Familial Adenomatous Polyposis)?
Autosomal dominant
germinline mutaiton to APC gene on chromosome 5 (over 825 mutations identified)
Penetrance ~ 100%
hundred to thousand of polyps through colon (polyps by 16yo, CRC 39yo on overage)
Attenuated FAP
later presentaiton than FAP (44yo)
fewer polyps (<100)
More likely right sided polyps
MYH associated polyposis
MUTY homologue-associated polyposis (MYH-AP)
autosomal recessive
Colorectal adenomas and polyps
MYH is a base-excision-repair gene that corrects oxidative DNA damage.
May account for 7-8% of familial FAP phenotype without a APC mutation identified
Main genetic pathways leading to CRC (2)
CIN (Chromosomal Instability)
- APC gene defect -> mutations to tumour suppressor genes
CIMP (CpG Island methylator pathway)
- via serrated neoplasia pathway
- initiating genes of BRAF or KRAS -> epigenetic silencing tumour suppressor or mismatch repair
(KRAS mutations -> respond to EGFRi such as cetuximab or panitumab)
MSI (Micro-satellite instability)
- defects in mismatch repair genes related to Lynch syndrome
General management of CRC
Surgery
Adjuvant Chemo (5-FU/ capecitabine and oxaliplatin)
( can measure circulating tumour DNA (ctDNA) to see who would benefit from)
RAS/RAF wildtype: EGFR directed therapy (cetuximab, panitumimab)
Radiotherapy: not helpful (except rectal Cx)
Monitoring post CRC treatment
CEA
CT CAP annually for three years
C’scope (3 years, 5 years)
Pattern of mets in CRC
Generally:
- liver (56%), lung (5%), peritoneum
Rectal: not to liver (skips portal system)
Right vs left CRC
R: worse prognosis, more immune active, more BRAF mutations (bad),
