colorectal cancer Flashcards
describe the pathophysiology behind CRC
CRC develops via a multi step process whereby the epithelial cell of the colon acquires a number of mutations which allows it to become genetically unstable and proliferate to eventually progress into an adenocarcinoma.
Epithelium – polyp – adenoma – adenocarcinoma
Usually starts with APC mutations (TSG) (more common on left side) or MMR mutation (more common on the right bowel)
Along the way other mutations such as kras and p53 develop
The adenocarcinoma is stenosing and ulcerating and can infiltrate through the bowel wall and spread to lymphatics, portal system or systemic system to other organs. I
where can CRC metastasise too?
Local spread to bladder
Portal system to the liver
Via vena cava and pulmonary artery to the lung
Also bone , skin and brain
where does CRC mainly arise?
Rectosigmoid colon therefore the left side
Then ascending, then transverse and then descending
what are the risk factors for CRC?
Usually sporadic with no obvious risk factors
Smoking
Family history - only significant if relative was <60yrs
Western diet - low fibre, red meat, overweight , high fat , alcohol
UC/ Crohns
Genetic conditions - FAP and HNPPC ad gardeners
name 3 genetic conditions which can increase risk of CRC
Familial adenomatous polyposis Coli
Hereditary non polyposis CRC /lynch syndrome
Gardeners
what is familial adenomatous polyposis coli?
Autosomal dominant condition where individuals carry APC gene. (Two hit hypotheses)
Most develop CRC by age 40
So prophylactic colonectomy is strong,y advised
what is lynch syndrome?
Autosomal dominant mutation in MMR gene
Less risk than FAP but still high.
Also associated with hepatobiliary, gastric, urinary, ovarian and endometrial cancer
what is gardeners syndrome?
Varient of FAP associated with other tumours (TODE): Thyroid tumours Osteomas of mandible and skull Dental abnormalities Epidermal cysts
how do right sided CRC presents?
Vague symptoms Symptoms of anaemia - tired, pallor, breathless, malaise, weakness Weight loss / cachexia May feel mass in right lower quadrant Sometimes diarrhoea
Do not notice blood in stool unless picked up on FOB
Rarely obstruction because large lumen
Therefore disease more likely to be advanced at presentation
how do left sided CRC present?
Change in bowel habit - increased frequency, diarrhoea
Blood in stools
Eventually mass can obstruction lumen and lead to obstipation
May feel mass in left lower quadrant
Weight loss
Not usually anaemia signs dbecasue usually caught earlier
May have tenesmus, bloating and flatulence
how does rectal cancer present?
Bleeding - bright red PR bleed
Urgency, wet wind, tenesmus (incomplete evacuation, pain and urges to strain)
Mass on DRE
Obstruction
how many advanced disease present?
Hepatomegaly
Jaundice
Ascites
Signs of mets to elesewhere
describe some emergency presentations in CRC
Bowel obstruction
- obstipation, colicky pain, bloating , previous history of diarrhoea and blood
Perforation and peritonitis
- gaurding, tenderness and rebound tenderness
Haemorrhage
what is the referral criteria for CRC?
> 40 and rectal bleeding AND change in bowel habit towards increased frequency ad looser stools for 6 weeks
Or >60yrs and EITHER rectal bleeding or the change in habit for 6 weeks
Any age with right lower abdomen mass consistent with colon origin
Any age and palpable rectal mass
Any aged malewith unexplained iron deficiency anaemia (Hb <11)
Non menstruating women with unexplained iron deficiency anaemia (Hb <10)
what should you examine in someone suspected of CRC?
DRE
Abdominal examination- mass, hepatomegaly, ascites
Lymph nodes - particularly Virchow node
General examination for iron deficiency anaemia and cachexia
what bloods should be ordered if you suspect CRC?
FBC - anaemia , white cells to rule out gastroenteritis
LFTs - deranged if liver mets , baseline before chemotherapy
UEs - diarrhoea can lead to dehydration and electrolyte imbalances
CEA - baseline before treatment so can be monitored
what is the gold standard for CRC diagnosis? and what can be done if this is contraindicated?
Colonoscopy and biopsy
Flexible sigmoidoscopy and barium