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
once CRC is diagnosed what further investigations are required?
CT CAP - staging for local invasion and mets
MRI - for rectal cancers to look at degree of local invasion
Barium enema - apple core sign to suggest stenosis and possible obstruction
Endoanal USS - assess stability for transanalnresection for early rectal cancers
CT colonography - alternative to colonoscopy
Liver USS / MRI
describe dukes staging
A - confined to bowel wall up to and including muscularis propria
B - through muscularis propria into serosa and beyond
C - lymph nodes
C1.- local lymph nodes
C2 - proximal lymph nodes
D : distant metastasis
describe TNM staging
To - no evidence of primary tumour T1 - tumour invading submucosa T2 - invading muscularis propria T 3 - through muscularis T4 - penetrates through peritoneum
N1 : 1-3 pericolic nodes
N2. : 4 or more pericolic nodes
N3 : lymph nodes on named vascular trunk
M1: distant mets
describe the clinical staging
Stage 0 - carcinoma in situ Stage 1 - dukes A Stage 2 - dukes B (2a into serosa, 2b into next organ) Stage 3 - dukes C 3a : 1-3 nearby nodes 3b : same as above + stage 2b 3c : 4 or more nodes Stage 4: dukes D
describe the grading for CRC
1 = well differentiated 2 = moderately differentiated 3= poorly differentiated
why is staging for CRC important?
Prognosis And treatment guidance
E.g, if liver mets no point in radical surgery because liver mets wont last long anyway
what surgery is required for:
a) right colon cancer
b) transverse colon cancer
c) left sided CRC
d) sigmoid CRC
Right hemicolectomy (remove ileocaecal, right colic and right branch of middle colic vessels )
Extended right hemicolectomy
Left hemicolectomy ( remove left branch of middle colic + Left colic vessels )
Sigmoidcolectomy (or Hartmann if emergency) - remove IMA
what are the surgical options for rectal cancers?
Those <5cm from anal margin = abdominoperineal resection. Distal colon, rectum and anal spinchter removed. Anus closed and permanent colostomy
Those > 5cm from anal margin - anterior resection. Anal sphincter left intact and anastomoses made so bowel functions normally. Can use defunctioning loop ilostomy to allow bowel to heal.
Ima removed for rectal cancers
what procedure can be used in an emergency setting where there is obstruction of rectosigmoid colon by CRC?
Hartmann - remove rectosigmoid colon and the distal stump and proximal colostomy bag. This can later be see.
Also used in diverticular disease
what is total mesorectal excision?
The removal of lymph nodes (usually up to 12 nodes removed) that track along vessels supplied by the CRC and thus the removal of vessels associated with these lymph nodes and then the removal of other parts of the bowel supplied by these vessels to prevent ischaemia
what determines whether bowel anastomoses can be made?
Healthy - therefore young people better tolerate anastomoses
Good blood supply - the further down the worse the blood supply
If the two bowel ends reach
what is the role of chemotherapy in CRC?
Mainly for Dukes C or D or palliative
5 flurouracil used as adjuvant chemo
For rectal tumours that have spread to lymph nodes often neoadjuvant chemo is used to shrink tumour before removal
what is the role of biologics in CRC?
Monoclonal Ab against EGFR e.g. Panitumumab / cetuximab
However if tumour also has kras mutation it can bypass the need for EGFR and thus such treatment is useful
Therefore cancer genetic is important before deciding treatment
what are the side effects of panitumumab ?
Skin toxicity - acne form rash, dry skin Hair growth disorder Pruritis and nail changes Fatigue Allergy
what is the role of radiotherapy in CRC?
Brachytherapy is used to shrink rectal tumours before surgery
Radiotherapy is not used for colon cancer because damage to small bowel is too extensive
However radiotherapy can be used in palliative cases
Radio frequency ablation can be used in liver metastasis that are not surgically resectable
what can be used in palliative care CRC patients?
Endoluminal stenting
Stokes for acute obstruction
when should stents not be used?
Low rectal cancers as can lead to tenesmus
Lesions that look at risk of perforating
what are the side effects of stents?
Perforation
Migration
Incontinene
how are liver metastasis treated?
Surgical resection - all patients with resectable liver mets should be considered for surgery Microwave ablation Radio frequency ablation Selective internal radiation therapy Chemo
overall how are CRC and rectal cancers treated?
colon - surgery +/- adjuvant chemo
Rectal cancer - neoadjuvant radiotherapy / chemoradiotherapy + surgical resection +/- adjuvant chemo
how can we prevent CRC?
There is a screening programme available for those aged 60-75
Yearly colonoscopy for IBD
Polypectomy
what does the CRC screening programme involve?
Faecal occult blood test every 2 years for those aged 60-75
If positive , repeat FOB
If 2 positive results - colonoscopy
why is CRC a suitable disease to be screened for?
Known pathophysiology and aetiology Easy, cheap and acceptable test Treatment available Common and significant mortality Premalignant stage can be treated
what is the prognosis for CRC?
Left sided has better prognosis than right because presents earlier
Dukes A = 90% prognosis
Dukes B = 50%
Spread to liver = poor prognosis
how are CRC patients followed up?
For those who have had CRC and been treated :
- minimum of 2 CT CAP in first 3 years
- regular CEA tests atleast every 6 months for first 3 years
What are the complications of CRC
Metastasis and death Obstruction Perforation, peritonitis and infection Fistula and UTI/ vaginal infections Anaemia Acute bleed
