Colorectal Cancer

This article refers to cancer of the large bowel.

Interestingly, the small bowel is a very rare site for carcinoma, despite the fact it has the highest cell turnover of anywhere in the body, and has a very large surface area.

Colorectal Cancer -epidemiology
-          Second most common cancer in the Western World (behind lung cancer)
-          50% of cases will result in death
-          Relatively rare in Africa, Asia and South America
-          Peak incidence in the 7th decade

-          Family history.
-          Age
-          Diet rich in fat and meat, and low in fibre – associated with a Western Lifestyle
-          IBD – due to high cell trunover
-          Diabetes
-          Atherosclerotic disease
-          Age and family history are the two best predictors for colorectal cancer

Benign Disease
This is characterised by the presence of adenomas. An adenoma is a benign epithelial neoplasm, with the potential to become malignant.

Clinical features and diagnosis
-          Often asymptomatic, usually only found incidentally
-          Rectal bleeding (rare)
-          Hypokalaemia (very rare)

-          Endoscopic mucosal resection (EMR) – removal of polyps by colonoscopy. Upon discover of one or more polyps, colonoscopy, and subsequent EMR is advisable, whereby all visible lesions should be removed. This should be followed by lifelong surveillance (every 3-5 years up to the age of 75) to check for the development of more polyps and / or colorectal cancer.
-          50% of patients will develop further polyps.

Pathology: Adenoma to Carcinoma
-          A minimum of three separate genetic defects have to occur:
§      Onocgene activation (k-ras, c-myc)
·         associated with small adenomas becoming big adenomas.
§      Loss / mutation of tumour suppressor genes
§      Loss / suppression of genes involved with DNA repair path ways.
·         E.g., genes involved in the inhibition of apoptosis may become over-expressed
-          It will take 8-10 on average for an adenoma to become a carcinoma.
-          The mutations can occur in any order!
-          Many of the genes associated with colorectal cancer are found in two specific locations: 5q & 18q - . Loss of herterzygositiy (LOH) in these regions is common during the formation of colorectal cancer, and some recognised genetic defects (e.g. FAP) are caused by LOH in these regions.
-          Over 90% of colorectal carcinomas show 2 or more of the above mutations, 40% show three or more. It is the number of mutations, and not the order that affects the development of cancer.

Malignant Disease
General Presentation
-          Iron Deficiency Anaemia
-          Weight loss
-          Malaise
-          Vague abdominal pain
-          Faecal occult blood loss
-          Palpable mass (e.g. in right iliac fossa, left flank etc)
-          Obstruction
-          Altered bowel habit
-          Tenesmus (desire to defecate)
-          Rectal bleeding
-          Anal and perianal pain
-          Faecal incontinence
-          Recurrent UTI – due to fistulation to the bladder
-          Sister Mary Joseph Nodule – this is a lymph node that can be felt at the umbilicus and is a sign of metastatic spread
-          Ascites – high in protein – due to local peritoneal cavity spread

Red flag symptoms: - patients with the following should be sent for 2 week referral immediately:
-          Palpable rectal mass (any age)
-          Iron deficiency anaemia in men of any age
-          Iron deficiency anaemia in non-menstruating women of any age
-          Rectal bleeding and change of bowel habit for more than six weeks in patients over 40
-          Rectal bleeding for 6 weeks or more in anybody over 50
-          Anybody with a palpable rectal mass

-          Usually occurs locally through the bowel wall, and to local lymph nodes
-          Spread to the liver is relatively common

-          Faecal Occult blood
o   Guaiac test – for Hb breakdown products. 98% specific, but only 40-80% sensitive
o   Antibody test – uses antibodies that bind to human blood to test for the presence of blood.
-          Routine biochemisty – U+E’s, FBC, LFT’s, CRP, ESR
-          Colonoscopy – Investigation of choice!
-          Barium enema – in cases where colonoscopy cannot be performed
-          USS/CT – can asses bowel wall thickness as well as looking for metastatic spread

Both Duke’s scale, and TNM are used, with a move towards TNM is recent years

The traditional Duke’s system works as follows:
-          Stage A – the tumour is confined to the mucosa – 5- year survival rate is 90%
-          Stage B – the tumour has spread through all the layers of the mucosa to the serosa. There are no lymph nodes metastasis. The 5-year survival rate is 60%
-          Stage C – the same as stage B, but there is lymph node involvement. Survival is about 30%. 
o   C1 – there is local lymph node involvement
o   C2 – there is distant lymph node involvement
o   C2 caries a worse prognosis than C1
-          Stage D – this category was not originally included, but later added to refer to disease with wide spread metastatic involvement.

-          80% of patients will have surgery
-          Resection is the treatment of choice for Dukes A-C
-          Radio and chemotherapies may be used as adjuvants in Dukes B-C, and as palliative treatments in Dukes D
-          Surgery
o   You should remove 2cm either side of the tumour (5cm in all directions in the rectum)
o   Can be a laparotomy or laparoscopy
o   Anastomosis is usually, although not always made afterwards

Genetic Disorders associated with Colorectal Cancer
Familial Adenomatous Polyposis (FAP)
-          Accounts for 1% of cases, prevalence is 1 in 10 000
-          Autosomal dominant
-          Patients inherited a ‘bad copy’ of the APC gene on chromosome 5. They have one remaining ‘good copy’ of the gene, which is still liable to mutation, and when it does, polyposis results
-          90% of these patients will develop bowel cancer

Hereditary non-polyposis colorectal cancer (HNPCC)
-          Autosomal dominant
-          Average onset of cancer is in the mid-forties
-          Despite the name, polyps are often still present
-          Also increase the risk of cancer in the small bowel, stomach, and other regions

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