Gastrointestinal Malignancy Conditions, Signs, Causes And Differentials

Question 1

What are the most common symptom of bowel cancer?

Answer 1

Sudden change in bowel habits (not a gradual change) - loose stools or hard stools and constipation

Rectal bleeding

Weight loss

Bowel obstruction:
Colicky abdominal pain (peristaltic motion) caused by eating
Abdominal distension (bloating) caused by eating
Appetite loss

Microcytic anaemia:
Fatigue
Dyspnoea
(occult/frank blood loss)

Question 2

What is Lynch syndrome?

Answer 2

Another name for hereditary non-polyploid colorectal cancer (HNPCC).

It is an autosomal dominant condition caused by a defect in mismatch repair genes.

It is the most common hereditary colorectal cancer syndrome - Familial cancer

Question 3

What is the pathophysiological sequence of normal colon to colorectal cancer?

Answer 3

Normal epithelium
Early adenoma
Intermediate adenoma
Late adenoma
Carcinoma

Sequence of mutations:

1. APC; tumour suppressor gene - adenamotous polyposis coli, a cell cycle entrance gene and the inherited mutation in FAP
2. K-RAS; oncogene
3. DCC; tumour suppressor gene
4. MMR; tumour suppressor gene - mismatch repair of DNA bases
5. P-53; tumour suppressor gene

Question 4

What is familial adenomatous polyposis?

Answer 4

FAP: A premalignant condition, it can vary in its inheritance. One example is an autosomal dominant mutation that can occur in one of the two APC genes on chromosome 5q. Another example is mutation of the MUTYH gene, an autosomal recessive gene.

It means that the patient will develop lots of polyps (adenoma) and will develop CRC: incidence of CRC is almost 100%.

MOA for the APC route: Two-hit hypothesis, means once the second APC gene is mutated or deleted, CRC is much more likely to develop.

95% penetrance of APC dominant gene(- no who express genes/no who carry genes)

Onset = 20-30’s; CRC while young - “Fapping while young”

Question 5

What does K-RAS do?

Answer 5

A GTPase signal transducer, one of the key genes mutated in the development of CRC.

An oncogene - permanently encouraging growth and proliferation.

Found mutated in 60% of CRC.

Question 6

What does the P-53 gene do?

Answer 6

P-53 is a tumour suppressor gene.

MOA: Increases in response to cellular stress, and arrests cell cycle, thereby inducing apoptosis.

Rarely found mutated in adenomas, normally one of the final genes to mutate in carcinomas.

Question 7

What is hereditary non polyposis colorectal cancer?

Answer 7

HNPCC: An inherited mutation in the mismatch repair (MMR) genes.

MOA: The mutation makes the DNA more prone to error during replication (the microsatellites are unstable), which increases the likelihood of a successful carcinoma developing.

70-80% penetrance.
Onset 30-50’s; CRC while young.
This has a rapid progression from adenoma to carcinoma - the WORST midlife crisis.

Most common HNPCC gene mutations are in:
MLH1 and MSH2 - these account for >90% of HNPCC

Question 8

Where does CRC most commonly occur in the bowel?

Answer 8

Sigmoid colon/rectum = 40-50%

Breakdown:
Sigmoid colon - 35%
Caecum - 22%
Rectum - 14%
Acs colon - 12%
Trans colon - 10%
Desc colon - 7%

Question 9

What are the anatomical forms of a colorectal malignant lesion?

Answer 9

Polyp, ulcer or circumferential lesion

Question 10

What are the six red flags for colon cancer?

Answer 10

Family history of bowel cancer
Unexplained weight loss
Anaemia
Change in bowel habits in a person over 60
Rectal bleeding 
Rectal/abdominal mass

Question 11

How might an elderly person differ from a younger person in their presentation of bowel cancer?

Answer 11

Less specific symptoms and signs - harder to diagnose, that’s why they need such a high degree of suspicion when presenting with bowel habit changes.

Question 12

Where does CRC spread to?

Answer 12

Liver
Lung
Bone