Colorectal Cancer Flashcards
Two categories of colorectal neoplasia?
Benign (adenoma)
Malignant (adenocarcinoma)
Types of colorectal polyps?
Inflammatory, e.g: in IBD
Hamartomatous are juvenile polyps
Metaplastic (change in mature mucosal type)
Neoplastic (ADENOMAS)
2 types of neoplastic polyps (adenomas) and which is assoc. with an increased malignancy risk?
Tubular - formation of glands and tubules
Villous - formation of villi (increased risk of malignancy)
Explain the steps in the adenoma-carcinoma sequence
- Small adenoma forms when there is the 1st mutation, usually in the APC gene (adenomatous polyposis coli)
- Large adenoma forms when other mutations occur, e.g: commonly in the Kras gene
- Mutations occur in p53 and other important genes; also, there can be chromosomal deletions
Which chromosomal deletion is assoc. with invasive cancer?
18q loss
4 gene types assoc. with cancer and their role?
Oncogenes - promote cell growth and division but, when mutated, cause excess growth and division
Tumour suppressor genes - suppress growth and division but, when mutated, allow cell growth and division
Macroscopic appearance of colorectal cancer?
Polypoidal - tumor arranged as finger-like processes or as a solid spherical nodule projecting from an epithelial surface
Ulcerative -
Annular - grow centripetally (ring-like) forming what radiologists call an apple core lesion, that constricts the colon
In which regions does colorectal carcinoma tend to occur?
Rectum, distal sigmoid colon and then caecum
3 types of adenocarcinoma, in relation to differentiation, and that these phrases mean?
Well differentiated - there are still normal features of the tissue, e.g: mucin producing
Moderately differentiated
Poorly differentiated - can no longer determine original tissue
Two staging methods of colorectal cancer?
Dukes’ - A, B, C and D
TNM (Tumour, Node, Metastases)
What do Dukes A, B, C and D mean?
A - limited to muscularis mucosae
B - extension through muscularis mucosae
C - involvement of regional lymph nodes
D - distant metastases
Explain the TNM staging?
T1 - submucosa only
T2 - into muscle
T3 - through muscle
T4 - adjacent structures (including peritoneum)
N0 - no lymph node involvement
N1 - 3 nodes involved
M0 - no distant metastases
M1 – distant metastases
What does local spread mean?
To adjacent structures
What does lymphatic spread of colorectal cancer mean?
To pericolic nodes and/or perivascular nodes
What does blood spread of colorectal cancer mean?
Usually, to liver and lungs
What does transcoelomic spread of colorectal cancer mean?
Peritoneal cavity
3 factors contributing to colorectal cancer development?
Environment, genetic factors and predisposing conditions
Protective factors against development of colorectal cancer?
Vegetable, fibre and EXERCISE
Causative factors against development of colorectal cancer?
Red and processed meat, smoking, alcohol and OBESITY
Describe the role of AMP kinase (AMPK) in colorectal cancer development
LKB1 (a tumour suppressor) activates AMPK, which increases glucose uptake my muscle cells and decreases cell turnover
How does exercise affect AMPK?
Exercise increases the activity of AMPK and so there is less cell turnover (and increased glucose uptake by muscle cells)
Two types of autosomal dominant inheritance of colorectal cancer?
FAP (Familial Adenomatous Polyposis)
HNPCC (Hereditary Non-Polyposis Colorectal carcinoma)
Describe FAP
Germ-line mutation in APC gene that dramatically increases colorectal cancer risk
Describe HNPCC
Mutation in DNA mis-match repair gene that also increases risk of colorectal cancer
Differences between FAP and HNPCC?
FAP - many polyps forms (100s)
HNPCC - do not form as many polyps
Diseases that predispose to colorectal cancer?
Adenomatous polyps
UC
Crohn’s disease
Main symptoms of rectal carcinoma?
Rectal bleeding
Tenesmus
Main symptoms of left-sided colorectal carcinoma?
Pain
Change in bowel habit
Rectal bleeding
Main symptoms of right-sided colorectal cancer?
Anaemia (bleeding small amounts for a long time)
Clinical findings in colorectal carcinoma?
General - anaemia, cachexia, lymphadenopathy
Abdomen - mass, hepatomegaly, distension (ascites or obstruction)
Rectum - mass and blood
Main Ix for diagnosis of primary colorectal carcinoma?
Barium enema
CT colography
Sigmoidoscopy
Colonoscopy (gold standard)
Screening tests for blood in stool?
Faecal Occult Blood Testing (FOBT)
Immunochemical testing (antibodies to human Hb)
Describe FOBT
Detection of cancer depends on sensitivity; it may be useful in symptomatic patients, at high-sensitivity, as a rule-out method
For screening programmes, it is used at a lower sensitivity (otherwise, too many false positives are detected)
Investigations required to stage colorectal carcinoma?
Lungs and liver require a CT scan; for primary rectal cancer, an MRI is used
How does colorectal cancer present as an emergency?
With OBSTRUCTION, i.e: there will be distension, constipation, pain and vomiting
Bleeding
Perforation
4 treatment options for obstructive colorectal carcinoma?
Colostomy alone
Resection + colostomy
Resection + anastamoses
Stenting
Elective treatment options for colorectal cancer?
Surgery (usually, the only curative option) - draining lymph nodes must also be removed
Radiotherapy - can be adjuvant (pre or post-operative) and reduces local recurrence after rectal excision; or can be palliative
Chemotherapy - can be used as an adjuvant, in addition to surgery, or for advanced disease (e.g: oxaliplatic, irinorecan, cetuximab, bevacizumab)
Surgery types for rectal cancer?
APER - excision of rectum through the abdomen and perineum
Anterior resection - for low sigmoid/high rectal tumours
Surgery types for colonic cancer?
Right hemicolectomy
Extended right hemicolectomy
Transverse colectomy
Left hemicolectomy
Sigmoid colectomy
Subtotal colectomy
