U10W5: Colorectal cancer Flashcards
What are some of the biological risk factors for colorectal cancer?
Age - longer time to accumulate mutations
Family history - genetic diseases such as FAP and Lynch syndrome
Inflammatory Bowel Disease
Previous Cancer - genomic instability
Diabetes - abnormally high insulin and abnormally high blood glucose - plentiful glucose for cancer cell growth
Gallstones - long term inflammation
Acromegaly - elevated growth hormones increase proliferation
Benign polyps in bowel - increase proliferation, higher chance of genomic instability
H.pylori infection - CagA cancer causing
What are some of the lifestyle risks for colorectal cancer?
Diet of high red and processed meat - breakdown of heme in gut releases N-nitroso chemicals that damage the bowel
Diet of very little fibre - fibre helps expel carcinogens in faeces
Overweight or obese - abnormal metabolites and inflammation promotion, increased levels on insulin
Low levels of exercise
Smoking tobacco - carcinogens, free radicals damage DNA.
Alcohol - acetaldehyde damages DNA
Radiation - such as UV in suntan.
How common is colorectal cancer?
4th most common cancer
Apprx 43,000 people are diagnosed a year
What is FAP? How does it increase the risk of colorectal cancer?
Mutation in APC - loss of function of TSG - on chromosome 5q21
Autosomal dominant pattern
Leads to a loss of
- phosphorylation and ubiquitination of Beta Catenin - so becomes free to act as Transcription factor
- Activation of Myc transcription factors
- initiate proliferative signals even in the absence of Wnt ligand.
results in large number of polyps int he distal colon, each has a small risk of becoming cancerous but the combined risk is high.
How does Lynch syndrome increase the risk of colorectal cancer?
Many genetic mutations are involved
MLH1, MSH2, MSG6, PMS2 -these are responsible for DNA mismatch repair
EPCAM - indirectly inactivate MSH2
Autosomal dominant
Results in small number of polyps in the proximal colon each has a high risk of becoming cancerous
What are the typical symptoms of colorectal cancer - specific to this?
Anaemia leading to fatigue
Abdominal mass
Unexplained weight loss and Abdominal pain - from obstruction
Rectal bleeding
Unexplained weight loss - cachexia (consumption of glucose by cancer cells) and tumour competing for nutrients, promotes gluconeogenesis
Change in bowel habit
Occult blood in faeces
Rectal mass
What are the general symptoms of cancer?
Unexplained weight loss
Appetite loss
Deep vein thrombosis (urogenital, breast, colorectal or lung)
Bleeding
Lumps
Bloating
Fatigue
Pain
What are the stool changes associated with colorectal cancer? Why does this happen?
Change is bowel habits - vary from constipation to diahorrea
Constipation - narrowed lumen as tumour grows into lumen (most common in descending colon napkin ring constriction)
Diahorrea - only liquid pass through narrowed lumen
Tenesmus - rectal tumour,activate stretch receptors and pressure in rectum
Blood - angiogenesis in tumour, new capillaries are fragile and easily burst
Mucus - tumour secreted- enhanced goblet cell function
Narrow ribbon like - narrowed lumen
What causes bright red blood in the rectal bleeding?
Normally from lower down near the rectum
Sign - colorectal cancer, anal fissures, colon polyps, crohns disease, diverticulitis, hemorrhoid, ulcerative colitis
What are the causes of dark brown blood in the faeces?
Upper GIT bleed
Crohns disease, eosophageal cancer, eosophageal carcies, eosophagitis, gastritis, GERD, liver cancer, pancreatic cancer, peptic ulcers, stomach cancer
How can you differentiate the cause of GI bleeds?
Rectal exam - hemorrhoids, anal tumour, anal fissures etc
Colonscopy - IBD, polpys, colorectal cancer
Endoscopy etc
CT scan, MRI, X-ray - identify tumours and collections of fluid
Angiography - make GIT blood vessels easier to see
Radiomuclide scan - radioactive highlight of rbcs in scan
What are hemorrhoids? Cause and clinical presentation
Cause: prolonged constipation - lack of fibre in the diet.
Same as piles
Swollen veins in the anus and lower rectum
Internal and external haemorrhoids are separated by the pectinate line.
Internal: painless bleeding during bowel movements, may prolapse which causes pain and irritation, stain when passing stool.
External: pain or discomfort, itching or irritation, swelling around the anus, bleeding
Can become thrombosed
What is diverticula/ diverticulitis? Cause and clinical presentation
Formation of diverticula – small pouch like protrusions in bowel wall (SC most likely) - areas not covered by Tenai coli.
Diverticulitis – when outgrowths become inflamed
Increased pressure in colon – presses on mucosa and submucosa bubble out through weak spots.
Weaken and burst blood vessels in the wall – leading to bleeding.
Bacteria and food can live in pouches causing infection. - lead to abscess
Can cause bowel obstruction, peritonitis if ruptures and fistulae.
Painless blood in faeces.
Often incidental diagnosis.
What are the treatments for diverticular disease?
Surgery to remove affected part of bowel
Bulk forming laxatives (increase feacal mass to stimulate peristalsis)
Should AVOID stimulate laxatives
What are the treatments for acute diverticulitis?
Oral co-amoxiclav
Anagesia (avpid NSAIDs and opiates)
Nill by mouth or clear liquids only
Follow up in 2 days to review symptoms
Patients with severe symptoms should be admitted to hospital and treated as other abdominal infections or sepsis patients.
What are the symptoms of acute diverticulitis?
Pain and tenderness in the left illiac fossa
Fever
Diarrhoea
Nausea and vomiting
Rectal bleeding
Palpable abdominal mass
Raised inflammatory markers
What are some common complications of diverticula?
Perforation
Peritonitis
Peridiverticula disease
Large haemorrhage requiring blood transfusions
Fistula
Ileus /obstruction
What are some risk factors for diverticulosis?
Increased age
Low fibre diets
Obesity - changes in gut microbiome can exaggerate diverticulosis symptoms
NSAIDs - increased risk of diverticular haemorrhage
What are the major types of polyp?
Pedunculated polyps - head attached by stalk to mucosa
Sessile polyps - relatively flat base attached to colon wall
Flat polyps - height less than one half of diameter
Depressed polyps - more likely high grade dysplasia
What types of polyps are considered to not have malignant potential?
Hyperplastic polyps - normal cellular components and architecture but increased proliferation, no dysplasia and characteristic serrated pattern
Hamartomas - tissue elements normally found there but growing in disorganised mass
Inflammatory pseduopolyps - IBD ulcerations with islands of healing/healed mucosa between
What types of polyps have malignant potential?
Adenomatous polyps
Serrated polyps ( traditional serrated protuberant growth and vilifrom projections sessile serrated serrations extend to crypt base and diated L or inverted T shaped crypts)
What are the different types of adenomatous polyps?
- Tubular adenomas - branching adenomatous in tubular shape, >75% glandular
- Villous adenoma - long extending glands from surface to centre >75% villous
- Tubulocvillous adenomas - mixture of both structures
What type of polyp has the highest malignant potential?
Tubulovillous adenoma
What are the risk factors in a polyp for malignant potential?
Villous histology
Increasing polyp size
High grade dysplasia
What are the histological features of dysplasia in the colon?
Hyperchromatic nuclei
Pseudostratified
Loss of goblet cells
What are the structural features of the villous?
Tubulovillous adenoma
tubulo on the left
Vilous on the right
What are some possible histological features of a polyp in the colon?
Increased mucin aand goblet cells
Hyperplastic with pseudostratified epithelium
Hyperchromatic
High grade dysplasia - poorly defined cell borders and poor representation of original cell structure, basal cells replace epithelium , mitotic cells present closer to the epithelium surface.
What are the histological features of Grad 1 tumour in colon?
Nuclei are uniform in size and shape
Low mitotic activity
Well-formed glandular structures - resembling normal tissue
Minimal abnormalities
Typically confined to the mucosa or with slight extension into the submucosa
What are the histological features of grade 2 colorectal tumours?
Variation in nucleus shape and colour as variation in chromatin
Increased mitotic activity
Glandular structures are somewhat displaced
Some tissue disorganization and dismoplasma (connective tissue growth)
Some clear abnormalities
Extend into submucosa or muscularis
What are the histological features of grade 3 colorectal tumours?
High grade cancer
Nuclei are very different in size and shape and are often hyperchromatic
High mitotic activity
Disrupted glandular structures or absence of recognisable glands
Architecture is highly distorted
Desmosplasia
Lumen of cell may contain necrotic depbris
Muscularis is fully involved and may be extension in adjacent structures
What is the difference between staging and grading of cancer?
Grade - degree of dysplasia/differentiation in the tumour itself (more histological)
Staging - more focused on tumour size, location and spread
How do tumours develop from a polyp, to an adenoma to a carcinoma?
Common pathway
1.Normal epithelium and glandular tissue
2. Loss of APC gene - small adenoma/polyp
3. Oncogenic mutation is Ras gene - large adenoma/polyp
4. Mutation or loss of function in p53 - invasive and malignant colon cancer or adenocarcinoma