6 - Lower GI Malignancy Flashcards
What are the RF for colorectal cancer?
What are the histological subtypes of polyps?
Adenomatous polymps (adenomas)
Hyperplastic polyps
Sessile serrated polyps
Non-neoplastic polyps (inflammatory)
What is the stepwise progression from normal bowel mucosa to bowel cancer known as?
Adenoma-carcinoma sequence
What is the peak incidence age for polyps and for BC?
Polyps = 60
BC = 71
How can polyps be managed?
They can be endoscopically removed during a colonoscopy or they can be surgically resected if too large.
Once a polyp has been removed - what determines whether further treatment is needed?
Depth of invasion
Which two scales predict lymphatic involvement for polyps?
Haggitt level (pedunculate)
Kikuchi level (sessile)
What age does screening for CRC take place? What is the process of screening?
From age 60-74 - although currently transitioning to 50.
Screening process = qFIT
How to most cases of CRC present?
1/3 from screening
Some incidental on screening for polyps
Most are from symptomatic Ps
25% are as an emergency presentation - e.g. BO
What symptoms could be suggestive of CRC?
A combination of sx are more likely to be indicative of CRC
- e.g. IDA and CIBH - 10% PPV
Which is the strongest single predictor of underlying bowel cancer?
Iron deficiency anaemia - has a PPV of 5%
Significant anaemia is more concerning - Hb<90 has a 10-15% PPV for CRC
What is the commonest cause of iron deficiency anaemia?
Coeliac disease
What is the diagnostic criteria for iron deficiency anaemia?
Hb <130/L M and <120/L F
Hypochromic / microcytic anaemia (low MCH / MCV)
Low ferritin levels
Transferrin sat low
When should you be more concerned about a CIBH?
When there are nocturnal Sx as these are not present usually in IBS. IBS usually biggest cause of CIBH.
How can CRC present as an emergency?
Acute PR bleeding
Bowel obstruction
Bowel perforation
Fistula formation
Infection/abscess
What does qFIT detect?
Presence of human globin in stool
What diagnostic imaging can be uses for CRC?
Colonoscopy - gold standard
Flexible sigmoidoscopy
Virtual colonoscopy (can’t see small <6mm polyps)
Which tumour marker is linked to CRC?
CEA
How is CRC staged?
Colonoscopy = biopsy - can then identify tumour immunohistochemically
CT Abdo, Chest & Pelvis
MRI - used for rectal cancer as colon to mobile for MRI (therefore CT needed)
PET - more often used for other types of cancer
Tumor marker - CEA
What Tx is available for CRC?
Radiotherapy (rectum only - again colon too mobile)
Surgery
Chemo
Immunotherapy
What temporary procedure can be used in emergency presentation as a bridge to surgery in CRC?
Insertion of a stent into the colon - can also be used as a palliative measure.
What are predictors of poor outcomes in CRC?
What does Lynch syndrome cause?
Genetic abnormalities to the mismatch repair genes - means that mutations in oncogenes or tumour suppressor genes are easier to acquire.
Different abnormalities to different mismatch repair genes give you different risk of different cancers - MLH1 and MSH2 are the biggest risks for endometrial and CRC.
Also inc risk of endometrial, renal cell, breast, upper GI and prostate cancers depending on phenotype.
Which criteria is used to identify families at risk of Lynch?
The Amsterdam criteria
How is Lynch syndrome managed?
Surveillance of colon every 2 years from 25 or 35 years depending on type of MMR gene affected.
Fs - should have hysterectomy and bilateral salpingo-oopherectomy from age 40.
Aspirin daily reduces risk of CRC by 50%.
Counselling
What is the commonest type of CRC?
Adenocarcinoma
What type of cancer involves the anus?
Anal squamous epithelial cancer
Why are rates of anal cancer expected to fall in the future?
Anal cancer is almost 100% caused by HPV 16 & 18 - is hoped that the HPV vaccination will almost remove the chances of getting anal cancer.
How do patients with anal cancer present?
PR bleeding
Anal mass
Anal pain
What is the pre-malignant phase of anal cancer known as?
Anal intra-epithelial neoplasia (AIN)
How is AIN graded? What percentage of these will progress to anal cancer?
AIN headed I to III
9-13% of Grade III will progress to anal cancer if untreated
20% of AIN III will regress to AIN I
How is AIN managed?
Confirm diagnosis = biopsy
Tx - can remove new anal / perianal lesions with surgery / laser / topical.
SCC is radiosensitive but relatively chemo resistant - primary treatment is radiotherapy.
Persistent or recurrent disease is treated with radical salvage surgery = extra-levator abdominoperineal excision (ELAPE)
What is the prognosis of anal cancer?
80% 5 year survival for non-metastatic disease
How common is CRC in the UK?
3rd most common cancer for M and F
Why is CRC more common in the West?
To do with dietary habits
What does survival depend upon for CRC?
Stage at presentation
What are the RF for bowel cancer?
What are the RF for squamous cell carcinoma of the anus or rectum?
Anal sex
Multiple sex partners
HPV
Immunosuppression - HIV / LT immunosuppressive drugs
What are the histological classifications of bowel cancer?
Adenocarcinoma - 90%
Squamous cell
Adenosquamous type
Neuroendocrine
Spindle cell
Where does adenocarcinoma arise from?
Glandular tissue
What is adenosquamous carcinoma?
Uncommon malignant neoplasm of the skin characterized by mixed squamous and glandular differentiation and aggressive clinical behavior, such as extensive local invasion, recurrence, and rare metastasis.
What is spindle cell sarcoma?
A rare malignant (cancerous) tumour which can develop in the bone or soft tissue. It can arise in any part of the body but is most common in the limbs (arms and legs).
In which part of the bowel is squamous cell carcinoma most commonly found?
Anus, Rectum and rectosigmoid junction
In which part of the bowel is adenocarcinoma most commonly found?
Can be found anywhere but large majority are found in the sigmoid colon and the caecum
Mutations of which tumour suppressor genes can lead to evasion of growth suppression of cells?
TP53
RB
Which type of pathways are responsible for proliferative signalling in cells?
How do cancer cells alter these?
Tyrosine kinase pathways
Cancer cells deregulate these pathways - allowing them to sustain proliferation without regulation.
Which cell adhesion molecule is down regulated by cancer cells to allow cells to invade and metastasise?
E-Cadherin
Which growth factor is linked to induction of angiogenesis by cancer cells?
VEGF
Down regulation of what in cells enables cancer cells to resist death?
Loss of P53 and dowregulation of BCI2 and RIP kinases
How can cancer cells avoid immune destruction?
They can lower their MHC1 expression to avoid detection
They cal also destroy apoptotic signalling pathway molecules - such as Cascade 8, VCL2 and IAP.
Which is the most common hereditary bowel cancer?
What risk of colon cancer does this give a patient?
What is the mean age of diagnosis?
HNPCC - Lynch Syndrome - is AD
80% lifetime risk of colon cancer
Mean age of diagnosis = 44-61 years
What type of cells are seen in cancer caused by Lynch Syndrome?
Mucinous adenocarcinomas - poorly differentiated
How does Lynch syndrome cause colon cancer?
It causes a germline mutation in one of the mismatch repair genes (MLH1, MSH2, MSH6, PMS2). This increases the risk of cancer as nucleotide base mistakes are not corrected during DNA replication.
How does Familial Adenomatosis Polyposis cause colon cancer?
Is an AD condition
It causes a loss or mutation of the APC gene at Chr 5. When this suffers an inevitable second hit => multiple polyps (hundreds) = inevitable progression to cancer.
What is the prognosis for Ps with FAP?
Not great - if untreated majority will die in their 4th decade
What is the treatment for FAP?
Total or partial colectomy +/- proctecomy (removal of rectum)
Prophylactic NSAID use
Why can colon cancers metastasise to the liver?
Due to the portal circulation - blood from the gut is drained directly to the liver. Just because you have liver mets doesn’t mean you will have mets elsewhere.
