Colorectal cancer Flashcards
Where does the colon start and end?
terminal ileum to anal canal
How long is the colon?
1-1.5m long
Name the different parts of the colon
Caecum -> Ascending Colon -> Hepatic flexure ->Transverse colon -> Splenic flexure -> Descending colon, sigmoid -> Rectum
Which arteries supply which regions of the colon?
Superior mesenteric artery (caecum - splenic flexure)
Inferior mesenteric artery (remainder of colon - rectum)
What are the common symptoms of right sided polyps?
less overt blood, intussusception (rare, one part of intestines goes into the other),
constipation, diarrhoea, obstruction
What are the symptoms of left sided polyps?
frank blood, constipation, diarrhoea,
obstruction
What are inflammatory polyps? Which conditions are the often associated with?
Polys caused by repeated cycles of injury and healing
non-neoplastic
They consist of a mix of epithelial and stromal elements
may be associated with inflammatory bowel disease, surgical anastomosis or with other causes of inflammation (eg: ischaemic colitis, infection)
incidence of ~10-20% in patients with ulcerative colitis
What are the histological features of a inflammatory poly?
may be relatively normal with a polypoid shape
may have ulceration, erosion and distortion of the normal crypt architecture
What is a hyperplastic poly? How large are they usually and on which side do they most often present?
Serrated polyp (saw tooth appearance) Due to reduced cell turn over Non dysplastic (non cancerous) asymptomatic Most common type of polyp Up to 5mm in size, rarely greater than 10mm More common on the Left sided
Hyperplastic lesions are usually not malignant. Under which circumstances are hyperplastic lesions at an increased risk of becoming malignant?
If they are sessile
SESSILE SERRATED LESIONS/POLYPS/ADENOMAS
What are hyperplastic sessile serrated polyps? How large are they?
They are Neoplastic masses with premalignant features (have the potential to be malignant)
Account for up to 9% of all colorectal polyps
>10mm in size (larger than nomal hyperplastic polyps)
SERRATED architecture, with crypt dilatation and MAY HAVE low-grade or high-grade dysplasia.
Which mutation is hyperplastic sessile serrated polyps associated with?
BRAF mutation (microsatellite instability)
What are Hamartomatous polyps, which mutations lead to their development, in which age group do they occur in and what do they often look like?
Polys that occur due to germ line mutations in tumour suppressor genes or proto oncogenes. They tend to occur in children and young adults. Mostly perduculated?
Name the 2 main types of Hamartomatous polyps?
Peutz-Jegher
Juvenile polyps
What are Peutz-Jegher polyps?
Autosomal dominant defect
Cuases multiple Hamartomatous polyp and mucocutaneous pigmentation
muscularis mucosa
Usually Manifest early (with first or second decade of life) - but can occur at any age
Does not undergo malignant transformation
But condition causes an increased life time risk of cancer
CAN develop into dysplasia and adenocarcinoma
Increases life time risk of developing breast, cervical, uterine, pancreas, and lung cancer
What is the criteria for the diagnosis of PEUTZ-JEGHER SYNDROME?
(a) 3 or more PJ polyps
(b) any number of PJ polyps with family history of PJS
(c) characteristic mucocutaneous pigmentation with family history of PJS
(d) any number of PJ polyps and mucocutaneous pigmentation
Which mutation is responsible for Peutz-Jegher polyps?
STK 11 mutation - tumour suppressor gene
On chromosome 19
What are Juvenile polyps, describe histological features, size, and usual age of onset?
Polyps which effect children under the age of 5.
Sessile or pedunculated, 5-50mm in size
similar to inflammatory polyps but usually have
cystically dilated crypts
What are the different types of Juvenile polyps ?
One polyp (no family history) = Retention polyp
Juvenile polyposis Syndrome= 5 or more juvenile polyps in Colo rectum
Or
Juvenile polyps throughout GI tract or any
number of juvenile polyps + family history.
What is the inheritance patter of Juvenile polyps and Peutz-Jegher polyps?
Autosomal dominant
There are 3 types of adenomas, name them
Tubular, villous, tubulovillous
What is the most common type of adenoma in colorectal cancer?
Tubular adenomas?
Which gene mutation is found in Juvenile polyps?
SMAD 4 gene
Which type of colorectal adenoma has the highest malignant potential?
Villous adenoma
What are the features of a colorectal adenoma that indicate it is at risk of malignancy and invasion?
Size: <1% if <1cm vs 10% of >2cm • Number: 3 or more • Architecture: villous component • Dysplasia: high-grade
presence of an invasive carcinoma
What is the Adenoma-Carcinoma Sequence and how long does it take to progress?
Time for progression: 5 to >20 years
•
Includes various mutations: APC, Beta-catenin, KRAS
and TP53
•
Associated with microsatellite instability
Which type of cancer is most commonly responsible for colorectal cancer?
ADENOCARCINOMA
What is the peak age incidence for colorectal cancer? What which age of presentation would a genetic cause be likely?
60-79 years
<20% before age 50
if before age 40, probably related to syndrome
On which side of the body is colorectal cancer most common? On which side does colorectal cancer present latest?
Left sided more than right sided
Present later on the right side
What are the risk factors for colorectal cancer?
older age
obesity
Smoking
physical inactivity
alcohol consumption
IBD
family history
Adenomatous polyposis syndromes
FAP (Familial adenomatous polyposis)
lynch syndrome, juvenile polyposis, PJS
DIETARY RISK FACTORS
low fibre, increased beef (red meat)
consumption
What are the symptoms of colorectal cancer? (difference between left and right)
Right: Often presents late, abdominal pain, anaemia, pain, Mass in right iliac fossa, occult bleeding
Left: change in bowel habit (pencil like stool), rectal bleeding, Presents earlier, may present with bowel obstruction, tenesmus, mass in lower iliac fossa or PR exam
Patient may be asymptomatic
Other include
- Unintentional weight loss
- Iron deficiency anaemia
- Change in bowel habits
- Abdominal masses
- Blood in stool
- Tiredness (malaise)
- Tenesmus (feeling of incomplete bowel evacuation)
Which tests are conducted for colorectal cancer screening?
Colonoscopy (Flexible sigmoidoscopy),
Faecal occult blood test,
Faecal Immunochemical Test
Which features would require a patient to be referred to the 2 week colorectal cancer pathway?
Aged 40 and over with unexplained weight loss and abdominal pain
Aged 50 and over with unexplained rectal bleeding
Aged 60 and over with:
Iron-deficiency anaemia or
Changes in their bowel habit
Patients with tests showing occult blood in their faeces
Patients with rectal or abdominal mass
Consider in any patient under 50 with -
- Abdominal pain or
- Change in bowel habit or
- Weight loss or
- Iron-deficiency anaemia
What are the common metastatic sites for colon cancer?
lymph nodes liver (most common) peritoneum lung ovaries
What is the general prognosis for someone with colorectal cancer?
5 year survival: 40-60%
Most recurrences are within two years
What are poor prognostic features of colorectal cancer? (6)
High stage,
positive margins - Cancer cells come right out to the edge of the removed tissue
Poor differentiation- Tumour cells no longer look like normal cells - indicates high grade tumour
Tumour budding
Tumour perforation- Tumour has caused a hole in he bowel so cancer cells can spread
Involvement of
peritoneal cavity - Cancer has spread to the peritoneum (metastasis)
What is the staging for colorectal cancer?
Tx: Primary tumour cannot be assessed T0: No evidence of primary tumour Tis: Ca in-situ T1: Tumour invades submucosa T2: Tumour invades muscularis propria T3: Tumour invades through muscularis propria T4: T4a: Tumour invades serosa/visceral peritoneum T4b: Tumour directly invades or adheres to adjacent organs or structures Nx: nodes cannot be assessed N1: metastasis in 1-3 nodes (N1a=1; N1b=2,3; N1c: soft tissue deposit; no nodes) N2: metastasis in 4 or more nodes (N2a: 4-6; N2b: 7 or more)
M0- No distant metastasis by imaging; no evidence of tumor in other sites or organs
M1- instant metastasis
1a - Metastasis confined to 1 organ or site without peritoneal metastasis. Also non regional lymph node spread
M1B Metastasis to 2 or more sites or organs is identified without peritoneal metastasis
M1C - Metastasis to the peritoneal surface is identified alone or with other site or organ metastases
Causes of angular stomatitis?
Iron deficiency anaemia
Crohn’s
What does Tumour budding mean?
The presence of single tumour cells or small tumour clusters of up to five cells. These “buds” are detached from the main mass and are
usually located in the stroma at the invasive front of the tumor.
Which investigations (imaging)are conducted in someone with suspected colorectal cancer (not screening)
Colonoscopy (to the terminal ilium)
Flexible sigmoidoscopy may also be used in individuals not able to undergo colonoscopy, with left sided lesions
In those not suitable for, or declining endoscopy a CT pneumocolon (CT virtual colonoscopy) may be used to identify lesions. Should also be used for the with right sided features when full colonoscopy can not be conducted
In those unable to tolerate a CT pneumocolon, a plain CT abdomen/pelvis (with or without contrast)
What is the difference between a Colonoscopy and a Flexible sigmoidoscopy?
Colonoscopy ends at the terminal ileum
Flexible sigmoidoscopy ends at the splenic flexure
What are the disadvantages of conducting a CT pneumocolon & CT abdomen/pelvis over a colonoscopy?
Does not allow removal of polyps or biopsy of lesions.
Some lesions may be missed.
Which FURTHER investigations are conducted on a patient suspected to have colorectal cancer?
Bloods- FBC Serum iron, transferrin saturation, TIBC Renal function LFT Clotting screen
Tumour markers (NOT FIRST LINE) used to monitor treatment or as a marker of recurrence or to assess disease burden - not specific enough to use for a diagnosis Carcinoembryonic antigen (CEA)
CT chest abdo and pelvis with contrast- Assess disease burden and sites of metastasis
MRI Mesorectum rectum- Better stage rectal tumours
Endoanal USS: Better stage rectal tumours
PET/CT - not routinely used, may help with staging when recurrence occurs
MRI liver- Assess liver metastasis
List the different types of colorectal cancer
Adenocarcinoma and subtypes • Adenosquamous carcinoma • Squamous cell carcinoma • Neuroendocrine carcinoma
Which types of polyps are malignant, which are not and which have the potential to be malignant.
Malignant -
All adenomatous polyps
Non malignant
Inflammatory
Hyperplastic
Hamartomatous
Potential -
Sessile hyperplastic polyps
What are the hereditary syndromes associated with adenomatous colorectal polyps?
Lynch syndrome -
Adenomatous polyposis syndromes including
Familial adenomatous polyposis (FAP)
Gardner syndrome
Turcot syndrome
MUTYH polyposis
All autosomal dominant conditions
Describe lynch syndrome. On which side does it usually present?
Most common inherited cause (Hereditary nonpolyposis colorectal cancer)
Caused by mutation to DNA mis match repair genes
Does not cause extensive polyps
Usually right sided
Increases risk of other malignancies e.g endometrial, ovary, small bowel, stomach and liver
Describe FAP
Caused by a mutation in the adenomatous polyposis coli (APC) gene
Usually presents in adolescents
Patients develop many colonic polyps (>100)
If not treated 90% will develop colon cancer before the age of 45
Increases risk of other cancers e.g. thyroid, pancreatic and hepatoblastomas
What is the most common treatment for colorectal cancer?
Surgical resection with a temporary stoma to to protect the anastomosis between the proximal and distal segments of remaining bowel
Stoma is usually reversed after several months
List the different surgical types and when they are used?
Tumour in cecum or ascending colon = Right hemi-colectomy
Cancer on the right side involving the transverse colon = Extended right hemicolectomy
Anterior resection and loop iliostomy - used for right recal tumours (greater than 5cm from the anal margin) (loop ileostomy is reversed)
Left hemicolectomy and end colostomy - for left sided tumours
How can you roughly differentiate a colostomy from an ileostomy?
Colostomy-left hand side
Ileostomy - Right hand side
Which gene is responsible for FAP?
adenomatous polyposis coli
Which type of polyp is most likley to cause intussusception?
Juvenile polyps
List 3 differential diagnosis for colorectal cancer
Diverticulitis
IBD
Large bowel lymphoma
