GI CANCERS Flashcards
Define cancer
A disease caused by uncontrolled division of abnormal cells in any part of the body
Difference between primary cancer and secondary cancer (metastasis)
Primary cancers arise directly from the cells of an organ
Secondary cancers spread to an organ, either directly or by other means (blood, lymph)
Name the types of cancers based on cell type, giving GI examples for each
What age group is most commonly affected by colorectal cancer?
> 50 years (more than 90% of cases)
What is lifetime risk of colorectal cancer in men and women?
How common is it?
- 1 in 10 for men
- 1 in 14 for women
- Most common GI cancer in the West
- 3rd most common cancer death
What are the three forms of colorectal cancer?
Sporadic- Absence of family history, older population, isolated lesion
Familial- Family history, higher risk if index case is young (<50years) and the relative is close (1st degree)
Hereditary-Family history, younger age of onset, specific gene defects
e.g. Familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome)
What is the histopathology (type of cancer) for colorectal cancer?
Adenocarcinoma
Describe the progression of colorectal cancer
b) What does this mean for people who have 1 polyp?
c) What does aspirin do?
b)- They get repeat colonoscopies to check for new polyps developing
- It’s straightforward to endoscopically take polyps away before they become cancer- prophylactic endoscopic polyp/adenoma resections
c)Protects against the development of this pathway below
What are the 3 types of risk factors for colorectal cancer
Past medical history
-Colorectal cancer
-Adenoma (polyps), ulcerative colitis, radiotherapy treated patients
Family history
- 1st degree relative <55 years
- Relatives with identified genetic predisposition e.g.
- FAP
- HNPCC
- Peutz-Jegher’s syndrome (increases risk of polyp development and cancer)
Diet/ environment- socioeconomic status, smoking, obesity, carcinogenic foods
What are the locations colorectal cancers are found in?
2/3 in descending colon and rectum
1/2 in sigmoid colon and rectum (i.e. within reach of flexible sigmoidoscopy)
How do caecal and right sided colorectal cancer patients present?
Iron deficiency anaemia (most common)
Change of bowel habit (diarrhoea)
Distal ileum obstruction (late sign)
Palpable mass (late sign)
How do left sided and sigmoid carcinoma colorectal cancer patients present?
PR (rectal) bleeding, mucus
Thin stool (late sign)
How do rectal carcinoma colorectal cancer patients present?
- PR bleeding, mucus
- Tenesmus- the feeling of needing to open bowels but nothing comes out when you try
- Anal, perineal, sacral pain (late sign)
What kind of a sign is bowel obstruction in colorectal cancers?
Late sign
What kind of signs show local invasion of colorectal cancers?
What kind of signs are these?
- Bladder symptoms
- Female genital tract symptoms
These are late signs
Where can colorectal cancers metastasise to (late sign) and how can these present?
- Liver (hepatic pain, jaundice)
- Lung (cough)
- Regional lymph nodes
- Peritoneum (Sister Mary Joseph nodule is metastasis in umbilicus)
What are the signs of primary colorectal cancer and how do we find these signs?
- Abdominal mass
- Abdominal tenderness and distension- large bowel obstruction
- DRE: most <12cm from dentate line and reached by examining finger
- Rigid sigmoidoscopy
What are the signs of metastasis and complications in colorectal cancer?
- Hepatomegaly
- Monophonic wheeze
- Bone pain
What investigations are performed for colorectal cancer?
Fecal occult blood
Blood tests
Colonoscopy
CT colonoscopy/ colonography
MRI pelvis
CT chest/ abdo/ pelvis
What are the 2 types of feral occult blood tests
- Guaiac test (Haemoccult)- based on pseudoperoxidase activity of haematin
- 40-80% sensitivity and 98% specificity
- Dietary restrictions- avoid red meat, melons, horse-radish, vitamin C and NSAIDs for 3 days before test
- FIT (faecal immunochemical test)- detects minute amounts of blood in faeces (faeces occult blood)
What 2 types of blood tests are conducted when diagnosing colorectal cancer?
- FBC- anaemia, haematinics- low ferritin
- Tumour markers- CEA (carcinoembryonic antigen) which is useful for monitoring evidence of recurrence but NOT as a diagnostic tool
Purpose of colonoscopy?
- Can visualise lesions <5mm
- Small polyps can be removed- reduced cancer incidence- see pic-pedunculated polyp (with a stalk) → we put wire around it and use heat to cut it and to close wound to prevent bleeding
Usually performed under sedation
How does CT colonoscopy/colonography compare with normal colonoscopy?
- Can visualise lesions >5mm
- No need for sedation
- Less invasive, better tolerated
- If lesions identified then patient needs colonoscopy for diagnosis
When is an MRI pelvis indicated?
If you have a tumour that you think is relatively advanced
What do you look at with pelvic MRI?
- Depth of invasion, mesorectal lymph node involvement- to see whether we can do an R0 resection (take all of cancer out with good margin)
- Help choose between preop chemoradiotherapy to reduce tumour size or go straight to surgery
- No bowel prep or sedation required
CT Chest/abdo/pelvis- why is this done?
Staging prior to treatment to exclude liver or lung metastases
What is the primary management for colorectal cancer?
Surgery
What can you do to give yourself time to plan surgery for colorectal cancer?
Put a stent in or use radio or chemo
a) What do you do with a right and transverse colon obstructing carcinoma?
b) Why do you have to be more careful with a left sided obstruction?
a)- Usually they don’t obstruct because there’s more leeway for carcinoma to expand
- If it is obstructing, we can resect and join up straight away with primary anastomosis because blood supply is good so it won’t leak
b)The blood supply on left colon isn’t as good
What is a Hartmann’s procedure?
Remove the tumour but then instead of joining proximal bowel and rectum, we bring proximal bowel up to skin and do a colostomy (leaving a stoma)- called a proximal end colostomy (LIF)
We can reverse in 6 months if patient is fine
What’s the difference between a stoma on the left or right side of a patient?
- left side means colostomy (large bowel)
- right side means ileostomy (small bowel)
What can you do with a left sided bowel obstruction?
Hartmann’s procedure
We can do a primary anastomosis (joining up proximal bowel and rectum)
- We would do an intraoperative bowel lavage with primary anastomosis
- However there’s a 10% chance of leak because the blood supply isn’t the bes
We can also put in a palliative stent
Study this pic of colonic bowel supply
What are the important right sided arteries in colon?
- Ileocolic
- Right colic
- Middle colic
What are the important left sided arteries in colon?
- Left colic
- When we get to pelvis, sigmoid arteries are important
What is a right hemicolectomy?
Remove right colon then anastomose terminal ileum to transverse colon
What is an extended right hemicolectomy?
Take around 2/3 of large bowel out- right colon and part of transverse
Then do ileocolic anastomosis
What is a left hemicolectomy?
Resect left colon then anastomose remaining colon parts
Why is a rectal cancer resection difficult?
- Blood supply around rectum/anus is poor
- We can do the resection and join up the other parts but then do an ileostomy (bring up loop of small bowel to skin to divert faeces going through delicate anastomosis)
How common/lethal is pancreatic cancer?
- Relatively common and highly lethal
- 4th commonest cause of cancer death
- Rare before 45 years, most occur between 60-80 years of age
- Men > women
Where in the world is pancreatic cancer more common?
Incidence is higher in Western/industrialised countries
How is incidence relative to mortality in pancreatic cancer?
Incidence and mortality are basically the same
What is the commonest form of pancreatic cancer?
Pancreatic ductal adenocarcinoma (PDA)
When does pancreatic cancer present and how does that affect survival?
- Usually late presentation
- Overall median survival is <6 months- by the time it starts causing symptoms it’s usually too late
- 5 year survival is 0.4-5%
How resectable is pancreatic cancer?
- 15-20% have resectable disease
- Virtually all patients dead within 7 years of surgery
What are the risk factors for developing pancreatic cancer?
Chronic pancreatitis (inflammation followed by healing inflammation)
Cigarette smoking (for PDAs)
T2DM
Occupation (insecticides, aluminium, nickel and acrylamide)
Cholelithiasis, previous gastric surgery and pernicious anaemia- Weak link
Diet (increased fat and protein, less fruit and veg, coffee and EtOH)- weak link
7-10% have a family history
List inherited syndromes that are associated with an increased risk of pancreatic cancer
Describe the commonest pathogenesis for pancreatic cancer
Pancreatic Intraepithelial Neoplasias (PanIN)
- PDAs evolve through non-invasive neoplastic precursor lesions (similar to polyps in colorectal cancer)
- The PanINs acquire clonally selected genetic and epigenetic alterations along the way
- PanINs are microscopic (<5mm diameter) and not visible by pancreatic imaging- usually only see them when examining cut up specimens of someone’s cancer
Why is it thought that the death rate is so high for pancreatic cancer?
Mutations develop slowly but as soon as it becomes cancerous it starts metastasising quick before causing local problems
Mutations in which genes are
a)PanIN1
b)PanIN2
c)PaniIN3
associated with
a)ERBB2, KRAS
b)CDKN2A
c)TP53, SMAD4, BRCA2
How does carcinoma of the head of the pancreas present?
-Jaundice
-Weight loss
-Pain
- Acute pancreatitis- 5% atypical attack
- Persistent vomiting- in advanced cases, duodenal obstruction can result in this
- GI bleeding- duodenal invasion or varices secondary to portal or splenic vein occlusion
At least 2/3 of PDAs arise in what part of the pancreas?
Head
Why does jaundice occur in carcinoma of the head of the pancreas?
How painful is it?
What sign is associated with it?
What if cancer is away from CBD?
- > 90% due to either invasion or compression of CBD
- Often painless
- Palpable gallbladder (Courvoisier’s sign)
-Cancer metastasises before going yellow so it’s harder to spot/people present late
Why weight loss in carcinoma of the head of the pancreas?
- Anorexia
- Malabsorption- secondary to exocrine insufficiency
- Diabetes- some get diagnosed 2 years before pancreatic cancer so it’s a big association
When and where does pain occur in carcinoma of the head of the pancreas?
- 70% at time of diagnosis
- Happens in epigastrium
- Radiates to back in 25%
What is pain usually a sign of in cancer?
What does back pain usually indicate?
That the cancer is locally invasive or locally advanced
Posterior capsule invasion and irresectability
How does carcinoma of the body and tail of pancreas present?
- Develop insidiously and are asymptomatic in early stages
- At diagnosis they’re often more advanced than lesions in head because there’s nothing really to block to show signs
- Marked weight loss with back pain in 60% of patients
- Jaundice is uncommon because it’s on the left side away from bile duct
- Vomiting sometimes occurs at a late stage from invasion of the DJ flexure
- Most unresectable at time of diagnosis
What investigations are carried out for pancreatic cancer?
- Tumour marker CA19-9
-Ultrasonography - Dual-phase CT
- MRI
- MRCP
- ERCP
- EUS
What Tumour marker CA19-9 concs confer with pancreatic cancer?
What is it falsely elevated in?
- Concs >200 U/ml confer 90% sensitivity
- Concs in 1000s associated with high specificity
Falsely elevated in
- Pancreatitis
- Hepatic dysfunction
- Obstructive jaundice
What can ultrasonography identify in pancreatic cancer?
Not too useful
- Pancreatic tumours
- Dilated bile ducts
- Liver metastases
What is dual phase CT useful for in pancreatitis?
Done commonly
- Accurately predicts resectability in 80-90% of cases
- Contiguous organ invasion
- Vascular invasion (coeliac axis and SMA)
- Distant metastases
What is MRI useful for in pancreatitis?
Not as useful as CT but detects and predicts resectability with accuracies similar to CT
What is MRCP useful for in pancreatitis?
Provides ductal images without complications of ERCP
What is ERCP useful for in pancreatitis?
Most useful
- Confirms the typical ‘double duct’ sign
- Aspiration/brushing of the bile-duct system
- Therapeutic modality → biliary stenting to relieve jaundice
What is EUS useful for in pancreatitis?
- Used when we can’t resect it but want to prove there’s cancer before chemo
- Highly sensitive in the detection of small tumours- do aspiration of single cells or biopsy
- Assessing vascular invasion
- FNA (fine needle aspiration)
How do we do HOP resection?
What 3 things need to be sorted after this?
Do a Whipple’s resection- remove HOP, distal bile duct and gallbladder, distal stomach and all of duodenum
- Pancreatic juice has to go somewhere
- Bile has to go somewhere
- Stomach has to empty contents somewhere
How do we do TOP resection?
TOP can just be removed along with spleen because if preserved it’s very likely to have some cancer cells on it
What is primary liver cancer (a.k.a. hepatocellular carcinoma)?
Cancer of liver hepatocytes
What are 2 causes of hepatocellular carcinoma?
- Cirrhosis due to Hep B, C or alcoholic liver disease
- Aflatoxin- toxin made by certain fungi
What happens to hepatocellular carcinoma patients if we do nothing?
What is 5 year survival rate?
What is systemic chemo response rate?
4-6 months of living
<5%
<20% so it’s ineffective
What is the optimal Rx (intervention) for hepatocellular carcinoma?
What other options are there?
- Surgical excision with curative intent (5 year survival is >30%)
- Only 5-15% suitable for surgery
Other options are:
- OLTx- liver transplant- if you have <3 hepatocellular cancers in liver and they’re <3cm you can do this
- TACE- transarterial chemo embolisation- put small catheters inside blood supply of tumour, giving high chemo dose then embolising (blocking) the blood supply
- RFA- radiofrequency ablation- stick a needle into tumour and burn it
Where does Cholangiocarcinoma (ChCA) most often occur?
Where else?
Bifurcation where common hepatic duct goes right and left- are small tumours but big operation to take it away
Otherwise
- You get distal ChCA through HOP for which you need Whipple’s resection
- You can get it them at periphery for which you need to take away that bit of liver
What is the aetiology of Cholangiocarcinoma (ChCA) ?
- Choledochal cyst- dilatation of bile duct with 10-15% risk of becoming cancer
- Associated with liver fluke (clonorchis sinesis) in Asia- comes from uncooked fish- worms inhabit bile ducts, cause irritation and cancer
- also associated with: ulcerative cholitis, primary sclerosing cholangitis
What is the median survival without Rx for ChCA?
What is 5 year survival rate?
How effective is systemic chemo?
<6 months
<5%
Ineffective although it’s improving
What is effective treatment for ChCA?
- Optimal Rx is surgical excision with curative intent
- 5 year survival is 20-40%
- Only 20-30% suitable for surgery
Gallbladder cancer (GB CA)- how does it usually spread?
GB CA spreads very quickly everywhere but doesn’t cause problems
What is the aetiology of GbCA?
Unknown
- It’s associated with gallstones
- Porcelain GB occurs- chronic inflammation in gall bladder causes calcification so it looks like porcelain
- Associated also with chronic typhoid infection
- All 3 of the above are long term inflammation
What is the median survival without Rx for GbCA?
Is systemic chemo effective?
What are effective Rx options?
5-8 months
No
Only surgical excision with curative intent
Only <15% suitable for surgery
What is 5 year survival for GbCA after surgical excision with curative intent at stages II, III, IV
- Stage II is 64%
- stage III is 44%
- stage IV is 8%
What happens at stage II GbCA
- Transmural invasion of cancer- going through mucosa to muscle
- We can take away a bit of the liver and lymph nodes
- If we do nothing, 64% die
What happens at stage III GbCA
Beginning to invade liver
What happens at stage IV GbCA
Invading liver >2cm and there’s distal metastases
How does colorectal cancer affect liver?
Through metastases
What is the median survival without Rx for colorectal cancer metastases affecting liver?
What is 5 year survival?
Less than a year
0%
What are effective Rx for colorectal cancer?
- Systemic chemo is improving
- Other effective Rx options (RFA and SIRT)
- Most effective is surgical excision with curative intent
- 5 year survival raves of 25-50%
- Only 25% is suitable for surgery
HCC resection
Take away that bit of liver and try not to take much else
ChCA resection
Take away a whole half of the liver for something only 1cm
GbCA resection
Take away GB, bit of liver and lymph nodes
Causes of neuroendocrine tumors
Sporadic tumours in 75%
Associated with a genetic syndrome in 25%
-Multiple Endocrine NeoplasiaType 1 (MEN1)
-Parathyroidtumours
-Pancreatic tumours
-Pituitarytumours
What are neuroendocrine tumors
Arise from the gastroenteropancreatic (GEP) tract (or bronchopulmonary system)
Diverse group of tumours
Regarded as common entity as arise from secretory cells of the neuroendocrine system
How do NETs present
Most NETs are asymptomatic & incidental findings
Secretion of hormones & their metabolites in 40%
serotonin, tachykinins (substance P) & other vasoactive peptides
< 10% of NETs produce symptoms
Can result in a variety of debilitating effects
Carcinoid syndrome
Vasodilatation
Bronchoconstriction
↑ed intestinal motility
Endocardial fibrosis (PR & TR)
Clinical features of NETs
What biochemical investigations are used to diagnose NETs
Chromogranin A is a secretory product of NETs
Other gut hormones: insulin, gastrin, somatostatin, PPY (Measured in fasting state)
Other screening: Calcium, PTH, prolactin, GH
24 hr urinary 5-HIAA (serotonin metabolite)
What imaging is used in NETs diagnosis?
Cross-sectional imaging (CT and/or MRI)
Bowel imaging (endoscopy, barium follow through, capsule endoscopy)
Endoscopic ultrasound
Somatostatin receptor scintigraphy (68Ga-DOTATATE PET/CT most sensitive)
How are NETs graded
Common sites of NETs metastasis
Small intestine
Appendix
Colon
Rectum
Stomach
Pancreas
Treatment Modalities for NETs
Curative resection (R0)
Cytoreductive resection (R1/R2)
Liver transplantation (OLTx)
RFA, microwave ablation
Embolisation (TAE), chemoembolisation (TACE)
Selective Internal RadioTherapy (SIRT)
90Y-Microspheres
Somatostatin receptor radionucleotide therapy
90Y-DOTA
177 Lu-DOTA
Medical therapy, targeted therapy, biotherapy
Octreotide, Lanreotide, SOM203
PK-inhibitors, mTOR-inhibitors
⍺-Interferon
