GI cancers Flashcards
What is cancer?
A term for diseases = abnormal cells divide without control and can invade nearby tissues
Cancer cells can also spread to other parts of the body through the blood and lymph systems
What is a primary cancer?
What is a secondary or metastasis cancer?
Arising directly from the cells in an organ
Spread from another organ, directly or by other means (blood or lymph)
What are the first 6 hallmarks of cancer?
6 biological capabilities acquired by tumours =
Sustaining proliferative signalling
Evading growth suppressors
Activating invasion and metastasis
Enabling replicative immortality
Evading angiogenesis - blood supply for growing tumour mass
Resisting cell death
What are the emerging hallmarks of cancer?
Deregulating cellular energetics
Avoiding immune destruction
What are the enabling characteristics of cancers?
What gives them selective advantage, acquired through genetic change AND/or epigenetic dysregulation (e.g. from chronic inflammation) =
Genome instability and mutation
Tumor promoting inflammation
What do we know about cancer?
Cancer is a genetic disease
Cancers contain multiple genetic errors
Cancers contain more than just malignant cells - stromal cells, neovascular cells etc.
Killing cancer cells is easy
ONLY killing cancer cells is very hard and not affecting the normal cells around them
Developing novel therapies for cancer fraught with problems
What are the cancers of the epithelial cells of the GI tract?
What are the cancers of the neuroendocrine cells of the GI tract?
What are the cancers of the connective tissue of the GI tract?
Squamous cell carcinoma - squamous
Adenocarcinoma - glandular epithelium
Neuroendocrine tumours - enteroendocrine cells
Gastrointestinal stromal tumours - interstitial cells of Cajal
Leiomyoma/Leiomyosarcomas - smooth muscle
Liposarcomas - adipose tissue
Where are GI neuroendocrine tumours found?
Throughout the GI tract, from the oesophagus to the stomach, duodenum pancreas, large bowel, small bowel and rectum
What is the most common GI cancer?
Why are GI cancers problematic?
Bowel (4th most common), but stomach, liver and pancreas cancer incidences are lower
2nd highest morbidity
Low incidence but high death rates
What is essential for lessening cancer morbidity?
Why is there a higher 5 year survival rate for colorectal cancer compared to pancreatic or oesophageal?
Cancer screening - catching the disease early = better chance of resecting it = better chance of 5 year survival after diagnosis
Large bowel = has a mesentery and keeps to itself
Other GI cancers e.g. pancreatic, oesophageal, gallbladder = involve other structures v. quickly
What is cancer screening?
Testing of asymptomatic individuals to identify cancer at an early stage
How do we identify whether a disease is suitable for screening?
Wilson & Jungner criteria
Depends on the epidemiology of a disease & features of the test:
The condition should be an important health problem - and affecting a significant number of people to make it cost-effective to offer the screenings
There should be an accepted treatment for patients with disease
Facilities for diagnosis and treatment should be available
There should be a recognisable latent or early symptomatic stage
There should be a suitable test or examination
The test should be acceptable to the population - not too unpleasant where the population does not turn up to the test
The natural history of the condition, including development from latent to declared disease should be adequately understood
How is colorectal cancer screened for?
Offered to healthy individuals:
Faecal immunochemical test (FIT) - detects haemoglobin in faeces, every 2 years for everyone aged 60-74
One-off sigmoidoscopy for everyone aged >55 to remove polyps (reducing future risk of cancer)
How is oesophageal cancer screened for?
Regular endoscopy to patients with:
Barrett’s oesophagus
OR
Have been found to previously had low- or high-grade dysplasia that has already been dealt with by local means rather than full resection for a full cancer
Are pancreatic and gastric cancers screened for?
No test exists that meets the W & J criteria
Depends on incidence - Japan screens for gastric cancer (high incidence): perform endoscopies
Makes economic and clinical sense to base this off incidence rate
How is hepatocellular cancer screened for?
Regular ultrasound & AFP (alpha faecal protein - tumour marker- looked for in a blood test) for high-risk individuals: With cirrhosis OR Viral hepatitis OR Alcoholic hepatitis OR NASH (non alcoholic steatotic hepatitis)
Who else is offered screening?
Specific screening programmes for those with genetic predisposition OR strong family histories
e.g. FAP (familial adenomatous polyposis) - multiple polyps in colon and duodenum, high risk of developing colorectal / duodenal cancer and so are offered prophylactic resections and yearly colonoscopies or OGD’s
OR
Hereditary pancreatitis - 40% lifetime risk of pancreatic cancer, offered prophylactic surgery and yearly imaging
What is the cancer journey?
Diagnosis - What symptoms and signs does the patient present with? How is the diagnosis made?
Staging - What investigations are needed to see how advanced the cancer is?
Treatment - Can the cancer be surgically removed? What systemic therapy (e.f. chemotherapy) or radiotherapy is available?
How does a patients journey with cancer and the cancer MDT start?
Initial presentation to a member of the MDT:
Worrying symptoms to GP or another doctor (e.g. A&E)
OR
The patient is identified through a screening programme (e.g. faecal occult blood test for colon cancer)
What happens next in the patient’s cancer journey involving the cancer MDT?
The patient is referred through the 2-week-wait cancer pathway
What is the third step in the cancer journey involving the Cancer MDT?
Diagnostic tests
What is the fourth step in the cancer journey involving the Cancer MDT?
MDT - MDT meeting in which diagnostic test results are discussed
What is the fifth step in the cancer journey involving the Cancer MDT?
Treatment
Who is involved in the cancer MDT?
Pathologist Radiologist Palliative care Gastroenterologist Oncologist Surgeon Cancer nurse specialist
What is the role of the pathologist?
Confirms the diagnosis of cancer using biopsy samples
Provide histologic typing - what type of cell does the cancer come from? e.g. epithelium (squamous cell carcinoma) or secretory cells (adenocarcinoma); non-epithelial cells less common in the GI tract; neuroendocrine tumours (pancreas); or GI stromal tumours (GISTS) – (stomach)
Provide molecular typing - what type of mutations does this particular cancer have? Useful to determine treatment options available (e.g. which chemo will be most effective)
Provides the tumour grade - determines how aggressive the cancer is and how abnormal the cells and nuclei are; how actively are the cancer cells dividing
What does the radiologist do?
Reviews scans:
- Interprets the imaging
- If diagnosis is unclear, comments on how likely the scan is to confirm cancer
- Suggests other imaging to clarify suspected diagnosis
- Should a biopsy be performed and from where?
Provides radiological tumour stage - i.e. how far has the cancer spread?
TNM system: T = size of Tumour; N = lymph Node involvement, M = presence of distant Metastases
Provides re-staging after treatment - did the cancer respond complete or partially? Has it remained stable or progressed
Interventional radiology - percutaneous biopsies, radiological stents
What does the surgeon do?
Decides whether surgery is appropriate - works alongside gastroenterologist as they offer endoscopic means for diagnosing cancers and therapeutic interventions
Is the tumour resectable?
Is the patient fit enough for surgery?
Performs operation & cares for patient in perioperative period
What does the gastroenterologist do?
Endoscopy – diagnostic & therapeutic
Upper GI
Oesophageal & gastric biopsies
Oesophageal stents
Liver & pancreas
ERCP & EUS biopsies
Biliary stents
Lower GI
Colonic biopsies
Colonic stents
What do oncologists do?
Decide on whether chemotherapy, radiotherapy or other systemic therapy is appropriate - determined by the scans, histological type and molecular type; is the patient fit for full intensity therapy?
Coordinates the overall treatment plan - should chemotherapy come before surgery (neoadjuvant) or after (adjuvant); takes into consideration the type, grade and stage; also patient fitness and wishes
Who decides what type of treatment plan the patient is getting and what are the different plan options?
MDT decides (taking into account the patients wishes)
Radical (Curative) VS palliative therapy (not a cure, but extending patient’s life) VS palliative care (no treatment at all, allow disease to progress)
Who looks after cancer patients in palliative care?
Palliative care physicians
Also involves the cancer nurse specialist
What is the major driver of gastric adenocarcinoma?
Anything causing a chronic gastritis
What causes gastric adenocarcinoma?
Anything causing chronic gastritis, e.g.:
H.pylori infection
- due to inflammation into gastric mucosa esp. in the entrance of the stomach = duodenal ulcers = chronic acid overproduction = epithelium increasingly exposed to chemical attacks = metaplasia of epithelium = progresses to cancer
Pernicious anaemia
- autoantibodies against parts and products of parietal cells
Previous partial gastrectomy (e.g. for an ulcer) joins the small bowel to the stomach
- leading to bile reflux from the small bowel into stomach = predisposition to gastric cancers
Epstein-Barr virus infection
High salt diet & smoking
What is important in the history taking to diagnose a cancer?
Family history (including heritable diffuse-type gastric cancer due to E-cadherin mutations)
Exposure to certain infections
What is the pathogenesis / stages of gastric cancer progression?
Chronic gastritis - consists of surface cells, stem cells, parietal cells which are inflammed and atrophied, so the cells respond with hyperplasia
Intestinal metaplasia
Progresses to dysplasia
Becomes a cancer - malignancy
What is the most common symptom of gastric cancer?
Dyspepsia (upper abdominal discomfort after eating or drinking)
What are the red flags for gastric cancer?
ALARMS55 Anaemia Loss of weight or appetite Abdominal mass on examination Recent onset of progressive symptoms Melaena or haematemesis Swallowing difficulty 55 years of age or above
How is gastric cancer diagnosed?
Endoscopy and biopsy
How is gastric cancer staged (i.e. see how extensive the cancer is)?
CT of the chest (look for lung metastases), abdo (look for local metastases) & pelvis will provide information on distant lesions
PET-CT
Diagnostic laparoscopy - camera put inside patient to look at the peritoneal & liver for micro-metastases that are not picked up on PET scans, performed prior to full operation
Endoscopic ultrasound - will give most detail about local invasion, local vessel involvement, and node involvement
What are the treatment options for gastric cancer?
Neoadjuvant chemotherapy - reducing the size of the tumour before surgery
Oesophago-gastrectomy
Total gastrectomy - if cancer is less than 5cm to the OG junction as the sphincter mechanism of the stomach cannot be saved
Subtotal gastrectomy - further than 5cm away from OG junction
Adjuvant chemotherapy
What are the main features of Neuroendocrine tumours (NETs)?
Arise from the gastroenteropancreatic (GEP) tract (or bronchopulmonary system)
Relatively rare but diverse group of tumours
Regarded as common entity as they arise from secretory cells of the neuroendocrine system
What causes NETs?
Sporadic tumours in 75%
But remaining 25% of patients have a genetic syndrome associated with it e.g.
Multiple Endocrine Neoplasia Type 1 (MEN1) - most common, involves:
- Parathyroid tumours
- Pancreatic tumours
- Pituitary tumours
How NETs present clinically?
Most NETs are asymptomatic and found incidentally
Secretion of hormones and their metabolites in 40% of these e.g. serotonin, tachykinins (substance P), other vasoactive peptides etc.
BUT < 10% of NETs produce symptoms from those metabolites
What are the consequences of NETs?
Can results in a variety of debilitating effects
Carcinoid syndrome - from secretion of serotonin from the tumour, causing:
Vasodilatation - flushing of face
Bronchoconstriction
Increased intestinal motility - diarrhoea
Endocardial fibrosis (PR & TR) = right sided heart problems e.g. right sided valvular lesions leading to incompetence / regurgitation
How can a serotonin secreting tumour be asymptomatic?
E.g. if tumour is in the small bowel, the serotonin secreted enters the portal circulation and is metabolised by the liver - so in the absence of metastatic liver deposits there are no symptoms
VS
Bronchipulmonary carcinoids - releases serotonin directly into systemic circulation and so present with carcinoid syndrome in the absence of hepatic metastases
OR
Hepatic metastases that cannot metabolise the serotonin
What is the most common NET?
How is it diagnosed clinically?
Pancreatic - Insulinoma - continuous production of insulin = too much insulin, causing
Hypoglycaemia
Diagnosed using - Whipple’s triad (symptoms of hypoglycaemia e.g. seizures, ‘drunk’, blurred vision etc., proven to have low plasma glucose at time of symptoms, symptoms relieved on eating)
What ‘episodes’ do insulinoma patients often present with?
How does this lead to a misdiagnosis?
Hypoglycaemia leading to seizures
Relieved by eating
Often misdiagnosed with epilepsy
What are the clinical features of glucagonoma?
Also pancreatic
Diabetes mellitus, necrolytic migratory erythema (red, blistering rash - spreads across skin at mouth and extremities)
Alpha cells
What are the clinical features of gastrinomas?
Pancreatic and duodenal
Zollinger-Ellison syndrome
Too much gastrin production from gastrinoma = leading to peptic ulcers causing:
Abdominal pain and diarrhoea
What are the clinical features of VIPomas?
Found within the entire GI tract
Too much VIP (vasoactive intestinal peptide) causing:
Verner-Morrison syndrome, watery diarrhoea
What are the clinical features of somatostatinomas?
Entire GI tract
Gallstones, diabetes mellitus, steatorrhoea
D-cells
What are the clinical features of midgut VS hindgut NETs?
Midgut = most are non-functioning, 40% develop carcinoid syndrome
Hindgut = most are non-functioning
How do you diagnose NETs?
When suspected, investigations to localise the tumour / prove it is there, and confirm the diagnosis with histology
Biochemical Assessment =
- Chromogranin A is a secretory product of NETs
- Other gut hormones measured in fasting state: insulin, gastrin, somatostatin, PPY (associated with appetite)
- Other screening: Calcium, PTH, prolactin, GH
- 24 hr urinary 5-HIAA (serotonin metabolite)
Imaging =
- Cross-sectional imaging (CT and/or MRI)
- Bowel imaging (endoscopy, barium follow through, capsule endoscopy)
- Endoscopic ultrasound (used to find pancreatic NETS)
- Somatostatin receptor scintigraphy (as NETs tend to express somatostatin)
- IV radio-labelled 68Ga-DOTATATE (somatostatin receptors) PET/CT most sensitive
What is a capsule endoscopy?
Capsule containing camera
Swallowed
Passes through GI tract
Used to particularly look at small bowel due to difficulty accessing it via oral or rectal endoscopies
How to we grade GEP-NETs?
Grade (1-3)
Mitoses
Ki-67 index
G1 = <2/10 H.P.F. = = 2% G2 = 2-20/10 H.P.F. = 3-20% G3 = >20/10 H.P.F. = >20%
Grade 3 = high grade (poorly differentiated) = neuroendocrine carcinoma
However, even in the lower grades, they act like cancers by metastasising often
Why is the grading so important?
Useful to predict prognosis
Which site metastasises the most?
Small intestine - metastasises especially to the liver, pancreas etc.
What are the treatment modalities for NETs?
Curative resection (R0)
Cytoreductive resection (R1/R2)
Liver transplantation (OLTx)
RFA (radio frequency embolisation), microwave ablation
Embolisation (TAE - trans arterial embolisation = bland embolisation), chemoembolisation (TACE - trans artertial chemo embolisation)
Selective Internal RadioTherapy (SIRT)
- 90Y-Microspheres (radiolabelled somatostatin)
Somatostatin receptor radionucleotide therapy
- 90Y-DOTA
- 177 Lu-DOTA
Medical therapy, targeted therapy, biotherapy
- Octreotide, Lanreotide, SOM203
- PK-inhibitors, mTOR-inhibitors
- ⍺-Interferon
