GI Cancers Flashcards
Define Cancer
A term for diseases in which 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 primary cancer?
Arising directly from the cells in an organ
What is secondary cancer?
Spread from another organ, directly or by other means (blood or lymph)
What are the first 6 hallmarks of cancer?
Sustaining proliferative signalling Evading growth suppressors Activating invasion and metastasis Enabling replicative immortality Evading angiogenesis Resisting cell death
What are the emerging hallmarks of cancer?
Deregulating cellular energetics
Genome instability and mutation
What are the enabling characteristics of cancers?
What gives them selective advantage
- Genome instability and mutation
Tumor promoting inflammation
What are the instant truths re. cancer?
Cancer is a genetic disease
Cancers contain multiple genetic errors
Cancers contain more than just malignant cells
Killing cancer cells is easy
ONLY killing cancer cells is very hard
Developing novel therapies for cancer fraught with problems
What is cancer of the glandular epithelium of the GI tract?
Squamous cell carcinoma
Adenocarcinoma
What is cancer of the neuroendocrine cells of the GI tract?
Neuroendocrine tumours
Gastrointestinal stromal tumours
What is cancer of the connective tissue of the GI tract?
Leiomyoma/Leiomyosarcomas
Liposarcomas
What are the connective tissues present in the GI tract?
Smooth muscle
Adipose tissue
What is the most common GI cancer?
Bowel (4th most common)
2nd highest morbidity
Why are GI cancers problematic?
Low incidence but high death rates
What is essential for lessening cancer morbidity?
Cancer screening - catching the disease early
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.
What are the Wilson and Jungner criteria?
The condition should be an important health problem
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
The natural history of the condition, including development from latent to declared disease should be adequately understood
How is colorectal 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 (screening program)?
Regular endoscopy to patients with:
Barrett’s oesophagus
Low- or high-grade dysplasia.
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
How is hepatocellular cancer screened for?
Regular ultrasound & AFP for high-risk individuals with cirrhosis
Viral hepatitis
Alcoholic hepatitis.
Who else is offered screening?
Those with genetic predisposition or strong family histories
e.g. FAP - multiple polyps in colon and duodenum, 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
Staging
Treatment
What is the first step in the pathway involving the Cancer MDT?
Initial presentation e.g. worrying symptoms to GP or A&E doctor
OR
The patient is identified through a screening programme (e.g. faecal occult blood test for colon cancer).
What is the second step in the pathway involving the Cancer MDT?
The patient is referred through the 2-week-wait cancer pathway
What is the third step in the pathway involving the Cancer MDT?
Diagnostic tests
What is the fourth step in the pathway involving the Cancer MDT?
MDT
What is the fifth step in the pathway involving the Cancer MDT?
Treatment
Who is 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
Provide molecular typing
Provides the tumour grade
How is histologic typing done?
i.e. what type of cell does the cancer come from?
Epithelium (squamous cell carcinoma) or secretory cells (adenocarcinoma).
Non-epithelial cells less common in the GI tract.
Neuroendocrine tumours (pancreas)
Gastrointestinal stromal tumours (GISTS) – (stomach)
What is molecular typing?
what mutations does this cancer have?
Alongside the histological type, this can determine types of treatment available.
What does the grade mean?
how aggressive is the cancer?
Determined by how ‘abnormal’ cells & their nuclei are and how actively they are dividing.
What does the radiologist do?
Reviews scans
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
Provides re-staging after treament
Interventional radiology
What is staging?
how far has the cancer spread?
The TNM system used.
T - size of Tumour.
N - lymph Node involvement
M - presence of distant Metastases.
A T2N0M0 tumour may be totally curable, but a T3N1M1 may not be.
What is asked in re-staging?
Has it remained stable or progressed?
Did the cancer respond completely or partially?
What is the role of interventional radiology?
Percutaneous biopsies
Radiological stents
What does the surgeon do?
Decides whether surgery is appropriate.
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?
Decides on whether chemotherapy, radiotherapy or other systemic therapy is appropriate.
Coordinates the overall treatment plan
What is considered by the oncologist?
scans, histological and molecular type.
Is the patient fit for full intensity therapy?
What choices are made when coordinating on treatment plan?
Should chemotherapy come before surgery (neoadjuvant) or after (adjuvant)?
Takes into consideration
Type, grade & stage
Patient fitness (‘performance status’) and wishes.
What do the MDT decide with regards to treatment plan?
MDT decides whether plan should be for radical (curative) or palliative therapy or palliative care
Palliative care
CNS (Cancer Nurse specialist)
What is the major driver of gastric adenocarcinoma?
Chronic gastritis is the major driver
What causes gastric adenocarcinoma?
H.pylori infection
due to chronic acid overproduction
Pernicious anaemia
autoantibodies against parts & products of parietal cells
Partial gastrectomy (e.g. for an ulcer) leading to bile reflux
Epstein-Barr virus infection
Family history (including heritable diffuse-type gastric cancer due to E-cadherin mutations)
High salt diet & smoking
What are the stages of gastric cancer progression (process)?
Chronic gastritis
Intestinal metaplasia
dysplasia
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 + biopsy
How is gastric cancer staged (procedures)?
CT of the chest, abdomen & pelvis will provide information on distant lesions
PET-CT
Diagnostic laparoscopy - peritoneal & liver metastases disease prior to full operation
Endoscopic ultrasound - will give most detail about local invasion & node involvement
What are the treatment options for gastric cancer?
Neoadjuvant chemotherapy
Oesophago-gastrectomy
Total gastrectomy
Subtotal gastrectomy
Adjuvant chemotherapy
What can neoadjuvant chemotherapy be used for?
Reducing the size of the tumour before surgery
What are the main features of Neuroendocrine tumours?
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
What causes NETs?
Sporadic tumours in 75%
Associated with a genetic syndrome in 25%
Multiple Endocrine NeoplasiaType 1 (MEN1)
Parathyroidtumours
Pancreatic tumours
Pituitarytumours
How 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
What are the consequences of NETs (symptoms)?
Carcinoid syndrome: Vasodilatation Bronchoconstriction ↑ed intestinal motility Endocardial fibrosis (PR & TR) = right sided heart problems Flushing of face
What is carcinoid syndrome?
Tumour secretes excess of Serotonin directly into system circulation
What is the most common NETs?
Insulinoma
Hypoglycaemia
Whipple’s triad (symptoms of hypoglycaemia, proven to have low plasma glucose at time of symptoms, symptoms relived on eating)
What are the clinical features of glucagonoma?
Diabetes mellitus, necrolytic migratory erythema (red, blistering rash - mouth and extremities)
Alpha cells
What are the clinical features of gastrinomas?
Zollinger-Ellison syndrome
Too much gastrin
Peptic ulcers
Abdominal pain and diarrhoea
What are the clinical features of VIPomas?
Verner-Morrison syndrome, watery diarrhoea
vasoactive intestinal peptide
What are the clinical features of somatostatinomas?
Gallstones, diabetes mellitus, steatorrhoea
D-cells
What are the clinical features of midgut NETs?
Most are non-functioning, 40% develop carcinoid syndrome
What are the clinical features of hindgut NETs?
Most are non-functioning
How do you diagnose NETs?
When suspected, investigations to localise the tumour & confirm the diagnosis with histology
Biochemical Assessment
Imaging
What comprises the biochemical assessment of 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 type of imaging is looked at for NETs?
Cross-sectional imaging (CT and/or MRI)
Bowel imaging (endoscopy, barium follow through, capsule endoscopy)
Endoscopic ultrasound
Somatostatin receptor scintigraphy
IV radiolabled 68Ga-DOTATATE PET/CT most sensitive
How to we grade GEP-NETs?
Grade (1-3)
Mitoses
Ki-67 index
What are the 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 (radiolabel somatostatin)
Somatostatin receptor radionucleotide therapy
90Y-DOTA
177 Lu-DOTA
Medical therapy, targeted therapy, biotherapy
Octreotide, Lanreotide, SOM203
PK-inhibitors, mTOR-inhibitors
⍺-Interferon
What is TAE and TACE?
Transarterial (chemo) embolisation
What are the causes of microcytic anaemia?
- Iron deficiency anaemia
- Anaemia of chronic disease
- Thalassaemia
- Sideroblastic anaemia
What are the causes of normocytic anaemia?
ABCDE Aplastic anaemia Bleeding Chronic disease Destruction (haemolysis) Endocrine disorders - Hypothyroidism - Hypoadrenalism
What are the causes of macroocytic anaemia?
FAT RBC:
Foetus (pregnancy)
Alcohol excess
Thyroid disorders
Reticulocytosis
B12/Folate deficiency
Cirrhosis
What are the GI causes of IDA?
- Aspirin/NSAID use
- Colonic adenocarcinoma
- Gastric carcinoma
- Benign gastric ulcer
- Angiodysplasia
- Coeliac disease
- Gastrectomy (decreased absorption)
- H.pylori
What are the non GI causes of IDA?
- Menstruation
- Blood donation
- Haematuria (1% of iron deficiency anaemias)
- Epistaxis
What is the organised structure for investigations?
Bedside tests Blood tests Imaging Microbiology Special/Invasive
