L14 - Screening of GI cancer Flashcards
Describe familial adenomatous polypsosis?
- autosomal dominant
- results from germ line mutation of tumour supressor gene, APC gene followed by acquired mutations from remaining allele
- mutation … truncated APC protein
Describe the normal role of APC and its role after mutation?
Normally
- APC binds and isolates B-catenin
After mutation
- can’t bind and isolate B-canetin
- B-canetin transolcates into nucleus
- causes upregulation of many genes
What is the MUTYH gene?
Involved in base excision repair.
May give rise to colonic polyposis.
Autosomal recessive inheritance.
Describe a desmoid tumour?
Abnormal growth that arises from connective tissue
- benign? may become very big causing compression of adjacent organs.
CHRPE - congenital hypertrophy of retinal pigment epithelium
- dark round pigmented retinal lesions.
- if present in at risk person it is 100% indicative of FAP
Turcot’s syndrome
Condition characterized by multiple adenomatous colon polyps, an increased risk of colorectal cancer and an increased risk of brain cancer.
May be associated with FAP.
Peutz-Jegher syndrome
Many harmatomatous polyps occur in small intestine and colon.
- melanin pigmentation of lips, mouth, digits
Asymptomatic usually but:
- chronic bleeding
- anaemia
- intussusception: where one segment of small intestine telescopes inside another/
Harmatoma
Benign, local malformation of cell resembling neoplasm of local tissue.
Usually due to an overgrowth of multiple aberrant cells.
Peutz-Jegher syndrome results from
Shortening mutation in serine-threonine kinase gene on chromosome 19p (STK11)
Autosomal dominant
Describe the occurrence of juvenile polyposis
- caused by germline mutations in the SMAD 4 gene
- family history of polyps
- colorectum contains many mucous filled hamartomatous polyps
Describe the dietary risk factors for colorectal cancer
Increased risk
Red meat : high saturated fat and protein, carcinogenic amines formed in cooking
Saturated animal fat: increased faecal bile and fatty acid level
Describe what kind of diet may decrease the risk of colorectal cancer?
Calcium
Folic acid: reverses DNA hypomethylation
Green veg: anti-carcinogen (flavonoid)
Risk factors for colorectal cancer
- obesity
- smoking
- cholecystecotomy (effect of bile acid in right colon)
- type 2 diabtes
- use of NSAIDs, COX-2 inhibitors
Compare left and right colon tumours?
RHS - anaemia - occult bleeding - altered bowel habit - obstruction is a late feature LHS - fresh rectal bleeding - obstruction occurs early
Signs of carcinoma of rectum
Early bleeding
Mucus discharge.
Feeling of incomplete emptying.
Prevention and screening of colon tumours
FOB: faecal occult blood test, checks for blood in faeces
Colonoscopy - gold standard
Flexible sigmoidoscopy - flexible tube inserted into the rectum
Diverticula
Protrusion of mucosa covered by peritoneum.
What may cause diverticulosa?
- deficiency in fibre
- small vol stools need increases in intracolonic pressure for propulsion.
- leads to herniation of mucosa between the taenia coli.
- hypertrophy of circular muscle coat
- inflammation, impact of diverticula with faecolith (hard stony faeces in intestinal tract)
Diverticulosa may progress to…
Haemorrhage Perforation Local abscess formation Fistula Peritonitis
Investigation of GI disease: what may be seen on CXR
- dilated loops of bowel in erect position
- calcified lymph nodes
- gall stones
- renal stones
Describe use of endoscopic USS
- Increased frequency transducer produces high res USS images
- allows visualisation through wall of GI tract and into surrounding tissue.
- can be used to perform fine needle aspiration
- used for biopsy of mass lesion
Describe capsule endoscopy
- Wireless, traverses small intestine.
- transmits images to battery powered recorder worn as a belt on patient.
- 8hr approx for capsule to be secreted
Describe endoscopic retrograde cholangiopancreatography?
- duodenoscope cannulates main pancreatic duct and common bile duct
How may anti-inflammatory drugs reduce cancer risk?
- nSAIDS inhibits prostaglandin synthesis by blocking cyclo-oxygenase COX
- link between chronic inflammation and carcinogenesis
Where are prostaglandins derived from and what is their role?
Prostaglandin’s derived from arachidonic pathway.
During inflammation PGE2 increases vasodilation and increases microvascular permeability - leading to redness and swelling.
Maintenance of gastroduodenal defence.
Celecoxib
works by:
- inhibiting COX-2 while sparing COX-1
- hene avoiding side effects of COX-1 inhibition
low dose aspirin will irreversibly inhibit platelet aggregation.
Action of nitric oxide on gastric mucosa
Increases and maintains gastric mucosal blood flow.
Stimulates mucus secretion.
Inhibits neutrophil adherence.
Types of screening
Mass screening
- whole population or large subgroup
Targeted screening
- high risk groups
Lead time bias
Appearance that early diagnosis of a disease prolongs survival with that disease.
However diagnoses happen roughly at the same time regardless.
Length time bias
Over estimation of survival duration due to the relative excess of cases detected that are asymptotically slowly progressing.
While fast progressing cases are detected after giving symptoms.
Components of NHS Bowel cancer screening
Bowel scope
- one-off flexible sigmoidoscopy >55 y/o
National bowel cancer screening
- Fecal occult blood test (FOB)
- Fecal immunochemical test (FIT)
What is a loop diathermy?
Biopsy taken using thin loop of electrified wire to remove abnormal cells.
- procedure known as a large loop excision of the transformation zone (LLETZ)
Argon plasma coagulation
Medical endoscopic procedure used to control bleeding from certain lesions in the GI tract.
Focal lesion
Lump / bump can be removed
Multifocal dysplasia
Squamous cell (pale pink), converted to dark pink columnar epithelium.
Argon plasma coagulation
Endoscopic procedure.
Jet of ionized argon (plasma) directed through a probe passed through endoscope.
Probe placed at some distance from bleeding lesion.
Argon gas emitted then ionized by a high voltage discharge.
Results in coagulation of bleeding lesion.
HALO Radiofrequency ablation
Use of radiowaves to destroy the dysplasia.
Can be used to treat entire area of Barrett’s oesophagus
Describe an innovative test for Barrett’s oesophagus?
Cytosponge.
- Pile swallowed, expands into small rough textured sponge in the stomach.
- sponge pulled back up collecting some cells lining food pipe.
- sent to lab for analysis
