Neoplastic Disease of the GI Tract Flashcards

Question

Describe GISTs

Answer 1

-Gastrointestinal stromal tumours -Soft tissue tumour that can arise anywhere in the GI tract =related to pacemaker (coordinate waves of peristalsis) cells in muscularis propria =malignant tumours are a type of sarcoma =75-80% of GISTs have activating mutations in the KIT receptor tyrosine kinase gene (diagnostic) -Stomach commonest site -Can be difficult to predict behaviour -Risk dependent on site, size, proliferative activity =GIST is an example of a tumour where one of the diagnostic tests also highlights a therapeutic target – monoclonal antibody therapy

Answer 2

-Inflammatory= IBD, lymphoid -Hamartomatous (normal elements in abnormal proportion) =juvenile polyps and polyposis =Peutz-Jegher Syndrome (associated with pigmentation of the lips) -Hyperplastic (sigmoid and rectum) -Lesions in submucosa (lipoma presenting as polyp)

Answer 3

-Adenomas =Tubular (short crypts with lots of rounded crypt profiles) =Tubulovillous =Villous (more high-grade, long finger-like projections) -Adenocarcinomas -Lymphoid

Answer 4

- Sessile= broad attachment and flat based | - Pedunculated= long stalk

Answer 5

- Peak incidence 60-79 - No gender difference with exception of rectal cancer (M>F) - 55% tumours rectum and sigmoid colon - 22% tumours caecum/ ascending colon - Most sporadic - 5% associated with known familial syndrome (FAR, HNPCC= Lynch syndrome) or IBD

Answer 6

-Excessive calories relative to requirement -Low fibre -High intake of refined carbohydrates -High intake of red meat -Low intake of protective micronutrient (vitamin A, C, D and E) -Exact mechanisms unclear =Production of reactive oxygen species by intestinal bacteria?

Answer 7

- First degree relative with CRC - Inherited syndromes (FAP, HNPCC) - Alcohol in rectal carcinomas - Smoking - Inflammatory bowel disease - Occupational factors (solvents) - Radiation - Schistosomiasis (parasitic infection)

Answer 8

-APC/ Beta-catenin =Inactivation of APC (Adenomatous Polyposis Coli) tumour suppressor gene seen in 80% of colorectal carcinomas =Genetic basis of inherited condition FAP =Early event in adenoma-carcinoma sequence =Subsequent accumulation of multiple mutations and chromosomal instability = APC involved in the degradation of the beta-catenin transcription factor. Patients with FAP have an inherited mutation in one copy of the APC tumour suppressor gene.

Answer 9

- Inherited or acquired mutation in tumour suppressor genes (first hit)= APC - Inactivation of normal allele (second hit)= APC, Beta-catenin - Mutation of proto-oncogenes= KRAS - Homozygous inactivation of other tumour suppressor genes, over-expression of COX-2= TP53, SMAD2, SMAD4 - Additional mutations and gross chromosomal alterations= Telomerase, multiple genes

Answer 10

-10-15% of sporadic colorectal carcinomas (R>L) -Inactivation of DNA mismatch repair genes =MSH2, MLH1 (90% of cases involve one of these) =Others include MSH6, PMS1, PMS2 -Inherited mutation in one of these genes is the basis of Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC) syndrome (Lynch syndrome) -Loss of one of these genes increases mutation rate by up to 1000-fold -Not associated with typical adenoma-carcinoma sequence -MSI-H tumours more commonly seen in the right side of the colon. -Inactivation of MMR genes may be caused by methylation of the gene promoter rather than mutation of the gene itself. -Microsatellite are regions of DNA containing repeated short sequences of several bases. These are prone to replication errors due to “slippage” of the replication machinery.

Answer 11

- More recently identified pathway - Associated with distinctive precursor lesions showing similarities to hyperplastic polyps (sessile serrated lesions) - More common in the right colon - Thought to have a more rapid progression to malignancy - Typically have a mutation in either BRAF or KRAS proto-oncogenes - Can also show microsatellite instability, often due to methylation of mismatch repair gene promoter regions rather than actual mutation - A proportion of “interval cancers” in the bowel screening programme may be accounted for by this type of tumour

Answer 12

- Flat - Covered in mucus cap - Can be highlighted by blue dye (chromo-endoscopy)

Answer 13

- About 1% of colorectal carcinomas are associated with FAP - Up to 5% associated with HNPCC -Of sporadic carcinomas, ≥30% may be associated with an inherited defect -Having a 1st degree relative with CRC increases risk by up to 8-fold over the general population =Shared genetic pool? =Shared environmental factors? =Both?

Answer 14

- STAGE: Higher = reduced survival - GRADE: Poorly differentiated tumours more aggressive - Presentation with obstruction or perforation (usually indicates advanced disease) - Involvement of surgical resection margins - Extramural vascular invasion - Pattern of invasion and host response - ?Genetic markers= can predict response to certain chemotherapy drugs

Answer 15

- Screening for colorectal carcinoma now established UK-wide - In Scotland, offered to all aged 50-74 years - Uses faecal occult blood test (FOBt) or faecal immunochemical test (qFIT), with referral for colonoscopy if positive result - England and Wales= can't request screening kit after 69 years

Answer 16

- Don't recognise intramucosal adenocarcinoma in colon and rectum so must invade submucosa - M stage dependent on where metastatic disease is - More stages

Neoplastic Disease of the GI Tract Flashcards

(40 cards)