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24 Cards in this Set
- Front
- Back
What are the strategies against cancer?
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Prevention
- Smoking, abestos - ? vaccines (e.g. HPV vaccine - cervical CA) Screening program - PAP smear - Mammograms Treatment - surgery - radiotherapy/chemotherapy - hormones - ? gene therapy |
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Ware we winning the battle against cancer?
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Incidence of cancer in males and females has increased.
Mortabilty has decreased in males and females. |
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What is the most common cancer in Australia?
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Colorectal cancer most common(2001)
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What is the cancer with the highest death rate in Australia?
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Pancreatic cancer (2001)
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What can a tumour be indicated by?
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Signs and Symptoms
- decreased weight, anorexia, mass General Biochem - LFTs (cholestatic) Increased Ca2+ Hormones - ADH, ACTH, PTHrP, hCG Tissue markers - PSA, thyroglobulin Strange protiens - paraproteins, AFP, CEA, CA125, CA 19-9, CA 15-3 Cell surface marker - beta2-microglobulin Enzymes - LD DNA - BRCA 1 & 2 for breast CA, ras oncogene for colon CA |
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Why do we measure tumour markers?
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1. Detection early, treatable CA
2. Confirmation diagnosis 3. Staging (classification) 4. Monitoring - response to treatment, recurrence 1,2,3 - limited use 4 - IMPORTANT use |
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What are features of an ideal tumour marker?
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- High sensitivity - detect early, treatable cancers
- High specificity - no false positive results - Reflect tumour activity and mass - help guide treatment - Prevents premature death from cancer Tumour marker levels correlate reasonably well with tumour volume. Lack of sufficient sensitivity and specificity limits its use in cancer screening. |
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What are some tumour marker problems?
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1. Tumours do not always produce markers
2. Sensitivity - poor - Negative result in people with cancer e.g. CEA only pikes 5% Dukes A colon CA, not for screeening fo cancer 3. Specificity - poor - positive result in people without cancer e.g. PSA in prostatitis, CA 19-9 in cholestasis 4. False +ve/-ve result due to assay problems |
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What are some assay problems?
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1. HIGH DOESE HOOK EFFECT - falsely low values
2. HETEROPHILE ANTIBODY INTERFERENCE - falsely high values e.g.heterophile antibody (human antimouse antibody) 3. Values from different labs are not interchangeable |
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What is PSA?
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Prostate specific antigen
- A glycoprotein (serine protease) secreted by prostatic epithelial cells. Confined to the gland but "leak" into the circulation - In teh glood, mostly bound to proteins: e.g. alpha-antichymotrypsin - PSA is tissue specific but not tumour specific - commonly used reference range - <mg/mL PRIMARY TUMOUR - Prostate BENIGN CONDITIONS - Prostatitis (8 weeks), BPH, prostatic trauma, after ejaculation (2d) DIAGNOSIS - yes MONITORING TREATMENT - very helpful FOLLOW-UP AFTER TREATMENT - 6 monthly x 5y then annually - any detectable PSA after radical proctectomy indicates recurrence SCREENING GENERAL POPULATION - controversial - not recommended in australia |
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What is the ideal for PSA as a tumour marker? What is teh reality for PSA with BPH?
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Ideal - Cut off at 4ng/mL
Reality - false positives, false negatives, grey area |
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What are problems with PSA?
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- PSA is neither sensitive or specific (PPV 20-30% at PSA >4ng/mL)
- Follow up procedure invasive - Treatment has significant complications - Many people with prostate CA die of other causes - Despite increase incidence due to introduction of PSA, mortality has not changed - ? Are we detecting clinically less important cases? |
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What are ways to increase PSA specificity?
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1. Clinical indication - lower threshold for +ve family Hx or abnormal DRE
2. Use age-adjusted reference ranges for different ethnic groups 3. Free PSA/total PSA ratio (fPSA) 4. PSA velocity - >0.75ug/L/year --> high risk for CA 5. PSA density - Against volume of prostate by ultrasound: ug/L/mL |
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What are some onco-foetal proteins?
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Carcinoembryonic Antigen (CEA)
Alpha foetal protein (AFP) Beta human chorionic gonadotrophin (beta-hCG) |
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What is CEA?
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Onco-foetal protein made by normal and malignant epithelial tissues.
PRIMARY TUMOUR - colorectal CA OTHER TUMOURS - breast, lung, GI epithelium, heat & neck BENIGN CONDITIONS - usually <20ng/mL; cigarette smoking, most GI conditions, hypothyroidism FOLLOW-UP AFTER Rx - 2-3 monthy, at least 2y |
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What are AFP?
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Alpha foetoprotein
- Foetal albumin made by yolk sack and liver - high in infants and ruing pregnancy - adults <10ug/mL - half life ~ 5 days PRIMARY TUMOURS - hepatoma, germ cell CA (non-seminomatous) |
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AFP and hepatoma
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- hepatoma is commonly a complication of chronic hepatitis (esp. Hep C)
- AFP > 1000ug/L usually indicate hepatoma - Current debates on its use in hepatoma screening - Problems: > small incrases can be due to early hepatoma or liver deases > increase in benign conditions (usually <200ug/L): hepatitis, cirrhosis |
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AFP and germ cell tumours
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- AFP and beta-hCG are important in the treatment of testicular nonseminomatous germ cell tumour
- levels failure to fall after surgery indicate residual disease - follow up: > at least 6 repeats in 1st year post op > then quaterly x 1 year > less frequent thereafter |
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Describe Beta-hCG as a tumour marker
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Normally produced by placenta - increased in pregnancy
PRIMARY TUMOUR - nonseminomatous germ cell tumour, gestational trophoblastic disease OTHER TUMOURS - rarely, GI cancers BENIGN CONDITIONS - hypogonadal state, marijuana use FOLLOW-UPAFTER Rx - For seminomatous germ cell tumour - same as AFP - For gestational trophoblastic disease - Monthly x 1 year |
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What are some carbohydrate antigens?
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CA 15-3
CA 19-9 CA 125 |
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CA 15-3
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- a monoclonal antibody developed to detect glycoprotein found on breast cell epithelium
- same levels in male and females - no change in pregnancy and lactation PRIMARY TUMOUR - breast OTHER TUMOURS - colon, lung, pancreas BENIGN CONDITIONS - benign breast, liver and kidney disorders, pancreatitis, biliary dis, cirrhosis MONITORING TREATMENT AND RECURRENCE - helpful FOLLOW-UP AFTER Rx - 4-6 monthly for recurrence |
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CA 19-9
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An intracellular adhesion molecule made by pancreatic and biliary cells
PRIMARY TUMOUR - Pancreatic CA, biliary tract CA OTHER TUMOURS - colon, esophageal and hepatic CA BENIGN CONDITIONS - usually <1000ng/mL, pancreatitis, biliary dis, cirrhosis MONITORING TREATMENT AND RECURRENCE: Helpful FOLLOW-UP AFTER Rx - 2-3 monthly, at least 2 yr |
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CA 125
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A monoclonal antibody developed to detect glycoprotein found on ovarian epithelial tumour cells
PRIMARY TUMOUR - ovarian CA OTHER TUMOURS - endometrial, fallopian, breast, lung, GI BENIGN CONDITIONS - menstruation, pregnancy, fibroids, ovarian cysts, endometriosis, pelvic inflammation, cirrhosis, ascites, and pleural & pericardial effusions FOLLOW-UP AFTER Rx - 3 monthly, at least 2 years |
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SUMMARY OF TUMOUR MARKERS
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Tumour markers can provide valuable assistance in management of patients with known malignancy if used appropriately
- Have limited role for cancer screening > thye do not have sufficient sensitivity or specificity > low prevalence of the disease in general population > +ve reulst are far more likely to be false +ve than true +ve - Tests can be also falsely +ve or -ve due to assay problems - talk to the lab if doubt - need to monitor levels by the same laboratory |