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HathsuDissanayakeY5 S1906245.ed.ac.uk Y1CancerTutorialLearningOutcomes • Understand the physiology of cancer • Understand how cancers progress • Understand how we treat cancerWhatwewillcover • Importance of Cancer • Properties of Cancer • Pre-malignancy • Cancer Microenviroment • Metastasis • Management and Prevention • MCQs • A disease of uncontrolled proliferationof abnormal cells WhatisCancer? • Genetic in origin • Causes death by metastasis usuallyCommonestCancers Adults Children • Breast (females) and Prostate • Leukaemias (Males) • Cancers of the CNS • Lung • Lymphomas • Colorectal • Wilms Tumours • Melanomas • Osteosarcomas • LymphomasCommonestCancers Adults Children • Breast (females) and Prostate • Leukaemias (Males) • Cancers of the CNS • Lung • Lymphomas • Colorectal • Wilms Tumours • Melanomas • Osteosarcomas • LymphomasCommonestCancers Adults Children • Breast (females) and Prostate • Leukaemias (Males) • Cancers of the CNS • Lung  Biggest Killer • Lymphomas • Colorectal • Wilms Tumours • Melanomas • Osteosarcomas • LymphomasRiskFactors? Age Familyhistory Lifestyle •Smoking •Alcohol •Obesity Environment RiskFactors •Sun exposure •Chemicalexposure •Occupational Medical causes •Viral infections – HPV, EBV,HIV •Immunosupression •RadiationWhyisCancerImportant?• Ageing population • Common comorbidity • Patient are very concerned about itNomenclature(manyexceptions) • Benign o “oma” o “papilloma” o “carcinomainsitu” • Malignant o “sarcoma” o “carcinoma” • Different rules for don’tneedto worryabout them)TumourStaging-TNM T – Primary Tumour • T0: Noevidenceof primarytumour • Tis:Carcinomain situ • T1,T2, T3, T4: Sizeand/orextentof primarytumour N – Regional Lymph Nodes • N0:Noregionallymphnodeinvolvement • N1,N2, N3:Regionallymphnodeinvolvement M – Distant Metastasis • M0:No metastasis • M1:DistantmetastasispresentMacroPropertiesof Cancer • Physical traits o Location o Size + shape o Infiltration • Dissemination routes o Local invasion? o Haematological metastasis? o Lymphatic metastasis? • Paraneoplastic complications o Endocrine – Cushing, SIADH o Neurological – Lambert-Eaton myasthenic syndrome o Various dermatological and haematological manifestationsMicroPropertiesofCancer • Tumours are genetically heterogenous • Don’t only contain cancer cells oECM oImmunecells oBlood vessels oSignalling molecules • Regional variation oCentre getspoorer vascularisation oLess metabolites/oxygen oCan get necrosisHallmarks of Cancer Mutations Oncogenes Tumour Suppressor Genes “Pressingthe accelerator” “Cutting the break lines” Mutations in proto-oncogenes turn them ON to Mutations in TSGsturn them OFF to drive drive progression progression Onlyrequires mutation in 1 copy to have aneffect Usuallyrequires mutations inboth copies to have an effect (“Two-hit Hypothesis”) E.g. p53, Rb, BRCA2, NF1 E.g. Ras, EGFR,VEGFR, HER2Pre-malignancy • Abnormal cells with morphological changes • E.g. oColorectal polyps/adenomas -> colorectal cancer oBarrett’soesophagus -> oesophageal cancer oActinic keratosis -> squamouscell skincancer oMonoclonal gammopathy of undetermined significance -> myeloma • Can take many years to become cancerous • Management options: surveillance, resection, chemopreventionInvasionandMetastasis • Invasion = enters surrounding tissue • Metastasis =spreads to distantsites • The pointwhere it becomesmalignant • Metastatic spread via bloodor lymphatics • Molecular level – loss of cell-cell adhesion • Surrounding tissues act as barriers with tight junctionsand basement membraneLocationofMetastasis Differentcancers like to spread to differentlocations Why?• often spreads toGItract duetoproximity • Blood supply– GIcancers often spread to the liver due tothe hepatic portal circulation • Lymphatics– drains fluid fromthe whole body,many and deposit in the nodes • interaction between thes – cancer cells and the host tissueHowtowemanagecancer? Howtomanage cancer PREVENTION TREATMENT FOLLOW UPPrevention • Legislation – smoking restriction • Cultural attitudes and behaviour changes • Screening • Vaccinations – HPV vaccine oNearly all cases of cervical cancer is caused by HPV oSimilar with vaginal, vulval, penile, and anal cancers oVaccine now availablefor children 11-13 and MSM up to the age of 45CancerScreening • Goodscreeningprogram • Scottish cancer screening o The conditionmust bean important programs health problem o Gooddiagnostictest available oBreast – mammogramoffered o Sensitiveand specific for ever female 50-70 every 3 years o Treatmentis moreeffectivewhen oBowel – faecal occult blood test started early offered for 50-70 every 2 years o Targets higher risk demographics o Cost considerations oCervical – cervical swab offered o Evidencebasefor efficacyof tofemale 25-64 every 5 years screeningprogramTreatmentoptions Surgery – cut it out! Radiotherapy – external beam, brachytherapy, radioisotope Chemotherapy – cytotoxic drugs(+/- autologous transplant) Targeted therapy – trastuzumab, imatanib Hormonal therapy – tamoxifen, letrozole Immunotherapy – own immune system to target cancerCurativevsPalliative GoalsofCare • Not everyonecan becured • palliativecaremptomswith • Canuse manyof thecurativeoptions in symptommanagement Followup CONSIDER CONSIDER GENETIC MANAGELONGTERM PSYCHOLOGICAL SURVEILLANCEFOR TESTING SIDE-EFFECTS OF SUPPORT RECURRENCE TREATMENTRecommendedResources • Davidson’s Principles and Practice of Medicine, Chapter 7 – availablefreely on DiscoverEd • Youtube: Oncogenetics - Mechanism of Cancer (tumor suppressor genes and oncogenes) by Armando Hasudungan - https://www.youtube.com/watch?v=1mo80kTZgW4&list=PLqTetb gey0acDW_2E0CIwzre1cDLcBxQs&index=1 • Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar 4;144(5):646-74. doi: 10.1016/j.cell.2011.02.013. PMID: 21376230.AnyQuestions?MCQs1.Whichofthefollowingcancerskillsthe mostpeople? a) Breast b) Prostate c) Lung d) Colorectal e) Brain1.Whichofthefollowingcancerskillsthe mostpeople? a) Breast b) Prostate c) Lung d) Colorectal e) Brain2.Whichofthefollowingisthebiggestrisk factorforcancer? a. Norovirus infection b. IV drug use c. Occupation in coal mines d. Receiving a single chest x-ray e. Long term immunosuppression2.Whichofthefollowingisthebiggestrisk factorforcancer? a. Norovirus infection b. IV drug use c. Occupation in coal mines d. Receiving a single chest x-ray e. Long term immunosuppression3.Whichofthefollowingtumoursisabenign lesion? a. Osteosarcoma b. Ductal carcinoma in situ of the breast c. Squamous cell carcinoma of the skin d. Malignant melanoma e. Chondrosarcoma3.Whichofthefollowingtumoursisabenign lesion? a. Osteosarcoma b. Ductal carcinoma in situ of the breast c. Squamous cell carcinoma of the skin d. Malignant melanoma e. Chondrosarcoma4.Whichofthefollowingtumoursistheleast concerning? a. T1 N1 M1 b. T4 N2 M1 c. T3 N0 M0 d. T4 N0 M0 e. T3 N1 M04.Whichofthefollowingtumoursistheleast concerning? a. T1 N1 M1 b. T4 N2 M1 c. T3 N0 M0 d. T4 N0 M0 e. T3 N1 M05.Whichofthefollowinggenesisfrequently turnedoffincancers? a. Ras b. EGFR c. VEGFR d. HER2 e. p535.Whichofthefollowinggenesisfrequently turnedoffincancers? a. Ras b. EGFR c. VEGFR d. HER2 e. p536.Whichofthefollowingstatementsabout pre-malignancyistrue? a. Pre-malignancy is often invasive into surrounding tissues b. Management can often be surveillance c. It usually takes < 1 year for a pre-malignant lesion to transform into a malignancy d. Pre-malignancy is normal cells in an abnormal distribution e. Multiple myeloma is an example of a pre-malignancy6.Whichofthefollowingstatementsabout pre-malignancyistrue? a. Pre-malignancy is often invasive into surrounding tissues b. Management can often be surveillance c. It usually takes < 1 year for a pre-malignant lesion to transform into a malignancy d. Pre-malignancy is normal cells in an abnormal distribution e. Multiple myeloma is an example of a pre-malignancy7.Whichofthefollowing malignancies are matched withthecorrectcommonmetastasis sites? a. Colon – brain, bone, adrenal gland, skin b. Lung – large intestines,small intestines,skin, kidneys c. Kidney – skin, thyroid gland, pancreas, large intestine d. Breast – bone, brain, liver,lung e. Melanoma – adrenal gland, thyroid gland, kidneys, small intestines7.Whichofthefollowing malignancies are matched withthecorrectcommonmetastasis sites? a. Colon – brain, bone, adrenal gland, skin b. Lung – large intestines,small intestines,skin, kidneys c. Kidney – skin, thyroid gland, pancreas, large intestine d. Breast – bone, brain, liver, lung e. Melanoma – adrenal gland, thyroid gland, kidneys, small intestines8.Thehuman papilloma virus(HPV)isNOT associated withwhichofthefollowing malignancies? a. Cervical b. Penile c. Anal d. Skin e. Mouth8.Thehuman papilloma virus(HPV)isNOT associated withwhichofthefollowing malignancies? a. Cervical b. Penile c. Anal d. Skin e. Mouth9.Whichofthefollowingcriteriaisneededfor agoodscreeningprogram? a. Early diagnosis of the condition does not require any treatment b. Efficacy of a screening program should be reviewed continuously c. A diagnostic test whichis specific but not necessarily sensitive is needed d. A diagnostic test which is sensitive but not necessarily specific is needed e. A screening program should be offered to everyone9.Whichofthefollowingcriteriaisneededfor agoodscreeningprogram? a. Early diagnosis of the condition does not require any treatment b. Efficacy of a screening program should be reviewed continuously c. A diagnostic test whichis specific but not necessarily sensitive is needed d. A diagnostic test which is sensitive but not necessarily specific is needed e. A screening program should be offered to everyone.10.Whichofthefollowingisnotusedinthe managementofprimarycancer? a. Antibiotics b. Surgery c. Beam radiotherapy d. Hormone blockers e. Autologous stem cell transplant10.Whichofthefollowingisnotusedinthe managementofprimarycancer? a. Antibiotics b. Surgery c. Beam radiotherapy d. Hormone blockers e. Autologous stem cell transplant Thankyou! Please fill out the feedback form in the chat!