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Oncology. With regard to the spread of neoplasms, which of the following statements is false? A. Metastatic cells enter the lymph nodes via the subcapsular.

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Presentation on theme: "Oncology. With regard to the spread of neoplasms, which of the following statements is false? A. Metastatic cells enter the lymph nodes via the subcapsular."— Presentation transcript:

1 Oncology

2 With regard to the spread of neoplasms, which of the following statements is false? A. Metastatic cells enter the lymph nodes via the subcapsular space and later permeate the sinusoids of the node B. Carcinoma in situ is a lesion with histopathologic characterisitics of malignancy but without detectable invasion beyond the basement membrane C. Lymphatic involvement is common with epithelial neoplasms, whereas most sarcomas metastasize hematogenously D. The Metastatic process is highly efficient, as evidenced by the fact that the number of circulating tunor cells correlates with the metastatic burden. Answer: D

3 Regarding oncogenes and proto-oncogenes, which of the following statements are true? A. Proto-oncogenes are proteins capable of inhibiting oncogenes. B. Oncogenes are nucleic acid sequences unique to the viral genome. C. Exposure to carcinogens causes insertion of oncogenes into the human genome. D. Proto-oncogenes may be activated by mutation, amplification, or translocation. Answer: D

4 Development of Cancer Oncogenes are genes that, when expressed, contribute to the devlopment of malignancy Proto-oncogenes are genes found in normal tissues that, when activated by mutation, amplification or translocation become oncogenes and may lead to transformation of the cell to a malignant phenotype. e.g. - RET (?) Tumor suppresor genes are different – the loss of their expression leads to devlopment of cancer. –Most common tumor suppressor gene - Medullary Thyroid Cancer p53

5 Regarding metastatic cancer, which of the following statements is true? A. Axillary lymph node dissection is essential for staging a sarcoma of the breast B. Melanoma tends to metastasize first to the lung, brain, and gastrointestinal tract. C. Bone is frequently the site of metastasis for cancer of the breast and prostate. D. Primary brain cancers have a predilection for metastasis to the lung. Answer: C

6 Which of the following options is/are appropriate for treatment of metastatic cancer? A. A Whipple procedure to relieve obstructive jaundice in a patient with adenocarcinoma of the head of the pancreas and multiple small metastatic lesions in the liver. B. Resection of three liver lesions, metastatic from a colorectal primary tumor, in the absence of another site of disease. C. Resection of two lung metastases from a sarcoma of the lower extremities in the absence of other metastatic disease. D. Radiation therapy for a painful hip lesion in a patient with diffuse metastases from prostate cancer. Answer: B,C,D

7 Which of the following historical characteristics of a mass suggest(s) malignancy? A. Sudden devlopment of a painful, tender mass. B. Slow, progressive, painless growth of mass. C. Sudden dramatic enlargement of a previously stable- sized mass D. A mass that waxes and wanes in size with or without associated tenderness. Answer: B

8 Performing which of the following operations would be inappropriate without first obtaining a biopsy specimen confirming the presence of cancer? A. Radical right hemicolectomy for an “apple core” narrowing of the ascending colon. B. Modified radical mastectomy for a clinically and mammographically obvious breast cancer with overlying “skin puckering”. C. A pancreaticoduodenectomy for a large, hard mass in the head of the pancreas that produces painless jaundice. D. Parotidectomy for a 2 cm, slowly growing solid parotid mass without evidence of facial nerve dysfunction. Answer: B

9 Which of the following tumors requires resection of the largest margin of normal tissue around the clinically obvious tumor to achieve an acceptable likelihood of control at the local primary site. Assume that no other treatment will be used. A. Adenocarcinoma of the colon B. Basal Cell carcinoma of the skin C. Invasive breast cancer D. Squamous carcinoma of the distal esophagus E. Squamous carcinoma of the skin Answer: D Colon – 2cm Esophageal and gastric malignancy can spread in submucosal plane as far as 10cm from primary site

10 Partial of complete resection of which of the following organs could be justified to prevent a future cancer? A. Colon B. Pancreas C. Breast D. Testicle E. Thyroid Answer: A, C, D, E in FAP, BRCA1 or 2, Undescended testicle, MEN II

11 In which of the following circumstances would palliative surgery not be indicated? A. Carcinoma of the body of the pancreas that produces severe back pain B. A large gastric cancer obstructing the gastroesophageal junction, associated with two small liver metastses C. A bleeding cecal cancer, 5cm in diamter, with multiple liver metastasis D. Adenocarcinoma of the head of the pancreas with partial portal vein involvement Answer: A

12 Which of the following statements concerning sentinel lymph node biopsy is not true? A. The technique utilizes injection of a vital blue dye and/or radioactive tracer to identify the sentinel node B. The sentinel node is the first draining node, from a particular location, in each basin. C. There is only one sentinel node in each basin. D. The technique is not useful in patients with suspicious palpable adenopathy. Answer: C

13 Which of the following chemotherapeutic agents is/are known to cause nephrotoxicity? A. Cisplatin B. Carboplatin C. Ifosfamide D. Methotrexate E. Cyclophosphamide F. 5-FU Answer: A,D

14 Rapid Fire Most sensitive phase of cell cycle to radiation –M–M–M–M Extremity Sarcoma – method of excisional biopsy –Longitudinal incision Ret proto-oncogene diagnostic for: –Medullary Thyroid Cancer –Medullary Thyroid Cancer -treatment? –Total Thyroidectomy Adverse effect of Tamoxifen –DVT and endometrial CA

15 Alphabet Soup CEA –Colon Ca AFP –Liver Ca CA 19-9 –Pancreatic Ca CA 125 –Ovarian Ca Beta-HCG –Testicular CA, choriocarcinoma PSA-Prostate NSE -Small cell Lung CA

16 Familial Cancer Syndromes Breast/ovarian – BRCA1 – breast, ovary, colon, prostate – BRCA2 – “ “, GB/biliary tree, pancreas, stomach, melanoma Cowden’s dis – breast, endometrium, thyroid FAP – APC – colorectal, duodenal, gastric, medulloblastomas, osteomas Familial melanoma – CDK4 – melanoma, pancreas, dysplastic nevi, atypical moles HNPCC – colorectal, endometrial, tcc of ureter, stomach, sb, pancreas, ovary Li-Fraumeni – p53 – breast/phyllodes, soft tissue and osteosarcoma, brain, adrenal, Wilms, pancreas, leukemia, neuroblastoma MEN1 – MEN1 – pancreas, parathyroid hyperplasia, pituitary MEN2 MEN2 – RET – MTC, pheo, parathyroid hyperplasia

17 Familial Cancer Syndromes NF1 NF1 – NF1 – Neurofibromas/fibrosarcoma, AML, brain NF2 NF2 – NF2 – Acoustic neuromas, meningiomas, gliomas, ependymomas Peutz-Jeghers Peutz-Jeghers – GI CAs, breast, testicular, pancreas, benign pigmentation of skin/mucosa Retinoblastoma Retinoblastoma – RB – Rb, sarcomas, melanoma Tuberous sclerosis Tuberous sclerosis – TSC1/2 – hamartomas, renal cell, astrocytoma VHL VHL – Renal cell, hemangioblastomas of retina and CNS, pheo Wilms Wilms – WT – wilm’s, aniridia, genitourinary abnormalities, mental retardation

18 Familial Adenomatous Polyposis APC gene, autosomal dominant APC gene, autosomal dominant – Scaffolding protein, cell adhesion, migration – Frameshift (68%), nonsense mutation (30%), deletion (2%) 1% of all colorectal cancers 1% of all colorectal cancers >90% develop cancers >90% develop cancers 100s to 1000s of adenomatous polyps 100s to 1000s of adenomatous polyps – Phenotype expressed in 20-30s with CA by – Polyps not inherently more cancerous Extracolonic manifestations Extracolonic manifestations – UGI polyps, desmoid tumors, thyroid CA Stomach/duodenum polyps(90%) by 70 years Stomach/duodenum polyps(90%) by 70 years Duodenal adenoCA 3 rd cause of death Duodenal adenoCA 3 rd cause of death

19 Familial Adenomatous Polyposis Attenuated FAP Attenuated FAP – <100 adenomas – Proximal colonic polyp distribution – Cancer occurs 15 years later Gardner’s syndrome Gardner’s syndrome – Colorectal CA, Osteomas of mandible/skull, epidermal cysts, skin/soft tissue tumors (desmoids and thyroid) MYH-associated polyposis (MAP) MYH-associated polyposis (MAP) – Autosomal recessive, 50% penetrance – Cancer occurs at 50 years – Extracolonic manifestations Breast (18%) Breast (18%) UGI polyps (33%) UGI polyps (33%)

20 Hereditary Nonpolyposis Colorectal Cancer Lynch’s Syndrome Autosomal dominant, mismatch repair genes 5-10% of all colorectal CA’s Type 1 (Colorectal), Type 2 (Extracolonic) Right sided colon CAs (70% proximal to splenic flexure) at earlier age (~44) Increased synchronous and metachronous lesions Increased speed of tumor progression – Adenomas progress to CA in 2-3 years vs 8-10 Extracolonic – Endometrium/ovary

21 BRCA1 / BRCA2 Tumor suppressor gene Tumor suppressor gene – Frameshift or nonsense mutations with truncated protein products – DNA repair, gene expression regulation, cell cycle control – 2 hit hypothesis 5-10% of all breast CAs are hereditary 5-10% of all breast CAs are hereditary 25% of high-risk families have mutations 25% of high-risk families have mutations 80% risk in 70 yo woman 80% risk in 70 yo woman Ovarian CA in 60%/27% (1 vs 2) ; Prostate CA in men Ovarian CA in 60%/27% (1 vs 2) ; Prostate CA in men

22 MEN 1 MEN 1 MEN 1 – Autosomal dominant germline mutations – Tumor suppressor, Loss of fx mutations (80%) Menin – transcription regulation, DNA repair Menin – transcription regulation, DNA repair – Parathyroid gland, pancreatic islet cell, pituitary gland Lipomas, adrenal/thyroid adenomas, cutaneous angiofibromas, carcinoid tumors Lipomas, adrenal/thyroid adenomas, cutaneous angiofibromas, carcinoid tumors

23 MEN 2 ret proto-oncogene (re-arranged during transfection) ret proto-oncogene (re-arranged during transfection) – Tyrosine kinase receptor becomes constitutively activated germline mutations germline mutations MEN 2A MEN 2A – MTC (100%), Pheocromocytoma (50%), Hyperparathyroidism (25%) MEN 2B MEN 2B – MTC, Pheo, mucosal neuromas (tongue, lips) Intestinal ganglioneuromatosis, marfanoid habitus Intestinal ganglioneuromatosis, marfanoid habitus – Sporadic ret mutations more common

24 UV – skin UV – skin – UVB most important (UVC filtered by ozone layer) Formation of pyrimidine dimers repaired by nucleotide excision repair pathway Formation of pyrimidine dimers repaired by nucleotide excision repair pathway – SCCA, basal cell, malignant melanoma – Xeroderma Pigmentosa Autosomal recessive, NER gene mutations Autosomal recessive, NER gene mutations Extreme photosensitivity, 2000x increased risk of skin CA Extreme photosensitivity, 2000x increased risk of skin CA Ionizing – multiple cancers Ionizing – multiple cancers – Electromagnetic, particulate – Carcinogen at low doses, therapeutic agent at high doses – Causes inflammatory reaction with production of reactive oxygen and nitrogen species – Leukemias and solid organ (breast, colon, thyroid, lung) tumors Head/neck irradiation in kids – thyroid CA as adults Head/neck irradiation in kids – thyroid CA as adults Radiation Carcinogenesis

25 Viral Carcinogenesis ~15% of all human tumors caused by viruses ~15% of all human tumors caused by viruses – Mostly cervical CA by HPV and HCC by HBV/HCV Establish long-term persistent infections in target cells Establish long-term persistent infections in target cells EBV Burkitt’s, Hodgkin’s, Immunosuppresion-related lymphoma, Nasopharyngeal CA Hep B/CHCC HIV type IKaposi’s HPV 16 & 18Cervical, Anal HTLV-1Adult T-cell leukemia H. pyloriGastric adenoCA Opisthorchis viverriniCholangioCA, HCC Schistosoma haematobiumUrinary bladder

26 Protein Tumor Markers α-Fetoprotein – HCC – Oncofetal antigen – synthesized by hepatocytes, endodermal GI tissues – Normal <25 ng/ml (nonpregnant), half-life 5 days – 10-20% of HCCs nondetectable levels – Also found in: nonseminomatous testicular CA > 5ng/ml in 20% of gastric, pancreatic 5% colorectal, lung Hepatitis, inflammatory bowel dis, cirrhosis – Sensitivity/Specificity 25-75% / 76-94% ; PPV 9-50% – AFP and ultrasound = 100% in one study – Reflects tumor size ; correlates with stage and prognosis >400 ng/ml associated with larger tumors – Drops after resection/ablation ; usually drops with chemo <10 ng/ml if complete rsxn AFP level (ng/ml)Sensitivity/Specificity 2030/ / /94

27 Protein Tumor Markers Carbohydrate Antigen 19-9 – pancreatic CA Carbohydrate Antigen 19-9 – pancreatic CA – Upper limit normal 37 U/ml – Sensitivity/Specificity 67-92% / 68-92% – Not a good diagnostic marker, better for monitoring therapy response Acute/chronic biliary dis elevates serum levels Acute/chronic biliary dis elevates serum levels Low sensitivity in early-stage disease Low sensitivity in early-stage disease Benign biliary dis can have levels up to 400 U/ml, 87% with concentrations >70 U/ml Benign biliary dis can have levels up to 400 U/ml, 87% with concentrations >70 U/ml Pts with negative Lewis a blood group (10% pop) cannot synthesize CA 19-9 Pts with negative Lewis a blood group (10% pop) cannot synthesize CA 19-9 Present in CAs of biliary tree (95%), stomach (5%), colon (15%), HCC (7%), Lung (13%) Present in CAs of biliary tree (95%), stomach (5%), colon (15%), HCC (7%), Lung (13%) – Levels correlate with tumor burden and tx response 95% of unresectable cancers have levels >1000 U/ml 95% of unresectable cancers have levels >1000 U/ml

28 Protein Tumor Markers Prostate specific antigen Prostate specific antigen – Tissue specific, not cancer specific, not present post prostatectomy or in women – Elevated in BPH, prostatitis, massage, bx, and DRE – Widely used screening tool for prostate CA 1:8 cancers kills host if left untreated 1:8 cancers kills host if left untreated – Upper limit normal 4ng/ml, >10ng/ml suspicious for malignancy Half-life 18 days Half-life 18 days Upper limit increases with age Upper limit increases with age – Measuring PSA as ratio to total volume or ratio of free to total PSA improves specificity when values in intermediate range – Levels should normalize within 2-3 weeks If levels elevated for 6 months – relapse almost certain If levels elevated for 6 months – relapse almost certain

29 Protein Tumor Markers Carbohydrate antigen 125 Carbohydrate antigen 125 – Present in the fetus and adult fallopian tubes, endometrium, endocervix, peritoneum, pleura, pericardium, amnion – NOT present in adult nor fetal ovarian epithelium – Upper limit normal 35 U/ml – Increased levels found in 80% ovarian cancers – Useful for monitoring disease course and recurrence – Sensitivity/Specificity 75% / 90% in pts with ovarian masses – Also present in cancer of: fallopian tube, endometrium, cervix, pancreas, colon, lung, liver – Elevated in endometriosis, adenomyosis, fibroids, PID, cirrhosis, ascites

30 Protein Tumor Markers α-Fetoprotein and Human Chorionic Gonadotropin α-Fetoprotein and Human Chorionic Gonadotropin – Nonseminomatous testicular cancers: embryonal CA, choriocarcinoma, yolk sac tumors, teratomas – HCG – 90% choriocarcinomas – AFP – 90-95% yolk sac tumors, 20% teratomas, 10% embryonal Cas – Pts with nonseminomatous testicular germ cell tumors: 50% HCG and 60% AFP, 90% either/or – AFP >500ng/ml or HCG >1000 ng/ml gives poor prognosis – Levels correlate with chemo response

31 THE END!


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