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Presentation on theme: "Oncology."— Presentation transcript:

1 Oncology

2 With regard to the spread of neoplasms, which of the following statements is false?
Metastatic cells enter the lymph nodes via the subcapsular space and later permeate the sinusoids of the node Carcinoma in situ is a lesion with histopathologic characterisitics of malignancy but without detectable invasion beyond the basement membrane Lymphatic involvement is common with epithelial neoplasms, whereas most sarcomas metastasize hematogenously 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?
Proto-oncogenes are proteins capable of inhibiting oncogenes. Oncogenes are nucleic acid sequences unique to the viral genome. Exposure to carcinogens causes insertion of oncogenes into the human genome. Proto-oncogenes may be activated by mutation, amplification, or translocation. Answer: D

4 Development of Cancer Most common tumor suppressor gene -
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?
Axillary lymph node dissection is essential for staging a sarcoma of the breast Melanoma tends to metastasize first to the lung, brain, and gastrointestinal tract. Bone is frequently the site of metastasis for cancer of the breast and prostate. 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 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. Resection of three liver lesions, metastatic from a colorectal primary tumor, in the absence of another site of disease. Resection of two lung metastases from a sarcoma of the lower extremities in the absence of other metastatic disease. 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?
Sudden devlopment of a painful, tender mass. Slow, progressive, painless growth of mass. Sudden dramatic enlargement of a previously stable-sized mass 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? Radical right hemicolectomy for an “apple core” narrowing of the ascending colon. Modified radical mastectomy for a clinically and mammographically obvious breast cancer with overlying “skin puckering”. A pancreaticoduodenectomy for a large, hard mass in the head of the pancreas that produces painless jaundice. 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. Adenocarcinoma of the colon Basal Cell carcinoma of the skin Invasive breast cancer Squamous carcinoma of the distal esophagus 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? Colon Pancreas Breast Testicle 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?
Carcinoma of the body of the pancreas that produces severe back pain A large gastric cancer obstructing the gastroesophageal junction, associated with two small liver metastses A bleeding cecal cancer, 5cm in diamter, with multiple liver metastasis 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?
The technique utilizes injection of a vital blue dye and/or radioactive tracer to identify the sentinel node The sentinel node is the first draining node, from a particular location, in each basin. There is only one sentinel node in each basin. 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?
Cisplatin Carboplatin Ifosfamide Methotrexate Cyclophosphamide 5-FU Answer: A,D

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

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

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 RET – MTC, pheo, parathyroid hyperplasia

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

18 Familial Adenomatous Polyposis
APC gene, autosomal dominant Scaffolding protein, cell adhesion, migration Frameshift (68%), nonsense mutation (30%), deletion (2%) 1% of all colorectal cancers >90% develop cancers 100s to 1000s of adenomatous polyps Phenotype expressed in 20-30s with CA by 35-40 Polyps not inherently more cancerous Extracolonic manifestations UGI polyps, desmoid tumors, thyroid CA Stomach/duodenum polyps(90%) by 70 years Duodenal adenoCA 3rd cause of death

19 Familial Adenomatous Polyposis
Attenuated FAP <100 adenomas Proximal colonic polyp distribution Cancer occurs 15 years later Gardner’s syndrome Colorectal CA, Osteomas of mandible/skull, epidermal cysts, skin/soft tissue tumors (desmoids and thyroid) MYH-associated polyposis (MAP) Autosomal recessive, 50% penetrance Cancer occurs at 50 years Extracolonic manifestations Breast (18%) 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
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 25% of high-risk families have mutations 80% risk in 70 yo woman Ovarian CA in 60%/27% (1 vs 2) ; Prostate CA in men

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

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

24 Radiation Carcinogenesis
UV – skin UVB most important (UVC filtered by ozone layer) Formation of pyrimidine dimers repaired by nucleotide excision repair pathway SCCA, basal cell, malignant melanoma Xeroderma Pigmentosa Autosomal recessive, NER gene mutations Extreme photosensitivity, 2000x increased risk of skin CA 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

25 Viral Carcinogenesis ~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 EBV Burkitt’s, Hodgkin’s, Immunosuppresion-related lymphoma, Nasopharyngeal CA Hep B/C HCC HIV type I Kaposi’s HPV 16 & 18 Cervical, Anal HTLV-1 Adult T-cell leukemia H. pylori Gastric adenoCA Opisthorchis viverrini CholangioCA, HCC Schistosoma haematobium Urinary bladder

26 Sensitivity/Specificity
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 20 30/80 100 72/56 400 70/94

27 Protein Tumor Markers Carbohydrate Antigen 19-9 – pancreatic CA
Upper limit normal 37 U/ml Sensitivity/Specificity % / 68-92% Not a good diagnostic marker, better for monitoring therapy response Acute/chronic biliary dis elevates serum levels Low sensitivity in early-stage disease Benign biliary dis can have levels up to 400 U/ml, 87% with concentrations >70 U/ml Pts with negative Lewisa blood group (10% pop) cannot synthesize CA 19-9 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

28 Protein Tumor Markers 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 Upper limit normal 4ng/ml, >10ng/ml suspicious for malignancy Half-life 18 days 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

29 Protein Tumor Markers 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
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


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