Cancer and Paraneoplastic Syndromes – Flashcards
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Carcinoma
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derived from epithelial tissues (solid tumor)
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Sarcoma
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derived from mesenchymal tissues (fleshy lumps)
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Paraneoplastic Symptoms
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symptoms that result from circulating substances secreted by tumor cells acting on normal cells OR circulating substances secreted by normal cells in response to the tumor -not direct effect of malignancy
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What do you need to diagnose cancer?
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NEED HISTOLOGIC OR CYTOLOGIC PROOF OF DISEASE (biopsy)
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Staging
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TNM system -tumor: size, location -nodes: involvement, location -metastases: presence, location staging guides treatment along with tumor markers, etc.
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Endobronchial Ultrasound (EBUS)
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lung cancer endoscopic staging
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Endoscopic Ultrasound (EUS)
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tumor stage and nodal stage -esophageal cancer -rectal cancer -pancreatic cancer
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Mediastinoscopy
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surgical staging evaluate mediastinal lymph nodes in lung cancer
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Diagnostic Laparoscopy
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evaluate for carcinomatosis in gastric cancer surgical staging
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Curative Cancer Treatment
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goal is to get rid of tumor -goal to complete all treatment -manageable toxicity but will tolerate more toxicity to complete treatment
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Palliative Cancer Treatment
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know can't get rid of tumor -goal is to prolong life when possible and to improve quality of life by improving symptoms -balance of QOL benefit and toxicity of treatment
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Performance Status
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ECOG scale, measures how robust or active the patient is 0: no limitations or symptoms 1: some symptoms but still active all day 2: active for more than 1/2 the day 3: more limitations, able to self care but active less than 1/2 the day 4: bed bound 5: dead if poor performance status, treatment may not be indicated if harm outweighs benefit
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Neoadjuvant therapy
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chemo/radiation before a planned surgery -shrink tumor so surgical resection can be done -improve overall survival
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Adjuvant therapy
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therapy after a surgery (chemo/radiation) -indication based on pathologic staging -treat microscopic disease -improve overall survival compared to surgery alone
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Definitive therapy
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chemoradiation treatment without need for surgery
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Local therapy
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therapy that affects only the tumor one can see -surgery -radiation -etc.
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Systemic therapy
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therapy that affects the tumor you can see as well as sites distant from the originating tumor -chemotherapy -targeted therapy -hormonal therapy (breast and prostate cancer) -immunotherapy
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How to treat localized disease
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confined to tissue of origin, no invasion of adjacent structures -treat with localized therapy: surgery or radiation -adjuvant therapy as indicated by pathology
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how to treat locally advanced disease
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regional LN involvement, large tumors, etc. -treat with combined modality therapy (chemotherapy, radiation, surgery) -concurrent chemoradiation **** (chemo sensitizes tissue to radiation) -chemoradiation can be neoadjuvant or definitive
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how to treat advanced disease (metastases)
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distant spread -primary treatment with systemic therapy -radiation or surgery to relieve local complications -occasionally indication for resection of metastasis
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R0 resection
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where they have resected the ENTIRE tumor and left nothing behind (including microscopic disease) -have negative margins
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Gray
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radiation absorbed dose -amount of energy imparted to matter from radiation
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Systemic Therapies
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-cytotoxic chemotherapy -hormonal therapy -targeted therapy -immunotherapy
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Targeted therapy
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targets a receptor expressed by the tumor that has a role in oncogenesis -EGFR: Cetuximab -Her2/neu: Trastuzumab
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Checkpoint inhibitors
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form of immunotherapy -cosignaling molecules that ligate each other between cells to tell them to stop or go -Anti PD1 mAbs -Anti PD-L1 mAbs -Anti CTLA4 mAbs
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PD1 and PDL1
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CD8 T cells express PD-1 -when interacts with PD-L1 on tumor cells, tells cell to stop (negative signal) agents block PD-1 or PD-L1 to block the negative signal to T cells -> get more cancer attacking
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Local effects of tumor on host
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-impingement of adjacent structures -bleeding and infections when tumor ulcerates through adjacent surfaces -acute symptoms caused by either rupture or infarction -destruction of normal tissue by tumor: replacement of functional tissue -space occupying effect: pressure or invasion of adjacent normal structure- LOCATION! -pressure on nerve: pain, paralysis -obstruction of lumen -seizure -brain herniation -obstruction of large vessel (superior vena cava syndrome) -tumor erosion of muscosa/vessel/skin/peripheral nerves
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Generalized effects of tumor on host
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-Cachexia (wasting) -Function of tumor: hormonal, paraneoplastic sndromes
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Superior Vena Cava Syndrome
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local effect of tumor -large LUNG TUMOR presses on and obstructs the SVC that drains venous branches in head and neck -get engorgement of facial and neck veins, edema, and blue discoloration
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Tumor erosion of mucosa/vessel/skin/peripheral nerves
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bleeding: melena, hematuria, coffee ground emesis, hemoptysis seconday infeciton perineural invasion: pain, Horner syndrome
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Horner syndrome
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pancoast tumor of sympathetic trunk -tumor a the apex of lung (top) invades into the brachial plexus and presses on the sympathetic nerve trunk get ptosis, miosis, and anhydrosis local effects of tumor (perineural invasion)
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Cachexia
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generalized tumor effect -up to 50% cancer patients -weight loss, muscle atrophy and wasting -weakness, fatigue, anorexia, edema, anemia -may be the presenting symptom -some correlation to tumor burden -suspect if involuntary weight loss of >10% premorbid weight basal metabolic rate has INCREASED causing equal loss of FAT and MUSCLE -cytokines produced by tumor and patient's body cause the increase in BMR leads to 1/3 of cancer treatments worse prognosis makes pt too weak for toxic chemo
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Hormonal Effects
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generalized tumor effect -hormone production by tumors of endocrine organs -paraneoplastic syndromes: ABERRANT production of hormones or hormone-like substances by tumors of non-endocrine organs
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Paraneoplastic Syndromes
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ABERRANT production of hormones or hormone like substances by tumors of non-endocrine organs (e.g. lung, colon) -due to dedifferentiation -NOT caused by local effect of the tumor -endocrinopathies
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Types of paraneoplastic syndromes
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-Endocrinopathies -Osseous/soft tissue syndromes -Dermatologic syndromes -Neuromyopathies -Vascular/coagulopathies
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Paraneoplastic Cushing Syndrome
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paraneoplastic endocrinopathy -tumors not from endocrine tissue tumor in LUNG dedifferenatiates and produces ACTH-like substance -this causes adrenal hyperplasia which increases cortisol production -production of ACTH or ACTH like peptides (e.g. POMC) ->50% caused by lung cancer
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Hypercalcemia
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paraneoplastic endocrinopathy -most common paraneoplastic syndrome -life threatening -symptomatic hypercalcemia is usually related to cancer most common cause: LUNG cancer, also breast, ovarian, renal (different than direct osteolysis by tumor) -production of CALCEMIC SUBSTANCES by extraosseous neoplasms that causes bone to break down and release Ca calcemic substances: PTHRP, TGF alpha, TNF, IL-1
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PTH related protein (PTHRP)
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produces in small amounts by normal tissues -CALCEMIC substance released by extraosseous neoplasms -resembles PTH -acts at PTH receptors on bone to dissolve it so Ca enters bloodtsream
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Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
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paraneoplastic endocrinopathy -secretion of ectopic ADH -due to small cell carcinoma of lung, intracranial tumors -ADH excess causes resorption of excessive amount of free water, get hyponatremia -cerebral edema and neurologic dysfunciton
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Hypoglycemia
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paraneoplastic endocrinopathy insulin like substance -various soft tissue sarcomas, hepatocellular carcinoma
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Polycythemia
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paraneoplastic endocrinopathy erythropoietin secreted by tumors
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Hypertrophic osteoarthropathy
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paraneoplastic syndrome -1-10% of lung cancer patients -new bone formation at ends of fingers -arthritis of adjacent joints -clubbing of fingers significant if it is NEW
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Acanthosis nigricans
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paraneoplastic syndrome -grey black patches of verrucous hyperkeratosis -commonly in the folds of skin due to TUMOR producing EPIDERMAL GROWTH FACTORS (lung, gastric) significant if it is NEW
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Neuromyoapthic paraneoplastic syndromes
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neural antigens are also expressed on tumors antibodies developed against tumor antigens cross react with neuronal cells!!!! -peripheral neuropathies -cortical cerebellar degeneration -polyyopathy resembling polymyositis -Myasthenic syndrome similar to myasthenia gravis - Eaton Lambert Syndrome
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Eaton Lambert Syndrome
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neuromyoapthic paraneoplastic syndrome antibodies made against tumor cells cross react with neuronal cells -myasthenic syndrome similar to myasthenia gravis -muscles that tire -ptosis usually due to lung CA
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DIC (Disseminated Intravascular Coagulation)
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paraneoplastic syndrome -tumors produce substances that activate the coagulation cascade -get spontaneous thrombotic events (migratory) -acute promyelocytic leukemia -mucinous carcinomas of the prostate, lung, pancreas, colon, stomach (mucin has procoagulant effect)
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Non-bacterial thrombotic endocarditis (NBTE)
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paraneoplastic syndrome coagulation cascade is activated -small nonbacterial fibrinous vegetations on cardiac valve leaflets -potential source of emboli -hypercoagulability -most in advanced cancers -can be part of Trousseau syndrome
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Trousseau syndrome
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paraneoplastic syndrome -migratory superficial thrombophlebitis, carcinogenic thrombophlebitis, Trousseau sign -deep seated cancers (PANCREAS or lung) -mucins activate clotting cascdae
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Tumor markers
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assays for tumor associated substances (proteins) -found in plasma or other body fluids -NOT for primary diagnosis (low specificity and sensitivity) -used to support diagnosis -correlates with tumor burden and stage -levels fall after treatment -rising levels indicate recurrence
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Important tumor markers
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PSA-prostate cancer (also for screening) CEA: colon, pancreas CA AFP: hepatocellular, testicular CA CA-125: ovarian tumors HCG: testicular cancers CA19-9: colon, pancreas CA
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PSA
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prostate cancer tumor marker *also used for screening
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CEA
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colon, pancreas CA tumor marker
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AFP
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hepatocellular, testicular CA tumor marker
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CA-125
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ovarian tumors tumor marker
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HCG
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testicular cancers tumor marker
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CA19-9
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colon, pancreas CA tumor marker
