Lecture 3: Cancer Pathological Changes CO Flashcards
The Disease of Cancer- Overview:
Cancer results from an accumulation of genetic mutations that causes dysregulation of cellular proliferation (alterations in cell’s DNA structure)
• Inherited traits
• Mutation of normal gene into an ?
• Inactivation of a ?
•Fundamental cellular event in malignancy: alteration in DNA structure
• Immune surveillance destroys many malignant cells
• HIV/ Immunosuppressants disrupt this protective mechanism
Most cancers produce ? tumors
TNM staging system = ?
- Inherited traits
- Mutation of normal gene into an oncogene
- Inactivation of a tumor suppressor gene (p53)
- Fundamental cellular event in malignancy: alteration in DNA structure
- Immune surveillance destroys many malignant cells
- HIV/ Immunosuppressants disrupt this protective mechanism
Most cancers produce solid tumors
TNM staging system
• Tumor size, nodes, distant metastatic disease
• Stage 1 (best prognosis) to stage 4 (worst prognosis)
Most Common Cancers
• Lung (#_ in men ↑in women)
• Breast (#_ in women)
• Colon/GI (#_ cause death overall in US)
• Prostate (#_ in men)
• Head & Neck
• Metastatatic tumors- brain, liver, spinal cord, superior vena cava compression
- Lung (#2 in men ↑in women)
- Breast (#1 in women)
- Colon/GI (#2 cause death overall in US)
- Prostate (#1 in men)
- Head & Neck
- Metastatatic tumors- brain, liver, spinal cord, superior vena cava compression
Cancer-Pathological changes:
Hematologic System?
• Anemia
-Bone marrow suppression
-GI ulceration and anemia due to invasion
• Neutropenia
• Thrombocytopenia
• Hypercoagulable state; risk of thromboembolic events
Cancer-Pathological changes:
Neuromuscular System?
- Myofascial pain and peripheral neuropathies
- Spinal cord compression
- Metastatic brain tumors, most often from lung and breast cancer,
- present initially as mental deterioration, focal neurologic deficits, or seizures.
Cancer-Pathological changes:
Pulmonary System
• Pulmonary _____ / ___
• Recurrent ?
• Pneumonitis
• Lung CA specifically:
• _________ cell (25-40% incidence)→ hypercalcemia
• _____carcinoma (30-50%)→ hypercoagulable/osteoarthritis
• _________ cell (10%) –gynecomastia
• **_________ cell (15-24%) → inappropriate ___ secretion/ ectopic corticotropin secretion/ ___________ syndrome (Myasthenic syndrome- muscle weakness/ resembles ________________)
• Pulmonary _______________- condition that affects some lung CA pts—clubbing, spoon-shaped nails, inflammation/swelling/pain in hands, fingers, knees, ankles
Pulmonary System
• Pulmonary edema / CHF
• Recurrent pleural effusions
• Pneumonitis
• Lung CA specifically:
• Squamous cell (25-40% incidence)→ hypercalcemia
• Adenocarcinoma (30-50%)→ hypercoagulable/osteoarthritis
• Large cell (10%) –gynecomastia
• **Small cell (15-24%) → inappropriate ADH secretion/ ectopic corticotropin secretion/ Eaton-Lambert syndrome (Myasthenic syndrome- muscle weakness/ resembles myasthenia gravis)
• Pulmonary osteoarthropathy- condition that affects some lung CA pts—clubbing, spoon-shaped nails, inflammation/swelling/pain in hands, fingers, knees, ankles
Cancer-Pathological changes:
• ___________/Weight loss- hyperalimentation
• ___________ abnormalities
-_____calcemia due to bone metastasis
-__++ & _+ changes with- N&V/ diarrhea
• Adrenal Insufficiency- tumor or suppression of adrenals with ?
• Ectopic hormone production
• Anorexia/Weight loss- hyperalimentation
• Electrolyte abnormalities
-Hypercalcemia due to bone metastasis
-Na++ & K+ changes with- N&V/ diarrhea
• Adrenal Insufficiency- tumor or suppression of adrenals with Corticosteroid Rx
• Ectopic hormone production
Cancer-Pathological changes:
Cardiac System
• __________ involvement of the pericardium (pericardial effusion)
-Electric alternans or paroxysmal ?
-Pericardial tamponade (Most common with ? CA)
• Drug induced ?
-Impairment of __ function for as long as 3 years after discontinuation of therapy.
Cardiac System
• Malignant involvement of the pericardium (pericardial effusion)
-Electric alternans or paroxysmal A-fib or Flutter
-Pericardial tamponade (Most common with lung CA)
• Drug induced cardiomyopathy
-Impairment of LVF for as long as 3 years after discontinuation of therapy.
Cancer-Pathological changes:
**SVC Obstruction-Metastatic spread to the ?
• Venous engorgement above the waist, dyspnea and airway obstruction
• Increased ? from increase in cerebral venous pressure
• Compression of great vessels may lead to ?
• Hoarseness/ dyspnea may indicate ?
**SVC Obstruction-Metastatic spread to the mediastinum
• Venous engorgement above the waist, dyspnea and airway obstruction
• Increased ICP from increase in cerebral venous pressure
• Compression of great vessels may lead to syncope
• Hoarseness/ dyspnea may indicate tracheal compression
Cancer- Pathological changes: Renal System • Inc/Dec clearance? • Drug induced ? • Ureteral obstruction >>> ? • Hyper?
Renal System
• Decreased clearance
• Drug induced nephrotoxicity/ nephrotic syndrome
• Ureteral obstruction»_space;> hydronephrosis
• Hyperuricemia
Cancer- Pathological changes: Hepatic System • Damage to ? • Coag? • \_\_\_ common with hepatic metastasis
Hepatic System
• Damage to hepatocytes
• Coagulopathies
• DIC common with hepatic metastasis
Cancer- Pathological changes: Metabolic Complications • Catabolic state -Diarrhea -Poor Nutritional Status -> ? -Volume depleted state -> ?
Metabolic Complications • Catabolic state -Diarrhea -Poor Nutritional Status -> Check Albumin levels -Volume depleted state -> Hypotension
Paraneoplastic Syndromes • Affect X% of pts with cancer • Fever and cachexia • Neurologic abnormalities: limbic encephalitis, cerebellar degeneration, ? syndrome (SCLC, major potential w/ NMBs), and ? • Endocrine abnormalities: ? (SCLC) (headache, nausea, ataxia, lethargy, seizures), \_\_\_\_\_calcemia, ? syndrome, \_\_\_\_\_glycemia • Renal abnormalities: ? • Dermatologic abnormalities • Rheumatologic abnormalities • Hematologic abnormalities
Paraneoplastic Syndromes
• Affect 8% of pts with cancer
• Fever and cachexia
• Neurologic abnormalities: limbic encephalitis, cerebellar degeneration, Lambert-Eaton myasthenia syndrome (SCLC), and myasthenia gravis
• Endocrine abnormalities: SIADH (SCLC) (headache, nausea, ataxia, lethargy, seizures), Hypercalcemia, Cushing syndrome, Hypoglycemia
• Renal abnormalities: nephritis, amyloidosis
• Dermatologic abnormalities
• Rheumatologic abnormalities
• Hematologic abnormalities
Cancer Treatments
• ___________ therapy is most common
• Surgery -> ?
• Traditional chemotherapy: various MOAs
• Targeted chemotherapy: eg monoclonal antibodies
• Radiation therapy: MOA is damage to ?
• Ablation therapy (RFA): primary ____ tumors and metastases, localized lung, kidney, adrenal gland, and bone tumors
• Cancer Vaccines & Immunomodulators
Cancer Treatments
• Multimodal therapy is most common
• Surgery -> cancer bleeds!!!
• Traditional chemotherapy: various MOAs
• Targeted chemotherapy: eg monoclonal antibodies
• Radiation therapy: MOA is damage to DNA
• Ablation therapy:
-RFA: primary liver tumors and metastases, localized lung, kidney, adrenal gland, and bone tumors
• Cancer Vaccines & Immunomodulators
Cardiotoxicity:
Anthracyclines are most commonly associated.
? and Daunorubicin
- dose related cardiomyopathy
- can be acute or chronic
- late onset form that may emerge much later
- Enhances myocardial depression with ? (acute LV failure during ?, up to 2 months after cessation)
PEARLS = ?
Anthracyclines are most commonly associated.
Doxorubicin (Adriamycin) and Daunorubicin
- dose related cardiomyopathy
- can be acute or chronic
- late onset form that may emerge much later
- Enhances myocardial depression with anesthetics (acute LV failure during GA, up to 2 months after cessation)
PEARLS = BL and periodic ECHO!
Cardiotoxicity:
Fluorouracil
- associated with pericarditis, angina, coronary artery vasospasm, __________-related EKG changes, conduction defects
“zumabs” and Sorafenib (targeted chemo)
- ___ (~X%)**
Radiation to chest
- Myocardial and valvular ________, pericarditis, conduction abnormalities, accelerated development of ?
- ___________ exposure is a factor
PEARLS = ?
Cardiotoxicity:
Fluorouracil
- associated with pericarditis, angina, coronary artery vasospasm, ischemia-related EKG changes, conduction defects
“zumabs” and Sorafenib (targeted chemo)
- HTN (~40%)**
Radiation to chest
- Myocardial and valvular fibrosis, pericarditis, conduction abnormalities, accelerated development of CAD
- Cumulative exposure is a factor
PEARLS: Preop EKG, CXR, Stress test, ECHO, BNP
- high degree of suspicion for early onset or accelerated CAD
Pulmonary toxicity:
____________ (Anti-tumor Antibiotic): dose-related toxicity –rare below 150mg/m2
• Endothelial damage (Looks like pneumonia→ type I and type II alveolar necrosis →pulmonary fibrosis- no Rx
• Pulmonary hypertension
• Increased A-a gradient
• Induced ________ pulmonary injury; free-radical formation
Recommend ?
Bleomycin (Anti-tumor Antibiotic): dose-related toxicity –rare below 150mg/m2
• Endothelial damage (Looks like pneumonia→ type I and type II alveolar necrosis →pulmonary fibrosis- no Rx
• Pulmonary hypertension
• Increased A-a gradient
• Induced hyperoxic pulmonary injury; free-radical formation
Recommend: • Baseline and serial PFTs and CXR • ABG, SaO2 • Adjust O2 for Sat >90% (ideally <30%) • Colloid v crystalloid • Corticosteroids
Pulmonary toxicity:
_____________ (Antimetabolite) - toxicity = X%
- fulminant non-cardiogenic pulmonary ______
- Progressive inflammation with ?
Radiation to chest ->
Pulmonary toxicity:
Methotrexate (Antimetabolite) - toxicity = 8%
- fulminant non-cardiogenic pulmonary edema
- Progressive inflammation with infiltrates and effusion
Radiation to chest
- interstitial pneumonitis
- fibrosis
- tracheal stenosis
Pulmonary toxicity: PEARLS
- Preop o2 sat, CXR, PFT, ABG
- Intraop exposure to high concentraiton o2 may exacerbate preexisting bleomycin induced lung injury and contribute to postop vent failure
- Periop coritcosteroid admin may be of benefit in treating bleomycin-induced pneumonitis
Renal toxicity:
Cisplatin: _____-limiting effect
• Decreased GFR within 3-5 days
• Renal insufficiency and hypo___________ are typical presenting signs
• ATN →___ → ___________
Renal toxicity:
Cisplatin: dose-limiting effect
• Decreased GFR within 3-5 days
• Renal insufficiency and hypomagnesemia are typical presenting signs
• ATN →ARF → Hemodialysis
Renal toxicity:
Methotrexate (Antimetabolite)
• Prehydration, Leucovorin, and avoidance of other nephrotoxic drugs reduce the incidence
Renal toxicity:
Methotrexate (Antimetabolite)
• Prehydration, Leucovorin, and avoidance of other nephrotoxic drugs reduce the incidence
Renal toxicity:
Cyclophosphamide
• Associated with SIADH syndrome of inappropriate antidiuretic hormone secretion
• Hemorrhagic cystitis
Renal toxicity:
Cyclophosphamide
• Associated with SIADH syndrome of inappropriate antidiuretic hormone secretion
• Hemorrhagic cystitis
Renal toxicity:
Ifosfamide
• Proximal tubule dysfunction
• Marked by proteinuria and glucosuria
Renal toxicity:
Ifosfamide
• Proximal tubule dysfunction
• Marked by proteinuria and glucosuria
Renal toxicity: Causing Drugs
Cisplatin
Methotrexate
Cyclophosphamide
Ifosfamide
Pulmonary toxicity: Causing Drugs
Bleomycin
Methotrexate
Cardiotoxicity: Causing Drugs
Doxorubicin (Adriamycin) and Daunorubicin
Fluorouracil and “zumabs”
Renal toxicity:
Induction Chemo and High-dose Radiation
• Induces tumor cell ____ (tumor ____ syndrome) that causes release of large amounts of uric acid, phosphate, and potassium
• Hyperuricemia can cause _______ crystals to precipitate in renal tubules, leading to acute RF
• Can cause glomerulonephritis or glomerulosclerosis with permanent injury marked by chronic renal insufficiency and systemic HTN
• Life threatening hyper________ can occur
• Hyperphosphatemia leads to hypocalcemia and can increase the likelihood for ?
• Preoperative tests?
Renal toxicity:
Induction Chemo and High-dose Radiation
• Induces tumor cell lysis (tumor lysis syndrome) that causes release of large amounts of uric acid, phosphate, and potassium
• Hyperuricemia can cause uric acid crystals to precipitate in renal tubules, leading to acute RF
• Can cause glomerulonephritis or glomerulosclerosis with permanent injury marked by chronic renal insufficiency and systemic HTN
• Life threatening hyperkalemia can occur
• Hyperphosphatemia leads to hypocalcemia and can increase the likelihood for dysrhythmias
• Preoperative BUN/Creatinine, urine analysis
Hepatic dysfunction:
____________ (Antimetabolite)
• Associated with acute liver dysfunction
Radiation (TBI)
• Associated with ? syndrome (severe liver dysfunction with high ?)
• Preop tests?
Hepatic dysfunction:
Methotrexate (Antimetabolite)
• Associated with acute liver dysfunction
Radiation (TBI)
• Associated with sinusoidal obstruction syndrome (severe liver dysfunction with high mortality)
• Preop LFTs, albumin
Airway and Oral Cavity Issues:
- Mucositis -> May cause AW compromise or risk of aspiration
- Radiation -> Limit mouth opening or neck ROM
PEARLS = ?
Preop AW assessment
Cervical ROM and X-ray
ENT consult
GI/ Endocrine changes:
• Nausea/ vomiting, diarrhea, enteritis are common after chem + radiation……… Results in ?
• Radiation to abdomen may produce permanent adhesions and stenotic lesions along GI tract
• ______glycemia as side effect of glucocorticoid therapy
• ______ seen with cyclophosphamide, ifosfamide, cisplatin
• Radiation to neck or TBI may cause ?
• Preop tests?
- Nausea/ vomiting, diarrhea, enteritis are common after chem + radiation……… Results in dehydration, electrolyte abnormalities, and malnutrition
- Radiation to abdomen may produce permanent adhesions and stenotic lesions along GI tract
- Hyperglycemia as side effect of glucocorticoid therapy
- SIADH seen with cyclophosphamide, ifosfamide, cisplatin
- Radiation to neck or TBI may cause hypothyroidism or panhypopituitarism
- Preop thyroid function tests, CMP, blood glucose, urine specific gravity
Hematolgic system changes:
Chemo
• ***______suppresssion
• ________________ dysfunction (leading to bleeding)
• Tumors release procoagulants that create ?
• ___ prophylaxis is essential in high risk patients
Radiation
• Coagulation necrosis of vascular endothelium
• Post-radiation bleeding
• Preop = ?
Hematolgic system changes:
Chemo
• ***Myelosuppresssion
• Thrombocytopenia and/or platelet dysfunction (leading to bleeding)
• Tumors release procoagulants that create hypercoagulable state
• VTE prophylaxis is essential in high risk patients
Radiation
• Coagulation necrosis of vascular endothelium
• Post-radiation bleeding
• Preop: CBC, PT/PTT, INR
Nervous system changes:
High dose Cyclophosphamide→?
Nervous system changes:
High dose Cyclophosphamide→acute delirium, encephalopathy, ataxia
Nervous system changes:
Methotrexate→?
Nervous system changes:
Methotrexate→dementia
Nervous system changes:
Vinca Alkaloids (Vincristine)
• Sensorimotor peripheral neuropathy- paresthesia in hands/feet
• Autonomic neuropathy- usually reversible->?
• Cisplatin-dose dependent damage to dorsal root ganglia→ large fiber neuropathy
• Caution with regional anesthesia->?
Nervous system changes:
Vinca Alkaloids (Vincristine)
• Sensorimotor peripheral neuropathy- paresthesia in hands/feet
• Autonomic neuropathy- usually reversible (hypoTN)
• Cisplatin-dose dependent damage to dorsal root ganglia→ large fiber neuropathy
• Caution with regional anesthesia: subclinical neurotoxicity may be present
Nervous system changes:
Alkylating Agents (Cytoxan) • Plasma cholinesterase inhibition • Anticholinesterase Effects-> prolongs effects of ? by reducing available acetylcholinesterase enzyme which metabolizes the drug
Nervous system changes:
Alkylating Agents (Cytoxan) • Plasma cholinesterase inhibition • Anticholinesterase Effects-> prolongs effects of succinylcholine by reducing available acetylcholinesterase enzyme which metabolizes the drug
Anesthesia Considerations with Cancer:
Symptom management important (nausea & vomiting, constipation)
Pain management crucial
• Recent evidence suggests anesthetics and analgesics have ___________________ properties
• IV opioids tend to blunt ___________ cell activity
• ________ anesthesia preferred
• watch coagulopathies
• Must assess and document baseline neuropathies if regional is considered
immunomodulatory
natural killer (NK) cell
Regional
Cancer- Other Medications
• Treatment of nausea and vomiting = ?
• Patients will often verbalize a high degree of anxiety related to the potential for nausea and vomiting
• Must provide reassurance that measures will be taken to control nausea and vomiting
Cancer- Other Medications • Treatment of nausea and vomiting - Metoclopramide - Droperidol - Zofran® - Cannabis • Patients will often verbalize a high degree of anxiety related to the potential for nausea and vomiting • Must provide reassurance that measures will be taken to control nausea and vomiting
Cancer-Other Medications:
• Pain management
• Be aware that patients who are receiving treatment for cancerrelated pain may have inc/dec requirements for analgesia
• Use visual analogue scale (VAS) to measure pain
• NSAIDs effective for ____ pain
- Most common type of cancer pain
• Opioid administration: tolerance may require?
• Adjuncts: antidepressants, anticonvulsants, gabapentin, ketamine
• Nerve Blocks- neurolysis
- Goal is sensory destruction while sparing motor/ autonomic function
• Corticosteroids
- Decrease pain perception, have a sparing effect on opioid requirements, improve mood, increase appetite, and lead to weight gain
- Preop supplemental ?
bone
increased
dose adjustment
steroids
Blood transfusion during surgical resection of colorectal cancers is associated with?
Blood transfusion during surgical resection of colorectal cancers is associated with a decrease in the length of patient survival.
