Lecture 3: Cancer Pathological Changes CO Flashcards

1
Q

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 = ?

A
  • 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)

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2
Q

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

A
  • 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
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3
Q

Cancer-Pathological changes:

Hematologic System?

A

• Anemia
-Bone marrow suppression
-GI ulceration and anemia due to invasion
• Neutropenia
• Thrombocytopenia
• Hypercoagulable state; risk of thromboembolic events

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4
Q

Cancer-Pathological changes:

Neuromuscular System?

A
  • 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.
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5
Q

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

A

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

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6
Q

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

A

• 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

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7
Q

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.

A

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.

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8
Q

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 ?

A

**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

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9
Q
Cancer- Pathological changes:
Renal System
• Inc/Dec clearance? 
• Drug induced ? 
• Ureteral obstruction >>> ? 
• Hyper?
A

Renal System
• Decreased clearance
• Drug induced nephrotoxicity/ nephrotic syndrome
• Ureteral obstruction&raquo_space;> hydronephrosis
• Hyperuricemia

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10
Q
Cancer- Pathological changes:
Hepatic System 
• Damage to ? 
• Coag? 
• \_\_\_ common with hepatic metastasis
A

Hepatic System
• Damage to hepatocytes
• Coagulopathies
• DIC common with hepatic metastasis

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11
Q
Cancer- Pathological changes:
Metabolic Complications 
• Catabolic state 
-Diarrhea 
-Poor Nutritional Status -> ? 
-Volume depleted state -> ?
A
Metabolic Complications 
• Catabolic state 
-Diarrhea 
-Poor Nutritional Status -> Check Albumin levels 
-Volume depleted state -> Hypotension
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12
Q
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
A

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

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13
Q

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

A

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

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14
Q

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 = ?

A

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!

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15
Q

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 = ?

A

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

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16
Q

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 ?

A

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
17
Q

Pulmonary toxicity:

_____________ (Antimetabolite) - toxicity = X%

  • fulminant non-cardiogenic pulmonary ______
  • Progressive inflammation with ?

Radiation to chest ->

A

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
18
Q

Pulmonary toxicity: PEARLS

A
  • 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
19
Q

Renal toxicity:

Cisplatin: _____-limiting effect
• Decreased GFR within 3-5 days
• Renal insufficiency and hypo___________ are typical presenting signs
• ATN →___ → ___________

A

Renal toxicity:

Cisplatin: dose-limiting effect
• Decreased GFR within 3-5 days
• Renal insufficiency and hypomagnesemia are typical presenting signs
• ATN →ARF → Hemodialysis

20
Q

Renal toxicity:

Methotrexate (Antimetabolite)
• Prehydration, Leucovorin, and avoidance of other nephrotoxic drugs reduce the incidence

A

Renal toxicity:

Methotrexate (Antimetabolite)
• Prehydration, Leucovorin, and avoidance of other nephrotoxic drugs reduce the incidence

21
Q

Renal toxicity:

Cyclophosphamide
• Associated with SIADH syndrome of inappropriate antidiuretic hormone secretion
• Hemorrhagic cystitis

A

Renal toxicity:

Cyclophosphamide
• Associated with SIADH syndrome of inappropriate antidiuretic hormone secretion
• Hemorrhagic cystitis

22
Q

Renal toxicity:

Ifosfamide
• Proximal tubule dysfunction
• Marked by proteinuria and glucosuria

A

Renal toxicity:

Ifosfamide
• Proximal tubule dysfunction
• Marked by proteinuria and glucosuria

23
Q

Renal toxicity: Causing Drugs

A

Cisplatin
Methotrexate
Cyclophosphamide
Ifosfamide

24
Q

Pulmonary toxicity: Causing Drugs

A

Bleomycin

Methotrexate

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Cardiotoxicity: Causing Drugs
Doxorubicin (Adriamycin) and Daunorubicin | Fluorouracil and "zumabs"
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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
27
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
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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
29
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
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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
31
Nervous system changes: High dose Cyclophosphamide→?
Nervous system changes: High dose Cyclophosphamide→acute delirium, encephalopathy, ataxia
32
Nervous system changes: Methotrexate→?
Nervous system changes: Methotrexate→dementia
33
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
34
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 ```
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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
36
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 ```
37
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
38
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.