Paraneoplastic Flashcards
• Disorders that accompany benign or malignant
diseases but are not directly related to mass effects or invasion
PARANEOPLASTIC SYNDROME:
ENDOCRINE/HEMATOLOGIC
Tumors of neuroendocrine origin, such as small
cell lung carcinoma (SCLC) and carcinoids,
produce a wide array of ____ and are
common causes of paraneoplastic syndromes.
peptide hormones
(expression of a hormone from its normal
tissue of origin)
o For example, ACTH of the pituitary
eutopic
hormone production from an atypical tissue source -For example, the squamous lung CA o Conveys abnormal physiology associated with neoplastic hormone production o Not fully understood
Ectopic
is often characterized by abnormal regulation of hormone production (e.g., defective feedback control) and peptide processing.
Ectopic
• Occurs in up to 20% of patients with cancer.
• Most common in cancers of lung, head and neck,
skin, esophagus, breast, genitourinary, multiple
myeloma, lymphomas
• PTHrP production probably cause osteolysis and
hypercalcemia
HUMORAL HYPERCALCEMIA OF MALIGNANCY (HMM)
Another cause of HHM is excess production of
1,25- dihydroxyvitamin D
o Structurally related to PTH and binds to the
PTH receptor, explaining the similar
biochemical features of HHM and
hyperparathyroidism
o Plays a key role in skeletal development and
regulates cellular proliferation and
differentiation in other tissues, including skin,
bone marrow, breast, and hair follicles
PTHrP
HMM is stimulated by:
- Hedgehog pathways
- Gli transcription factors
- TGF-ß
- Ras oncogene
- Loss of p53
HMM clinical manifestations:
Hypercalcemia, fatigue, mental status changes, dehydration, symptoms of nephrolithiasis
is the initial presenting
feature of malignancy
Hypercalcemic
o With a Calcium level of >3.5 mmol/L
(>14 mg/dL)
HMM: Elevated _________ confirms the diagnosis
PTHrP
HMM treatment: Oral phosphorous (250 mg po 3-4x daily) until
serum phosphorus _____
> 1mmol/L (>3 mg/dL)
Saline rehydration to dilute serum calcium and
promote _______
calciuresis
Used for acute management of life thereatening hypercalcemia
Furosemide (loop diuretic)
Used for chronic management of life thereatening hypercalcemia
Bisphosphonates used for chronic treatment;
o Pamidronate 30-90 mg IV
o Zolendronate 4-8 mg IV
o Etidronate 7.5 mg/kg/day po for 3-7 days
o 2-8 U/kg sc every 12 hrs)
o Severe hypercalcemia
Calcitonin
for patients with;
o Lymphoma
o Multiple myeloma
o Leukemia
Glucocorticoids (prednisone 40-100 mg po in 4
divided doses)
Tumor-Association SIADH compensatory mechanisms:
decreased thirst,
suppression of aldosterone, production of atrial
natriuretic peptide
Examples of tumors causing SIADH are
Small Cell
Lung CA and carcinoids (most common)
SIADH clinical manifestations
• Asymptomatic • Hyponatremia • Weakness, lethargy, nausea, confusion, depressed mental status, seizures • Suppressed thirst mechanism
SIADH DIAGNOSIS
- Hyponatremia
- Decreased serum osmolality
- Normal or increased urine osmolality
o Inhibit vasopressin action along the renal
distal tubule
o Slow onset of action (1-2 weeks)
Demeclocycline (150-300 mg 3-4x daily)
Hypertonic saline (3%) or NSS plus furosemide for severe hyponatremia (< 115 meq) - treatment for:\_\_\_\_
SIADH
• Slow Na correction (0.5-1 meq/L per hr)
o to prevent_________
central pontine
myelinolysis
• 10-20% of cases
• Neuroendocrine tumors
• Increased expression of the
proopiomelanocortin (POMC) gene.
Cushing’s Syndrome
is the most
common cause of ectopic ACTH
Small Cell Lung CA (>50%)
Cushing’s syndrome clinical manifestations:
-Less marked weight gain (centripetal fat
distribution)
• Fluid retention, hypertension, hypokalemia,
metabolic alkalosis, glucose intolerance, steroid
psychosis
• Increased skin pigmentation
• Marked skin fragility, easy bruising (due to
increased glucocorticoids)
• Severe hypokalemia
• Depression or personality changes
• Diabetes mellitus
• Poor wound healing
• Opportunistic infections (P. carinii, mycotic)
Cushing’s syndrome diagnosis: Urine free cortisol levels
> 2-4x normal
Cushing’s syndrome diagnosis: Plasma ACTH level
> 22 pmol/L (> 100pg/mL)
High dose ______ (8mg per orem)
suppresses 8:00 am serum cortisol (50%
decrease from baseline) in 80% of pituitary
ACTH-producing adenomas
dexamethasone
CUSHING SYNDROME TREATMENTS:
KMMG • Ketoconazole (200-400 mg bid po) • Metyrapone (250-500 mg q 6 hrs) • Mitotane 3-6 g po in 4 divided doses • Glucocorticoids (to avoid adrenal insufficiency
Hmm calcium level
> 3.5mmol (14md/dL)
Tumor-induced hypoglycemia:excess production of IGF-II
- Mesenchymal tumors
- Hemangiopericytomas
- Hepatocellular tumors
- Adrenal carcinomas
Erythrocytosis
Renal CA, hepatocarcinoma, cerebellar hemangioblastomas
granulocytosis
Lung Ca, GIT ca, Ovarian ca
Thrombocytosis
Lung CA, git, breast, ovarian CA
The most significant risk factor for cancer overall is
AGE (2/3 over 65 y.o)
NINE MODIFIABLE RISK FACTORS FOR
MORE THAN ONE-THIRD OF CANCERS WORLDWIDE
- Smoking
- Alcohol consumption
- Obesity
- Physical inactivity
- Low fruit and vegetable consumption
- Unsafe sex
- Air pollution
- Indoor smoke from household fuels
- Contaminated injections – HIV
The first priority in patient management after the diagnosis of cancer is established and shared with the
patient
staging
is an anatomically based system
that categorizes the tumor on the basis of the size of
the primary tumor lesion, the presence of nodal
involvement, and the presence of metastatic disease
TNM classification (most widely used)
are the ones with bad prognosis, tumor has involved other organs.
T3, N2, N3, M1
second major determinant of treatment outcome is
the
physiologic reserve of the patient
Instead,
surrogate markers for physiologic reserve are used, such as
the patient’s age or Karnofsky
performance status or Eastern Cooperative
Oncology Group (ECOG) performance status.
Older patients and those with a Karnofsky
performance status ___ or ECOG __ have a poor prognosis unless the poor
performance is a reversible consequence of the
tumor.
<70, ≥3
chemotherapy or
chemotherapy plus radiation therapy delivered before the use of definitive surgical treatment
Neo adjvant therapy
The most common side effects of treatment are:
o nausea and vomiting
o febrile neutropenia
o Myelosuppression
Delayed emesis tx
cisplatin
