PRESENTED BY DR HITESH GOUR JR PULMONARY MEDICINE DEFINATION Paraneoplastic syndromes refer to the disorders that accompany benign or malignant tumors but are not directly related to mass effects or invasion by the primary tumor or its metastases ID: 776208
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Slide1
Paraneoplastic syndromes
PRESENTED BY:
DR. HITESH GOUR
J.R. PULMONARY MEDICINE
Slide2DEFINATION
Paraneoplastic
syndromes refer to the disorders that accompany benign or malignant tumors but are not directly related to mass effects or invasion by the primary tumor or its metastases.
Although, almost every type of malignancy has the potential to produce hormones or cytokines or to induce immunologic responses , tumors of
neuroendocrine
origin, such as small cell lung carcinoma and
carcinoids
are common causes of
paraneoplastic
syndromes.
So, atypical clinical manifestations in a patient with cancer should prompt consideration of a
paraneoplastic
syndrome.
Slide3PARANEOPLASTIC SYNDROMES
ETIOLOGY:
Ectopic hormones refers to hormone production from an atypical tissue source.
Several molecular mechanisms has been suggested to cause ectopic hormone production, but this process remains incompletely understood.
Genetic rearrangements can explain aberrant hormone expression e.g., translocation of the parathyroid hormone (PTH) gene resulted in high levels of PTH expression in an ovarian carcinoma, because the genetic rearrangement brings the PTH gene under the control of ovary-specific regulatory elements
Slide4ectopic expression is typically characterized by abnormal regulation of hormone production (e.g., defective feedback control)that can lead to substantial morbidity and can complicate the cancer treatment plan
Slide5Paraneoplastic sundromes associated with bronchogenic carcinoma Endocrine:
Cushing's syndrome
SIADH
Hypercalcemia
Carcinoid
syndrome
Hyperglycemia
/
hypoglycemia
Gynecomastia
Galactorrhea
Growth hormone excess
Calcitonin
secretion
Thyroid-stimulating hormone
Slide6Neurological
Lambert-Eaton
myasthenic
syndrome
Peripheral neuropathy
Encephalopathy
Myelopathy
Cerebellar
degeneration
Psychosis
Dementia
Cancer related retinopathy
Opsoclonus
and
myoclonus
MUSCULOSKELETAL
Clubbing
Hypertrophic
osteoarthropathy
Polymyositis
Osteomalacia
Myopathy
Slide8Cutaneous
Dermatomyositis
Acanthosis
nigricans
Pruritus
Erythema
multiforme
Hyperpigmentation
Urticaria
Scleroderma
Slide9Vascular/hematologic
Thrombophlebitis
Arterial thrombosis
Granulocytosis
Nonbacterial thrombotic
endocarditis
Thrombocytosis
Polycythemia
Hemolytic
anemia
Red cell
aplasia
Dysproteinemia
Leukemoid
reaction
Eosinophilia
Thrombocytopenic
purpura
Slide10Miscellaneous
Cachexia
Fatigue
Hyperuricemia
Nephrotic
syndrome
Slide11Ectopic Corticotropin Syndrome
Ectopic production of
corticotropin
or
corticotropin
-releasing hormone with associated Cushing's syndrome has been identified in patients who have SCLC,
carcinoid
tumor
(lung, thymus, or pancreas), and
neurocrest
tumors
such as
pheochromocytoma
,
neuroblastoma
, and
medullary
carcinoma of the thyroid.
SCLC accounts for 75% of cases, although only 1% to 2% of patients with SCLC develop Cushing's syndrome. Cushing's syndrome is seldom caused by NSCLC
Slide12Classic features of Cushing's syndrome include
truncal
obesity,
striae
, rounded (moon)
facies
,
dorsocervical
fat pad (buffalo hump),
myopathy
and weakness, osteoporosis, diabetes mellitus, hypertension, and personality changes.
Because of rapid growth of SCLC ,patients are more likely to present with
edema
, hypertension, and muscular weakness than with the classic features of Cushing's syndrome.
Hypokalemic
alkalosis and
hyperglycemia
are usually present.
Slide13Slide14Patients with SCLC and Cushing's syndrome have shortened survival compared to those without the syndrome, perhaps because of frequent opportunistic infections.
The best screen for Cushing's syndrome is the 24-hour urine free
cortisol
measurement.
Elevation of
cortisol
production, lack of suppression with high-dose
dexamethasone
, and plasma
corticotropin
levels greater than 200 pg/
mL
(40
pmol
/L) are highly suggestive of ectopic
corticotropin
as the cause of Cushing's syndrome in the absence of a pituitary adenoma. The plasma level of
corticotropinis
elevated in many, but not in all patients.
Slide15Treatment:
Adrenal enzyme inhibitors such as
metyrapone
,
aminoglutethimide
, and
ketoconazole
, given alone or in combination.
Ketoconazole
given orally at a dosage of 400 to 1200 mg/day or
metyrapone
250 to 750 mg three times per day control
hypercortisolism
within a few days to weeks,
Dose adjustments are based on achieving normal urinary free
cortisol
levels or morning plasma
cortisols
of 7 to 11
ýg
/
mL.
Symptomatic
hypoadrenalism
may result from treatment.
When Cushing's syndrome arises from SCLC, it is advisable to proceed with appropriate chemotherapy and carefully watch for superimposed infections.
Cushing's syndrome related to a bronchial
carcinoid
or
thymic
carcinoid
is best treated by surgical resection of the
tumor
.
Slide16Syndrome of Inappropriate Antidiuretic Hormone Secretion
SIADH production defined as low serum and a dilute plasma
osmolality
along with a higher or “inappropriate” urine
osmolality
in the presence of
continous
urinary sodium
excreation
.
10% of patients with SCLC exhibit SIADH,.SCLC accounts for approximately 75% of cases of SIADH.
Antidiuretic
hormone (vasopressin) is secreted in the anterior hypothalamus and exerts its action on the renal collecting ducts by enhancing the flow of water from the lumen into the
medullary
interstitium
, thereby concentrating the urine.
Slide17The criteria for the diagnosis of SIADH include (1)
hyponatremia
associated with serum
hypoosmolality
(<275
mOsm
/kg), (2) inappropriately elevated urine
osmolality
(>200
mOsm
/kg) relative to serum
osmolality
; (3) elevated urine sodium (>20
mEq
/L); (4) clinical
euvolemia
without
edema
; and (5) normal renal, adrenal, and thyroid function.
The serum uric acid is usually low, and the urine
osmolality
–to–serum
osmolality
ratio is frequently greater than 2.
The severity of symptoms is related to the degree of
hyponatremia
and the rapidity of the fall in serum sodium.
Slide18Slide19Symptoms of
hyponatremia
include anorexia, nausea, and vomiting. With a rapid onset of
hyponatremia
, symptoms caused by cerebral
edema
may include irritability, restlessness, personality changes, confusion, coma, seizures, and respiratory arrest.
Slide20Treatment:
In minimally symptomatic or asymptomatic patients, fluid restriction of 500 to 1000
mL
/24 hr is the initial treatment of choice.
Conivaptan
is an intravenous vasopressin receptor antagonist that has been shown to be useful in correcting
hyponatremia
but its use is limited to the hospital.
Slide21If further treatment is needed, oral
demeclocycline
(900–1200 mg/day) is given. It induces a
nephrogenic
diabetes
insipidus
and blocks the action of
antidiuretic
hormone on the renal tubule, thereby increasing water excretion.
The onset of action varies from a few hours to a few weeks, so this drug is not recommended for acute emergency treatment.
Demeclocycline
has potential kidney toxicity.
In patients who have more severe or life-threatening symptoms (serum sodium <115
mEq
/L), treatment consists of intravenous saline, supplemental potassium, and
diuresis
with loop diuretics such as
furosemide
or
ethacrynic
acid.
Slide22With severe confusion, convulsions, or coma, treatment is with 300
mL
of 3% saline given over 3 to 4 hours in combination with a loop diuretic (saline without a diuretic will not increase the sodium concentration).
Rapid correction of the sodium may have life-threatening consequences, and caution is advised.
The rate of correction of the sodium is best limited to a maximum of 20
mEq
/L/day, until a level of 120 to 130
mEq
/L is reached.
Faster correction has been associated with the development of central
pontine
myelinolysis
, which may result in quadriplegia, cranial nerve abnormalities that manifest as
pseudobulbar
palsy, alteration in mental status, and subsequent death.
Slide23For patients with SIADH due to SCLC, treatment with chemotherapy should be initiated as soon as possible and is likely to result in improvement in the
hyponatremia
within a few weeks.
After an initial response to chemotherapy, SIADH may recur when the
tumor
relapses
Slide24Hypercalcemia
Hypercalcemia
in association with malignancy may arise from a bony metastasis or, less commonly, from secretion by the
tumor
of a parathyroid hormone–related protein (
PTHrP
) or other bone-
resorbing
cytokine.
The most common cancers to cause
hypercalcemia
are those of the kidney, lung, breast, head, and neck and myeloma and lymphoma.
Squamous
cell histology is the most common cell type associated with
hypercalcemia
, and generally patients have advanced disease (stage III or IV) and are
unresectable
.
Slide25Symptoms of
hypercalcemia
include anorexia, nausea, vomiting, constipation, lethargy,
polyuria
,
polydipsiaand
dehydration. Confusion and coma are late manifestations, as are renal failure and
nephrocalcinosis
.
Cardiovascular effects include shortened QT interval, broad T wave, heart block, ventricular arrhythmia, and
asystole
. Individual patients may manifest any combination of these signs and symptoms in various degrees.
Hypercalcemia
of malignancy that is not caused by bony metastases results from accelerated bone
resorption
, decreased bone deposition, or increased renal tubular
reabsorption
of calcium.
Slide26Slide27Accelerated bone
resorption
is caused by activation of
osteoclasts
by cytokines or
PTHrP
in most cases.
Serum parathyroid hormone levels are usually normal or low, but an elevated level of
PTHrP
can be detected in the serum in approximately one half of these patients. Cytokines or
PTHrP
are secreted autonomously by the
tumor
.
Not only does
PTHrP
cause renal calcium
reabsorption
, but also it interferes with renal mechanisms for
reabsorption
of sodium and water, with resultant
polyuria
.
Polyuria
and vomiting result in dehydration; decreases in
glomerular
filtration further aggravate the
hypercalcemia
.
Slide28Treatment:
Mild elevation of serum calcium may not require treatment, so the decision is based on the patient's symptoms.
For patients who have widely metastatic and incurable malignancy, it may be most appropriate to give supportive care only and not treat the
hypercalcemia
. The average life expectancy in this situation is 30 to 45 days, even with aggressive treatment.
Slide29Most patients who have a serum calcium of 12 to 13 mg/
dL
or higher are treated.
The four basic goals of treatment are to (1) correct dehydration; (2) increase renal excretion of calcium; (3) inhibit bone
resorption
; and (4) treat the underlying malignancy.
Because of the
polyuria
, patients with
hypercalcemia
are volume contracted. Initial treatment is with intravenous normal saline, using 3 to 6 L/24 hr as tolerated, with careful attention to volume status.
Slide30Zoledronate
is given 4 mg intravenously over 15 minutes.
Adverse effects are generally mild and transient and include fever,
hypophosphatemia
, asymptomatic
hypocalcemia
and, occasionally, renal failure.
Calcitonin
inhibits bone
resorption
, increases renal calcium excretion, and has a rapid onset of action, but the duration of action is short-
lived.Given
when the calcium is greater than 14 mg/
dL
or needs to be lowered urgently (onset of action is 4–6 hr)
Slide31The effects of
calcitonin
and
bisphosphonates
are additive.
Tachyphylaxis
may occur to
calcitonin
after 48 hours.
Thiazide
diuretics are not used because they increase calcium
reabsorption
in the distal tubule.
Normal calcium levels are achieved within 4 to 10 days in 85% of patients and last a median of 30 to 40 days
Slide32Musculoskeletal Effectsclubbing of digits
May be a manifestation of lung cancer or other diseases.
Most commonly seen in
adenocarcinoma
of the lung and less frequently in other cell types.
Clubbing may involve the fingers and toes and consists of selective enlargement of the connective tissue in the terminal phalanges.
Physical findings include loss of the angle between the base of the nail bed and the cuticle, rounded nails and enlarged fingertips.
Slide33In digital clubbing proliferation of connective tissue beneath the nail matrix is observed.
Clubbing is an isolated finding and is usually asymptomatic.
Non-malignant causes of clubbing include pulmonary fibrosis, congenital heart disease, and
bronchiectasis
.
Slide34Slide35Hypertrophic pulmonary osteoarthropathy (HPO)
I
s an uncommon process associated with lung cancer.
HPO is characterized by painful
arthropathy
that usually involves the ankles, knees, wrists, and elbows and is most often symmetrical.
The pain and
arthropathy
are caused by proliferative
periostitis
that involves the long bones but may also affect metacarpal, metatarsal, and
phalangeal
bones. Patients may have clubbing of fingers and toes in addition to the painful
arthralgias
.
Slide36The pathogenesis of HPO is uncertain, but it may arise from a
humoral
agent(VEGF/PDGF).
For patients who smoke and have a new onset of
arthralgias
, HPO must be considered
A radiograph of the long bones (i.e., tibia and fibula) usually shows characteristic
periosteal
new bone formation. An isotope bone scan typically demonstrates diffuse uptake by the long bones.
Slide37Large cell and
adenocarcinoma
are the most common
histologic
types associated with HPO.
The symptoms of HPO may resolve after tumour resection.
For inoperable patients, treatment is with
nonsteroidal
anti-inflammatory agents. Recently, case reports have observed resolution or marked improvement of symptoms with
bisphosphonate
treatment
Slide38Dermatomyositis-polymyositis
Dermatomyositis
and
ploymyositis
are associated with
neoplasms
in 40% of all cases.
Besides ovarian cancer SCLC is the most frequent type of cancer.
Dermatomyositis
is characterized by infarcts,
perifascicular
atrophy , endothelial cell swelling and necrosis, vessel wall membrane attack complex deposition and
myocyte
-specific MHC-1
upregulation
in the muscle.
Histopathological
findings include hyperkeratosis , epidermal basal cell vacuolar degeneration and
apoptosis,increased
dermal
mucin
deposition cell poor interface dermatitis.
Slide39Myositis
is
charcterized
by muscle weakness and muscle pain.
Typically proximal muscles are involved.
Myositis
-specific
autoantigens
are expressed at high levels in regenerating cell in
myositic
muscles and cancer cells. This may provide a link between cancer and
paraneoplastic
myositic
syndrome.
Slide40Slide41Hematologic/vascular Effects
Anemia
frequently occurs in patients who have lung cancer and may be caused by iron deficiency, chronic disease, or bone marrow infiltration.
Eosinophilia
is more commonly associated with Hodgkin's disease but may occur in patients who have lung cancer.
Production of various cytokines by
neoplastic
cells may result in
eosinophilia
,
leukocytosis
, or
thrombocytosis
, of which
thrombocytosis
is by far the most common.
Slide42The association of deep venous thrombosis and malignancy was described by Trousseau over a century ago, and lung cancer is the most common malignancy associated with Trousseau's syndrome
Thromboembolism
in the patient who has malignancy is often refractory to
warfarin
treatment.
Treatment with low-molecular-weight heparin (LMWH) on a chronic basis may be effective
Slide43.
In a randomized trial, patients with cancer and deep vein thrombosis, pulmonary embolism, or both were randomized to receive LMWH (
dalteparin
) subcutaneously once daily or oral
warfarin
daily for 6 months.
At 6 months, the probability of recurrent
thromboembolism
was 9% with
dalteparin
treatment and 17% with
warfarin
, a difference that was highly significant.
The risks of major bleeding or any bleeding were not different in the two groups.
The other advantage of LMWH is that it is unnecessary to monitor the anticoagulant effect, except in some patients with renal insufficiency.
A recent Cochrane analysis concluded that, for long-term treatment in patients with cancer, LMWH reduced venous
thromboembolism
events, but not death, as compared with vitamin K antagonists. There was no significant difference in the risk of bleeding.
Slide44Granulocytosis
Granulocytosis
with absolute cell count of 10,000 to 25,000 occurs in 20% of patients of non-small cell lung cancer.
The specific ectopic
harmone
responsible for
paraneoplastic
granulocytosis
has not been characterized, although some non-small
cel
tumours
may produce various cytokines like IL-6, G-CSF or GM-CSF.
Bone marrow biopsy is usually normal.
Diagnosis is made on exclusion,
granulocytosis
per se does not produce any symptom in these patients.
Slide45Thrombocytosis
It is common phenomena observed in 40% patients of both small cell and non small cell carcinomas.
Exact mechanism of
thrombocytosis
is not known, it is most likely linked to
megakaryocyte
cytokine i.e. IL-6.
It is asymptomatic , diagnosed if bone marrow biopsy is normal and platelet count exceeds 500,000/mm2.
Slide46Acromegaly
Carcinoid
tumour
is the most common cause of
acromegaly
associated with lung cancer.
SCLC can also produce
acromegaly
.
Its due to the release of GHRH & rarely by GH.
Pts develop thick leathery skin, prominent skin folds, hypertrophy of face & extremities, diabetes & hypertension.
Slide47Increased levels of GHRH & IGF-1 in presence of lung
tumour
establishes diagnosis.
Respond to surgical resection as well as radiotherapy.
Pts ineligible for resection/irradiation should receive
octreotide
, which inhibits GHRH secretion form the
tumour
& decreases GH & IGF-1 levels in serum.
Slide48Slide49Neurologic Effects
The
paraneoplastic
neurologic syndromes associated with lung cancer, mostly small cell type, are quite variable. They include LEMS,
subacute
sensory neuropathy,
encephalomyelopathy
,
cerebellar
degeneration, autonomic neuropathy, retinal degeneration, and
opsoclonus
.
The frequency of any of these neurologic syndromes in SCLC is approximately 5%, and neurologic symptoms may precede the diagnosis by months to years.
Slide50Careful radiographic evaluation of the lungs and
mediastinum
is indicated in a smoker who has a suspected
paraneoplastic
neurologic syndrome.
In this setting, even subtle abnormalities of the
mediastinum
require a biopsy. A PET scan may help identify an occult lesion and facilitate biopsy confirmation of the diagnosis.
Slide51Patients with
paraneoplastic
neurologic syndromes have a better prognosis than those without the
paraneoplastic
syndromes with similar stage and histology.
These
paraneoplastic
neurologic syndromes are thought to be immune-mediated, based on the identification of a number of antibodies in the serum that react with both the nervous system and the underlying
cancer.However
, not all patients with
paraneoplastic
syndromes have identifiable antibodies in their Serum.
Slide52Predominantly
antineuronal
nuclear antibody type 1(ANNA-1) , have been associated with SCLC. ANNA-1 binds to the nuclei of all neurons in the central and peripheral nervous system, including the sensory and autonomic ganglia, the
myenteric
plexus, and cells of the adrenal medulla.
Such antibodies should not be confused with the anti–Purkinje cell antibody (anti-
Yo
), which is characteristically found in patients who have
subacute
cerebellar
degeneration as a manifestation of
gynecologic
malignancy or breast cancer.
The CRMP-5 antibody, also known as anti–CV-2, has been associated with SCLC and
thymomas
.
Slide53In a review of 162 sequential patients who had elevated ANNA-1 (anti-
Hu
), 142 (88%) were proved to have cancer, 132 of whom had SCLC.
In 97% of these cases, the diagnosis of SCLC followed the onset of the associated neurologic syndrome, usually by less than 6 months but, in 20%, the period was greater than 6 months.
Of special note is that 90% of cases had disease limited to the lung or to the lung and
mediastinum
(LD-SCLC).
Slide54In a report from Europe, 144 patients out of 200 with anti-
Hu
antibodies had a tumour in the chest. Of these, 111 were proved to be SCLC.
In one large series, ANNA-1 antibodies were identified in 16% of all patients with SCLC.
These antibodies were associated with limited-stage disease, complete response to therapy, and longer survival compared with patients who had SCLC and no ANNA-1 antibody.
Slide55These neurologic syndromes seldom improve with treatment, so the goal is to prevent progression by starting treatment of the underlying
tumor
as soon as possible.
Less common manifestations of neurologic
paraneoplastic
syndromes are orthostatic hypotension and intestinal
dysmotility
.
The gastrointestinal symptoms may present as nausea, vomiting, abdominal discomfort, or altered bowel habits suggestive of intestinal pseudo-obstruction.
Many of these patients present with gastrointestinal symptoms and significant weight loss prior to the diagnosis of SCLC.
Slide56Lambort eaten myasthenic syndrome
Proximal muscle weakness,
hyporeflexia
, and autonomic dysfunction characterize LEMS.
Cranial nerve involvement may be present and does not differentiate LEMS from myasthenia gravis.
LEMS has been strongly associated with antibodies directed against P/Q-type
presynaptic
voltage-gated calcium channels (anti-VGCC antibodies) of peripheral cholinergic nerve terminals
.
These anti-VGCC antibodies, identified in over 90% of patients with LEMS, block the normal release of acetylcholine at the neuromuscular junction.
In contrast, myasthenia gravis is associated with anti–acetylcholine receptor antibodies, which are present in approximately 90% of
myasthenic
patients.
Slide58Malignancy is present in approximately one half of patients who have LEMS, and SCLC is by far the most common malignancy.
In a recent study of 63 patients with SCLC examined prospectively, only 3% had clinical and electrophysiological signs of LEMS, 8% had elevated anti-VGCC antibodies and 26% had other neurologic symptoms unrelated to LEMS.
Slide59Diagnosis:
The diagnosis of LEMS is based on characteristic
electromyographic
findings that show a small amplitude of the resting compound muscle action potential and facilitation with rapid, repetitive,
supramaximal
nerve stimulation or after brief exercise of the muscle.
A single-
fiber
electromyogram
is optimal for making the diagnosis.
Slide60Treatment:
LEMS is the predominant
paraneoplastic
neurologic syndrome that may improve with successful treatment of the associated lung cancer.
The use of
acetylcholinesterase
inhibitors is of limited benefit in LEMS.
Diaminopyridine
enhances the release of acetylcholine and has been used with sustained improvement over months in the majority of patients with LEMS either with or without cancer.
Slide61LEMS
MYASTHENIA GRAVIS
Antibodies against the nerve where acetylcholine is released.
Starts at extremeties and moves up.Weakness improves upon activity.Associated with SCLC.Therapy - aminopyridines
Antibodies against the muscle receptors for acetylcholine.
Starts at eye and moves down.
Weakness worsens
u
pon activity.
Associated with
thymoma
.
Therapy- acetylcholine esterase inhibitors.
Slide62Encephalomyelitis and sensory neuropathy
It is associated with small cell lung cancer and the neuronal damage is mediated by
IgG
anti-HU antibody known as ANNA-1.
These patients may present with progressive sensory loss in hands and
feets
,
myelopathy
, brainstem, cerebellum, cerebral cortex, spinal cord and dorsal root ganglia.
Patients present with sensory loss in hands and feet and brainstem involvement.
Slide63Diagnosis of encephalomyelitis is suggested by the MRI which shows increased T2 signal in the affected areas of the brain and is confirmed by demonstration of anti-
hu
antibody in the serum.
Removal of culprit
IgG
by
plasmaphresis
and corticosteroids administration is effective in only 15% of these patients.
Slide64Cerebellar degenration
Some patients of small cell lung cancer develop
cerebellar
degeneration leading to
nystagmus
, impaired coordination and ataxia.
These patients have anti-
hu
antibodies in serum and frequently tend to develop encephalitis or sensory neuropathy.
Slide65Cancer associated retinopathy
It is a rare
paraneoplastic
that occurs as the first sign of occult small cell carcinoma.
Ganglion cells of retina are
characterstically
damaged by binding of auto-antibodies to
recoverin,a
photoreceptor-specific protein.
These patients have
photosenstivity
,rapid loss of vision, night blindness, visual field defects and arteriolar narrowing.
Anti-
recoverin
antibody establishes the diagnosis.
It responds to systemic steroids
bt
not to the
chemothrapy
for primary
tumour
.
Slide66Opsoclonus and myoclonus
These are rare
paraneoplastic
syndrome associated with both small cell and non small cell lung cancers.
These patients show rapid involuntary conjugate eye movements in both the horizontal and vertical directions.
Some SCLC patients with this syndrome have anti-
hu
antibody in serum.
Slide67Miscellaneous Cachexia and fatigue
Cancer
cachexia
is the most common manifestation of advanced malignant disease(50%) and is responsible for almost 25% of deaths from cancer.
Symptoms of
cachexia
include anorexia, weight loss, muscle loss,
anaemia
, alterations in carbohydrate, lipid and protein metabolism.
In cancer patients increased levels of free tryptophan are found which are closely related to reduced food intake.
Proinflammatory
cytokines including TNF-A , IL-1,6 IFN-G have been implicated in
cachexia
.
Medroxy
progesterone acetate may improve appetite and stabilize weight.
Eicosa
pentaenoic
acid can lower the production of
proinflammtory
cytokines.
Slide68Cancer related fatigue is also extremely common.
Upto
90% of cancer patients report fatigue symptoms.
Basic mechanism of fatigue are broadly
charcterized
into two main components: peripheral and central.
Peripheral fatigue occurs in the N-M junctions and muscle tissues.
Central fatigue arises from the
progrsseive
failure to transmit motor neuron impulses.
Hemotopoeitics
, antidepressants, corticosteroids and new wake promoting agent
modafinil
may be used for the cancer related fatigue.
Slide69conclusions
Paraneoplastic
sydromes
are common in lung cancer patients.
Some
paraneoplastic
syndromes can severely affect organ function and quality of life.
Treating the underlying cancer is the first step.
However specific therapy may also be necessary.
Slide70Thank you