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Paraneoplastic syndromes - PowerPoint Presentation

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Paraneoplastic syndromes - PPT Presentation

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

Slide2

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.

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.

Slide3

PARANEOPLASTIC 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

Slide4

ectopic 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

Slide5

Paraneoplastic 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

Slide6

Neurological

Lambert-Eaton

myasthenic

syndrome

Peripheral neuropathy

Encephalopathy

Myelopathy

Cerebellar

degeneration

Psychosis

Dementia

Cancer related retinopathy

Opsoclonus

and

myoclonus

Slide7

MUSCULOSKELETAL

Clubbing

Hypertrophic

osteoarthropathy

Polymyositis

Osteomalacia

Myopathy

Slide8

Cutaneous

Dermatomyositis

Acanthosis

nigricans

Pruritus

Erythema

multiforme

Hyperpigmentation

Urticaria

Scleroderma

Slide9

Vascular/hematologic

Thrombophlebitis

Arterial thrombosis

Granulocytosis

Nonbacterial thrombotic

endocarditis

Thrombocytosis

Polycythemia

Hemolytic

anemia

Red cell

aplasia

Dysproteinemia

Leukemoid

reaction

Eosinophilia

Thrombocytopenic

purpura

Slide10

Miscellaneous

Cachexia

Fatigue

Hyperuricemia

Nephrotic

syndrome

Slide11

Ectopic 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

Slide12

Classic 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.

Slide13

Slide14

Patients 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.

Slide15

Treatment:

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

.

Slide16

Syndrome 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.

Slide17

The 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.

Slide18

Slide19

Symptoms 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.

Slide20

Treatment:

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.

Slide21

If 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.

Slide22

With 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.

Slide23

For 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

Slide24

Hypercalcemia

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

.

Slide25

Symptoms 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.

Slide26

Slide27

Accelerated 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

.

Slide28

Treatment:

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.

Slide29

Most 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.

Slide30

Zoledronate

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)

Slide31

The 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

Slide32

Musculoskeletal 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.

Slide33

In 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

.

Slide34

Slide35

Hypertrophic 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

.

Slide36

The 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.

Slide37

Large 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

Slide38

Dermatomyositis-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.

Slide39

Myositis

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.

Slide40

Slide41

Hematologic/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.

Slide42

The 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.

Slide44

Granulocytosis

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.

Slide45

Thrombocytosis

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.

Slide46

Acromegaly

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.

Slide47

Increased 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.

Slide48

Slide49

Neurologic 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.

Slide50

Careful 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.

Slide51

Patients 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.

Slide52

Predominantly

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

.

Slide53

In 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).

Slide54

In 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.

Slide55

These 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.

Slide56

Lambort 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

.

Slide57

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.

Slide58

Malignancy 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.

Slide59

Diagnosis:

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.

Slide60

Treatment:

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.

Slide61

LEMS

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.

Slide62

Encephalomyelitis 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.

Slide63

Diagnosis 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.

Slide64

Cerebellar 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.

Slide65

Cancer 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

.

Slide66

Opsoclonus 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.

Slide67

Miscellaneous 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.

Slide68

Cancer 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.

Slide69

conclusions

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.

Slide70

Thank you