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USE OF ANTI OXIDANTS INTREATMENT OF

LEUKOPLAKIA

ASIF

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INTRODUCTION Leukoplakia is a white lesion of the oral mucosa

particularly those that appear leathery and cannotbe dislodged easily

A white patch or plaque that cannot be

characterized clinically or pathologically as anyother disease- WHO collaboration (1978)

At an international seminar on oral leukoplakia

and an associated lesion related tobacco habitheld in Malrno Sweedan in 1983 the proposal was

made to modify the WHO collaborating reference

center definition for leukoplakia to read

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Leukoplakia is a whitish patch or plaque that cannot

be characterized clinically or pathologically as any

other disease and is not associated with any physical

or chemical causative agent except the use of

tobacco

Total life time risk of malignant transformation isestimated to be 4-6% (Leurman H etal 1995)

Lesions of the tongue and floor of the mouth

account for more than 90% of cases that showdysplasia or carcinoma (Waldron etal 1975)

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ETIOLOGY A number of locally acting etiological agents

including tobacco, alcohol,candidiasis habe beenimplicated as causative factors

True leukoplakia is often related to tobacco usage(Axell T etal 1996)

More than 80% of the leukoplakia are smokers,development of leukoplakia in smokers also dependson dose, duration of use as shown by heavy smokers

having a more frequent incidence of lesion thanlight smokers

Cessation of smoking often results in partial to totalresolution of leukoplakia

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Candidia aibicans is frequently found in histological

section of leukoplakia and is consistently (60% of

cases) identified in nodular leukoplakia but rarely inhomogenous leukoplakia (3%) term candidia

leukoplakia and hyper plastic candidiasis have been

used to describe such lesions (Cawson etal 1988)

Sun light is well known to be an etiologic factor for

the formation of leukoplakia of vermilion border of

the lower lip

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CLINICAL FEATURES

Majority of leukoplakia are a symptomatic Development of carcinoma from leukoplakia has

been reported to occur in 4-17.5% of patients withmean observation period ranging from 3.7 11.7yrs

(Silverman etal 1984)

Buccal mucosa are most frequently affected (Silverman etal1984)

More commonly found in men, occurs in adultsolder than 50yrs of age prevalence increase rapidlywith age especially for males and 8% of men olderthan 70yrs of age are affected

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TYPES

HOMOGENOUS LEUKOPLAKIA:

It has well defined patch, localized orextensive that is slightly elevated and that has afissured wrinkled or corrugated surface on palpation

these lesions may feel leathery to dry cracked mud-like

NODULAR OR SPECKLED LEUKOPLAKIA

It is a mixed red and white lesion in which whitekeratotic white nodules or patches are distributedover an atrophic erythematous back ground. Thistype of leukoplakia is associated with high

malignant transformation rate

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VERRUCOUS LEUKOPLAKIA

Thick white lesion with papillary surface in the oral

cavity. These lesions are usually heavily keratinizedand are most often seen in older age group

PROLIFERATIVE VERRUCOUS

LEUKOPLAKIA:

They are verrucoid white plaques that tend to be

slowly involve multiple mucosal sites in the oral

cavity PVL has a very high risk of transformation to

dysplasia, squamous cell carcinoma or verrucous

carcinoma

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HISTO PATHOLOGY

Benign form of leukoplakia are characterized byvariable patterns of hyperkeratosis and chronic

inflammation

Waldron and Shafer in a land mark study of over3,000 cases of leukoplakia, found that 80% of the

lesions represented benign hyperkeratosis with or

with out thickened spinous layer(acanthosis)

About 17% of the leukoplakia shows dysplastic

changes in the basal or parabasal zones of the

epithelium

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DIFFERENTIAL DIAGNOSIS

Lichen planus Leukoedema

Lupus erythematosis

White sponge nevus

Verruca vulgaris

Hairy leukoplakia

Cheek biting

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MANAGEMENT BY ANTI

OXIDANTS

Antioxidants are the products which are derivedmainly from green or colored vegetables foodgrains, animal fats and also from some spices likecucuramin (turmeric) or garlic

The function of anti oxidants is to remove the freeoxygen radical from the body and as a resultprevents the cell damage or undergoing any

carcinomatous changes Beta carotene, retinoic acid, ascorbic acid and

alpha tocopherol are examples of anti oxidants

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BETA CAROTENE

It is primarily found in the green vegetables, the deeperthe color of vegetable or fruit greater the carotenecontent

Approx 16% of the ingested beta carotene is transformedin to retinol with in the intestinal mucosa by a two stepprocess that converts 6micro grams of BC into 1mm ofretinol

Fate of beta carotene after it reaches liver

Very small amount can be converted in to retinol It can be incorporated in to very low densit lipo protein

cholesterol

Can be stored in liver

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RELATION SHIP TO HUMAN

CANCER

In dietary studies low beta carotene intake has beenassociated with an increased risk of lung,

laryngeal, gastric, ovarian, breast, cervical and oral

cancer Several studies have shown that a low intake of

fruits and vegetables which are the primary source

of beta carotene is also related to generalizedincreased cancer risk and mortality

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THERAUPETIC USE

OF ORAL

LEUKOPLAKIA

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RETINOL AND RETINOIDS

Vitamin A also known as retinol, is an alcohol that

can be converted in to aldehyde or retinoic acid

Retinol is found in dairy products, eggs and meats

Silverman etal showed that doses exceeding300,000 IU/day of vitamin A ester for more than

3mths can exceed liver storage capacity and cause

side effects that include rashes, dry skin and pruritis

Of more than 1500 synthetic analogues of vitamin A

13-cRA (isotretinoin) has generated the most

interest

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RELATIONSHIP TO HUMAN

CANCER

The first study that associated Vitamin A deficiency with

cancer appear in 1941

Low intake of Vitamin A has been linked with an

increased risk of developing cancer of the lung, colon,breast, pharynx, larynx and bladder

The theories proposed to explain Vitamin A include

Deficiency of Vitamin A disturbs normal epithelial growth Tumor surveillance is dependent on levels of vitA

Vitamin A directly influences gene expression

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THERAPEUTIC USE

OF ORAL

LEUKOPLAKIA

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ASCORBIC ACID

Ascorbic acid commonly known as Vitamin C, isfound in citrus fruits, cruciferous vegetables

The (RDA) recommended daily allowance range

from 60mg/day for non smokers to 100mg/dayfor smokers

It is because they have a decreased concentrationof A.A in their serum and leukocytes

It is reported that many people ingest more than1gmof ascorbic acid per day with out anyapparent ill effects

RELATIONSHIP WITH

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RELATIONSHIP WITH

HUMAN CANCER

Numerous studies have shown that a low intake

of AA is associated with increased of cancer of

the stomach, esophagus, oral cavity

The protective effect of dietary AA is more

attributable to intake from fruits compared with

vegetables

Low serum level of AA have been associatedwith an increased risk of cancer, especially of the

stomach

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ALPHA-TOCOPHEROL

The most active and common form of Vitamin E

Found in plant oils, wheat germ and green leafy

vegetables

The RDA for adult males is 10mg/day, and theaverage daily intake for adult males in USA is

11mg/day

The absorption of AT ranges from 20% to 80%,and the efficiency decreases as the intake exceeds

30mg/day

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RELATIONSHIP TO HUMAN

CANCER

The patients with low serum level of AT had a

relative risk of > 2.0 for gastrointestinal cancers

The role of AT in cancer risk reduction is unclear,

but the proposed mechanism includes

The control of free radical damage

Blockade of chemical reactions by mutagens orcarcinogens

Enhancement of detoxification

Enhanced immune response

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ANTI OXIDANT

COMBINATIONS

THERAPEUTIC USE FORLEUKOPLAKIA

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CONCLUSION

The use of anti oxidant supplements has shownsome promise but the predictability of success

remains uncertain and long term results are un

availableBefore the decision to use any antioxidant is made

it is critical to obtain a histopathologic diagnosis of

the lesion

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THANK YOU

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