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ORAL SUBMUCOUS FIBROSIS
AND ITS MANAGEMENT
Maxfac
Center for Cranio - Maxillofacial & Head and Neck Surgery, Siliguri
Cont...
CONTENTS
• Introduction
• Definition
• WHO definition of precancerous condition
• Epidemiology
• Etiology/Predisposing fac...
INTRODUCTION
• Oral Submucous Fibrosis is a chronic debilitating
disease characterized by gradually increasing
fibrosis of...
DEFINITION
"An insidious chronic disease affecting any
part of the oral cavity and sometime the
pharynx. Although occasion...
Diffuse oral submucous fibrosis
Idiopathic scleroderma of mouth
Idiopathic palatal fibrosis
Sclerosing stomatitis
Juxtaepi...
Upper Digestive Tract
Submucous fibrosis
Pharynx
WHO Definition of
‘Oral Precancerous Condition’
“A generalized pathological state of the oral mucosa
associated with a sig...
• VIDARI ~ 600AD (Sushruta)
• Atrophia Idiopathica (tropica)
Mucosae Oris ~ Schwartz(1952)
• Oral Submucous Fibrosis ~ Jos...
EPIDEMIOLOGY
• Adolescents and adults (16 – 35 years)
• 0.2 – 0.5 % prevalence rate in India.
ETIOLOGY / PREDISPOSING FACTORS
(multifactorial)
ARECANUT & PRODUCTS
TOBACCO
CHILIES(CAPSAICIN)
GENETIC & IMMUNOLOGICAL PR...
COMMON PRODUCTS
BETEL QUID
(areca nut, tobacco, slaked lime and other species)
TOBACCO PREPARATIONS
Gutkha, Pan Masala, Mawa, Flavoured Supari, Khaini etc.
MISI
(sodium bicarbonate, alum, myrobalan charcoal and filler earth)
Symptoms
• Burning sensation
• Difficulty in mouth opening
• Difficulty in swallowing
• Taste changes
• Dryness of mouth
•...
Signs
• Blanching of oral mucosa
• Presence of fibrous bands
• Leathery texture of oral mucosa
• Trismus
• Restriction of ...
Presence of fibrous bands
Blanching of oral mucosa
Leathery texture of oral mucosa
Trismus
Restriction of Tongue Movements
Erosions
Vesicles
Ulcers
Blisters/ Erythematous areas
Depapillation of Tongue
Atrophic tongue
Bud like Uvula
Shrunken Uvula
Deviated Uvula
Bilateral pouching-in while opening mouth / Sunken cheeks
Angular cheilitis
Secondary Changes
Malignancy
Leukoplakia Erythroplakia
DIAGNOSTIC MEASUREMENTS
INTERINCISAL DISTANCE (MAXIMUM MOUTH OPENING)
Normal distance between Central Incisor Tips:
Males:...
TONGUE PROTRUSION
Normal Mesio-Incisal Angle of the Upper Central Incisor to the Tip of the Tongue when
maximally extended...
CHEEK FLEXIBILITY: CF= V1-V2
.
V2- Point measured
between at one-third the
distance from the angle of
the mouth on a line
...
1/3
V2
V1
1/3
When normally
When cheeks fully blown
StageI:EarlyOSMF
•IID
•TP
•CF
StageII:ModerateOSMF
•IID-
↓33%
•TP-
↓33%
•CF-
↓33%
StageIII:SevereOSMF
•IID-
↓66%
•TP-
↓66%...
QUID
“A substance or mixture of substances, placed
in the mouth or chewed or remaining in
contact with the mucosa, usually...
ARECA NUT
ALKALOIDS FLAVANOIDS
 ARECOLINE
 ARECAIDINE
 ARECOLIDINE
 GUYACOLINE
 GUACINE
 TANNINS
CATECHINS
ALKALOIDS (Arecoline)
NITROSATION
N-NITROSAMINE
CYTOTOXIC EFFECTS
PATHOGENESIS [P.Rajlalitha, S.Vali (2005)]
COLLAGEN PRODUCTION PATHWAY COLLAGEN DEGRADATION PATHWAY
Initial events of the disease
Oral
mucosa
Betel quid
habit
Chronic
inflammation
Activated T cell &
Macrophage at
the site
...
COLLAGEN PRODUCTION PATHWAY
ACTIVATION OF PRO-COLLAGEN GENES
ELEVATION OF PROCOLLAGEN PROTEINASES LEVELS
PNP PCP
UPREGULAT...
COLLAGEN DEGRADATION PATHWAY
ACTIVATION OF TISSUE INHIBITOR OF MATRIX
METALLOPROTEINASE GENE(TIMPs)
ACTIVATION OF PLASMINO...
OVER ALL EFFECT
INCREASE IN COLLAGEN
PRODUCTION
DECREASE IN
COLLAGEN
DEGRADATION
INCREASED COLLAGEN
(INSOLUBLE FORM— CROSS...
HISTOPATHOLOGY
EARLY STAGE ADVANCED STAGE
STAGING
Chandramani B. More et al (2011)
CLINICAL STAGING
Stage 4 (S4)
• Any one of the
above stage with
other PMDs (oral
leukoplakia, oral
erythroplakia, etc)
• Any one of the
abo...
FUNCTIONAL STAGING
Interincisal
mouth
opening:
≥ 35 mm.
Interincisal
mouth
opening:
15 — 25 mm.
Interincisal
mouth
opening...
BLOOD CHEMISTRY &
HEMATOLOGICAL VARIATIONS
↓ Vit. B12
↓ Serum
Albumin
↓Fe
↓ Folate
Slight
Eosinophilia
↑
Gammaglobulin
↑ T...
MANAGEMENT
ELIMINATION OF HABITS
NUTRITIONAL SUPPORT
IMMUNO-MODULATORY
DRUGS
LOCAL DRUG DELIVERY
INTRALESIONAL INJECTIONS
PHYSIOTHERA...
BETEL QUID
CHEWING HABIT
CHRONIC
INFLAMMATORY PROCESS
TGF-β
COLLAGEN
PRODUCTION
COLLAGEN
DEGRADATION
TIMPPCPPNP PLASMINOGE...
Type Drug
ANTI-INFLAMMATORY /
IMMUNE-MODULATORY
DRUGS
Pirfenidone
(ESBRIET, INTERMUNE)
(immunosuppressant)
IFN-gamma (immu...
ELIMINATION OF HABITS
As gum, skin patch, nasal spray, or inhaler.
Chewing gums Skin Patch
Nasal Spray
Lozenge
Inhaler
Bupropion Hydrochloride (ZYBAN)
Varenicline (CHANTIX)
ZYBAN prescribed under another name“WELLBUTRIN” to treat depression....
NUTRITIONAL SUPPORT
HIGH PROTEINS & HIGH- CALORIE DIET
VITAMIN B COMPLEX & OTHER VITAMINS
MINERALS
Intake of red tomatoes, fresh foods, green ...
DRUG NAME BRAND NAME DOSAGE CLASSIFICATION
Lycopene LYCOPENE (NOW)
(lycopene ~10mg)
SM FIBRO
(lycopene ~5mg)
LYCOSTAR
(Lyc...
MECHANISM OF ACTION ADVERSE
EFFECTS
Reducing the free radical
reaction
That can cause DNA mutations and
changes in lipid p...
LOCAL DRUG DELIVERY
Topical Application:
TRIAMCINOLONE GEL 0.1% (Kenacort) / TRIAMCINOLONE IN ORA-BASE
BETAMETASONE 0.5% (Betnesol)
KENALOG S ...
IMMUNO-
MODULATORY DRUGS
GLUCOCORTICOIDS & PLACENTAL EXTRACTS
(LOCAL & SYSTEMIC APPLICATION)
SUPPRESS INFLAMMATORY RECATION
PREVENT FIBROSIS
Placen...
DRUG NAME BRAND NAME DOSAGE CLASSIFICATION
Levamisole DEWORMIS
BIOVAM
LEVOMOL
150 mg
Three times daily
Three consecutive d...
MECHANISM OF ACTION ADVERSE EFFECTS CONTRAINDICATIONS
Immunomodulator
(modifies both cellular
and humoral immunity)
In OSF...
DRUG NAME BRAND NAME DOSAGE CLASSIFICATION
Pentoxyfylline TRENTAL-400
FLEXITAL 400mg SR
tabs
400 mg TDS
For 6-7 months
Per...
MECHANISM OF
ACTION
ADVERSE EFFECTS CONTRAINDICATIONS
It increases mucosal
vascularity.
Anti inflammatory
properties
Immun...
INTERFERON GAMMA-1 D
(IMMUNOKINE OF BOEHRINGER)
200 µg/ml have been tried (Anti-fibrotic cytokine)
Adverse effects: Fever, chills, headache, myalgia, arthralgia, injectio...
DRUG NAME BRAND NAME DOSAGE CLASSIFICATION
Interferon γ
(intralesional injection)
ACTIMMUNE (0.01- 10.0 U/mL)
3 times dail...
MECHANISM OF
ACTION
ADVERSE EFFECTS CONTRAINDICATIONS
Regulation of
fibroblast
proliferation &
collagen synthesis
Upregula...
MOUTH RINSES
Listerine Mouthwash
Essential Oils :
Menthol (mint) 0.042%
Thymol(thyme) 0.064%
Methyl Salicylate (wintergreen) 0.06%
Euca...
INTRALESIONAL
INJECTIONS
INTRALESIONAL INJECTIONS
(IN MODERATE PHASE)
ENZYMES GLUCOCORTICOIDS AQEOUS EXTRACT
HYALURONIDASE
CHYMOTRIPSIN
COLLAGENASE...
ENZYMES
HYALURONIDASE
INTRALESIONAL INJECTIONS
DRUG NAME BRAND NAME DOSAGE CLASSIFICATION
Hyaluronidase
(intralesional injection)
HYNIDASE
HYA
1500 IU (0.5-2 ml)
With 2%...
MECHANISM OF ACTION ADVERSE EFFECTS CONTRAINDICATIONS
Breaks down Hyaluronic
acid
(Depolymerizing)
Lowers the viscosity of...
ENZYMES
CHYMOTRIPSIN
INTRALESIONAL INJECTIONS
DRUG NAME BRAND NAME DOSAGE CLASSIFICATION
Chymotripsin
(intralesional injection)
TRYPSIN
CHOMISIN
CHYMASE
CHYMOTRIP
5000 ...
MECHANISM OF ACTION ADVERSE EFFECTS
Endopeptidase
Hydrolyses peptide
bonds and esters
Local: Injection site
reaction
Aller...
COLLAGENASE
ENZYMESINTRALESIONAL INJECTIONS
DRUG NAME BRAND NAME DOSAGE CLASSIFICATION
Collagenase
(intralesional injection)
XIAFLEX
SANTYL
COLLAGENASE
SANTYL
2mg of ...
MECHANISM OF
ACTION
ADVERSE EFFECTS
Degrading,
Phosphate esters
Proteins
Polysaccharides
Glycosides
Sulphate Esters
Pain
S...
INTRALESIONAL INJECTIONS
(IN MODERATE PHASE)
ENZYMES GLUCOCORTICOIDS AQEOUS EXTRACT
HYALURONIDASE
CHYMOTRIPSIN
COLLAGENASE...
HYDROCORTISONE
(SHORT ACTING)
GLUCOCORTICOIDSINTRALESIONAL INJECTIONS
DRUG NAME BRAND NAME DOSAGE CLASSIFICATION
Hydrocortisone
(intralesional injection)
WYCORT
EFCORLIN
CORT-S
MOSACORT
25 mg/...
TRIAMCINOLONE
ACETONIDE
(INTERMEDIATE ACTING)
GLUCOCORTICOIDSINTRALESIONAL INJECTIONS
DRUG NAME BRAND NAME DOSAGE CLASSIFICATION
Triamcinolone
acetonide
(intralesional injection)
KENACORT
TRICORT
P-CORT-40
KE...
DEXAMETHASONE SODIUM
PHOSPHATE
(LONG ACTING)
GLUCOCORTICOIDSINTRALESIONAL INJECTIONS
DRUG NAME BRAND NAME DOSAGE CLASSIFICATION
Dexamethasone
sodium phosphate
(intralesional injection)
DECADRON
PHOSPHATE
DEX...
MECHANISM OF
ACTION
ADVERSE EFFECTS CONTRAINDICATIONS
Anti inflammatory
action
Inhibits the
proliferation of
fibroblasts
I...
BETAMETHASONE SODIUM
PHOSPHATE
(LONG ACTING)
GLUCOCORTICOIDSINTRALESIONAL INJECTIONS
DRUG NAME BRAND NAME DOSAGE CLASSIFICATION
Betamethasone
sodium phosphate
(intralesional injection)
BETNESOL
BETACORTRIL
C...
MECHANISM OF ACTION
Anti inflammatory action
Inhibits the proliferation of
fibroblasts
Immunosuppressive action
INTRALESIONAL INJECTIONS
(IN MODERATE PHASE)
ENZYMES GLUCOCORTICOIDS AQEOUS EXTRACT
HYALURONIDASE
CHYMOTRIPSIN
COLLAGENASE...
PLACENTAL EXTRACT
AQEOUS EXTRACTINTRALESIONAL INJECTIONS
DRUG NAME BRAND NAME DOSAGE CLASSIFICATION
Placental extract
(intralesional injection)
PLACENTREX 2 ml
Once a week
For 10 ...
MECHANISM OF
ACTION
ADVERSE EFFECTS CONTRAINDICATIONS
Anti-inflammatory and
significant analgesic
effect
Increase in blood...
BETEL QUID
CHEWING HABIT
CHRONIC
INFLAMMATORY PROCESS
TGF-β
COLLAGEN
PRODUCTION
COLLAGEN
DEGRADATION
TIMP
LOX
(Lysyl
Oxida...
DRUG NAME BRAND NAME DOSAGE CLASSIFICATION
Colchicine COLCHINDON
GOUTNIL
ZYCOLCHIN
0.5 mg orally
Twice a day
Antigout agen...
MECHANISM OF
ACTION
ADVERSE EFFECTS DRUG INTERACTIONS
Disruption of the
microtubule
formation and
Depolymerizes
microtubul...
SURGICAL MANAGEMENT
SEVERE PHASE
SUBMUCOSAL RESECTION OF FIBROUS BANDS (FIBROTOMY)
BILATERAL TEMPORALIS MYOTOMY or CORONOIDECTOMY
NASOLABIAL F...
PHYSIOTHERAPY
MOUTH OPENING EXCERCISES
USE OF APPLIANCE (HEISTER’S JAW OPENER)
STICK BALLOONING
HEAT THERAPY
MOUTH OPENING EXERCEISES US...
COMBINED THERAPY
VASODILATORS
PENTOXYFYLLINE
NYLIDRIN HYDROCHLORIDE
VITAMIN D, E, B-COMPLEX
IODINE
PLACENTAL EXTRACT
LOCAL & SYSTEMIC
CORTI...
OTHER THERAPIES
IMMUNISED COW MILK
SKIMMED MILK FORM COW IMMUNISED WITH MULTIPLE HUMAN INTESTINAL BACTERIA
VIT A, C , B1, B2 , B6, B12, NI...
TURMERIC
(Curcuminoids)
TURMERIC OIL & OLEORESIN
IN VITRO FREE RADICAL SCAVENGER
INJ OF GOLD, VITAMIN A & COLLAGENASE
CHEMOTHERAPEUTIC AGENTYS LIKE TOPICAL
BLEOMYCIN
DIATHERMY
Microwave diathermy
Low current (20 Watts x 2450 cycles)
Early – Moderate stage
ULTRASOUND
Efficient deep heating modality
(Frequency 0.8-1 MHz Intensity 0.5-3 w/sq.cm)
SURGICAL INTERVENTION
AN OVERVIEW
J Maxillofac Oral Surg. 2015 Sep; 14(3): 521–531.
TONGUE FLAP
PALATAL FLAP
Palatal island flap based on
greater palatine artery (contd.)
J N Khanna, N N Andrade
BUCCAL PAD OF FAT
NASO-LABIAL FLAP
RADIAL FOREARM FREE FLAP
ANTERO-LATERAL THIGH (ALT)
FLAP (Huang et al)
SPLIT SKIN GRAFT
COLLAGEN MEMBRANE
ARTIFICIAL DERMIS
HUMAN PLACENTA / AMNION GRAFT
CORONOIDECTOMY
MUSCLE MYOTOMY
ORAL STENTS
CONCLUSION
• OSF is one of the most poorly understood and unsatisfactorily treated
diseases.
• Among the above mentioned m...
References
• Shafer’s Textbook of Oral Pathology(seventh edition)~ Shafer, Hine, Levy. Editors- R Rajendran, B Sivapathasu...
• Venkatesh Viswanath Kamath, Shruti Krishnamurthy, Krishnanand P. Satelur, and Komali
Rajkumar. Transforming growth facto...
Thank You
Maxfac
Center for Cranio - Maxillofacial & Head and Neck Surgery, Siliguri
Contact us at : maxfacmail@gmail.com
...
Oral Submucous Fibrosis and its Management.
Oral Submucous Fibrosis and its Management.
Oral Submucous Fibrosis and its Management.
Oral Submucous Fibrosis and its Management.
Oral Submucous Fibrosis and its Management.
Oral Submucous Fibrosis and its Management.
Oral Submucous Fibrosis and its Management.
Oral Submucous Fibrosis and its Management.
Oral Submucous Fibrosis and its Management.
Oral Submucous Fibrosis and its Management.
Oral Submucous Fibrosis and its Management.
Oral Submucous Fibrosis and its Management.
Oral Submucous Fibrosis and its Management.
Oral Submucous Fibrosis and its Management.
Oral Submucous Fibrosis and its Management.
Oral Submucous Fibrosis and its Management.
Oral Submucous Fibrosis and its Management.
Oral Submucous Fibrosis and its Management.
Oral Submucous Fibrosis and its Management.
Oral Submucous Fibrosis and its Management.
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Oral Submucous Fibrosis and its Management.

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Oral Submucous Fibrosis and its various treatment modalities inclusive of both non-surgical and surgical management.

Mentor: Dr Saikat Saha MDS, OMFS, SIliguri, West Bengal, India
Address: MAXFAC Center for Oral and Maxillofacial and Head & Neck Surgery, Siliguri
Email : maxfacmail@gmail.com

Veröffentlicht in: Gesundheit & Medizin

Oral Submucous Fibrosis and its Management.

  1. 1. ORAL SUBMUCOUS FIBROSIS AND ITS MANAGEMENT Maxfac Center for Cranio - Maxillofacial & Head and Neck Surgery, Siliguri Contact us at : maxfacmail@gmail.com Mentor & Guide : Dr Saikat Saha MDS OMFS Presenter : Dr Mukesh Chhetri BDS Fellow Trainee at Maxfac
  2. 2. CONTENTS • Introduction • Definition • WHO definition of precancerous condition • Epidemiology • Etiology/Predisposing factors • Common products • Symptoms • Signs • Diagnostic measurements • Constituents of arecanut • Pathogenesis • Histopathology • Staging • Blood chemistry & hematological variations • Management • Surgical management • An overview • Conclusion • Reference
  3. 3. INTRODUCTION • Oral Submucous Fibrosis is a chronic debilitating disease characterized by gradually increasing fibrosis of the oral cavity and pharynx, mainly the buccal mucosa, resulting in trismus. • Most treatment modalities in OSMF have centered on release of the fibrotic bands to assist oral opening and some to provide symptomatic relief to the patient.
  4. 4. DEFINITION "An insidious chronic disease affecting any part of the oral cavity and sometime the pharynx. Although occasionally preceeded by and/or associated with vesicle formation, it is always associated with juxta-epthelial inflammatory reaction followed by fibro- elastic change of lamina propria, with epithelial atrophy leading to stiffness of the oral mucosa and causing trismus and inability to eat" -Pindborg (1966)
  5. 5. Diffuse oral submucous fibrosis Idiopathic scleroderma of mouth Idiopathic palatal fibrosis Sclerosing stomatitis Juxtaepithelial fibrosis Also called:
  6. 6. Upper Digestive Tract Submucous fibrosis Pharynx
  7. 7. WHO Definition of ‘Oral Precancerous Condition’ “A generalized pathological state of the oral mucosa associated with a significantly increased rick of cancer”– accords well with the characteristics of OSF
  8. 8. • VIDARI ~ 600AD (Sushruta) • Atrophia Idiopathica (tropica) Mucosae Oris ~ Schwartz(1952) • Oral Submucous Fibrosis ~ Joshi(1953)
  9. 9. EPIDEMIOLOGY • Adolescents and adults (16 – 35 years) • 0.2 – 0.5 % prevalence rate in India.
  10. 10. ETIOLOGY / PREDISPOSING FACTORS (multifactorial) ARECANUT & PRODUCTS TOBACCO CHILIES(CAPSAICIN) GENETIC & IMMUNOLOGICAL PROCESSES NUTRITIONAL DEFICIENCIES SMOKING ALCOHOL MISI (BLACK POWDER USED BY WOMEN IN U.P.)
  11. 11. COMMON PRODUCTS BETEL QUID (areca nut, tobacco, slaked lime and other species)
  12. 12. TOBACCO PREPARATIONS Gutkha, Pan Masala, Mawa, Flavoured Supari, Khaini etc.
  13. 13. MISI (sodium bicarbonate, alum, myrobalan charcoal and filler earth)
  14. 14. Symptoms • Burning sensation • Difficulty in mouth opening • Difficulty in swallowing • Taste changes • Dryness of mouth • Excessive salivation • Difficulty in speaking • Vesicles & Ulcers • Hearing difficulty • Hoarseness of voice • Nasal twang
  15. 15. Signs • Blanching of oral mucosa • Presence of fibrous bands • Leathery texture of oral mucosa • Trismus • Restriction of Tongue Movements • Blisters/Erythematous areas/ Ulcers/Vesicles/Erosions • Depapillation of Tongue • Shrunken/Deviated/Bud like Uvula • Atrophic tongue • Bilateral pouching-in while opening mouth/Sunken cheeks • Lymphadenopathy • Anaemia • Secondary/Malignant changes
  16. 16. Presence of fibrous bands Blanching of oral mucosa
  17. 17. Leathery texture of oral mucosa
  18. 18. Trismus Restriction of Tongue Movements
  19. 19. Erosions Vesicles Ulcers Blisters/ Erythematous areas
  20. 20. Depapillation of Tongue Atrophic tongue
  21. 21. Bud like Uvula Shrunken Uvula Deviated Uvula
  22. 22. Bilateral pouching-in while opening mouth / Sunken cheeks Angular cheilitis
  23. 23. Secondary Changes Malignancy Leukoplakia Erythroplakia
  24. 24. DIAGNOSTIC MEASUREMENTS INTERINCISAL DISTANCE (MAXIMUM MOUTH OPENING) Normal distance between Central Incisor Tips: Males: 35 to 45 mm Females: 30 to 42 mm
  25. 25. TONGUE PROTRUSION Normal Mesio-Incisal Angle of the Upper Central Incisor to the Tip of the Tongue when maximally extended with the mouth wide open: Males: 5 to 6 cm Females: 4.5 to 5.5 cm
  26. 26. CHEEK FLEXIBILITY: CF= V1-V2 . V2- Point measured between at one-third the distance from the angle of the mouth on a line joining the tragus of the ear to the angle of the mouth The patient is then asked to blow his cheeks fully and the distance between the two points is marked on the cheek as V1 Mean values for cheek flexibility: Males 35 to 45 mm Females 30 to 40 mm [Patil S. and Maheshwari S.(2014)]
  27. 27. 1/3 V2 V1 1/3 When normally When cheeks fully blown
  28. 28. StageI:EarlyOSMF •IID •TP •CF StageII:ModerateOSMF •IID- ↓33% •TP- ↓33% •CF- ↓33% StageIII:SevereOSMF •IID- ↓66% •TP- ↓66% •CF- ↓66% [Bailoor D.N. (1993)]
  29. 29. QUID “A substance or mixture of substances, placed in the mouth or chewed or remaining in contact with the mucosa, usually containing one or both of the two basic ingredients tobacco and/or arecanut, in raw or any manufactured or processed form”
  30. 30. ARECA NUT ALKALOIDS FLAVANOIDS  ARECOLINE  ARECAIDINE  ARECOLIDINE  GUYACOLINE  GUACINE  TANNINS CATECHINS
  31. 31. ALKALOIDS (Arecoline) NITROSATION N-NITROSAMINE CYTOTOXIC EFFECTS
  32. 32. PATHOGENESIS [P.Rajlalitha, S.Vali (2005)] COLLAGEN PRODUCTION PATHWAY COLLAGEN DEGRADATION PATHWAY
  33. 33. Initial events of the disease Oral mucosa Betel quid habit Chronic inflammation Activated T cell & Macrophage at the site Constant irritation ↑Cytokines & Growth factors Duration & Frequency of habit Deficiency of Iron &Vit. B12 mechanical chemical 15 MINS - HOUR X 5-6 TIMES A DAY
  34. 34. COLLAGEN PRODUCTION PATHWAY ACTIVATION OF PRO-COLLAGEN GENES ELEVATION OF PROCOLLAGEN PROTEINASES LEVELS PNP PCP UPREGULATION OF LYSYL OXIDASE(LOX) ACTIVITY
  35. 35. COLLAGEN DEGRADATION PATHWAY ACTIVATION OF TISSUE INHIBITOR OF MATRIX METALLOPROTEINASE GENE(TIMPs) ACTIVATION OF PLASMINOGEN ACTIVATOR INHIBITOR GENE(PAI)
  36. 36. OVER ALL EFFECT INCREASE IN COLLAGEN PRODUCTION DECREASE IN COLLAGEN DEGRADATION INCREASED COLLAGEN (INSOLUBLE FORM— CROSS-LINKING OF INSOLUBLE COLLAGEN) FIBROSIS ORAL SUBMUCOUS FIBROSIS
  37. 37. HISTOPATHOLOGY EARLY STAGE ADVANCED STAGE
  38. 38. STAGING Chandramani B. More et al (2011) CLINICAL STAGING
  39. 39. Stage 4 (S4) • Any one of the above stage with other PMDs (oral leukoplakia, oral erythroplakia, etc) • Any one of the above stage along with oral carcinoma.
  40. 40. FUNCTIONAL STAGING Interincisal mouth opening: ≥ 35 mm. Interincisal mouth opening: 15 — 25 mm. Interincisal mouth opening: < 15 mm Interincisal mouth opening: 25 – 35 mm. M 1 M 4 M 2 M 3
  41. 41. BLOOD CHEMISTRY & HEMATOLOGICAL VARIATIONS ↓ Vit. B12 ↓ Serum Albumin ↓Fe ↓ Folate Slight Eosinophilia ↑ Gammaglobulin ↑ TIBC Microcytic Hypochromic Anaemia↑ESR Macrocytic Normochromic Anaemia
  42. 42. MANAGEMENT
  43. 43. ELIMINATION OF HABITS NUTRITIONAL SUPPORT IMMUNO-MODULATORY DRUGS LOCAL DRUG DELIVERY INTRALESIONAL INJECTIONS PHYSIOTHERAPY INTERFERON GAMMA-1 D (IMMUNOKINE OF BOEHRINGER) COMBINED THERAPY MOUTH RINSES SURGICAL MANAGEMENT
  44. 44. BETEL QUID CHEWING HABIT CHRONIC INFLAMMATORY PROCESS TGF-β COLLAGEN PRODUCTION COLLAGEN DEGRADATION TIMPPCPPNP PLASMINOGEN ACTIVATOR SYSTEM COLLAGENASE - - - - 1. Anti-inflammatory/ Immune-modulatory drugs 2. Anti- TGF-β 3. Cu Chelators 4. Anti-LOX drugs 5. Collagenase activators + LOX (Lysyl Oxidase)
  45. 45. Type Drug ANTI-INFLAMMATORY / IMMUNE-MODULATORY DRUGS Pirfenidone (ESBRIET, INTERMUNE) (immunosuppressant) IFN-gamma (immunoregulatory cytokine) Still in research 200 µg/ml have been tried ANTI- TGF-Β Mouse monoclonal antibodies: Anti-TGF-β1 (8A11) (NovusBio®, USA) (Cat No: NB110- 59988) Anti-TGF-β2 (TB21) (NovusBio®, USA) (Cat No: NBP1- 51749) Dilution: 4 μl/100 μl (for anti-TGF-β1) 1 μl/100 μl (for anti-TGF-β2) CU CHELATORS Penicillamine Still in research ANTI-LOX DRUGS β-aminopropionitrile (BAPN, 100 µM) an irreversible LOX inhibitor Still in research COLLAGENASE ACTIVATORS Colchicine 0.5 mg orally twice a day
  46. 46. ELIMINATION OF HABITS
  47. 47. As gum, skin patch, nasal spray, or inhaler. Chewing gums Skin Patch
  48. 48. Nasal Spray Lozenge Inhaler
  49. 49. Bupropion Hydrochloride (ZYBAN) Varenicline (CHANTIX) ZYBAN prescribed under another name“WELLBUTRIN” to treat depression. As tablets
  50. 50. NUTRITIONAL SUPPORT
  51. 51. HIGH PROTEINS & HIGH- CALORIE DIET VITAMIN B COMPLEX & OTHER VITAMINS MINERALS Intake of red tomatoes, fresh foods, green leafy vegetables Green tea Routine Hb % levels followed by Iron supplementation LYCOPENE
  52. 52. DRUG NAME BRAND NAME DOSAGE CLASSIFICATION Lycopene LYCOPENE (NOW) (lycopene ~10mg) SM FIBRO (lycopene ~5mg) LYCOSTAR (Lycopene~5000mcg) 8 – 10 mg Twice daily For 2 months (16mg in 2 divided doses) Powerful antioxidant obtained from tomatoes Manufactured by the Lyc-O-Mato™ process
  53. 53. MECHANISM OF ACTION ADVERSE EFFECTS Reducing the free radical reaction That can cause DNA mutations and changes in lipid peroxidation of cellular membranes and changes in enzymatic activities Generally well tolerated. The scientific literature documents some GI complaints
  54. 54. LOCAL DRUG DELIVERY
  55. 55. Topical Application: TRIAMCINOLONE GEL 0.1% (Kenacort) / TRIAMCINOLONE IN ORA-BASE BETAMETASONE 0.5% (Betnesol) KENALOG S EYE OINTMENT (triamcinolone acetonide 1 mg, gramicidin 0.25 mg, neomycin sulphate 2.5 mg/1 g) IN EARLY STAGES 3-4 TIMES A DAY
  56. 56. IMMUNO- MODULATORY DRUGS
  57. 57. GLUCOCORTICOIDS & PLACENTAL EXTRACTS (LOCAL & SYSTEMIC APPLICATION) SUPPRESS INFLAMMATORY RECATION PREVENT FIBROSIS Placentrix injection intralesionally (Aqueous extract) Levamisole (Dewormis) Pentoxifylline (Trental)
  58. 58. DRUG NAME BRAND NAME DOSAGE CLASSIFICATION Levamisole DEWORMIS BIOVAM LEVOMOL 150 mg Three times daily Three consecutive days in a week Three alternate weeks Or, In combination with Two capsules of Antaoxid daily For Six weeks. Anthelminthic drugs
  59. 59. MECHANISM OF ACTION ADVERSE EFFECTS CONTRAINDICATIONS Immunomodulator (modifies both cellular and humoral immunity) In OSF it reduces the level of IgG, IgA and IgM thus slow down the chronic inflammatory process CENTRAL NERVOUS SYSTEM Memory loss, loss of consciousness MISCELLANEOUS Muscle weakness Pre-existing blood disorders Pregnancy and lactation Inflammation of joints Severe kidney problems
  60. 60. DRUG NAME BRAND NAME DOSAGE CLASSIFICATION Pentoxyfylline TRENTAL-400 FLEXITAL 400mg SR tabs 400 mg TDS For 6-7 months Peripheral Vasodilators (Methylxanthine derivative)
  61. 61. MECHANISM OF ACTION ADVERSE EFFECTS CONTRAINDICATIONS It increases mucosal vascularity. Anti inflammatory properties Immuno-modulating actions Nausea, Vomiting, Dyspepsia, Bloating Severe allergic reactions Allergic to any ingredient in Pentoxifylline / Methylxanthines (eg, theophylline, caffeine, theobromine) Recent bleeding in the brain or eye
  62. 62. INTERFERON GAMMA-1 D (IMMUNOKINE OF BOEHRINGER)
  63. 63. 200 µg/ml have been tried (Anti-fibrotic cytokine) Adverse effects: Fever, chills, headache, myalgia, arthralgia, injection site reactions Contraindication: Severe hepatitis, renal impairment & cardiac disease.
  64. 64. DRUG NAME BRAND NAME DOSAGE CLASSIFICATION Interferon γ (intralesional injection) ACTIMMUNE (0.01- 10.0 U/mL) 3 times daily For 6 months or, (50 mg / 0.25 ml) Twice a week 8 weeks Anti-fibrotic cytokine
  65. 65. MECHANISM OF ACTION ADVERSE EFFECTS CONTRAINDICATIONS Regulation of fibroblast proliferation & collagen synthesis Upregulation of antifibrotic cytokine and collagen synthesis in the basal layer of epithelium and lamina propria Fever Chills Headache myalgia Arthralgia injection site reactions Severe hepatitis Renal impairment Cardiac disease
  66. 66. MOUTH RINSES
  67. 67. Listerine Mouthwash Essential Oils : Menthol (mint) 0.042% Thymol(thyme) 0.064% Methyl Salicylate (wintergreen) 0.06% Eucalyptol (eucalyptus) 0.092% With Powdered Dexamethasone tablet (2mg in 5mL) 3 – 4 times a day
  68. 68. INTRALESIONAL INJECTIONS
  69. 69. INTRALESIONAL INJECTIONS (IN MODERATE PHASE) ENZYMES GLUCOCORTICOIDS AQEOUS EXTRACT HYALURONIDASE CHYMOTRIPSIN COLLAGENASE SHORT ACTING HYDROCORTISONE INTERMEDIATE ACTING TRIAMCINOLONE ACETONIDE LONG ACTING DEXAMETHASONE SODIUM PHOSPHATE BETHAMETHASONE SODIUM PHOSPHATE PLACENTAL EXTRACT
  70. 70. ENZYMES HYALURONIDASE INTRALESIONAL INJECTIONS
  71. 71. DRUG NAME BRAND NAME DOSAGE CLASSIFICATION Hyaluronidase (intralesional injection) HYNIDASE HYA 1500 IU (0.5-2 ml) With 2% lignocaine Twice daily For 10 weeks Hydrolytic enzyme
  72. 72. MECHANISM OF ACTION ADVERSE EFFECTS CONTRAINDICATIONS Breaks down Hyaluronic acid (Depolymerizing) Lowers the viscosity of intracellular substances Decreases collagen formation Local Injection site reactions such as Pain Itching Redness Swelling Urticaria, Angioedema (in less than 0.1% ) Hypersensitivity to Hyaluronidase
  73. 73. ENZYMES CHYMOTRIPSIN INTRALESIONAL INJECTIONS
  74. 74. DRUG NAME BRAND NAME DOSAGE CLASSIFICATION Chymotripsin (intralesional injection) TRYPSIN CHOMISIN CHYMASE CHYMOTRIP 5000 IU Twice a week For 10 weeks Proteolytic enzyme Anti-inflammatory agent
  75. 75. MECHANISM OF ACTION ADVERSE EFFECTS Endopeptidase Hydrolyses peptide bonds and esters Local: Injection site reaction Allergic reactions rare
  76. 76. COLLAGENASE ENZYMESINTRALESIONAL INJECTIONS
  77. 77. DRUG NAME BRAND NAME DOSAGE CLASSIFICATION Collagenase (intralesional injection) XIAFLEX SANTYL COLLAGENASE SANTYL 2mg of collagenase materials dissolved in 1ml of distilled water Lysosomal enzyme
  78. 78. MECHANISM OF ACTION ADVERSE EFFECTS Degrading, Phosphate esters Proteins Polysaccharides Glycosides Sulphate Esters Pain Swelling Trismus
  79. 79. INTRALESIONAL INJECTIONS (IN MODERATE PHASE) ENZYMES GLUCOCORTICOIDS AQEOUS EXTRACT HYALURONIDASE CHYMOTRIPSIN COLLAGENASE SHORT ACTING HYDROCORTISONE INTERMEDIATE ACTING TRIAMCINOLONE ACETONIDE LONG ACTING DEXAMETHASONE SODIUM PHOSPHATE BETHAMETHASONE SODIUM PHOSPHATE PLACENTAL EXTRACT
  80. 80. HYDROCORTISONE (SHORT ACTING) GLUCOCORTICOIDSINTRALESIONAL INJECTIONS
  81. 81. DRUG NAME BRAND NAME DOSAGE CLASSIFICATION Hydrocortisone (intralesional injection) WYCORT EFCORLIN CORT-S MOSACORT 25 mg/ml (1.5cc) Once a week For a duration of 12 weeks Short acting Glucocorticoid (t½ < 12 hours)
  82. 82. TRIAMCINOLONE ACETONIDE (INTERMEDIATE ACTING) GLUCOCORTICOIDSINTRALESIONAL INJECTIONS
  83. 83. DRUG NAME BRAND NAME DOSAGE CLASSIFICATION Triamcinolone acetonide (intralesional injection) KENACORT TRICORT P-CORT-40 KENALOG-40 40 mg/ml (1.5cc) Once a week For a duration of 12 weeks Intermediate acting Glucocorticoid (t½ > 12-36 hours)
  84. 84. DEXAMETHASONE SODIUM PHOSPHATE (LONG ACTING) GLUCOCORTICOIDSINTRALESIONAL INJECTIONS
  85. 85. DRUG NAME BRAND NAME DOSAGE CLASSIFICATION Dexamethasone sodium phosphate (intralesional injection) DECADRON PHOSPHATE DEXONA WYMESONE DECDAN DEXASONE 4 mg/ml (0.5-1 ml bilaterally) At multiple sites Once a week For 6 weeks Long acting Glucocorticoid (t½ > 36 hours)
  86. 86. MECHANISM OF ACTION ADVERSE EFFECTS CONTRAINDICATIONS Anti inflammatory action Inhibits the proliferation of fibroblasts Immunosuppressive action Cushing habitus Suppression of Hypothalamo- Pituitary- Adrenal(HPA) axis Hyperglycemia Recent myocardial infarction Osteoporosis (post-menopausal females are particularly at risk) Peptic ulcer HTN/CHF Renal failure
  87. 87. BETAMETHASONE SODIUM PHOSPHATE (LONG ACTING) GLUCOCORTICOIDSINTRALESIONAL INJECTIONS
  88. 88. DRUG NAME BRAND NAME DOSAGE CLASSIFICATION Betamethasone sodium phosphate (intralesional injection) BETNESOL BETACORTRIL CELESTONE BETAGIN 4 mg/ml (0.5-1 ml bilaterally) At multiple sites Once a week For 6 weeks Long acting Glucocorticoid (t½ > 36 hours)
  89. 89. MECHANISM OF ACTION Anti inflammatory action Inhibits the proliferation of fibroblasts Immunosuppressive action
  90. 90. INTRALESIONAL INJECTIONS (IN MODERATE PHASE) ENZYMES GLUCOCORTICOIDS AQEOUS EXTRACT HYALURONIDASE CHYMOTRIPSIN COLLAGENASE SHORT ACTING HYDROCORTISONE INTERMEDIATE ACTING TRIAMCINOLONE ACETONIDE LONG ACTING DEXAMETHASONE SODIUM PHOSPHATE BETHAMETHASONE SODIUM PHOSPHATE PLACENTAL EXTRACT
  91. 91. PLACENTAL EXTRACT AQEOUS EXTRACTINTRALESIONAL INJECTIONS
  92. 92. DRUG NAME BRAND NAME DOSAGE CLASSIFICATION Placental extract (intralesional injection) PLACENTREX 2 ml Once a week For 10 weeks Biogenic stimulants Aqueous extract of human placenta
  93. 93. MECHANISM OF ACTION ADVERSE EFFECTS CONTRAINDICATIONS Anti-inflammatory and significant analgesic effect Increase in blood circulation and tissue vascularity Arrest of tissue growth stagnation Lower immune response factor Local: Injection site reaction Hypersensitivity to placental extract
  94. 94. BETEL QUID CHEWING HABIT CHRONIC INFLAMMATORY PROCESS TGF-β COLLAGEN PRODUCTION COLLAGEN DEGRADATION TIMP LOX (Lysyl Oxidase) PCPPNP PLASMINOGEN ACTIVATOR SYSTEM COLLAGENASE 5. Collagenase activators +
  95. 95. DRUG NAME BRAND NAME DOSAGE CLASSIFICATION Colchicine COLCHINDON GOUTNIL ZYCOLCHIN 0.5 mg orally Twice a day Antigout agent Collagenase activators
  96. 96. MECHANISM OF ACTION ADVERSE EFFECTS DRUG INTERACTIONS Disruption of the microtubule formation and Depolymerizes microtubules which prevent the Extrusion of collagen fibers from the fibroblast and increases Collagenolytic activity Dose related Overdose: Kidney damage CNS Depression Chronic Therapy: Aplastic anaemia Azole antifungals (Itraconazole, Ketoconazole) Macrolide antibiotics (Clarithromycin, Erythromycin) Can affect the removal of colchicine from your body
  97. 97. SURGICAL MANAGEMENT
  98. 98. SEVERE PHASE SUBMUCOSAL RESECTION OF FIBROUS BANDS (FIBROTOMY) BILATERAL TEMPORALIS MYOTOMY or CORONOIDECTOMY NASOLABIAL FLAP OR LINGUAL PEDICAL FLAP SPLIT SKIN GRAFT / MUCOSAL GRAFT BUCCAL PAD OF FAT COLLAGEN
  99. 99. PHYSIOTHERAPY
  100. 100. MOUTH OPENING EXCERCISES USE OF APPLIANCE (HEISTER’S JAW OPENER) STICK BALLOONING HEAT THERAPY MOUTH OPENING EXERCEISES USING WOODEN SPATULA / ICE CREAM STICKS MOUTH GAG/ ACRYLIC SURGICAL SCREW
  101. 101. COMBINED THERAPY
  102. 102. VASODILATORS PENTOXYFYLLINE NYLIDRIN HYDROCHLORIDE VITAMIN D, E, B-COMPLEX IODINE PLACENTAL EXTRACT LOCAL & SYSTEMIC CORTICOSTEROIDS PHYSIOTHERAPY
  103. 103. OTHER THERAPIES
  104. 104. IMMUNISED COW MILK SKIMMED MILK FORM COW IMMUNISED WITH MULTIPLE HUMAN INTESTINAL BACTERIA VIT A, C , B1, B2 , B6, B12, NICOTINIC ACID, PANTHOTENIC ACID, FOLIC ACID, IRON, COPPER, ZINC 20-30% HIGHER IgG ANTIBODY 2L DAILY / 45g MILK POWDER TWICE DAILY FOR 3 MONTHS
  105. 105. TURMERIC (Curcuminoids) TURMERIC OIL & OLEORESIN IN VITRO FREE RADICAL SCAVENGER
  106. 106. INJ OF GOLD, VITAMIN A & COLLAGENASE CHEMOTHERAPEUTIC AGENTYS LIKE TOPICAL BLEOMYCIN
  107. 107. DIATHERMY Microwave diathermy Low current (20 Watts x 2450 cycles) Early – Moderate stage
  108. 108. ULTRASOUND Efficient deep heating modality (Frequency 0.8-1 MHz Intensity 0.5-3 w/sq.cm)
  109. 109. SURGICAL INTERVENTION
  110. 110. AN OVERVIEW J Maxillofac Oral Surg. 2015 Sep; 14(3): 521–531.
  111. 111. TONGUE FLAP
  112. 112. PALATAL FLAP
  113. 113. Palatal island flap based on greater palatine artery (contd.) J N Khanna, N N Andrade
  114. 114. BUCCAL PAD OF FAT
  115. 115. NASO-LABIAL FLAP
  116. 116. RADIAL FOREARM FREE FLAP
  117. 117. ANTERO-LATERAL THIGH (ALT) FLAP (Huang et al)
  118. 118. SPLIT SKIN GRAFT
  119. 119. COLLAGEN MEMBRANE
  120. 120. ARTIFICIAL DERMIS
  121. 121. HUMAN PLACENTA / AMNION GRAFT
  122. 122. CORONOIDECTOMY
  123. 123. MUSCLE MYOTOMY
  124. 124. ORAL STENTS
  125. 125. CONCLUSION • OSF is one of the most poorly understood and unsatisfactorily treated diseases. • Among the above mentioned modalities for treatment of OSF none of them can be considered to be completely effective. • All available treatments provide symptomatic relief, which is short lived. • This is mainly due to the fact that the etiology of the disease is not fully understood and the disease is progressive in nature. • The wide range of treatment modalities currently used for OSF is ample evidence that there is no simple answer to how it should be managed. • Therefore, an evidence based practice will help to provide the best possible treatment for the disease.
  126. 126. References • Shafer’s Textbook of Oral Pathology(seventh edition)~ Shafer, Hine, Levy. Editors- R Rajendran, B Sivapathasundharam. • DIAGNOSTIC ORAL MEDICINE (first edition, 2013)- B K Venkataraman (Chief Editor); Asha R Iyengar, K S Ganapathy, C V Mohan, K S Nagesh (Associate Editors). • Venkatesh V. Kamath. Surgical Interventions in Oral Submucous Fibrosis: A Systematic Analysis of the Literature. J Maxillofac Oral Surg. 2015 Sep; 14(3): 521–531.Published online 2014 Dec 25. doi: 10.1007/s12663-014-0639-3.Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4510093/ • Kumar L. K. Surej, Nikhil M. Kurien, and Nasil Sakkir. Buccal fat pad reconstruction for oral submucous fibrosis. Natl J Maxillofac Surg. 2010 Jul-Dec; 1(2): 164–167. doi: 10.4103/0975-5950.79222. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3304196/. • P. Rajalalitha, S. Vali. Molecular pathogenesis of oral submucous fibrosis- a collagen metabolic disorder(Review article). J Oral Pathol Med. 2005 Jul;34(6):321-8. • More C B, Gupta S, Joshi J, Varma S N. Classification system of Oral Submucous Fibrosis(Review article). J Indian Aca Oral Med Radiol 2012;24(1):24-29. • Vikas Berwal, Monika Khangwal, Ravinder Solanki, Rakshit Khandeparker, Kiran Savant, Omkar Shetye. CLASSIFICATION SYSTEMS FOR ORAL SUBMUCOUS FIBROSIS- FROM PAST TO PRESENT: A REVIEW. Berwal V. et al., Int J Dent ealth Sci 2014; 1(6):900-913. • Harsha Pradhan, Hemant Gupta, VP Sinha, Sumit Gupta, MC Shashikanth. Two wound-covering materials in the surgical treatment of oral submucous fibrosis: a clinical comparison. Journal of Oral Biology and Craniofacial Research 2012 April Original Article Volume 2, Number 1; pp. 10–14. doi: 10.1016/S2212-4268(12)60004-9. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941626/pdf/main.pdf • Shobha Nataraj, Yadavalli Guruprasad, Jayaprasad N.Shetty. A Comparative Clinical Evaluation of Buccal Fat Pad and Collagen in Surgical Management of Oral Submucous Fibrosis. Archives of Dental Sciences, Vol.2, Issue 4, 17-24 (http:www.archdent.org). Available at https://www.researchgate.net/publication/232702355_A_Comparative_Clinical_Evaluation_of_Buccal_Fat_Pad_and_Collagen_in_Surg ical_Management_of_Oral_Submucous_Fibrosis
  127. 127. • Venkatesh Viswanath Kamath, Shruti Krishnamurthy, Krishnanand P. Satelur, and Komali Rajkumar. Transforming growth factor-β1 and TGF-β2 act synergistically in the fibrotic pathway in oral submucous fibrosis: An immunohistochemical observation. Indian J Med Paediatr Oncol. 2015 Apr-Jun; 36(2): 111–116. doi: 10.4103/0971-5851.158842. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477373/ • L. Ashok, G. P. Sujatha. Targeted therapy for oral submucous fibrosis - Future strategies. Journal of Medicine, Radiology, Pathology & Surgery ● Vol. 1:6 ● Nov-Dec 2015. • Usha Dayanarayana, Nagabhushana Doggalli,Karthikeya Patil, Jai Shankar, Mahesh K.P, Sanjay. Non surgical approaches in treatment of OSF. IOSR Journal of Dental and Medical Sciences (IOSR- JDMS) e-ISSN: 2279-0853, p-ISSN: 2279-0861.Volume 13, Issue 11 Ver. III (Nov. 2014), PP 63-69 www.iosrjournals.org. • Manas Gupta, Pankaj Mishra ,Kirti Shrivastava ,Neha Singh ,Pushpraj Singh. Oral Submucous Fibrosis- Current Concepts of Aetiology & its Management(Review article). Journal Of Applied Dental and Medical Sciences 1(1);2015 28-39. Available online at www.joadms.org
  128. 128. Thank You Maxfac Center for Cranio - Maxillofacial & Head and Neck Surgery, Siliguri Contact us at : maxfacmail@gmail.com Mentor & Guide : Dr Saikat Saha MDS OMFS Presenter : Dr Mukesh Chhetri BDS Fellow Trainee at Maxfac

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