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Correction of literature review with tittle

Comparison of Surgical excision and Mitomycin C

of Ocular Surface Squamous Neoplasia cases :

1. Page 7 (line 1) : Tweleve studies published between 2000 and

2008.

Should be : Seven studies published between 2002 and 2008.

2. Page 7 (table III.1 ):

Shoud be :

4 Starges A,et all,

2007

III/Retrospe

ctive

SE + AMG

+ Interferon

29 12

months

4 Starges A,et all,

2007

III/Retrospe

ctive

SE + AMG

+

Interferon

29 2 months

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3. Page 7 (line 9) : Mean of follow up time were 2 months 50

months.

Should be : Mean of follow up time were 3 months 50 months

4. Page 9 (line 3) : tire current rateme

Should be : of recurrence rate.

5. Page 13 (line 5-7) :Based on journals in this literary review, thefollow-up time in OSSN treatment reported in all studies ranged

from 2 months until 50 months. The minimal follow-up time on

both procedures was 2 months (Shields CL, et all)

Should be : Based on journals in this literary review, the follow-

up time in OSSN treatment reported in all studies ranged from 3months until 50 months. The minimal follow-up time on both

procedures was 3 months (Rahimi F, et /ll)

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COMPARISON

OF SURGERY AND MITOMYCIN C TREATMENT

OF OCULAR SURFACE SQUAMOUS NEOPLASIA CASES

LITERATURE REVIEW

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CHAPTER IINTRODUCTION

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BACKGROUND

Ocular surface squamous neoplasia

(OSSN)

slowly progressing cancerous lesion

of the ocular surface caused by

a neoplastic proliferation of dysplasticsquamous epithelium

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OSSNmost common

conjunctiva malignancyin the United States

the third most commonocular tumor after

melanoma andlymphoma in the older

population

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Differentialdiagnosis

pannus, actinic disease, pinguecula, pterygium,benign intraepithelial dyskeratosis,

keratinization of the corneal epithelium,anterior basement membrane dystrophy,

malignant melanoma, conjunctival papillomata, nevi,and pseudoepitheliomatous hyperplasia.

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Treatment of choice : Surgical excision (SE) +

cryotherapy.

Reported recurrence rates after surgical treatment

are significant

Various topical agents advocate :

Mitomycin C (Mit C), 5-fluorouracil, and interferonalfa-2b

>> Mit C

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PROBLEM

Tabin et al : RR 11.5 years after primary treatment.

Frucht-Pery and Rozenman : RR by Mit C : 35%.

Hirst, L.W. : RR after SE: >50%.

(?) efficacy and safety the treatment of OSSN

SEMit C

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PURPOSE

To compare the efficacy and safety resultof SE and Mit C treatment

in OSSN

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CHAPTER IIMATERIAL AND METHODS

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Internet browsing Highwire & PUBMED (2002 2008)

Keywords : OSSN, SE & Mit C.

The inclusion criteria :

Minimum follow-up six weeks

OSSN treatment with SE + AMG and Mit C.

I/ : typically elevated lesion, involve the limbus,

gelatinous, papilliform or leukoplakic, with tufts of

blood vessels

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Efficacy : primary & secondary outcomemeasure

The primary outcome : complete clinical resolution

slit-lamp biomicroscopy

The secondary outcome : recurrance rate pathologyreports

Safety : complication during the study.

Most study : follicular conjunctivitis, corneal ephitelial

and eyelid skin erythema

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OCULAR SURFACE SQUAMOUSOCULAR SURFACE SQUAMOUS

NEOPLASIANEOPLASIA

OSSN : simple dysplasia carcinoma in situ invasive

squamous cell carcinoma involving conjunctiva & cornea

Histopathologically : features of overgrowth of conjunctival

epithelium with neovascularization, disruption of the basement

membrane and inflammatory cell infiltrates

Pizzarello , et al have described the macroscopic appearanceas being either gelatinous, velvety or papilliform or leukoplakic

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Retrobulbar anesthesia lesions wereremoved by superficial keratectomy (3-4mm tumor-free margin at the corneal andconjunctival side)

The corneal epithelium 2 mm anterior tothe tumor is treated with absolute alcohol

The AMG was sutured to the adjacentconjunctiva and episcleral tissue usinginterrupted 10-0 nylon sutures with thebasement membrane side facing up

SURGICAL

EXCISION

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Is an antibiotic isolated fromStreptomyces caespitosis

inhibits the synthesis of RNA,DNA, and protein

damages cells by cross linkingDNA and has significant anti-tumor activity

MYTOMCIN CMYTOMCIN C

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Mitomycin C 0.04% prepared by :Mitomycin powder content of a 2-mg +5 ml artificial tears

Put into sterile eye drop bottles shakenfor several times apply four times a day(seven days) followed by more sevendays put in refrigerator.

Close the eye (5) after using the drop close the punctum by finger pressure (1).

MYTOMCIN CMYTOMCIN C

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CAPTER IIIRESULT

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No Author RatingLevel/design Procedure Number of

eyes

Follow-up

(/mean/average/

range)

1 Hirst L. W., 2007 I/Prospective Mit-C 26 6-12 months

2 Rahimi F, et all,2008

III/Retrospective Mit-C 17 3 months

3 Masoomeh E,et

all, 2008

III/Retrospective Mit-C 17 4-36 months

4 Starges A,et all,

2007

III/Retrospective SE + AMG +

Interferon

29 12 months

5 Chen C,et all,

2004

III/Retrospective Mit C 27 27 months

6 Yeh LK et all,

2003

III/Retrospective SE + AMG + Cryo 5 27 months

7 Shields CL, et

all, 2002

III/Retrospective Mit-C 10 6-50 months

Table III.1 Characteristics of Journal articles

collected

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Table III.2 Complete resolution ofOSSN(Primary Outcome)

No Author, year Procedure No of eyes Resolutions

(mean/average)1 Hirst L. W., 2007 Mit C 26 2 months

2 Rahimi F, et all,2008

Mit C 17 2.5-41 months

3 Masoomeh E,et all,

2008

Mit C 17 2-16 months

4 Starges A,et all,

2007

SE + AMG +

Interferon

14 2 months

5 Chen C,et all, 2004 Mit C 27 NA6 Yeh LK et all, 2003 SE + AMG + Cryo 5 NA

7 Shields CL, et all,

2002

Mit C 10 NA

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Tabel III.3Recurrence rate of Mit C and SE.

(Secondary Outcome)

No Author, year Procedure Noumber

of eyes

Recurrence

rate

1 Hirst L. W., 2007 Mit C 26 NA

2 Rahimi F, et all,

2008

Mit C 17 5%

3 Masoomeh E,et all,

2008

Mit C 17 NA

4. Starges A,et all,

2007

SE + AMG +

interferon

14 0%

5 Chen C,et all, 2004 Mit C 27 0%

6 Yeh LK et all, 2003 SE + AMG + Cryo 5 0%

7 Shields CL, et all,

2002

Mit C 10 0%

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Table III.4 Complication of Mit C and SE

No Author, year Procedure Number of

eyes

Granuloma Red eye Chemosis

1 Hirst L. W., 2007 Mit C 26 NA 100% NA

2 Rahimi F, et all,

2008

Mit C 17 NA NA NA

3 Masoomeh E,et

all, 2008

Mit C 17 NA 24% 24%

4 Starges A,et all,

2007SE + AMG

+ Interferon

14 NA NA NA

5 Chen C,et all,

2004

Mit C 27 19% NA NA

6 Yeh LK et all,

2003

SE + AMG

+ Cryo

5 NA 40% NA

7 Shields CL, et all,

2002

Mit C 10 NA NA NA

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CHAPTER IVDISCUSSION

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Mit C has been used over many years in studies of

small numbers of patients with OSSN.

It also has been used in conjunction with surgery and

interferon and by direct application.

Mit C eye drop 0.04% has shown good clinical

results and no serious side effects when used as

alternate seven-day courses.

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Standard treatment for OSSN traditionally : surgical

excision + cryotherapy recurrence rates are high

(5% - 56%) depending on surgical approach, status

of surgical margins, and length of follow-up

Positive margins in pathology specimens indicative

of incomplete excision the most important predictor

of recurrence

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Promotes epithelialization and restores ocular surface

integrity without inflammation or scarring.

Contains protease inhibitors reduce inflammation-

associated proteolytic activity after application. Prevent subsequent conjunctival ingrowth and corneal

vascularization.

Excellent cosmetic outcome and a normal conjunctival

epithelial phenotype as demonstrated by impressioncytology

AMG

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Mit C Recurrence rate :

Frucht-Pery and Rozenman : no recurrence

Shield et al : no recurrence

Mit C related side effects :

conjunctival erythema,

chemosis

punctate epithelial keratopathy.

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Systemic side effects of Mit C : bone marrow suppression

profound leucopenia, thrombocytopenia

gastrointestinal toxicity

dermatitis

alopecia

fever, malaise, and

cardiotoxicity

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In these study

successfully controlled the tumors only 5%recurrence

related side effects : red eye, granuloma,

chemosis

long-term side effects : not defined

Summary : Mit C to be effective treatment forextensive and recurrent OSSN with minimal

ocular toxicity

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SE Recurrence Rate : 5% to 56% depending on surgical approach.

Akpek E.K. et al : 50%.

Chen C, et al : no recurrences.

Lynn B. McMahan (1994): 33% - 56%

Hirst, L.W. (2007) : 50%.

Tabin et al : 11.5 years after primary treatment

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SE related side effects :

Secondary tissue granulation

Pseudopterygium

Symblepharon Diplopia from tissue foreshortening

Blepharoptosis

SE sistemic side efects : -

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In these study

All cases had good results with no specialcomplications

Limited short-term complications :

redness and chemosis

Complete epithelialization occurred within2 months

(mean following-up period of 27 months)

No recurrence was note

The cosmetic outcome was good

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CHAPTER V

CONCLUSION & SUGGESTION

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CONCLUSION

Mitomycin C drop as safe and effective assurgical excision combined with AMG and cryoor interferon alfa 2b seems for OSSNtreatment

SUGGESTION

Larger population + longer follow-up periods to further assessing the risk of recurrence andother possible side effects.

Combining surgical excision and Mit C :alternative method

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