Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

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Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Dentistry
Year : 2011 | Month : August | Volume : 5 | Issue : 4 | Page : 882 - 888 Full Version

The Response of Oral Submucous Fibrosis to Lycopene – A Carotenoid Antioxidant: A Clinicopathological Study


Published: August 1, 2011 | DOI: https://doi.org/10.7860/JCDR/2011/.1485
Bhagavan Banige Komary Gowda, Yathish T.R., Sinhasan Sankappa P., Kumar Naik H., Purushotham Somayaji, Anand D.

Corresponding Author. Assistant Professor, Department of Physiology, Hassan Institute of Medical Sciences, Hassan. Associate Prof, Department of Pathology, Hassan Institute of Medical Sciences, Hassan. Associate Prof, Department of Pathology, Hassan Institute of Medical Sciences, Hassan. Assistant Prof, Department of Dentistry, Hassan Institute of Medical Sciences, Hassan. Tutor, Department of Dentistry, Hassan Institute of Medical Sciences, Hassan.

Correspondence Address :
Dr. Bhagavan Komary Gowda M.D.S.
Oral and Maxillofacial Surgeon
Professor and Head of Department
Department of Dentistry
Hassan Institute of Medical Sciences (HIMS),
Hassan –573 201, Karnataka. INDIA.
E-mail: F, yathi_aradhya@yahoo.co.in
Mobile: +91 94480 25810

Abstract

Introduction: The oral submucous fibrosis (OSMF) is a precancerous condition of the oral cavity. Untreated and neglected cases of OSMF might end up as invasive squamous cell carcinoma. Some pernicious habits like smoking, pan chewing and tobacco addiction for which human being has succumbed to are causing various dreaded diseases, the important among them being oral submucous fibrosis, leukoplakia and erythroplakia. Free radicals have more recently emerged as mediators of other phenotypic and genotypic changes that lead from mutation to neoplasia. The role of free radicals in the various oxidation processes in the body has lead to the identification of antioxidants in inhibiting and reversing the disease process. Lycopene is a safe antioxidant of utmost importance. Lycopene is a bright red carotene and carotenoid pigment and phytochemical found in tomatoes andother red fruits and vegetables, such as red carrots, watermelons and papayas.

Objectives: The main aim and objective of this study is to evaluate the clinical and histopathological response of oral submucous fibrosis to Lycopene-a carotenoid antioxidant.

Methods and Materials: The material for this study constitutes 12 adult patients picked from the regular outpatient attending the Department of Dentistry, Hassan institute of Medical Sciences, Hassan, Karnataka, India. Clinically, they are diagnosed as having oral submucous fibrosis.

Conclusions: Responses are assessed clinically and histopathologically. We observed clinical and histological improvement in various parameters used in our study. No significant toxicity attributable to Lycopene is encountered in this study.

Keywords

Lycopene, Antioxidant, Submucous Fibrosis, Free Radical theory

Oral submucous fibrosis (OSMF) has a very interesting history. Sushrutha, a renowned Indian physician who lived in the era from 2500 to 3000BC, had already recognized it as a mouth and throat melady and had labeled it as Vidhari (1). The features of which were described as a progressive narrowing of the mouth, blanching of the oral mucosa, pain and burning sensation on taking food, hypomobility of the soft palate and tongue, loss of gustatory sensation and occasional mild hearing impairment due to the blockage of the Eustachian tube [2, 3]. There has been nearly no change in these symptoms till today. This condition has a reference in modern literature due to the works of Schwartz in 1952. Joshi was the first to describe this condition in India in 1952 and he coined the name ‘oral submucous fibrosis’ (4). The aetiological studies on this condition still remain obscure. Various reasons have been put forth as the predisposing factors, some of which are capsaicin, betel nut alkaloids, hypersensitivity, autoimmunity, genetic predisposition and perhaps malnutrition (2), (3).

Neoplasm is a multistage disease process, where a single cell can develop from an otherwise normal tissue into malignancy that can eventually destroy the very base. The series of cellular and molecular changes that occur through the development of cancers can be mediated by a diversity of endogenous and other free radicals which have long been known to be mutagenic. Further, these free radicals have more recently emerged as the mediators of the other phenotypic and genotypic changes that can lead from mutation to neoplasia. It has therefore been felt that free radicals may have a major contribution to the cancer development in humans (4), (5).

The role of free radicals in the various oxidation processes in the body has led to the identification of antioxidants in inhibiting and reversing the disease process. The mode of action of antioxidants may involve the stimulation of the immune system or direct action on the tumour cells. They are antimutagenic and antimitogenic and operate by the common mechanism of breaking the free radical chain reactions (6).

Lycopene is a safe antioxidant of utmost importance. Lycopene is a bright red carotene and carotenoid pigment and a phytochemical found in tomatoes and other red fruits and vegetables, such as red carrots, watermelons and papayas. Preliminary research has shown an inverse correlation between the consumption of tomatoes and cancer risk. It has been shown to have several potent anticarcinogenic and antioxidant properties and has demonstrated profound benefits in precancerous lesions such as leukoplakia. Lycopene exhibits the highest physical quenching rate constant with singlet oxygen (7).

OSMF has a similarity in behaviour and malignant changes to other premalignant lesions of the oral cavity. So, it has been felt that the disease process in OSMF also could be reversed and inhibited by the use of anti oxidants, as is observed in other pre malignant lesion therapies of the oral cavity (8), (9).

The main aim and objective of this study was to evaluate the clinical and histopathological response of OSMF to the antioxidant, lycopene.

Materials and methods: The material for this study constituted 12 adult patients selected from the regular outpatients who attendedthe Department of Dentistry, Hassan Institute of Medical Sciences, Hassan, Karnataka, India, who were clinically diagnosed as having oral submucous fibrosis.

The history and the clinical findings of each patient who were recorded as having submucous fibrosis was diagnosed by the presence of pallor of the oral mucous membrane, presence of palpable fibrous bands, lack of pliability of the oral mucous membrane and limited mouth opening. Consent was taken from each participant. The required investigations are carried out. All the patients were biopsied, both to confirm the diagnosis and to reveal any dysplasia which was present.

All the selected cases who were in the habit of chewing arecanuts, were advised to give up the habit and they were kept under observation for six weeks. No improvement was observed and later, the treatment was instituted.

Examination of the oral cavity was carried out under artificial light. Any abnormality and variation in the colour and the pliability of the oral mucosa was noted. The inter arch distance was measured in millimeters by using a graduated calipers kept between the incisal tips of the upper and lower central incisor with the mouth opening being maximum. The above measurement was taken bimonthly and it was recorded.

An incisional biopsy was performed in each patient at entry. The biopsies were taken from the buccal mucosa at the level of the cervical margin of the lower second molar, so as to avoid frictional keratosis at the level of the occlusal line.

In this study, the following parameters were evaluated: 1. Clinical parameters: a) Symptomatic relief in the form of absence of burning sensation in the mouth and spontaneous healing of the ulcers when present. b) Change in the colour of the mucosa and its texture. c) Improvement in mouth opening

2. Histological parameters: a) Surface mucosa showing non keratinization b) Rete-ridge formation with an increase in the epithelial layer c) Less infiltration of the inflammatory cells, mainly polymorphs, in the connective tissue.

Study Design
After the clinical examination, investigation and biopsy confirmed the diagnosis as oral submucous fibrosis, each patient was given the commercially available anti-oxidant which was used in this study, LycoRed (Jagsonpal Pharmaceutical Company, New Delhi, India) capsule containing 100% natural lycopene with zinc, selenium and added phytonutrients. The zinc and selenium are essential for the proper assimilation of carotenes in our metabolism. This capsule was given orally, twice daily for 3 months, where each capsule contained 2000 μg of lycopene. The responding patients continued to take lycopene for an additional 3 months. The responses were assessed clinically and by bimonthly evaluation with examination and photographs. The increase in the mouth opening was measured by using graduated calipers.

All the biopsies were reviewed by a single pathologist at the entry level before the start of the treatment. After 3 months of treatment, a second biopsy was done as close as possible to the initial site and a histological evaluation was performed to confirm a clinical response.

Several factors should be considered when assessing these trials.

1. Choice of the agent: Although oral submucous fibrosis is premalignant, only chemo-preventive agents with minimal toxicity are justifiable for clinical testing (such as the antioxidant, lycopene)

2. Assessment response: It is difficult to apply oral photography consistently. The response can be best assessed, based on the examination of the condition by two examiners who can independently agree on a category with photographs as a helpful adjunct (Table/Fig 1), (Table/Fig 2), (Table/Fig 3), (Table/Fig 4). The increase in the mouth opening may be measured by using calipers (Table/Fig 5),(Table/Fig 6),(Table/Fig 7), (Table/Fig 8).

3. Evaluation of the histopathological response: The comparison of the pre treatment biopsy with a biopsy specimen obtained after 3 to 6 months of the treatment was done. This is done to confirm a clinical response where a biopsy may show whether normalization has also occurred at the microscopic level (Table/Fig 9),(Table/Fig 10).

4. Effect of habit changes on the response: Patients who were in the habit of chewing betel nuts alone or in combination, were strictly advised to give up the habit and were kept under observation for six weeks. No improvement was observed and later, the treatment was initiated with lycopene.

5. Study duration: At least 3 months of treatment should be planned. The response can occur 3 to 6 months after the beginning of the treatment.

All the patients were grouped into four categories, based on the clinical and histological criteria (as described by Khanna J.N (10)(11)(12):

Group1: Very early case
Clinical: A burning sensation in the mouth was reported. Acute ulceration and recurrent stomatitis were seen. The mouth opening was normal.

Histological: A fine fibrillar collagen network interspersed with marked oedema. Young fibroblasts were seen, with abundant cytoplasm. Inflammatory cells mainly polymorphonuclear leucocytes were seen. The epithelium was essentially normal.

Group 2: Early cases
Clinical: The limitation of mouth opening was evident. The soft palate and the faucial pillars were the areas primarily affected. The buccal mucosa appeared to be mottled, with varying degrees of fibrosis. Histological: The results showed varing degrees of keratinisation, atropy of the epithelium and juxta epithelial earely hyalinization, decrease in fibroblasts and increase in fibrocytes. There was a dense infiltration of mixed inflammatory cells predominantly polymorphs.

Group 3: Moderately advanced cases
Clinical: Trismus was evident, ranging from 9mm to 15mm. The buccal mucosa was pale and was firmly attached to the underlying tissues. The vertical fibrous bands were palpated in the premolar area.

Histological: The results showed a marked reduction of the thickness of the epithelium and basal layer proliferation. The reteridges showed flattening and intercellular oedema in the focal areas. All the cases showed varing degrees of keratinization. The connective tissue showed moderate hyalinization with amorphous changes. Thick collagen bundles were seen, which were separated by slight oedema and they were infiltrated by lymphocytes and plasma cells, also occasionally by eosinophils.

Group 4: Advanced cases with pre malignant and malignant changes
Clinical: Trismus was severe . The mouth opening varied from 2-9 mm. The uvula was involved .The tonsils which were compressed could have been associated with leukoplakia and squamous cell carcinoma.

Histological: The collagen hyalization had a smooth sheath which eliminated all evidence of the individual bundles. Fibroblasts were markedly absent within the hyalinized zone. There was total loss of the epithelial rete pegs. There was mild to moderate atypia. Extensive degeneration of the muscle fibers was seen.

In our study, the groups 2 and 3 were selected: group 1 had normal mouth opening and in group 4, the disease was advanced, with malignant changes. Hence, the groups 1 and 4 were omitted.

Results: The responses are assessed clinically by bi-monthly evaluation with examination and photography. The responses were classified as:

1. Complete
• When the colour of the mucosa turned from blanched white to normal pale pink. • When there was a definite improvement in the burning sensation, which reduced to an appreciable extent. • When there was an increase in the mouth opening which ranged from 2mm to 3mm. 2. Partial • When there was a partial improvement in the above said signs and symptoms and the mouth opening was increased by 0.4mm to 1mm. 3. Stable • When there was no response and no improvement. 4. Disease progression • When there was a progressive increase in the signs and symptoms in spite of having undergone the treatments.

Patient characteristics: A total of 12 eligible patients were included in this study, 3 females and 9 males. The age group of the study sample ranged from 18 to 52 years. Among the 12 patients, 6 were in the habit of pan chewing. Two patients were in the habit of smoking. Four patients were using pan with tobacco and slaked lime. No one was alcoholic. Four patients were using chillies in excess, whereas 8 patients had a normal intake of chillies. Seven patients were in group II (early cases). Their mouth opening ranged between 15mm to 35mm. Five patients were in group III (moderately advanced) and their mouth opening was between 9mm to14mm [Table./Fig-13 and 14].

Post Treatment Evaluation: The number of cases in which the following improvement was seen after the treatment with lycopene, 2000 μg twice daily for 3 months, is shown in [Table/Fig-13 & 14].The responses were assessed clinically and histologically as described below:

IN GROUP II (EARLY CASES)

Clinical evaluation
1. Showed a mild degree of inflammatory infiltration in the connective tissue (Table/Fig 10). 2. The epithelial changes were more appreciable where in, they showed rete ridge formation with an increase in the epithelial layer. 3. In few cases, the surface mucosa almost showed a loss of keratinization.

IN GROUP III (MODERATELY ADVANCED CASES)

Clinical Evaluation:
1. Disappearance of the burning sensation was observed. 2. Healing of the ulcers when present, was noticed. 3. There was a definite change in the colour of the mucosa from pale blanching to normal pink (Table/Fig 3),(Table/Fig 4). 4. There was improvement in the mouth opening, ranging from 1mm to 3mm (Table/Fig 7),(Table/Fig 8).

Histological Evaluation 1. Showed a decrease in the keratinization layer. 2. An increase in the number of layers which reformed the rete ridges, with basal cell proliferation were seen [Table/Fig-12].

RESPONSE DATA
Often, the first change which was noted was a decrease in the burning sensation and the appearance of the normal pink colouration of the mucosa. Subsequently, a definite reduction in the burning sensation and an increase in the mouth opening were noted. In a majority of the responding patients, the first signs of the response were visible within the second and third follow up visits i.e. 4 patients at 1 month, 5 at 1½ months and 3 at 2 months. See [Table/Fig-15].

Discussion

Oral submucous fibrosis (OSMF) is a disease associated with the habit of betel nut chewing and it is characterized by extensive collagen deposition in the soft tissues of the mouth (8). Various researchers, in their studies on the mutagenic properties of arecanuts have found that the constituents and the extracts of the nuts cause chromosomal aberrations and DNA damage(8). In the review of literature, starting from Pay Master, 1959 to J.N. Khanna, 1995, every one is of the opinion that submucous fibrosis is a precancerous condition with a malignant transformation rate which varies from 3 to 7.6% (9). The development of cancers can be mediated by a diversity of endogenous and environmental stimuli. Free radicals have long been known to be mutagenic. Further, these agents have more recently emerged as the mediators of the other phenotypic and genotypic changes that lead from mutation to neoplasia.

OSMF is an incurable disease. No treatment modality, either surgical or medical has been successful in completely eliminating the disease. In view of the strong relationship between oral cancer and pre cancerous lesions, chemo-prevention is said to be feasible and practicable. A safe and simple mode of treatment as described in this study, along with proper habit restriction is required in OSMF to ensure that the progression of the disease is retarded and that maximum relief is obtained by the patient.

Many authors are of the opinion that conservative treatment is preferable than the conventional ones (3). Hazardous treatments like the submucosal injections of steroids, hyaluranidase and placental extracts should be avoided. Several studies in humans have confirmed the cancer preventive nature of antioxidants. The oral intake of retinoids has a significant toxic effect on the normal tissue. A less toxic group of micronutrients are the carotenoids, which include lycopene. Its mode of action may involve stimulation of the immune system or a direct action on the tumour cells. Lycopene has been shown to inhibit hepatic fibrogenesis in LEC ratsby Kitade et al., and it may also exert a similar inhibition on the abnormal fibroblasts in submucous fibrosis. The findings of this study are in concurrence with those of another study on OSMF, which was performed by Haque et al, who reported a positive result in the OSMF cases with a therapeutic modality which was used for liver fibrosis. Lycopene also upregulates the lymphocyte resistance to stress and suppresses the inflammatory response (10).

The results of the recent studies are encouraging. The unifying mechanism which underlies these diseases is cumulative oxidative damage. So, antioxidants can influence or prevent seemingly unrelated conditions (11).

It is clear from this, that a long term maintenance treatment is necessary, if there has to be an impact on oral cancer incidence. Lycopene may be more suitable for this purpose than the more toxic retinoids. Lycopene has been shown to inhibit various types of cancers and it has been shown to have potent benefits in oral pre malignant lesions such as oral leukoplakia, where it has been reported to modulate dysplastic changes. Another point in favour of the use of lycopene for the prevention of OSMF is that it is relatively non toxic and can be easily supplemented in the diet.

This was a short term study with a small sample size and the patients in this study were advised to give up the habit of pan and betel nut chewing. As we could not have a control group due to the limited number of patients, it was felt that a long term study with a larger sample size with all the above variables being taken into consideration would be necessary to get a clear picture about the utility of the drug.

References

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Khanna JN , Andrade NN. Oral submucosal fibrosis: a new concept in surgical management. Inter J Oral and Maxillofacial Surgery. 1995;24(6):433-39.

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