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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
Original article / research
Full Version
Evaluation of Salivary Lactate Dehydrogenase Level as a Biomarker for Early Detection in Oral Cancer and Potentially Malignant Disorders: A Systematic Review and Meta-analysis
Correspondence Address :
Dr. Sunil S Mishra,
Professor and Head, Department of Oral Medicine and Radiology, Dr. DY Patil Dental College and Hospital, Dr. DY Patil Vidyapeeth, Pimpri, Pune-411018, Maharashtra, India.
E-mail: arunimasarma44@gmail.com; sunil.mishra@dpu.edu.in
Introduction: Saliva diagnostics are emerging tools which are being explored as a non invasive method for early detection of oral premalignant lesions and Oral Cancer (OC). Salivary Lactate Dehydrogenase (LDH) is one such promising biomarker which has shown potential to be utilised in future for detection of premalignant lesions and conditions. The rationale behind this systematic review was to evaluate whether salivary LDH can be considered as biomarker for OC and Oral Potentially Malignant Disorders (OPMDs).
Aim: To review the literature for levels of salivary LDH in patients with OC and OPMD.
Materials and Methods: A comprehensive search was done and this systematic review was conducted in the Department of Oral Medicine and Radiology, Dr. DY Patil Dental College and Hospital, Pimpri, Pune, Maharashtra, India, following (Preferred Reporting Items for Systematic Reviews and Meta-analyses) PRISMA guidelines. Literature search was done for the period of 10 years from 2012-2022, while the study duration was 18 months, from January 2021-July 2022. The International Prospective Register of Systematic Reviews (PROSPERO) registration Identity Document (ID) was (CRD42022366117). Electronic data was searched through the database PubMed, ScienceDirect and Cochrane Library from 2012-2022. Observational and analytical studies, original longitudinal or case-control, randomised clinical trials, prospective controlled clinical trials with the inclusion of cases diagnosed with oral leukoplakia, Oral Lichen Planus (OLP), Oral Submucous Fibrosis (OSMF), OC and having salivary LDH levels were included. The data was collected from the studies that were included based on study design, eligibility criteria, histological differentiation, collection method, LDH level and the data were subjected to meta-analysis.
Results: A total of 16 articles were included. The meta-analysis showed increased salivary LDH levels between cases with OC and Control Group (CG). The pooled estimate was 5.71 (95% CI: 3.89-7.53) with statistical significance of <0.05. In OSMF and controls the levels of salivary LDH was significantly increased. The pooled estimate was 30.38 (95% CI: 15.82-44.94) with statistical significance of <0.05. The level of salivary LDH among cases with premalignant lesions and controls was increased. The pooled estimate was 9.10 (95% CI: 3.45-14.75) with statistical significance of <0.05. In case of OLP and controls, the levels of salivary LDH were seen elevated. The pooled estimate was 6.76 (95% CI: 6.86-20.38) with no statistical significance of p-value <0.05.
Conclusion: To sum up, the results of this systematic review showed that levels of salivary LDH were higher in OC and OPMD patients than in healthy patients. Furthermore, the levels of salivary LDH are more in OC than OPMDs.
Premalignant lesion, Saliva, Salivary bionomics, Squamous cell carcinoma
The OC has been accounted as a concerning problem in many parts of the globe with highest incidence seen in Southeast Asia. Globally, 300,000 to 700,000 new cases are reported every year with mortality rate being 145,000 deaths (1). Oral and pharyngeal cancer together, is considered the sixth most common cancer in the world with highest incidence seen in males than females (1). Almost all the cases of OC are preceded by some visible changes or alterations to the oral mucosa. These alterations are in the form of either white or red lesions, with a variable risk of malignant transformation. Due to this risk, these lesions and conditions are termed as the potentially malignant disorders (2),(3).
In recent times the prevalence of OPMD has increased worldwide including conditions such as OSMF, OLP which are seen most commonly in Asian population (4). The OPMDs vary in their malignant transformation with OSMF reported to have a malignant transformation of about 4.5% to 7.6% (5). The potential for malignant transformation is generally credited to fibrosis, hypoxia and a shift to anaerobic glycolysis (6). The prevalence of OLP and other Oral Lichenoid Reactions (OLRs) in the general population is 1-2% and 2.4%, respectively (7). However, sufficient data regarding malignant transformation of different types of OLRs is lacking, but it appears that different types of graft versus host disease and oral lichenoid contact lesions have higher malignant transformation risk than drug-induced OLRs (7). As the percentage seems to be relatively high so a timely recognition of such OPMDs not only favours a decreased rate of OC but also improves the chances of survival in subjects developing OC. It has been found that the prognosis rate varies i.e. up to 80% when diagnosed at Stage-I, 65% in Stage-II and 50% when diagnosed at Stage-III or higher (8),(9).
Biopsy is generally considered as a gold standard for cancer diagnosis, but the process of biopsy has few limitations such as the method is invasive, time consuming, technique sensitive, difficult in inaccessible areas, patients with blood disorders and other systemic conditions and most importantly subjective patient compliance. Pertaining to the various challenges and disadvantages of biopsy many alternatives are used for early detection of OC. One such alternative and promising technique is the use of tumour biomarkers. LDH is one of the biomarkers which is being used in the early detection of premalignant lesions and conditions. The mechanism of increase in LDH enzyme in tissues in OPMDs and OC is in glycolytic pathway which manifests as a shift from aerobic to anaerobic glycolysis (10). However, the levels of LDH found in the healthy oral epithelium and in whole saliva are similar (4). Therefore, salivary LDH serves as early promising tool in the diagnosis of OC at its preliminary stage by acting as a diagnostic marker (11).
Saliva as a diagnostic tool can be used in the diagnosis and screening of OPMDs and OC, yet its routine usage is lacking. More studies are required to establish its correlation as biomarkers for early detection of OC. The rationale behind this systematic review was to evaluate whether salivary LDH can be considered as biomarker for OC and OPMDs.
Objectives
To review the literature for levels of salivary LDH in patients with OC and OPMD
PICO
• Patient population: Patients with oral leukoplakia, OLP, OSMF, OC
• Intervention: Salivary LDH level
• Outcome: Potential biomarker for early diagnosis of OC and OPMDs.
A comprehensive search was done and this systematic review was conducted in the Department of Oral Medicine and Radiology, Dr. DY Patil Dental College and Hospital, Pimpri, Pune, Maharashtra, India, following PRISMA guidelines. The present systematic review was prepared by following PRISMA guidelines (Table/Fig 1). Literature search was done for the period of 10 years from 2012-2022, while the study duration was 18 months, from January 2021-July 2022. The systematic review was registered before commencing the study with (PROSPERO registration id CRD42022366117).
Inclusion criteria: Observational and analytical studies, original longitudinal or case-control studies published in scientific journals between 2012-2022 were included. Studies done to assess the Salivary LDH levels in patients with OC or OPMD when compared to a healthy CG, studies in English or studies in other languages where translation to English was possible and studies using Unstimulated Whole Saliva (UWS) or Stimulated Whole Saliva (SWS), which could be used to detect salivary LDH levels which must be presented in IU/L or μ/L units and could be analysed by spectrophotometers, autoanalysers, semi-autoanalysers, and standardised kits, were included.
Exclusion criteria: Review articles, animal studies, case reports, commentaries, and letters to the editor. Studies that did not have full text, different languages and studies, where in patients have been treated for OC or OPMDs and studies in which salivary LDH values were not reported, were excluded.
Information sources: Electronic data was searched through the database PubMed, ScienceDirect and Cochrane Library from 2012-2022. Manual electronic search was done and articles were handpicked. Language barriers such as English were applied. All electronic strategies had similar title/abstract and MeSH terms and texts. Search terms for PubMed were: “Leukoplakias Oral”, “Oral Submucous Fibrosis” and “Mouth Neoplasm”.
Data collection: The data was collected from the studies that were included based on the author’s name, study design, eligibility criteria, age, histological differentiation, collection method, LDH level. Two independent authors screened the initial titles and abstracts to find all the eligible studies. All differences of opinions were discussed and resolved.
Study selection and data extraction: The data was extracted based on the eligibility criteria by two independent authors after assessing the titles and abstracts of potential studies identified by the search strategy. After obtaining the full texts of the articles they were screened by reading the whole article by the first author. Whenever there was uncertainity regarding any study to be eligible for inclusion, the problem was resolved by discussing it with the second author.
Assessment of bias in included studies: Newcastle-Ottawa scale modified for cross-sectional analytical studies was used to assess appropriateness of research design, recruitment strategy, response rate, representativeness of sample, objectivity/reliability of outcome determination, power calculation provided, and appropriate statistical analysis (12). This tool consists of three domains namely, selection, comparability and outcome assessment. Maximum score of nine could be assigned to each study. According to this tool, a score of >7 implies good quality, score 5-6 implies moderate quality and score <4 implies poor quality (Table/Fig 2) (4),(5),(6),(7),(9),(11),(13),(14),(15),(16),(17),(18),(19),(20),(21),(22). Among the sixteen included studies, six studies showed good quality (score of >7), nine showed moderate quality (score of 5-6) and one study showed poor quality (score <4). In the selection domain, all the studies included population that truly represented the target population. A validated measurement tool (Newcastle-Ottawa scale) was used for ascertainment of exposure in five studies (7),(11),(12),(15),(21).
After screening the studies for 364 titles, 245 studies were excluded. The abstract of the remaining 18 articles was included for the full text review. After reading full text articles, two articles were excluded. Total of 16 articles were included for analysis. All the studies were cross-sectional analytical studies published between 2012-2022. Among all the studies, there was no mention of age group in three of the 16 selected studies (11),(13),(14).
Nine studies evaluated salivary LDH levels between cases with OC and CG (5),(7),(11),(14),(15),(17),(19),(20),(21). The pooled estimate was 5.71 (95% CI 3.89-7.53). The cumulative difference between case and CG was 5.7, implying that salivary LDH levels were more in case group as compared to controls. Random effects model was used because I2 indicates heterogeneity >50%. These results were statistically significant (p-value <0.05) (Table/Fig 3). Four studies evaluated salivary LDH levels among cases with OSMF and controls (4),(5),(6),(17). The pooled estimate was 30.38 (95% CI: 15.82-44.94). The cumulative difference between case and CG was 30.38, implying that salivary LDH levels were more in case group as compared to controls. Random effects model was used because I2 >50%. These results were statistically significant (p-value <0.05) (Table/Fig 4).
Three studies evaluated salivary LDH levels among cases with premalignant lesions and controls (4),(20),(22). The pooled estimate was 9.10 (95% CI: 3.45-14.75). The cumulative difference between case and CG was 9.1, implying that salivary LDH levels were more in case group as compared to controls. Random effects model was used because I2 >50%. These results were statistically significant (p-value <0.05) (Table/Fig 5). Two studies evaluated salivary LDH levels among cases with OLP and controls. The pooled estimate was 6.76 (95% CI: 6.86-20.38) (7),(19). The cumulative difference between case and CG was 6.76, implying that salivary LDH levels were more in case group as compared to controls. Random effects model was used because I2 >50%. These results were not statistically significant (p-value >0.05) (Table/Fig 6).
The present systematic review showed that the salivary LDH levels are higher in OC and OPMD patients than in healthy patients. However, the elevated salivary LDH levels were more significant in OC than OPMD (Table/Fig 7) (4),(5),(6),(7),(9),(13),(14),(15),(16),(17),(18),(19),(20),(21),(22).
The LDH is an enzyme present in any tissue and body fluid. It seems that various epithelial changes results in change of levels of salivary LDH levels. The positive correlation of which were shown by all the studies [4-7,11,14,15,17-22]. The levels of LDH was increased proportionally in relation to the differentiation grade of OC, showing higher values when OC was poorly differentiated in comparison with moderately or well-differentiated tumours (11),(14),(15). Elevated level of salivary LDH in OSMF has been reported in six studies compared to that of CG (4),(5),(6),(9),(17),(18) and two studies showed lower level of LDH compared to that of OC (5),(16). In case of OL, eight studies showed elevated level of LDH [4,11,13,14,16,18,20,21] and seven studies showed lower level of LDH compared to that of OC (4),(11),(13),(16),(19),(20),[(21). Only one study was conducted on OLP and OLR, and the level of LDH was noticeably higher in the OSCC group followed by the OLR, OLP and CGs (7). Three studies evaluated levels of LDH in tobacco users without PMD but the results were not significant (13),(17),(18). Only one study compared the level of LDH with the stages of OSMF. The result showed a non significant difference in Stage-III than Stage-II (6).
Several LDH measurement methods were used in the included studies, out of which spectrophotometer was most commonly used. Only one study used agarose gel electrophoresis method (16). Various LDH kits were used for analysis, out of which three studies did not specify the kit [5,14,15]. Salivary LDH is an epithelium-dependent enzyme any tissue alterations which could compromise the results of the test. Only two studies selected patients subjected for ultrasonic scaling two weeks prior to sample collection [15,18]. Hence, in future studies these cofounding factors should be pointed out, so as to avoid the risk of bias.
Both stimulated and unstimulated saliva were used, two studies had used stimulated saliva [6,7]. While, 12 studies used unstimulated saliva. As the enzymes levels in saliva vary at different time periods and on its precollection measures. Most studies showed collection time period in the morning, from 7-12 am. Seven out of 14 studies did not specify the saliva collection time interval [9,13,16-19,22]. Therefore, in future studies some protocolised measures should be followed to ensure the reliability of the results. Results from the present review showed that most of the studies were being carried out in South East Asian countries. Henceforth, more studies are needed to be carried out in other developed and developing countries, so that a precise cut-off value can be established.
Limitation(s)
Only PubMed, web of science, Scopus and Cochrane databases were searched. The articles published in English language were only considered with duration of 10 years. Also, the confounding factors were not considered for the variation analysis.
In the present systematic review and meta-analysis, authors found that the salivary LDH levels are higher in OC and OPMD patients than in healthy patients. However, the elevated salivary LDH levels were more significant in OC than OPMD. In future, standardised protocol should be developed in terms of saliva collection method and analysis in perspective longitudinal studies having a large sample size. Studies should be conducted in different demographic regions and variation in terms of confounding conditions should be considered and analysed.
DOI: 10.7860/JCDR/2023/60586.18162
Date of Submission: Oct 05, 2022
Date of Peer Review: Dec 07, 2022
Date of Acceptance: Apr 01, 2023
Date of Publishing: Jul 01, 2023
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? No
• Was informed consent obtained from the subjects involved in the study? No
• For any images presented appropriate consent has been obtained from the subjects. No
PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Oct 06, 2022
• Manual Googling: Feb 22, 2023
• iThenticate Software: Mar 24, 2023 (8%)
ETYMOLOGY: Author Origin
EMENDATIONS: 8
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