Displaying all 13 publications

Abstract:
Sort:
  1. Sathasivam HP, Saw CL, Lau SH
    BMC Oral Health, 2021 03 18;21(1):129.
    PMID: 33736630 DOI: 10.1186/s12903-020-01365-3
    BACKGROUND: Malignant odontogenic tumours are extremely rare tumours occurring within the jaws. Our study was performed to determine the demographic and clinico-pathological features of malignant odontogenic tumours amongst a multi-ethnic Asian population.

    METHODS: This was a retrospective cross-sectional study of malignant odontogenic tumours diagnosed at the Institute for Medical Research, Malaysia, from 2009 to 2019. All cases were independently reviewed and reclassified following the criteria set out in the latest edition of the World Health Organization 2017 reference text. Demographic and clinico-pathological data were recorded for each case.

    RESULTS: Twenty-four cases of malignant odontogenic tumours were identified. The patients' age ranged from 16 to 79 years with the mean age at diagnosis being 50.8 years (SD = 16.18). There was a male predominance (66.7%) in this cohort of patients. The ethnic distribution appeared to reflect the Malaysian population with most cases seen amongst the Malay ethnic group (66.7%). Ameloblastic carcinoma was the most frequently diagnosed malignant odontogenic tumour (45.8%) and was also predominantly seen in males (90.9%). All patients with clear cell odontogenic carcinoma were females. There was no obvious sex predilection in primary odontogenic carcinoma not otherwise specified (NOS). The mandible (79.2%) was more frequently involved compared to the maxilla.

    CONCLUSIONS: Diagnosis and management of malignant odontogenic tumours are challenging due to the rarity of these tumours. Our study has elucidated the clinico-pathological features of malignant odontogenic tumours seen in a multi-ethnic Asian population.

  2. Sathasivam HP, Davies GR, Boyd NM
    Head Neck, 2018 Jan;40(1):46-54.
    PMID: 29149496 DOI: 10.1002/hed.24907
    BACKGROUND: Osteoradionecrosis of the jaw (ORNJ) is a well-recognized complication of radiotherapy. The purpose of this study was to assess predictive factors for the development of ORNJ.

    METHODS: A retrospective study of 325 patients with head and neck squamous cell carcinoma (HNSCC) treated at one institution between January 1, 1999, and December 31, 2008, was conducted. Outcome measure was the presence/absence of ORNJ. Time to event was recorded and Cox proportional hazard regression analysis was used to determine statistically significant predictive factors.

    RESULTS: Fifty-nine patients had ORNJ. Statistical analysis using Cox regression analysis identified several statistically significant variables: dentoalveolar surgery; peri-resective surgery of the jaw; continued tobacco usage after radiotherapy, diabetes mellitus type 2 (DM2); and total radiation dose.

    CONCLUSION: Patients at greater risk of developing ORNJ can be identified and measures can be instituted to reduce its incidence and expedite management when it does occur.

  3. Sathasivam HP, Sloan P, Thomson PJ, Robinson M
    J Oral Pathol Med, 2022 Feb;51(2):180-187.
    PMID: 34797585 DOI: 10.1111/jop.13262
    INTRODUCTION: Clinical management of oral potentially malignant disorders relies on accurate histopathological assessment of the presence and grade of oral epithelial dysplasia. While adjunctive laboratory tests have provided useful prognostic information, none are in widespread clinical use. This study was performed to assess the clinical utility of two contemporary oral epithelial dysplasia grading systems.

    METHODS: Patients were identified from a clinical database. Oral epithelial dysplasia grading was performed by three oral and maxillofacial pathologists blinded to clinical outcome using the WHO 2017 system and a binary classification. The primary outcome measure was the development of oral squamous cell carcinoma, termed 'malignant transformation'.

    RESULTS: One hundred thirty-one cases satisfied the inclusion criteria, of which 23 underwent malignant transformation. There was substantial inter-rater agreement between the study pathologists for both grading systems, measured using kappa statistics (κ = 0.753 - 0.784). However, there was only moderate agreement between the consensus WHO 2017 dysplasia grade for the study against the original grade assigned by a pool of six pathologists in the context of the clinical service (κ = 0.491). Higher grade categories correlated with an increased risk of developing cancer using both grading systems.

    CONCLUSION: This study demonstrates that the WHO 2017 and binary grading systems are reproducible between calibrated pathologists and that consensus reporting is likely to improve the consistency of grading. The WHO and binary systems were prognostically comparable. We recommend that institutions implement consensus oral epithelial dysplasia grading and prospectively audit the effectiveness of risk stratifying their patients with oral potentially malignant disorders. (249 words).

  4. Mathew R, Sathasivam HP, Mohamednor L, Yugaraj P
    BMC Oral Health, 2023 Mar 08;23(1):132.
    PMID: 36890517 DOI: 10.1186/s12903-023-02780-y
    BACKGROUND: Orthodontic treatment is a time-consuming and highly technique-sensitive clinical procedure. A patient's comprehension and compliance with oral hygiene instructions and appliance maintenance are critical to the success of orthodontic treatment. This study was performed to assess the knowledge, attitude and practice of patients seen at government orthodontic clinics in the Federal Territories of Kuala Lumpur and Putrajaya towards orthodontic treatment.

    METHODS: A validated, bilingual, self-administered questionnaire comprising fifteen questions across the domains of Knowledge, Attitude and Practice was used and responses were assessed with 3 responses; one correct, one incorrect and one reflecting uncertainty. 507 patients from five orthodontic centres participated in this study. Data was analysed using SPSS. Continuous data was summarised as mean and standard deviation or median and inter-quartile range, as appropriate. Categorical data was summarised as frequency and percentage, then univariable analysis was carried out with Pearson's chi-square test or Fisher's exact test, as appropriate.

    RESULTS: The mean age of respondents was 22.5 years (SD ± 2.8). A majority of respondents were female (64.1%) and from the lowest income bracket or B40 group (71%). Overall, for the knowledge domain, a majority of the respondents got all questions correct. 69.4% of patients were aware that incomplete treatment could lead to worsening of their malocclusion. 80.9% of respondents were aware of the need for a retainer upon completion of their orthodontic treatment. For the attitude section, 64.7% felt that they had to wait a very long time to see the orthodontist. In the Practice domain, the majority only got two of the five questions correct. Only 39.8% of respondents made an effort to alter dietary habits all of the time. In general, females and those with tertiary education fared better for all three domains.

    CONCLUSIONS: The orthodontic patients in the Federal Territories of Kuala Lumpur and Putrajaya possess good knowledge about their treatment however their attitude and orthodontic related practices need to be improved.

  5. Sathasivam HP, Nayar D, Sloan P, Thomson PJ, Odell EW, Robinson M
    J Oral Pathol Med, 2021 Feb;50(2):200-209.
    PMID: 33151583 DOI: 10.1111/jop.13121
    BACKGROUND: Oral potentially malignant disorders are a clinical conundrum as there are no reliable methods to predict their behaviour. We combine conventional oral epithelial dysplasia grading with DNA ploidy analysis to examine the validity of this approach to risk assessment in a cohort of patients with known clinical outcomes.

    METHODS: Sections from diagnostic biopsies were assessed for oral epithelial dysplasia using the WHO grading system, and DNA ploidy analysis was performed using established methods. Patients reviewed for a minimum of 5 years who did not develop oral squamous cell carcinoma were classified as "non-transforming" cases. Patients that developed oral squamous cell carcinoma ≥ 6 months after the initial diagnostic biopsy were classified as having "malignant transformation."

    RESULTS: Ninety cases were included in the study. Seventy cases yielded informative DNA ploidy results. Of these 70 cases, 31 progressed to cancer. Oral epithelial dysplasia grading and DNA ploidy status were both significantly associated with clinical outcome (P 

  6. Sathasivam HP, Casement J, Bates T, Sloan P, Thomson P, Robinson M, et al.
    J Oral Pathol Med, 2021 Jan;50(1):60-67.
    PMID: 32740996 DOI: 10.1111/jop.13090
    BACKGROUND: A large number of oral squamous cell carcinomas (OSCCs) are believed to be preceded by oral potentially malignant disorders (OPMD) that have an increased likelihood of malignant transformation compared to clinically normal mucosa. This study was performed to identify differentially expressed genes between OPMDs that underwent malignant transformation (MT) and those that did not, termed "non-transforming" (NT) cases.

    METHODS: Total RNA was extracted from formalin-fixed paraffin-embedded tissue biopsies of 20 OPMD cases with known clinical outcomes (10 MT vs. 10 NT). Samples were assessed for quantity, quality and integrity of RNA prior to sequencing. Analysis for differential gene expression between MT and NT was performed using statistical packages in R. Genes were considered to be significantly differentially expressed if the False Discovery Rate corrected P-value was  1.90). Analysis of RNA-Sequencing outputs revealed 41 genes (34 protein-coding; 7 non-coding) that were significantly differentially expressed between MT and NT cases. The log2 fold change for the statistically significant differentially expressed genes ranged from -2.63 to 2.48, with 23 protein-coding genes being downregulated and 11 protein-coding genes being upregulated in MT cases compared to NT cases.

    CONCLUSION: Several candidate genes that may play a role in malignant transformation of OPMD have been identified. Experiments to validate these candidates are underway. It is anticipated that this work will contribute to better understanding of the etiopathogenesis of OPMD and development of novel biomarkers.

  7. Sathasivam HP, Kist R, Sloan P, Thomson P, Nugent M, Alexander J, et al.
    Br J Cancer, 2021 Aug;125(3):413-421.
    PMID: 33972745 DOI: 10.1038/s41416-021-01411-z
    BACKGROUND: This study was undertaken to develop and validate a gene expression signature that characterises oral potentially malignant disorders (OPMD) with a high risk of undergoing malignant transformation.

    METHODS: Patients with oral epithelial dysplasia at one hospital were selected as the 'training set' (n = 56) whilst those at another hospital were selected for the 'test set' (n = 66). RNA was extracted from formalin-fixed paraffin-embedded (FFPE) diagnostic biopsies and analysed using the NanoString nCounter platform. A targeted panel of 42 genes selected on their association with oral carcinogenesis was used to develop a prognostic gene signature. Following data normalisation, uni- and multivariable analysis, as well as prognostic modelling, were employed to develop and validate the gene signature.

    RESULTS: A prognostic classifier composed of 11 genes was developed using the training set. The multivariable prognostic model was used to predict patient risk scores in the test set. The prognostic gene signature was an independent predictor of malignant transformation when assessed in the test set, with the high-risk group showing worse prognosis [Hazard ratio = 12.65, p = 0.0003].

    CONCLUSIONS: This study demonstrates proof of principle that RNA extracted from FFPE diagnostic biopsies of OPMD, when analysed on the NanoString nCounter platform, can be used to generate a molecular classifier that stratifies the risk of malignant transformation with promising clinical utility.

  8. Martinez RC, Sathasivam HP, Cosway B, Paleri V, Fellows S, Adams J, et al.
    Br J Oral Maxillofac Surg, 2018 May;56(4):332-337.
    PMID: 29628167 DOI: 10.1016/j.bjoms.2018.03.011
    Our aim was to examine the clinicopathological features of squamous cell carcinoma (SCC) of the oral cavity and oropharynx in a group of young patients who were dignosed during a 15-year period (2000-2014). Patients' clinical details, risk factors, and survival were obtained from medical records. Formalin-fixed, paraffin-embedded, tissue was tested for high-risk human papillomavirus (HPV). The results were compared with those of a matching group of older patients. We identified 91 patients who were younger than 45 years old, and the 50 youngest patients were studied in detail. The male:female ratio was 2:1, with more tumours located in the oral cavity than in the oropharynx (35 compared with 15). HPV-related SCC was restricted to the oropharynx. When matched for site, stage and HPV status, five-year overall survival was similar in young and matched older patients (log-rank test, p=0.515). Our findings suggest that young patients with oral SCC have a disease profile similar to that of older patients with the condition. It is plausible that prognostic information generally available for oral cancers is applicable to young patients with the disease.
  9. Sathasivam HP, Ismail S, Ahmad AR, Basri NN, Muhamad H, Mohd Tahir NF, et al.
    PMID: 27727102 DOI: 10.1016/j.oooo.2016.08.005
    This study was performed to obtain the clinicodemographic data regarding patients with trigeminal neuralgia (TN) treated at oral-maxillofacial medicine clinics, as there is a paucity of such information in the Asian setting.
  10. Lee HM, Sia APE, Li L, Sathasivam HP, Chan MSA, Rajadurai P, et al.
    Sci Rep, 2020 04 09;10(1):6115.
    PMID: 32273550 DOI: 10.1038/s41598-020-63150-0
    Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we identify for the first time a role for monoamine oxidase A (MAOA) in NPC. MAOA is a mitochondrial enzyme that catalyzes oxidative deamination of neurotransmitters and dietary amines. Depending on the cancer type, MAOA can either have a tumour-promoting or tumour-suppressive role. We show that MAOA is down-regulated in primary NPC tissues and its down-regulation enhances the migration of NPC cells. In addition, we found that EBV infection can down-regulate MAOA expression in both pre-malignant and malignant nasopharyngeal epithelial (NPE) cells. We further demonstrate that MAOA is down-regulated as a result of IL-6/IL-6R/STAT3 signalling and epigenetic mechanisms, effects that might be attributed to EBV infection in NPE cells. Taken together, our data point to a central role for EBV in mediating the tumour suppressive effects of MAOA and that loss of MAOA could be an important step in the pathogenesis of NPC.
  11. Yap LF, Lai SL, Rhodes A, Sathasivam HP, Abdullah MA, Pua KC, et al.
    Infect Agent Cancer, 2018;13:21.
    PMID: 29942347 DOI: 10.1186/s13027-018-0193-6
    Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been rising in Western countries and this has been attributed to human papillomavirus (HPV) infection. p16 expression is a marker for HPV infection and p16 positive OPSCC is now recognized as a separate disease entity. There are only limited data available regarding HPV-related OPSCC in Asian countries and no data from Malaysia.

    Methods: We identified 60 Malaysian patients with OPSCC over a 12-year period (2004-2015) from four different hospitals in two major cities, Kuala Lumpur and Penang. The detection of HPV was carried out using p16 immunohistochemistry and high risk HPV DNA in situ hybridisation.

    Results: Overall, 15 (25%) tumours were p16 positive by immunohistochemistry, 10 of which were also positive for high risk HPV DNA by in situ hybridisation. By comparison, a matched cohort of UK patients had a p16 positive rate of 49%. However, between 2009 and 2015, where cases were available from all four hospitals, 13 of 37 (35%) cases were p16 positive. In our Malaysian cohort, 53% of patients were of Chinese ethnicity and 80% of the p16 positive cases were found in these patients; no Indian patients had p16 positive disease, despite representing 35% of the total cohort.

    Conclusion: The proportion of OPSCCs associated with HPV in Malaysia appears to be lower than in European and American cohorts and could possibly be more prevalent amongst Malaysians of Chinese ethnicity. Further, our data suggests that the burden of HPV-related OPSCC could be increasing in Malaysia. Larger cross-sectional studies of Malaysian patients are required to determine the public health implications of these preliminary findings.

  12. Sathasivam HP, Chew SYL, Kim WR, Saw CL, Tan LP, Tengku Din TADA, et al.
    Clin Otolaryngol, 2022 Feb 16.
    PMID: 35170855 DOI: 10.1111/coa.13917
    1. Majority of adolescent nasopharyngeal carcinoma (NPC) patients present with advanced locoregional disease. 2. The ethnic distribution of patients with adolescent NPC could be different from that of adult NPC suggesting a possible difference in aetiopathogenesis. 3. The late presentation of adolescent NPC underlies the importance of recognizing the clinical presentation and characteristics of this cancer.
  13. Sathasivam HP, Davan SP, Chua SM, Rohaizat RF, Japar R, Zakaria Z, et al.
    Infect Agent Cancer, 2023 Nov 28;18(1):74.
    PMID: 38017493 DOI: 10.1186/s13027-023-00557-0
    BACKGROUND: In addition to the conventional aetiologic agents of oropharyngeal squamous cell carcinoma (OPSCC) such as tobacco usage, alcohol consumption and betel quid usage, it has been established that a proportion of OPSCC are driven by persistent oncogenic human papillomavirus (HPV) infections. Currently, there is a lack of data on the burden of HPV- associated OPSCC in Asian countries including Malaysia.

    METHODS: A cross-sectional multicentre study with tissue analysis of Malaysian patients diagnosed with primary OPSCC within a five-year period, from 2015 to 2019 between 01/01/2015 to 31/12/2019 was undertaken. Determination of HPV status was carried out using p16INK4a immunohistochemistry on tissue microarrays constructed from archived formalin-fixed paraffin-embedded tissue.

    RESULTS: From the cases identified, 184 cases had sufficient tissue material for analysis. Overall, median age at diagnosis was 63.0 years (IQR = 15) and 76.1% of patients were males. In our cohort, 35.3% of patients were Indian, 34.2% were Chinese, 21.2% were Malay and 9.2% were from other ethnicities. The estimated prevalence of HPV-associated OPSCC in our cohort was 31.0% (CI 24.4-38.2%). The median age for the HPV-associated OPSCC sub-group of patients was not significantly lower than the median age of patients with HPV-independent OPSCC. More than half of HPV-associated OPSCC was seen in patients of Chinese ethnicity (54.4%). Patients with HPV-associated OPSCC had a much better overall survival than patients with HPV-independent OPSCC (Log rank test; p 

Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links