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  1. Abukhder M, Sahovaler A, Vrakas P, McGurk M, Thavaraj S, Schilling C
    JAMA Otolaryngol Head Neck Surg, 2024 Oct 10;150(11):1021-8.
    PMID: 39388171 DOI: 10.1001/jamaoto.2024.3094
    IMPORTANCE: Frozen section (FS) analysis of sentinel nodes offers potential on-table diagnosis and treatment for occult metastasis in oral squamous cell cancer. Systematic analysis of FS during sentinel node biopsy has not been illuminated in the literature.

    OBJECTIVE: To systematically review pooled data from studies using FS analysis in evaluating sentinel nodes in patients with cT1-T2 N0 oral squamous cell cancer.

    DATA SOURCES: An academic librarian led the search of CENTRAL, CINAHL, Cochrane Database of Systematic Reviews, Embase, and MEDLINE for studies published in English between January 2000 and January 2023.

    STUDY SELECTION: Two authors independently screened cohort studies, case series, and randomized clinical trials, in which FS analysis was used to evaluate sentinel nodes in patients with cT1-T2 N0 oral squamous cell cancer.

    DATA EXTRACTION AND SYNTHESIS: Data were extracted by 2 reviewers. Reporting quality was estimated using the Diagnostic Precision Study Quality Assessment Tool. Data analysis was performed between April and July 2023, and the meta-analysis was completed using the bivariate random-effects model.

    MAIN OUTCOMES AND MEASURES: The primary outcome was the pooled sensitivity of FS sentinel node analysis. Secondary outcomes included evaluation of the FS technique, rate of occult metastasis, false-negative rate, and survival.

    RESULTS: Seventeen articles with 878 patients met the eligibility criteria. Although protocols varied, confirmatory serial step sectioning was performed in all studies. Occult metastasis was found in 263 of 878 patients (30%), and FS analysis identified 173 cases (65.8%). Following serial sectioning, an additional 90 positive results were identified, leading to 47 patients undergoing staged completion neck dissection. The pooled sensitivity of FS was 0.71 (95% CI, 0.60-0.80), the diagnostic odds ratio was 110, and the false-negative rate was 34.2%. The Cochrane Q value was 15.62 (df = 16; P = .48) and τ2 = 0.36.

    CONCLUSION AND RELEVANCE: In this systematic review and meta-analysis, evaluated studies showed various techniques, in which pooled sensitivity reached 0.71, providing a benchmark for comparison to other 1-stop approaches. Due to the high false-negative rate of approximately one-third of patients, intraoperative FS must always be supplemented by serial sectioning. On-table diagnosis remains a key objective for sentinel node biopsy, and FS detection may be improved by standardizing protocols.

  2. Patel V, Kumar M, Schache A, Hunter KD, Carey B, Rogers SN, et al.
    PMID: 39709299 DOI: 10.1016/j.oooo.2024.11.086
    OBJECTIVE: The management of large central giant cell granuloma (CGCG) can pose a significant surgical challenge. In such circumstances, the use of denosumab has been proposed with the literature reporting varying degrees of success. Histopathological assessment of CGCG post-denosumab treatment remains unknown. The current case series aims to address this lack of information and supplement the literature and the debate with evidence.

    STUDY DESIGN: The current case series is a retrospective review of historic cases accumulated from 3 different hospitals. Patients treated with denosumab for large or unresectable GCGC who subsequently underwent either surgical debulk or resection post drug treatment with histological tissue for assessment were included.

    RESULTS: A total of 4 patients were included in this study. All cases showed radiographic response. However histological assessment identified giant cells in 3 of the 4 cases, 2 of which showed clinical recurrence. All cases demonstrated irregular woven bone formation toward the periphery of the lesion suggesting partial response.

    CONCLUSIONS: The current case series provides some insight regarding the response of CGCG to denosumab and preliminary histopathological information toward the ongoing debate regarding the medical management of CGCG. (Oral Surg Oral Med Oral Pathol Oral Radiol YEAR;VOL:page range).

  3. Bates T, Kennedy M, Diajil A, Goodson M, Thomson P, Doran E, et al.
    Cancer Epidemiol Biomarkers Prev, 2016 Jun;25(6):927-35.
    PMID: 27197272 DOI: 10.1158/1055-9965.EPI-15-0949
    BACKGROUND: Oral squamous cell carcinoma (OSCC) is a global healthcare problem associated with poor clinical outcomes. Early detection is key to improving patient survival. OSCC may be preceded by clinically recognizable lesions, termed oral potentially malignant disorders (OPMD). As histologic assessment of OPMD does not accurately predict their clinical behavior, biomarkers are required to detect cases at risk of malignant transformation. Epidermal growth factor receptor gene copy number (EGFR GCN) is a validated biomarker in lung non-small cell carcinoma. We examined EGFR GCN in OPMD and OSCC to determine its potential as a biomarker in oral carcinogenesis.

    METHODS: EGFR GCN was examined by in situ hybridization (ISH) in biopsies from 78 patients with OPMD and 92 patients with early-stage (stages I and II) OSCC. EGFR ISH signals were scored by two pathologists and a category assigned by consensus. The data were correlated with patient demographics and clinical outcomes.

    RESULTS: OPMD with abnormal EGFR GCN were more likely to undergo malignant transformation than diploid cases. EGFR genomic gain was detected in a quarter of early-stage OSCC, but did not correlate with clinical outcomes.

    CONCLUSION: These data suggest that abnormal EGFR GCN has clinical utility as a biomarker for the detection of OPMD destined to undergo malignant transformation. Prospective studies are required to verify this finding. It remains to be determined if EGFR GCN could be used to select patients for EGFR-targeted therapies.

    IMPACT: Abnormal EGFR GCN is a potential biomarker for identifying OPMD that are at risk of malignant transformation. Cancer Epidemiol Biomarkers Prev; 25(6); 927-35. ©2016 AACR.

  4. 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.

  5. Yap LF, Velapasamy S, Lee HM, Thavaraj S, Rajadurai P, Wei W, et al.
    J Pathol, 2015 Feb;235(3):456-65.
    PMID: 25294670 DOI: 10.1002/path.4460
    Undifferentiated nasopharyngeal carcinoma (NPC) is a highly metastatic disease that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we have investigated the contribution of lysophosphatidic acid (LPA) signalling to the pathogenesis of NPC. Here we demonstrate two distinct functional roles for LPA in NPC. First, we show that LPA enhances the migration of NPC cells and second, that it can inhibit the activity of EBV-specific cytotoxic T cells. Focusing on the first of these phenotypes, we show that one of the LPA receptors, LPA receptor 5 (LPAR5), is down-regulated in primary NPC tissues and that this down-regulation promotes the LPA-induced migration of NPC cell lines. Furthermore, we found that EBV infection or ectopic expression of the EBV-encoded LMP2A was sufficient to down-regulate LPAR5 in NPC cell lines. Our data point to a central role for EBV in mediating the oncogenic effects of LPA in NPC and identify LPA signalling as a potential therapeutic target in this disease.
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