A 3 dimensional assessment of the depth of tumor invasion in microinvasive tongue squamous cell carcinoma. A case series analysis

BACKGROUND: Accurate assessment of the depth of tumor invasion (DI) in microinvasive squamous cell carcinoma (MISCC) of the tongue is critical to prognosis. An arithmetic model is generated to determine a reliable method of measurement of DI and correlate this with the local recurrence. MATERIAL AND METHODS: Tumor thickness (TT) and DI were measured in tissue sections of 14 cases of MISCC of the tongue, by manual ocular micrometer and digital image analysis at four reference points (A, B, C, and D). The comparison of TT and DI with relevant clinicopathologic parameters was assessed using Mann Whitney U test. Reliability of these methods and the values obtained were compared and correlated with the recurrence of tumors by Wilcoxon Signed Ranks Test. 3D reconstruction of the lesion was done on a Cartesian coordinate system. X face was on the YZ plane and Z face was on the XY plane of the coordinate system. RESULTS: Computer generated 3D model of oral mucosa in four cases that recurred showed increased DI in the Z coordinate compared to the XY coordinate. The median DI measurements between XY and Z coordinates in these cases showed no significant difference (Wilcoxon Signed Ranks Test, p = 0.068). CONCLUSIONS: The assessment of DI in 3 dimensions is critical for accurate assessment of MISCC and precise DI allows complete removal of tumor

A 3 dimensional assessment of the depth of tumor invasion in microinvasive tongue squamous cell carcinoma--A case series analysis.

BACKGROUND: Accurate assessment of the depth of tumor invasion (DI) in microinvasive squamous cell carcinoma (MISCC) of the tongue is critical to prognosis. An arithmetic model is generated to determine a reliable method of measurement of DI and correlate this with the local recurrence. MATERIAL AND METHODS: Tumor thickness (TT) and DI were measured in tissue sections of 14 cases of MISCC of the tongue, by manual ocular micrometer and digital image analysis at four reference points (A, B, C, and D). The comparison of TT and DI with relevant clinicopathologic parameters was assessed using Mann Whitney U test. Reliability of these methods and the values obtained were compared and correlated with the recurrence of tumors by Wilcoxon Signed Ranks Test. 3D reconstruction of the lesion was done on a Cartesian coordinate system. X face was on the YZ plane and Z face was on the XY plane of the coordinate system. RESULTS: Computer generated 3D model of oral mucosa in four cases that recurred showed increased DI in the Z coordinate compared to the XY coordinate. The median DI measurements between XY and Z coordinates in these cases showed no significant difference (Wilcoxon Signed Ranks Test, p = 0.068). CONCLUSIONS: The assessment of DI in 3 dimensions is critical for accurate assessment of MISCC and precise DI allows complete removal of tumor.

The Diagnostic Dilemma of a Granulomatous Gingival Enlargement.

INTRODUCTION: The oral cavity is considered an easily accessible window to the body. The mouth is frequently involved in conditions that affect multiple organs. In many instances, oral involvement precedes the appearance of many other symptoms or lesions. A complete examination of the oral cavity provides a gateway for an accurate diagnosis and precise management of many systemic conditions. Gingival enlargement is one of the varied manifestations of many systemic diseases. Here, a case report of a gingival enlargement is presented that provided information for the diagnosis of post-primary pulmonary tuberculosis. CASE PRESENTATION: A 62-year-old female presented with a persistent gingival enlargement of 6-month duration, which was non-responsive to periodontal therapy. A complete general examination with the help of additional diagnostic aids provided the diagnosis of post-primary pulmonary tuberculosis. CONCLUSION: Clinicians should be aware of the unusual forms of common diseases, which will aid in early diagnosis and proper patient management.

Overexpression of S100A4 as a biomarker of metastasis and recurrence in oral squamous cell carcinoma.

UNLABELLED: S100A4, a biomarker of epithelial mesenchymal transition (EMT), plays an important role in invasion and metastasis by promoting cancer cell motility. In oral squamous cell carcinoma (OSCC), metastasis results in 90% of cancer associated mortality. OBJECTIVE: To investigate the role of S100A4 expression as an important component of the epithelial mesenchymal transition (EMT) program in oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: S100A4 protein expression was assessed semi-quantitatively by immunohistochemistry in 47 histologically confirmed cases of oral squamous cell carcinoma (OSCC) and 10 normal oral mucosal biopsies. The association between the S100A4 overexpression and the aggressive features of OSCC were analyzed by X2 test. RESULTS: Moderate to strong cytoplasmic expression of S100A4 was observed in 30 out of 47 specimens of OSCC (64%). Overexpression of S100A4 was significantly associated with the clinical stage, lymph node involvement, metastases, pattern of invasion and recurrence (p<0.05). CONCLUSION: S100A4 expression represents an important biomarker of prognostic significance that may be used to identify a subset of patients at high risk of invasion and metast.

Critical biomarkers of epithelial-mesenchymal transition in the head and neck cancers.

Epithelial-mesenchymal transition (EMT), a key developmental program has been shown to occur in wound healing, organ fibrosis and in the initiation of metastasis for cancer progression. EMT is a process that describes the development of motile, mesenchymal-like cells from non-motile parent epithelial cells. Plasticity of the cells enable significant changes in cell phenotypes and this process is governed by the interplay among different functional classes of regulatory molecules. The process typically involves the control of specific gene expression programs with distinct functional impacts on the behavior of cells. An important feature of cellular plasticity, EMT has in the recent times attracted broad interest in the field of cancer research, tumor invasion and metastases. A complete understanding of the molecular events of EMT and a search for novel molecular regulators is required for prospective targets for therapeutic interventions. This review summarizes the critical biomarkers of EMT in the head and neck cancers.

Primary synovial sarcoma of the maxilla.

An innocuously appearing gingival mass in the maxilla revealed extensive osteolysis on radiographic examination. A rare clinical presentation of synovial sarcoma, appropriate diagnostic strategies and suitable treatment protocol in a 21-year-old male is reported herewith. It is only the third case of primary monophasic synovial sarcoma of the maxilla to be reported to the best of our knowledge and the first to have occurred in a male patient. The importance of considering synovial sarcoma in the differential diagnosis of any mass in the oral cavity is highlighted.

Overexpression of S100A4 as a biomarker of metastasis and recurrence in oral squamous cell carcinoma

S100A4, a biomarker of epithelial mesenchymal transition (EMT), plays an important role in invasion and metastasis by promoting cancer cell motility. In oral squamous cell carcinoma (OSCC), metastasis results in 90% of cancer associated mortality. Objective: To investigate the role of S100A4 expression as an important component of the epithelial mesenchymal transition (EMT) program in oral squamous cell carcinoma (OSCC). Material and Methods: S100A4 protein expression was assessed semi-quantitatively by immunohistochemistry in 47 histologically confirmed cases of oral squamous cell carcinoma (OSCC) and 10 normal oral mucosal biopsies. The association between the S100A4 overexpression and the aggressive features of OSCC were analyzed by X2 test. Results: Moderate to strong cytoplasmic expression of S100A4 was observed in 30 out of 47 specimens of OSCC (64%). Overexpression of S100A4 was significantly associated with the clinical stage, lymph node involvement, metastases, pattern of invasion and recurrence (p<0.05). Conclusion: S100A4 expression represents an important biomarker of prognostic significance that may be used to identify a subset of patients at high risk of invasion and metast .

Orthokeratinized odontogenic cyst – critical appraisal of a distinct entity

The orthokeratinized odontogenic cyst (OOC) is a rare developmental jaw cyst. Recognition of OOC as a unique entity has long been due, yet its inexplicable radiographic presentation resembling dentigerous cyst, histological likeness to odontogenic keratocyst (OKC) and inconsistent cytokeratin expression profiles overlapping with both as well as with the epidermis, makes it rather confounding. Diagnosis of OOC is important as the pathologic behavior, clinical outcome and the surgical management of OOC is disparate. This is the report of a case of OOC in relation to an impacted mandibular third molar and critical review of this entity with an emphasis on its biologic characteristics is highlighted.

A randomized study of the effects of food on the pharmacokinetics of once-daily extended-release hydromorphone in healthy volunteers.

This randomized, open-label, crossover study investigated the influence of food on the pharmacokinetics of extended-release hydromorphone in 30 healthy volunteers. Participants received extended-release hydromorphone 16 mg in the fasted state and immediately after a high-fat breakfast. In addition, the pharmacokinetics of a 16-mg dose of extended-release hydromorphone and a 16-mg daily dose (4 mg qid) of immediate-release hydromorphone in the fasted state were compared. Treatments were separated by washout periods of 7 to 14 days. Naltrexone was given throughout each treatment period to block the opioid effects of hydromorphone. The 90% confidence intervals (CIs) of the ratios of geometric means for maximum plasma concentrations (C(max)) and area under the plasma concentration-time curve (AUC) for extended-release hydromorphone in the fed and fasted states were within the bioequivalence criteria range of 80% to 125%. In the fasted state, the 90% CIs of the ratios of AUC geometric means for extended-release hydromorphone and immediate-release hydromorphone were also within the bioequivalence range. Both hydromorphone treatments were well tolerated. This study shows that the bioavailability of extended-release hydromorphone is not affected by food and that the bioavailability of extended-release hydromorphone under fasting conditions is comparable with that of the immediate-release formulation when administered at the same total daily dose.

Steady-state pharmacokinetics of extended-release hydromorphone (OROS hydromorphone): a randomized study in healthy volunteers.

The steady-state pharmacokinetics of an extended-release formulation of hydromorphone, OROS hydromorphone, was investigated in a randomized, open-label, crossover study in healthy volunteers. Participants were randomly assigned to receive 16 mg of OROS hydromorphone once daily and 4 mg of immediate-release hydromorphone four times daily for five consecutive days. The two treatments were separated by a washout period of 7-14 days. Naltrexone was given throughout both treatment periods to block the opioid effects of hydromorphone. Steady-state hydromorphone concentrations were statistically analyzed using Helmert contrasts to determine when steady state was reached. A total of 30 participants were enrolled, of whom 29 completed both treatment periods. The two treatments produced comparable steady-state plasma drug concentrations, but peak-to-trough fluctuations were smaller with OROS hydromorphone (61 percent vs 172 percent) in comparison with immediate release hydromorphone. Overall systemic exposure to hydromorphone was similar between the two formulations. The ratio of the geometric means between the two formulations for the area under the concentration-time curves at steady state was 105.2 percent with a 90% confidence interval (CI) of 99.8-110.8 (geometric mean: 102.7 percent; 90% CI: 97.6-108.2 after correcting for measured drug content), which was within the bioequivalence range (80-125 percent). The analysis of Helmert contrasts showed that steady state conditions were attained by day 4. Both treatments were well tolerated. This study shows that OROS hydromorphone maintains steady-state plasma drug concentrations within the same range as immediate-release hydromorphone at the same total daily dose, with less fluctuation.