Farah, CS (Camile S)
Head Neck. 2012 Jun 28;: 22740333
High specificity of combined narrow band imaging and autofluorescence mucosal assessment of patients with head and neck cancer.
Phan Nguyen, Farzad Bashirzadeh, Robert Hodge, Julie Agnew, Camile S Farah, Edwina Duhig, Belinda Clarke, Joanna Perry-Keene, David Botros, Ian Brent Masters, David Fielding
The Department of Thoracic Medicine, The Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.
BACKGROUND: The purpose of this study was to evaluate combined autofluorescence (AF) and narrow band imaging (NBI) for detection of mucosal lesions additional to known primary head and neck cancers and to determine impact on management. METHODS: Patients with head and neck cancer requiring preoperative screening or posttreatment surveillance had white light (WL), AF and NBI inspection of the head and neck and bronchus. Known primary cancers were not analyzed, only additional lesions. Moderate dysplasia or worse was considered significant. RESULTS: In all, 73 patients were recruited. Respectively, there were 24 and 18 additional lesions in the head and neck and bronchus that had significant histopathology. In both regions, AF and NBI were more sensitive than WL for detecting significant dysplasia with NBI demonstrating better specificity than AF (p =.003); 11 of 73 patients (15.1%) had additional findings detected by AF and NBI, which had an impact on management. CONCLUSION: Combined AF and NBI inspection is highly specific at panendoscopy and can influence management. © 2012 Wiley Periodicals, Inc. Head Neck, 2012.
J Oral Pathol Med. 2012 May 29;: 22643025
Organotypic culture of normal, dysplastic and squamous cell carcinoma-derived oral cell lines reveals loss of spatial regulation of CD44 and p75(NTR) in malignancy.
UQ Centre for Clinical Research, The University of Queensland, Herston, Qld, Australia School of Dentistry, The University of Queensland, Brisbane, Qld, Australia Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Qld, Australia.
J Oral Pathol Med (2012). Oral squamous cell carcinomas (OSCC) often arise from dysplastic lesions. The role of cancer stem cells in tumour initiation is widely accepted, yet the potential existence of pre-cancerous stem cells in dysplastic tissue has received little attention. Cell lines from oral diseases ranging in severity from dysplasia to malignancy provide opportunity to investigate the involvement of stem cells in malignant progression from dysplasia. Stem cells are functionally defined by their ability to generate hierarchical tissue structures in consortium with spatial regulation. Organotypic cultures readily display tissue hierarchy in vitro; hence, in this study, we compared hierarchical expression of stem cell-associated markers in dermis-based organotypic cultures of oral epithelial cells from normal tissue (OKF6-TERT2), mild dysplasia (DOK), severe dysplasia (POE-9n) and OSCC (PE/CA P J15). Expression of CD44, p75(NTR), CD24 and ALDH was studied in monolayers by flow cytometry and in organotypic cultures by immunohistochemistry. Spatial regulation of CD44 and p75(NTR) was evident for organotypic cultures of normal (OKF6-TERT2) and dysplasia (DOK and POE-9n) but was lacking for OSCC (PE/CA PJ15)-derived cells. Spatial regulation of CD24 was not evident. All monolayer cultures exhibited CD44, p75(NTR), CD24 antigens and ALDH activity (ALDEFLUOR(®) assay), with a trend towards loss of population heterogeneity that mirrored disease severity. In monolayer, increased FOXA1 and decreased FOXA2 expression correlated with disease severity, but OCT3/4, Sox2 and NANOG did not. We conclude that dermis-based organotypic cultures give opportunity to investigate the mechanisms that underlie loss of spatial regulation of stem cell markers seen with OSCC-derived cells.
Most cited papers:
Oral Biology and Pathology, The University of Queensland, St Lucia, Brisbane, Queensland, Australia.
BACKGROUND Cell-mediated immune responses in oral lichen planus (OLP) may be regulated by cytokines and their receptors. METHODS In situ cytokine expression and in vitro cytokine secretion in OLP were determined by immunohistochemistry and ELISA. RESULTS The majority of subepithelial and intraepithelial mononuclear cells in OLP were CD8+. In some cases, intraepithelial CD8+ cells were adjacent to degenerating keratinocytes. CD4+ cells were observed mainly in the deep lamina propria with occasional CD4+ cells close to basal keratinocytes. Mononuclear cells expressed IFN-gamma in the superficial lamina propria and TNF-alpha adjacent to basal keratinocytes. Basal keratinocytes expressed TNF-alpha as a continuous band. TNF R1 was expressed by mononuclear cells and basal and suprabasal keratinocytes. There was variable expression of TGF-beta1 in the subepithelial infiltrate while all intraepithelial mononuclear cells were TGF-beta1-. Keratinocytes in OLP stained weakly for TGF-beta1. Unstimulated OLP lesional T cells secreted IFN-gamma in vitro. TNF-alpha stimulation down-regulated IFN-gamma secretion and up-regulated TNF-alpha secretion. IL-4, IL-10 and TGF-beta1 secretion were not detected. CONCLUSIONS These data suggest the development of a T helper 1 immune response that may promote CD8+ cytotoxic T-cell activity in OLP.
Oral Biology and Pathology, School of Dentistry, University of Queensland, Brisbane, Queensland, Australia. email@example.com
Candida albicans is a common opportunistic pathogen, causing both superficial and systemic infection. Clinical observations indicate that mucocutaneous infections are commonly associated with defective cell-mediated immune responses, whereas systemic infection is more frequently seen in patients with deficiencies in neutrophil number or function. Analysis of mechanisms of host resistance against gastrointestinal and oral infection in mouse models has demonstrated an absolute dependence on CD4(+) T cells, although clearance also involves phagocytic cells. Both IL-12 and TNF-alpha appear to be important mediators, but mouse strain-dependent variations in susceptibility to infection may be related to T-cell enhancement of production of phagocytic cells by the bone marrow. In murine systemic infection, the role of innate and adaptive responses is less well defined. Studies in immunodeficient and T-cell-depleted mice suggest that clearance of the yeast may be predominantly a function of the innate response, whereas the adaptive response may either limit tissue damage or have the potential to cause immunopathology, depending on the host genetic context in which the infection takes place.
Oral Medicine and Pathology, School of Dentistry, The University of Queensland, Brisbane, Australia.
BACKGROUND Bisphosphonate-related osteonecrosis of the jaws (BRONJ) presents the clinician with significant management dilemmas. The purpose of this study was to distil information related to this disorder by comprehensively reviewing the literature. METHODS The structure and function of bisphosphonates, and their role in the development of BRONJ will be discussed, as will the possible mechanisms through which this pathology develops. A review of cases presented in the literature will be undertaken, and suggestions offered as to the management of this pathology in terms of surgical and conservative approaches. RESULTS Presentation of BRONJ is currently more common in patients taking intravenous forms of bisphosphonates, but there is a fear that the long-term cumulative effects of oral bisphosphonates may see BRONJ increasingly occurring in this patient group. CONCLUSIONS Prevention is superior to treatment, and the establishment of meticulous oral hygiene and pre-emptive surgical treatment prior to commencement of bisphosphonate therapy is recommended.
Role of complement C5 and T lymphocytes in pathogenesis of disseminated and mucosal candidiasis in susceptible DBA/2 mice.
Robert B Ashman, John M Papadimitriou, Alma Fulurija, Karen E Drysdale, Camile S Farah, Owen Naidoo, Theo Gotjamanos
School of Dentistry, Oral Biology and Pathology, University of Queensland, Brisbane, Qld 4072, Australia. firstname.lastname@example.org
The aims of the study were to compare the pathogenesis of Candida albicans infection in various organs and anatomical regions of C5-deficient (DBA/2) and C5-sufficient (BALB/c) mice, and to evaluate the importance of complement C5 and T lymphocytes as factors that determine host susceptibility or resistance. The kidneys of DBA/2 mice showed higher colonisation and more severe tissue damage than those of BALB/c, but infection at other sites, including oral and vaginal mucosa, was generally similar in the two strains. Passive transfer of C5-sufficient serum into DBA/2 mice decreased the fungal burden in the kidney, and prolonged survival of the reconstituted animals. Depletion of CD4(+) and/or CD8(+) cells did not exacerbate either systemic or mucosal infection when compared to controls, and passive transfer of splenocytes from infected donors caused only a small and transient reduction in numbers of yeasts recovered from the kidney of sub-lethally infected recipients. It is concluded that the acute susceptibility of the kidneys in this mouse strain is due to C5 deficiency expressed on a susceptible genetic background. T lymphocytes, however, appear to have minimal influence on recovery from systemic infection with this isolate of C. albicans.
A pilot case control study on the efficacy of acetic acid wash and chemiluminescent illumination (ViziLite) in the visualisation of oral mucosal white lesions.
Department of Oral Medicine and Pathology, School of Dentistry, The University of Queensland, Brisbane QLD 4072, Australia. email@example.com
Conventional screening practice for oral lesions involves visual scrutiny of the oral tissues with the naked eye under projected incandescent or halogen illumination. Visualisation is the principal strategy used to assess patients' lesions at risk for malignant transformation; hence, any procedure which highlights such lesions should aid the clinician. The aim of this pilot study was to examine the efficacy of acetic acid wash and chemiluminescent light (ViziLite) in enhancing visualisation of oral mucosal white lesions, and its ability to highlight malignant and potentially malignant lesions. Fifty five patients referred for assessment of an oral white lesion, were prospectively screened with ViziLite, and an incisional scalpel biopsy performed for a definitive diagnosis. The size, location, ease of visibility, border distinctness, and presence of satellite lesions were recorded. The ViziLite tool enhanced intra-oral visualisation of 26 white lesions. Indeed, all lesions appeared "aceto-white", regardless of the definitive diagnosis. Examination of the oral tissues with ViziLite illumination did not change the provisional diagnosis, nor alter the biopsy site. ViziLite illumination does not discriminate between keratotic, inflammatory, malignant or potentially malignant oral mucosal white lesions and thus, a high index of suspicion, expert clinical judgment, and scalpel biopsy are still essential for proper patient care.
The assessment of diffused light illumination and acetic acid rinse (Microlux/DL) in the visualisation of oral mucosal lesions.
School of Dentistry and UQ Centre for Clinical Research, The University of Queensland, Herston, QLD 4029, Australia.
Oral examination alone cannot always distinguish benign from premalignant and malignant lesions, thereby resulting in delayed patient referral and poorer prognosis. Thus, any non-invasive technology which highlights oral premalignant and malignant lesions in a highly sensitive and specific manner will undoubtedly aid clinicians in early diagnosis and treatment of these conditions. The aim of this study was to assess the efficacy of acetic acid mouthwash and diffused light illumination (Microlux/DL) as a diagnostic aid in the visualisation of oral mucosal lesions and its ability to highlight malignant and potentially malignant lesions. Fifty patients referred for assessment of an oral white lesion were initially examined under routine incandescent operatory light. The location, size, ease of visibility, border distinctness and presence of satellite lesions were recorded. Clinical examination was repeated using the Microlux/DL diffused light illumination kit. An incisional biopsy was performed to provide a definitive histopathological diagnosis. Microlux/DL examination enhanced the visibility of 34 lesions, however, it did not help uncover any clinically undetected lesions, change the provisional diagnosis, or alter the biopsy site. Microlux/DL showed a sensitivity of 77.8% and a specificity of 70.7%, with a positive predictive value of 36.8%. Although Microlux/DL appears useful at enhancing lesion visibility, it is a poor discriminator for inflammatory, traumatic and malignant lesions.
The assessment of the DNA content of oral cytology via virtual microscopy for the early detection of epithelial dysplasia and neoplasia in oral mucosal lesions.
University of Queensland, School of Dentistry and UQ Centre for Clinical Research, Herston, Queensland 4029, Australia. firstname.lastname@example.org
Recent technological innovation has now made it possible to turn the computer into a microscope. This has entailed a shift from light microscopy to virtual microscopy. This development then foregrounds the issue of the pedagogy involved in this move from the analogue technology of the light microscope to the digital, computerized instance of virtual microscopy. In order to address this issue, undergraduate students enrolled in the Bachelor of Dental Science program at the University of Queensland School of Dentistry were surveyed to ascertain their preference for light or virtual microscopy. The value of this study is that it was conducted on the same cohort of students in two separate courses in 2006 and 2008, giving it longitudinal validity. The responses were overwhelmingly in favor of virtual microscopy. When it came to completely replacing the light microscope with virtual microscopy, however, students were much more ambivalent about such a wholesale change although this was less of an issue in the senior year. This shift from light to virtual microscopy signals larger changes in the tertiary sector from print-literate to electronic forms of knowledge and from teacher-centered to student-focused frames of learning. In short, we are in the midst of the e-evolution of microscopy in dental education.
Effector function of leucocytes from susceptible and resistant mice against distinct isolates of Candida albicans.
School of Dentistry, University of Queensland, Brisbane, Queensland, Australia.
Neutrophils and macrophages were generated in vitro from mice that display either high or low tissue susceptibilities to Candida albicans infection and their ability to phagocytose and kill three isolates of the yeast with different virulence characteristics was evaluated. In the absence of opsonization, phagocytosis by BALB/c and CBA/CaH neutrophils was comparable, but the killing was very poor. Opsonization with normal serum slightly decreased phagocytosis, but it had markedly different effects on killing, either enhancing or inhibiting candidacidal activity, depending on the combination of yeast isolate and mouse strain. In contrast, BALB/c macrophages showed high levels of phagocytosis and killing of both unopsonized yeasts and opsonized yeasts; whereas killing of unopsonized yeasts by CBA/CaH macrophages was poor, it was markedly enhanced by opsonization.
Oral Medicine & Oral Pathology, The University of Queensland, School of Dentistry & UQ Centre for Clinical Research, Herston, Queensland, Australia.
Canine transmigration is a rare dental anomaly unique to the mandibular arch, involving intraosseous migration of the unerupted tooth across the midline. Currently, there is a lack of consensus on the definition of transmigration. This report suggests a unified definition of transmigration, that being when a canine has crossed the midline by more than half its length. Numerous publications reporting mandibular canine transmigration therefore cannot be considered as being truly transmigrated. Here we undertake a comprehensive review of the literature, and report 4 new cases of transmigrated mandibular canines, 2 of which present with unique features. One case shows a vertically positioned transmigrated canine, whereas the other shows a horizontally transmigrated canine underlying an impacted canine. Furthermore, this cohort is the first to be reported in an Australian population.