TP53 mutation and human papilloma virus status as independent prognostic factors in a Norwegian cohort of vulva squamous cell carcinoma.

INTRODUCTION: Vulva squamous cell carcinoma (VSCC) develops through two separate molecular pathways-one involving high-risk human papilloma virus infection (HPV-associated), and the other without HPV infection (HPV-independent) often involving TP53 mutation. HPV-associated VSCC generally has a better progression-free survival than HPV-independent VSCC. The aim of this study was to determine TP53 mutation status using immunohistochemistry, compare different methods of HPV detection and correlate both with survival in a retrospective cohort of 123 patients with VSCC. MATERIAL AND METHODS: Immunohistochemistry for p53, Ki67 and p16INK4A (a surrogate marker for HPV infection) was performed on formalin-fixed paraffin-embedded tissues from a cohort of surgically treated VSCC patients to identify molecular subtypes of VSCC. Presence of HPV infection was detected by HPV DNA PCR and HPV mRNA in situ hybridization (ISH). The Pearson chi-square test and multivariable Cox regression model were used to investigate the association of different parameters with progression-free survival and disease-specific survival (DSS), and Kaplan-Meier curves were used to show the association of different parameters with survival. RESULTS: The results of p53 and p16INK4A immunohistochemistry confirmed three VSCC subtypes associated with different prognosis. The TP53 mutation status was identified as an independent prognostic factor of worse progression-free survival (p = 0.024) after adjustment for FIGO stage. p16INK4A immunohistochemistry, mRNA ISH, and DNA PCR had excellent concordance in terms of HPV detection. According to the multivariable Cox regression model, the presence of hrHPV mRNA correlated significantly with increased progression-free survival (p = 0.040) and DSS (p = 0.045), after adjustment for other confounders. CONCLUSIONS: p53 and p16INK4A immunohistochemistry stratify VSCC cohort into three subtypes with TP53mutated patients having the worst prognosis. The detection of hrHPV mRNA by ISH was an independent predictor of increased survival. Thus, the combined detection of p53 and HPV mRNA might improve risk stratification in VSCC.

Establishment of a novel cancer cell line derived from vulvar carcinoma associated with lichen sclerosus exhibiting a fibroblast-dependent tumorigenic potential.

Vulvar squamous cell carcinoma associated with lichen sclerosus (VLS-VSCC) are rare tumors but with higher recurrence and worse prognosis than other types of VSCC. Lack of experimental models has limited the search for better understanding of the biology and development of treatment modalities. In this study, we isolated and characterized primary cells from VSCC (n = 7) and normal vulvar tissue adjacent to tumor (n = 7). Detailed characterization of the novel spontaneously immortalized cell line, VCC1 revealed a characteristic epithelial morphology in vitro and a well-differentiated keratinizing SCC histology in vivo, closely resembling the tumor of origin. VCC1 expressed higher levels of epithelial-mesenchymal transition markers and higher clonogenic properties as compared to other established non VLS-VSCC cell lines. In vitro 3D organotypic assays and in vivo xenografts revealed a prominent role of cancer-associated fibroblasts in VCC1 invasion and tumor formation. In conclusion, VCC1 mirrored several major VLS-VSCC features and provided a robust experimental tool for further elucidation of VLS-related oncogenesis and drug testing.

Profiling and Functional Analysis of microRNA Deregulation in Cancer-Associated Fibroblasts in Oral Squamous Cell Carcinoma Depicts an Anti-Invasive Role of microRNA-204 via Regulation of Their Motility.

Background: Knowledge on the role of miR changes in tumor stroma for cancer progression is limited. This study aimed to investigate the role of miR dysregulation in cancer-associated fibroblasts (CAFs) in oral squamous cell carcinoma (OSCC). Methodology: CAF and normal oral fibroblasts (NOFs) were isolated from biopsies of OSCC patients and healthy individuals after informed consent and grown in 3D collagen gels. Total RNA was extracted. Global miR expression was profiled using Illumina version 2 panels. The functional impact of altered miR-204 expression in fibroblasts on their phenotype and molecular profile was investigated using mimics and inhibitors of miR-204. Further, the impact of miR-204 expression in fibroblasts on invasion of adjacent OSCC cells was assessed in 3D-organotypic co-cultures. Results: Unsupervised hierarchical clustering for global miR expression resulted in separate clusters for CAF and NOF. SAM analysis identified differential expression of twelve miRs between CAF and NOF. Modulation of miR-204 expression did not affect fibroblast cell proliferation, but resulted in changes in the motility phenotype, expression of various motility-related molecules, and invasion of the adjacent OSCC cells. 3' UTR miR target reporter assay showed ITGA11 to be a direct target of miR-204. Conclusions: This study identifies differentially expressed miRs in stromal fibroblasts of OSCC lesions compared with normal oral mucosa and it reveals that one of the significantly downregulated miRs in CAF, miR-204, has a tumor-suppressive function through inhibition of fibroblast migration by modulating the expression of several different molecules in addition to directly targeting ITGA11.

Grading of oral squamous cell carcinomas - Intra and interrater agreeability: Simpler is better?

BACKGROUND: Numerous studies have been presented on histological grading of oral squamous cell carcinomas (OSCC) for predicting survival, but uncertainty of their usefulness rises due to discordances of results. A scoring system should be robust and well validated, and intra- and interrater agreement can be used as a tool to visualize the strength of reproducibility. METHODS: Here, we present an intra- and inter-observer study on evaluation of OSCC using some of the most common histopathological parameters. The observers were from different Norwegian university hospitals, and calibration to ensure accuracy was first performed. Percentage of the agreement was calculated for the score made by the individual observer at different times, as well as between pairs of observers. RESULTS: The evaluation made by the same observer at two different time points (intrarater) correlated better than observations made by different participants (interrater). In an attempt to increase the rate of agreement, many of the parameters were either dichotomized into simply low- and high grade, or to a three-tier system when more than three options in the original design. This increased the concurrence with 15.4% for the intrarater and with 23% for the interrater comparisons. CONCLUSION: High agreement for histopathological parameters can be difficult to obtain on hematoxylin and eosin staining in scoring systems with many options. A simpler system might be more advantageous to achieve higher degree of reproducibility.

Isolation and characterization of cells derived from human epithelial rests of Malassez.

The epithelial rests of Malassez (ERMs) might represent a valuable source of oral epithelial cells with stem cell properties. The purpose of this study was to isolate and characterize cells derived from human ERM, and compare them with cells derived from matched normal oral mucosa (NOM). Matched tissue specimens of the periodontal ligament of extracted tooth and NOM were collected. Cells were isolated in culture, then characterized by immunohistochemistry and flow cytometry for expression of pancytokeratin, ESA, PDGFRB, CD31 and CD44. 3D organotypic cultures were constructed by growing epithelial cells on top of fibroblast-populated collagen gels. Both ERM and NOM-isolated cells expressed the markers of epithelial lineage (ESA and pancytokeratin), and to some extent PDGFR, an indicator of a more mesenchymal phenotype, but not the endothelial cell marker CD31. Cells with epithelial morphology were isolated from periodontium of cervical, middle and apical parts of the root, but contained a significantly lower percentage of ESA and pancytokeratin-positive cells than when isolating cells from NOM (p < 0.001). ERM cells expressed a significantly higher percentage of the stem cell-related molecule CD44 (cervical 92.93 ± 0.25%, middle 93.8 ± 0.26%, apical 94.36 ± 0.41%) than cells isolated from NOM (27.8 ± 1.47%, p < 0.001). When grown in 3D organotypic cultures and in collagen gels, ERM cells formed a less differentiated epithelium than NOM cells, but expressing pancytokeratin and vimentin. In conclusion, epithelial cells could be isolated from human periodontium and grown in culture; their in vitro characterization indicates that they have a less differentiated phenotype compared with cells derived from normal oral epithelium.

The PTEN hamartoma tumor syndrome: how oral clinicians may save lives.

INTRODUCTION: Patients with the PTEN hamartoma tumor syndrome (PHTS) have an 81%-90% cumulative lifetime risk of developing cancer. Around 90% of these patients have recognizable oral features. Receiving a diagnosis may save these patients' lives. This is the first presentation of a family with the PHTS diagnosis with focus on the oral and periodontal findings and treatments. CASE PRESENTATION: All three children (one son and two daughters) inherited the same heterozygous variant in the PTEN gene from their father. Gingival overgrowth was observed in all patients in addition to macrocephaly. Other findings included fissured tongue, high arched palate, papules, and trichilemmomas. The father had experienced severe tooth loss. Surgery was performed to treat the gingival overgrowth and periodontal pockets; however, the treatment was characterized by multiple recurrences of the overgrowth. CONCLUSIONS: Oral changes, macrocephaly, tumors, and/or a family history of benign or malignant lesions are important features that oral clinicians should be aware of for a possible PHTS diagnosis. Patients suspected of having PHTS should be referred to a medical practitioner, specifically a geneticist, for further diagnostic investigations. The periodontal problems seemed to be difficult to control for these patients. They will likely need an active and frequent maintenance therapy to control the persistent inflammation and gingival overgrowth. In addition, they need a thorough monitoring for benign or malignant changes in the orofacial regions. Why are these cases new information? Oral features are found in 90% of the cases with the PHTS diagnosis. The periodontal findings showed a persistent recurrence of gingival overgrowth with a strong probability of serious periodontal diseases. What are the keys to successful management of these cases? A suspicion of a PHTS diagnosis with a referral to a medical practitioner, specifically a geneticist, for complete workup may help save these patients' lives. Close monitoring during maintenance therapy with re-treatment as needed to prevent further periodontal complications. Continued monitoring and treatment throughout the patient's lifetime for development of recurrent or new, benign or malignant lesions at relevant sites. What are the primary limitations to success in these cases? A failure to identify the PHTS syndrome with the accompanying oral and periodontal complications. Complications may lead to a delay in appropriate treatment. Inability to control the persistent gingival overgrowth and a deteriorating periodontal condition. A failure to discover benign and malignant lesions in the orofacial region.

Inflammatory tissue reactions around aseptically loose cemented hip prostheses: A retrieval study of the Spectron EF stem with Reflection All-Poly acetabular cup.

The cemented Spectron EF stem in combination with the cemented non-crosslinked Reflection All-Poly cup showed a high rate of mid-term aseptic loosening. However, the failure mechanisms are not fully known. We assessed the inflammatory tissue reactions and wear particles in periprosthetic tissues, implant wear and blood metal ion levels in 28 patients with failed implants. Histological analysis showed a macrophage pre-dominant pattern with randomly distributed lymphocytes, with various amounts of neutrophils and giant cells. The number of different cell types in the tissue samples from patients in the cup group and in the stem group was similar. Wear particles, mainly ZrO2 , CoCrMo, and polyethylene particles of different sizes and shapes, were associated with macrophages/giant cells, and total particle load/mm2 was higher in cases of stem loosening. The Spectron EF stems were heavily worn, abraded, and polished. Stem abrasion correlated with metal ion concentrations in blood. The median polyethylene wear rate of the Reflection cups was 0.23 mm/year. The high proximal roughness of the Spectron EF stem resulted in excessive cement wear during loosening. The resulting inflammatory tissue responses to the degradation products both from the cup and the stem led to massive osteolysis and subsequent implant loosening.

MicroRNA-138 Abates Fibroblast Motility With Effect on Invasion of Adjacent Cancer Cells.

Background: Recent studies have shown aberrant expression of micro-RNAs in cancer-associated fibroblasts (CAFs). This study aimed to investigate miR-138 dysregulation in CAFs in oral squamous cell carcinoma (OSCC) and its effects on their phenotype and invasion of adjacent OSCC cells. Methods: Expression of miR-138 was first investigated in OSCC lesions (n = 53) and OSCC-derived CAFs (n = 15). MiR-138 mimics and inhibitors were used to functionally investigate the role of miR-138 on CAF phenotype and the resulting change in their ability to support OSCC invasion. Results: Expression of miR-138 showed marked heterogeneity in both OSCC tissues and cultured fibroblasts. Ectopic miR-138 expression reduced fibroblasts' motility and collagen contraction ability and suppressed invasion of suprajacent OSCC cells, while its inhibition resulted in the opposite outcome. Transcript and protein examination after modulation of miR-138 expression showed changes in CAF phenotype-specific molecules, focal adhesion kinase axis, and TGFß1 signaling pathway. Conclusions: Despite its heterogeneous expression, miR-138 in OSCC-derived CAFs exhibits a tumor-suppressive function.

Characterization of immune cell infiltrate in tumor stroma and epithelial compartments in oral squamous cell carcinomas of Sudanese patients.

BACKGROUND: Tumor immune infiltrate has been explored in oral squamous cell carcinoma (OSCC), but studies on simultaneous characterization of multiple immune cell subtypes separately in stromal and intraepithelial tumor compartments are limited. OBJECTIVES: We aimed to investigate the immune cell infiltrate in OSCC by using immunohistochemistry (IHC) for a panel of inflammatory cells in stromal and epithelial tumor compartments for a better characterization of the tumors. METHODS: Thirty-six OSCC lesions and nine normal oral mucosa (NOM) samples from patients attending Khartoum Dental Teaching Hospital, Sudan were investigated for presence of tumor infiltrating lymphocytes, tumor-associated macrophages, tumor-associated neutrophils, and PD-L1 positive cells in the inflammatory infiltrate by single and double IHC. Digital quantitative analysis (Aperio Technologies Inc.) was performed separately for stromal and epithelial compartments. RESULTS: OSCC cases displayed a higher inflammatory infiltrate in the associated stroma, but not in the epithelial compartment when compared to NOM. The immunosuppressive type of inflammatory infiltrate, that is, T regulatory cells (FoxP3+ cells) was identified to be significantly higher in the epithelial compartment of tumors with advanced clinical state. An immunoscore developed by combining intraepithelial FoxP3+ and CD4+ cells was found significantly higher in lesions from elderly patients, localized at toombak dipping-related sites, poorly differentiated OSCCs, or with loco-regional lymph node spreading. CONCLUSIONS: Despite heavy immune cell infiltration in tumor-associated stroma, the majority of OSCCs in this cohort displayed a low intraepithelial immune infiltration. An immunoscore based on combined CD4 and FoxP3 intraepithelial expression may serve as an indicator of advanced tumor progression and should be further investigated for its use as potential prognostic biomarker in OSCC.

Combined In Situ Hybridization and Immunohistochemistry on Archival Tissues Reveals Stromal microRNA-204 as Prognostic Biomarker for Oral Squamous Cell Carcinoma.

Micro-RNAs (miRs) are emerging as important players in carcinogenesis. Their stromal expression has been less investigated in part due to lack of methods to accurately differentiate between tumor compartments. This study aimed to establish a robust method for dual visualization of miR and protein (pan-cytokeratin) by combining chromogen-based in situ hybridization (ISH) and immunohistochemistry (IHC), and to apply it to investigate stromal expression of miR204 as a putative prognostic biomarker in oral squamous cell carcinoma (OSCC). Four different combinations of methods were tested and ImageJ and Aperio ImageScope were used to quantify miR expression. All four dual ISH-IHC methods tested were comparable to single ISH in terms of positive pixel area percentage or integrated optical density of miRs staining. Based on technical simplicity, one of the methods was chosen for further investigation of miR204 on a cohort of human papilloma virus (HPV)-negative primary OSCC (n = 169). MiR204 stromal expression at tumor front predicted recurrence-free survival (p = 0.032) and overall survival (p = 0.036). Multivariate Cox regression further confirmed it as an independent prognostic biomarker in OSCC. This study provides a methodological platform for integrative biomarker studies based on simultaneous detection and quantification of miRs and/or protein and reveals stromal miR204 as a prognostic biomarker in OSCC.

Feasibility of a Portable Electronic Nose for Detection of Oral Squamous Cell Carcinoma in Sudan.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is increasing at an alarming rate particularly in low-income countries. This urges for research into noninvasive, user-friendly diagnostic tools that can be used in limited-resource settings. This study aims to test and validate the feasibility of e-nose technology for detecting OSCC in the limited-resource settings of the Sudanese population. METHODS: Two e-nose devices (Aeonose™, eNose Company, Zutphen, The Netherlands) were used to collect breath samples from OSCC (n = 49) and control (n = 35) patients. Patients were divided into a training group for building an artificial neural network (ANN) model and a blinded control group for model validation. The Statistical Package for the Social Sciences (SPSS) software was used for the analysis of baseline characteristics and regression. Aethena proprietary software was used for data analysis using artificial neural networks based on patterns of volatile organic compounds. RESULTS: A diagnostic accuracy of 81% was observed, with 88% sensitivity and 71% specificity. CONCLUSIONS: This study demonstrates that e-nose is an efficient tool for OSCC detection in limited-resource settings, where it offers a valuable cost-effective strategy to tackle the burden posed by OSCC.

Analysis of Salivary Mycobiome in a Cohort of Oral Squamous Cell Carcinoma Patients From Sudan Identifies Higher Salivary Carriage of Malassezia as an Independent and Favorable Predictor of Overall Survival.

Background: Microbial dysbiosis and microbiome-induced inflammation have emerged as important factors in oral squamous cell carcinoma (OSCC) tumorigenesis during the last two decades. However, the "rare biosphere" of the oral microbiome, including fungi, has been sparsely investigated. This study aimed to characterize the salivary mycobiome in a prospective Sudanese cohort of OSCC patients and to explore patterns of diversities associated with overall survival (OS). Materials and Methods: Unstimulated saliva samples (n = 72) were collected from patients diagnosed with OSCC (n = 59) and from non-OSCC control volunteers (n = 13). DNA was extracted using a combined enzymatic-mechanical extraction protocol. The salivary mycobiome was assessed using a next-generation sequencing (NGS)-based methodology by amplifying the ITS2 region. The impact of the abundance of different fungal genera on the survival of OSCC patients was analyzed using Kaplan-Meier and Cox regression survival analyses (SPPS). Results: Sixteen genera were identified exclusively in the saliva of OSCC patients. Candida, Malassezia, Saccharomyces, Aspergillus, and Cyberlindnera were the most relatively abundant fungal genera in both groups and showed higher abundance in OSCC patients. Kaplan-Meier survival analysis showed higher salivary carriage of the Candida genus significantly associated with poor OS of OSCC patients (Breslow test: p = 0.043). In contrast, the higher salivary carriage of Malassezia showed a significant association with favorable OS in OSCC patients (Breslow test: p = 0.039). The Cox proportional hazards multiple regression model was applied to adjust the salivary carriage of both Candida and Malassezia according to age (p = 0.029) and identified the genus Malassezia as an independent predictor of OS (hazard ratio = 0.383, 95% CI = 0.16-0.93, p = 0.03). Conclusion: The fungal compositional patterns in saliva from OSCC patients were different from those of individuals without OSCC. The fungal genus Malassezia was identified as a putative prognostic biomarker and therapeutic target for OSCC.

Adverse effects of Sudanese toombak vs. Swedish snuff on human oral cells.

BACKGROUND: The high incidence of oral cancer in Sudan has been associated with the use of toombak, the local type of smokeless tobacco. However, its specific effects on human oral cells are not known. We aimed to investigate the effects of toombak on primary normal human oral keratinocytes, fibroblasts, and a dysplastic oral keratinocytic cell line, and to compare them with the effects induced by Swedish snuff. METHOD: Aqueous extracts were prepared from moist toombak and Swedish snuff and added in serial dilutions on in vitro monolayer cultured cells. Cell viability, morphology and growth, DNA double-strand breaks (gammaH2AX staining), expression of phosphatidylserine (Annexin V staining), and cell cycle were assessed after various exposure time periods. RESULTS: Significant decrease in cell number, occurrence of DNA double-strain breaks, morphological and biochemical signs of programmed cell death were detected in all oral cell types exposed to clinically relevant dilutions of toombak extract, although to a lesser extent in normal oral fibroblasts and dysplastic keratinocytes. G2/M-block was also detected in normal oral keratinocytes and fibroblasts exposed to clinically relevant dilutions of toombak extract. Swedish snuff extract had less adverse effects on oral cells, mainly at non-clinically relevant dilutions. CONCLUSION: This study indicates a potential for toombak, higher than for Swedish snuff, to damage human oral epithelium. Dysplastic oral keratinocytes were less sensitive than their normal counterparts, suggesting that they might have acquired a partially resistant phenotype to toombak-induced cytotoxic effects while still being prone to DNA damage that could lead to further malignant progression.

A Comparison of p53 Isoform Profiles and Apoptosis Induced by Camptothecin or a Herbal Khat Extract (Catha Edulis (Vahl) Forssk. ex Endl.) in Leukemic Cell Lines: Exploring Cellular Responses in Therapy Development.

Khat (Catha edulis (Vahl) Forssk. ex Endl.) is habitually used as a natural stimulant by millions of people, but is associated with adverse effects on gastrointestinal, cardiovascular and central neural systems. At the cellular level khat toxicity involves p53 induction and cell cycle arrest, decreased mitochondrial function and activation of receptor- and mitochondria-mediated cell death pathways. In this study we have examined an extract of khat for induction of p53 post-translational modifications (PTMs) and the functional role of p53 in khat-mediated cell death. Khat was shown to induce phosphorylation and acetylation of p53 in both the khat-sensitive MOLM-13 and the khat-resistant MV-4-11 cell line, but accumulation of the full-length p53 isoform was only observed in the khat sensitive cell line. Small molecule inhibitors of p38 MAP kinase sensitized MV-4-11 cells for khat-treatment without concomitant stabilization of p53. Experiments using a p53 knock-down cell line and murine p53 knock-out bone marrow cells indicated that p53 was redundant in khat-mediated cell death in vitro. We suggest that analysis of isoform patterns and p53 PTMs are useful for elucidation of biological effects of complex plant extracts, and that p53 protein analysis is particularly useful in the search for new chemical probes and experimental cancer therapeutics.

Helicobacter pylori was not detected in oral squamous cell carcinomas from cohorts of Norwegian and Nepalese patients.

Helicobacter pylori (HP) infection is an established causative agent for gastric cancer. Although the oral cavity is a part of the gastrointestinal system, the presence and possible causative role of HP in oral squamous cell carcinoma (OSCC) is a subject of controversy. Therefore, the current study aimed to investigate HP infection in two cohorts of OSCC patients with different demographic characteristics, lifestyles and habitual risk factors. A total of 242 formalin-fixed paraffin-embedded OSCC specimens from two different patient cohorts (Norway, n = 171 and Nepal, n = 71) were used to examine HP using immunohistochemistry (IHC) and quantitative polymerase chain reaction (qPCR). Two different HP specific genes (23S rRNA and ureA) were used for TaqMan-based qPCR, and for subsequent verification using HP specific RIDAGENE HP kit and SYBR Green based qPCR. All of the OSCC specimens from both cohorts were found to be negative for HP infection with IHC and qPCR, although the positive control specimens tested positive. Our findings suggest that HP is absent in the examined OSCC cohorts, irrespective of race, lifestyle and habitual risk factors. This indicates that, in contrast to gastric cancer, HP is an unlikely contributing factor for OSCC pathogenesis.

Fusobacterium nucleatum enters normal human oral fibroblasts in vitro.

BACKGROUND: Fusobacterium nucleatum, a commensal opportunistic oral bacterium, is capable of invading gingival epithelial cells, but the entrance into human primary oral fibroblast cells has not been documented. This study evaluated the ability of three strains of F. nucleatum (F. nucleatum ssp. nucleatum, F. nucleatum ssp. polymorphum, and F. nucleatum ssp. vincentii) to enter gingival fibroblasts (GFs) and periodontal ligament fibroblasts (PLFs). METHODS: GFs and PLFs were cocultured for various periods of time with different strains of F. nucleatum. Scanning and transmission electron microscopy, together with confocal laser scanning microscopy, were used to visualize the entrance and presence of bacteria in host cells. Flow cytometry was performed to compare the load of internalized bacteria in GFs and PLFs exposed for 3 and 5 hours to live F. nucleatum labeled with fluorescein isothiocyanate. RESULTS: All three strains of F. nucleatum were found entering and located in the cytoplasm of GFs and PLFs after 1 hour of exposure. Flow cytometry tests revealed a significant increase in the fluorescent signal, compared to baseline, derived from bacteria internalized in fibroblasts exposed for 3 hours (P <0.001); a further increase was found at 5 hours. The greatest bacterial mass in exposed fibroblasts of both types was of F. nucleatum ssp. polymorphum; the smallest was of F. nucleatum ssp. vincentii. Although not statistically significant, PLFs had a higher bacterial load than corresponding GFs. CONCLUSION: F. nucleatum was capable of entering GFs and PLFs in a manner that is dependent on the cell type and the bacterial strain.

Hyperbaric oxygen treatment did not significantly affect radiation injury in the mandibular area of rats.

OBJECTIVE: Hyperbaric oxygen therapy (HBOT) has been used to enhance microcirculation and thereby oxygen tension in tissues. The present study aimed to investigate the effect of HBOT on radiation injury in the mandibular area of rats. STUDY DESIGN: The left mandibles of rats were irradiated by external radiotherapy (15 Gy every other week for a total of 75 Gy). Four HBOT strategies were used: 2 prophylactic groups receiving HBOT either between each radiation treatment or immediately following terminated radiation treatment, and 2 therapeutic groups receiving HBOT after the latent period of 6 weeks after irradiation either every day (standard HBOT protocol) or 3 days a week for 6 weeks. Tissue samples of the irradiated area were taken from skin, the salivary gland, and the mandible. All tissues were stained with hematoxylin and eosin for morphologic examination. Furthermore, skin samples were stained with CD31 for blood vessel analysis. RESULTS: There was no change in blood vessel density or morphology between controls and HBOT tissues after radiation. The dentin of 2 of the 5 rats that received HBOT either normalized or was not affected by irradiation. CONCLUSIONS: HBOT did not affect radiation injury of the mandibular area in rats within 12 weeks after irradiation.

[Diseases that affect both skin and oral mucosa]. / Sykdommer som affiserer hud og munnslimhinne.

BACKGROUND: Several diseases may affect both skin and oral mucosa. This article presents hereditary, autoimmune and other inflammatory conditions within this group. MATERIAL AND METHODS: Review of the literature as well as the authors' own experience in the field. RESULTS AND INTERPRETATION: Lichen planus, erythema multiforme and lupus erythematosus are relatively common disorders with generally favourable prognosis. The much less frequent bullous diseases pemphigoid and pemphigus are characterized by a high morbidity, often requiring a deliberate use of immunosuppressants. Stevens-Johnson syndrome, toxic epidermal necrolysis and the more severe forms of epidermolysis bullosa are potentially life-threatening conditions. It is recommendable that medical doctors and dentists are familiar with the clinical presentations and diagnostic procedures of diseases affecting skin and oral mucosa.