Osteonecrosis of the jaw induced by receptor activator of nuclear factor-kappa B ligand (Denosumab): review

Background: Denosumab, an anti-resorptive agent, IgG2 monoclonal antibody for human Receptor activator of nuclear factor-kappa B ligand (RANKL), has been related to the occurrence of osteonecrosis of the jaws. Thus, the aim of this study was to review the literature from clinical case reports, regarding the type of patient and the therapeutic approach used for osteonecrosis of the jaws induced by chronic use of Denosumab. Material and Methods: For this, a literature review was performed on PubMed, Medline and Cochrane databases, using the keywords “Denosumab” “anti-RANK ligand” and “Osteonecrosis of jaw”. To be included, articles should be a report or a serie of clinical cases, describing patients aged 18 years or over who used denosumab therapy and have received any therapy for ONJ. Results: Thirteen complete articles were selected for this review, totaling 17 clinical cases. The majority of ONJ cases, patients receiving Denosumab as treatment for osteoporosis and prostate cancer therapy. In most cases, patients affected by ONJ were women aged 60 or over and posterior mandible area was the main site of involvement. Diabetes pre-treatment with bisphosphonates and exodontia were the most often risk factors related to the occurrence of this condition. Systemic and local antibiotic therapy with or without surgical debridement was the most used treatment for ONJ resolution. Conclusions: It is concluded that the highest number of ONJ cases caused by the use of anti-RANKL agents occurred in female patients, aged 60 years or older, under treatment for osteoporosis and cancer metastasis, and the most affected region was the mandible posterior

Is immunohistochemistry more sensitive than hematoxylin-eosin staining for identifying perineural or lymphovascular invasion in oral squamous cell carcinoma? A systematic review and meta-analysis

This study aimed to analyze whether immunohistochemistry (IHC) is more sensitive than hematoxylin-eosin (H&E) staining for identifying perineural invasion (PNI) or lymphovascular invasion (LVI) in oral squamous cell carcinoma (OSCC). In this systematic review and meta-analysis (Prospective Register of Systematic Reviews ? CRD 42021256515), data were obtained from six databases (PubMed, Scopus, LILACS, Web of Science, EBSCO, LIVIVO, Embase) and the grey literature. Cross-sectional observational studies of the diagnostic sensitivity of IHC for PNI and LVI were included. Studies were selected in two phases: first collection and reference retrieval. The Quality Assessment of Diagnostic Accuracy Studies-2 tool assessed study quality, while the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach assessed evidence quality. The meta-analysis (random effects model) was performed using MedCalc 18.2.1 software (MedCalc®) (p<0.05). Four studies (560 patients with 295 biopsies) were analyzed. The combined sensitivity was 76% (95% confidence interval [CI], 44.30?97.19%) and specificity was 42% (95% CI, 23.40?62.02%). The positive predictive value (PPV) and negative predictive value (NPV) were 61% (95% CI, 49.78?71.53%) and 70% (95% CI, 37.63?94.43%). The overall accuracy was 58% (95% CI, 45.17?70.65%). The risk of bias was low, and GRADE analysis showed a very low certainty of evidence. Our data suggest that IHC staining to highlight PNI/LVI may be useful in cases in which H&E analysis results in a negative decrease in the prevalence of false-negative cases and underestimated treatment

TNF-alpha expression, evaluation of collagen, and TUNEL of Matricaria recutita L. extract and triamcinolone on oral ulcer in diabetic rats

Diabetes mellitus (DM) is a disease associated with delayed wound healing of oral ulcers by increased expression of proinflammatory cytokines and cellular apoptosis. Objective to evaluate the influence of Tumor Necrosis Factor alpha (TNF-α) and apoptosis in rats with DM treated with chamomile extract or triamcinolone. Material and Methods Wistar male rats (210.0±4.2 g) were divided into five groups: negative control group (NCG) without diabetes; positive control group (PCG) with DM (alloxan, 45 mg/kg); and groups treated with chamomile extract (normoglycemic= NCG group and diabetic= DCG group) and with triamcinolone (TG). Traumatic ulcers were performed on all animals that received topical triamcinolone, chamomile extract or saline 12/12 hours for ten days. Results On days five and ten the animals were euthanized and the ulcers were analyzed by light microscopy, TUNEL assay, and immunohistochemically (TNF-α). The NCG (p=0.0062), PCG (p=0.0285), NCG (p=0.0041), and DCG (

Calcifying odontogenic cyst associated with complex odontoma treated with a conservative approach: a case report / Cisto odontogênico calcificante associado a odontoma complexo tratado com abordagem conservadora: relato de caso

Calcifying odontogenic cysts (COCs) are uncommon benign lesions arising from the odontogenic epithelium which are currently considered cysts. Histopathologically, it presents as an epithelial lining with ameloblastic characteristics, in addition to ghost cells with tendency to undergo calcifications. The objective of this study was to describe a case of a calcifying odontogenic cyst associated with odontoma, which was treated with a conservative two-step approach. A 29-year-old female presented with increased volume on the right side of the face with a lesion detected at the bottom of the buccal groove, extending from tooth 53 to 16. Radiographically, a wide, unilocular lesion was observed, involving tooth 13 that was impacted. Histopathological examination was consistent with COC associated with complex odontoma. No recurrence was seen at 6-month follow-up. The case addresses the importance of anatomopathological diagnosis of the lesion, since characterization of the cyst is fundamental to treatmen

Multifocal oral melanoacanthoma associated with Addison’s disease and hyperthyroidism: a case report

SUMMARY Oral melanoacanthoma is a mucocutaneous, pigmented, rare, benign, and probably reactive lesion. This paper reports for the first time in the literature a case of multifocal oral melanoacanthoma in a patient diagnosed with Addison’s disease and concomitant Graves’ disease with hyperthyroidism. The patient presented with oral pigmented lesions, which were hypothesized to be mucosal pigmentation associated with Addison’s disease. Due to their unusual clinical pattern, these oral lesions were biopsied and diagnosed as oral melanoacanthoma on histopathology and immunohistochemistry for HMB-45. At the moment of this report, the patient was being treated for her systemic conditions, but the lesions had not regressed. Reactive hyperpigmentation of the skin and mucous membranes may be found in Addison’s disease and hyperthyroidism. This case reinforces the hypothesis of a reactive nature for oral melanoacanthoma and highlights the need for investigation of endocrine disorders in patients with multifocal oral melanoacanthoma

Experimental model of traumatic ulcer in the cheek mucosa of rats Modelo experimental de úlcera traumática em mucosa jugal de ratos

PURPOSE: To establish an experimental model of traumatic ulcer in rat cheek mucosa for utilization in future alternative therapy studies. METHODS: A total of 60 adult male rats (250 - 300g) were used. Ulceration of the left cheek mucosa was provoked by abrasion using a nº 15 scalpel blade. The animals were observed for 10 days, during which they were weighed and their ulcers were measured. The histological characteristics were analyzed and scored according to the ulcer phase. In the statistical analysis, a value of p<0.01 was considered a statistically significant response in all cases. RESULTS: During the five first days, the animals lost weight (Student t test, p<0.01). The ulcerated area receded linearly over time and was almost completely cicatrized after 10 days (ANOVA, Tendency posttest, p<0.0001). Groups on days 1, 2 and 3 days displayed similar results, but a decrease in scores were observed after the 4th day. CONCLUSION: The proposed cheek mucosa ulcer model in rats can be considered an efficient, low-cost, reliable, and reproducible method.<br>OBJETIVO: Estabelecer um modelo experimental de úlcera traumática em mucosa jugal de ratos para utilização em futuros testes de terapias alternativas. MÉTODOS: Foram utilizados 60 ratos, adultos, machos, pesando entre 250 a 300g. A ulceração na mucosa jugal esquerda foi provocada por meio da abrasão desta com uma lâmina de bisturi número 15. Os animais foram observados por um período de 10 dias, sendo estes pesados e suas escoriações mensuradas. As características histológicas foram analisadas e descritas adotando escores para comparação dos estágios da fase da úlcera. Na análise estatística um valor de p<0,01 foi considerado uma resposta estatisticamente significante em todos os casos. RESULTADOS: Durante os cinco primeiros dias os animais perderam peso ("t" Student - p<0,01). A área da úlcera regrediu linearmente com o tempo, estando quase que completamente cicatrizada ao final de dez dias (ANOVA, pós-teste de Tendência - p<0,0001). Os grupos do 1º, 2º e 3º dias tiveram comportamento semelhante havendo uma diminuição dos escores a partir do 4º dia. CONCLUSÃO: O modelo de úlcera na mucosa jugal de ratos proposto pode ser considerado eficaz, apresentando reprodutibilidade confiável e baixo custo

Clinicopathological study of patients with head and neck sarcomas Avaliação clínico-patológica de pacientes com sarcomas em cabeça e pescoço

Sarcomas are rare tumors, mainly stemming from the embryonic mesoderm, with a high grade of morbidity and mortality. OBJECTIVE: To carry out a retrospective study of head and neck sarcoma cases between 1999 and 2008 in three specialized centers in the city of Fortaleza. MATERIALS AND METHODS: Data collection was based on the charts of the patients in the study. For statistical analysis purposes we used the chi-square associations and the z test for proportions. RESULTS: We found records of 36 patients, and the most affected ones were adult brown males, in the age range between 20 and 59 years - mean age of 39.7. The man/woman ratio was 1.76:1. The most prevalent histological type was the rhabdomyosarcoma and their most common locations were the face and the neck. Most of the sample was made up of live patients without evidence of the disease in the last visit - 41.6% of the cases. The most common treatment modes were the combination of surgery + radiotherapy + chemotherapy and surgery + radiotherapy, with 27.8% of the cases each. CONCLUSION: Sarcomas have a great histological variability and may have numerous locations. Since these are rare and not well-known lesions, new epidemiological studies must be carried out in order to enhance our understanding of the disease.<br>Sarcomas são tumores raros originados predominantemente do mesoderma embrionário e que apresentam elevado grau de morbidade e mortalidade. OBJETIVO: Realizar estudo retrospectivo dos casos de sarcomas em cabeça e pescoço no período de 1999 a 2008 em três centros especializados. MATERIAL E MÉTODO: A coleta de dados teve base nos prontuários dos pacientes estudados. Para análise estatística, foram utilizados os testes de associações qui-quadrado e o teste z para proporções. RESULTADO: Foram encontrados registros de 36 pacientes, sendo os indivíduos mais acometidos homens adultos, da raça parda, na faixa etária de 20 a 59 anos, com idade média de 39,7. A relação homem/mulher foi de 1,76:1. O tipo histológico mais prevalente foi rabdomiossarcoma e as localizações mais comuns foram face e região cervical. A maior parte da amostra foi de pacientes vivos sem evidência de doença na última consulta, com 41,6% dos casos. As formas mais comuns de tratamento foram a combinação de cirurgia+radioterapia+quimioterapia e cirurgia + radioterapia, com 27,8% dos casos cada. CONCLUSÃO: Os sarcomas apresentam grande variedade histológica e podem acometer diversas localizações. Por se tratar de lesões raras e pouco conhecidas, novos estudos epidemiológicos devem ser realizados para que se aumente o conhecimento sobre a doença

TNF-alpha expression, evaluation of collagen, and TUNEL of Matricaria recutita L. extract and triamcinolone on oral ulcer in diabetic rats

ABSTRACT Diabetes mellitus (DM) is a disease associated with delayed wound healing of oral ulcers by increased expression of proinflammatory cytokines and cellular apoptosis. Objective to evaluate the influence of Tumor Necrosis Factor alpha (TNF-α) and apoptosis in rats with DM treated with chamomile extract or triamcinolone. Material and Methods Wistar male rats (210.0±4.2 g) were divided into five groups: negative control group (NCG) without diabetes; positive control group (PCG) with DM (alloxan, 45 mg/kg); and groups treated with chamomile extract (normoglycemic= NCG group and diabetic= DCG group) and with triamcinolone (TG). Traumatic ulcers were performed on all animals that received topical triamcinolone, chamomile extract or saline 12/12 hours for ten days. Results On days five and ten the animals were euthanized and the ulcers were analyzed by light microscopy, TUNEL assay, and immunohistochemically (TNF-α). The NCG (p=0.0062), PCG (p=0.0285), NCG (p=0.0041), and DCG (p<0.0001) groups were completely healed on the 10th day, however, there was no healing on the TG (p=0.5127) group. The TNF-α expression showed a significant reduction from the 5th to the 10th day in NCG (p=0.0266) and DCG (p=0.0062). In connective tissue, the TUNEL assay showed a significant reduction in the number of positive cells in NCG (p=0.0273) and CNG (p=0.0469) and in the epithelium only in CDG (p=0.0320). Conclusions Chamomile extract can optimize the healing of traumatic oral ulcers in diabetic rats through the reduction of apoptosis in the epithelium and TNF-α expression