Overexpression of heat-shock protein 47 impacts survival of patients with oral squamous cell carcinoma.

BACKGROUND: The expression of heat-shock protein 47 (HSP47) has been linked to collagen synthesis control and implicated in fibrotic disorders, but more recent studies have demonstrated its role in solid tumors. In this study, we explored the prognostic impact of HSP47 in oral squamous cell carcinomas (OSCC) and determined the in vitro effects of its loss-of-function on viability, proliferation, migration, invasion, and resistance to cisplatin of OSCC cells. METHODS: The HSP47 expression in tumor samples was assessed by immunohistochemistry in two independent cohorts totaling 339 patients with OSCC, and protein levels were associated with clinicopathological features and survival outcomes. The OSCC cell lines HSC3 and SCC9 were transduced with lentivirus expressing short hairpin RNA to stably silence HSP47 and used in assays to measure cellular viability, proliferation, migration, and invasion. RESULTS: HSP47 was overexpressed in OSCC samples, and its overexpression was significantly and independently associated with poor disease-specific survival and shortened disease-free survival in both OSCC cohorts. The knockdown of HSP47 showed no effects on cell viability or cisplatin sensitivity, but impaired significantly proliferation, migration, and invasion of OSCC cells, with stronger effects on SCC9 cells. CONCLUSION: Our results show a significant prognostic impact of HSP47 overexpression in OSCC and reveal that HSP47 inhibition impairs the proliferation, migration, and invasion of OSCC cells. HSP47 may represent a potential therapeutic target for OSCC.

Prognostic significance of the neural invasion in oral squamous cell carcinoma.

BACKGROUND: Although nerve involvement can predict recurrence and prognosis in oral squamous cell carcinomas, there still have controversies and limitations regarding the standardization for its detection. In this study, we explore the impact of neural invasion in oral squamous cell carcinomas prognosis, comparing intraneural invasion (tumor cells inside nerve structure) and perineural invasion (cells involving the nerve, but not invading its sheath). METHODS: Surgical slides stained with hematoxylin and eosin from 235 patients with oral squamous cell carcinomas were carefully verified for the presence of intraneural invasion and perineural invasion. The location in the tumor (intratumoral vs. peritumoral) and number of foci (unifocal or multifocal) were also explored. Survival analyses for cancer-specific survival and disease-free survival were performed with Cox proportional model. RESULTS: Neural invasion was identified in 74 cases, 64.9% displayed intraneural invasion and 35.1% displayed perineural invasion. Univariate analysis revealed a significantly poorer cancer-specific survival, but not disease-free survival, in patients with intraneural invasion, in contrast to cases with perineural invasion that did not achieve significant association with both cancer-specific survival and disease-free survival. Further analyses revealed that the location in the tumor and number of foci had little impact on discriminatory ability of intraneural invasion. Multivariate analysis confirmed that intraneural invasion is significantly and independently associated with poor cancer-specific survival (hazard ratio: 2.50, 95% CI: 1.31-3.79, p = 0.003). CONCLUSION: This study provides evidence that intraneural invasion, but not perineural invasion, is a relevant predictor of survival in patients with oral squamous cell carcinomas, suggesting that its association with other clinical and pathological prognostic factors should be consider in determining the optimal treatment protocol and prognosis of these patients.

Exploring the combination of tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding with WHO histopathological grading on early-stage oral squamous cell carcinoma prognosis.

BACKGROUND: While the relevance of the World Health Organization histopathological grading system as a prognostic tool for oral squamous cell carcinoma has received many critics, other histopathological features such as tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding are displaying promising results. Here, we evaluated the prognostic impact of the incorporation of tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding into World Health Organization histopathological grading for patients with oral squamous cell carcinoma. METHODS: A total of 95 patients with early-stage oral squamous cell carcinoma were enrolled in the study, and World Health Organization tumor grading, tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding were evaluated in surgical slides stained with hematoxylin and eosin. Survival analyses for cancer-specific survival and disease-free survival were performed using Cox regression models, and receiver operating characteristic curves were applied for assessment of the performance of the combinations. RESULTS: Tumor-stroma ratio (stroma-rich) was significantly and independently associated with both shortened cancer-specific survival and poor disease-free survival, individually and in combination with World Health Organization histopathological grading. The combination of tumor-stroma ratio with World Health Organization grading did not improve the discriminatory ability compared to tumor-stroma ratio alone. Although low tumor-infiltrating lymphocytes were associated with shortened cancer-specific survival, the association did not withstand multivariate analysis. However, in combination with World Health Organization grading, low tumor-infiltrating lymphocytes were independently associated with poor cancer-specific survival. The combination of tumor-infiltrating lymphocytes and World Health Organization histopathological grading displayed a better discrimination of poor cancer-specific survival than tumor-infiltrating lymphocytes alone, but not at a significant level. CONCLUSION: Our findings support tumor-stroma ratio as a potential prognostic marker for patients with oral squamous cell carcinoma, and the incorporation of tumor-infiltrating lymphocytes into the World Health Organization grading system improves the prognostic ability of the tumor grading alone.

Trophoblast cell surface antigen 2 expression predicts outcome in oral squamous cell carcinomas.

BACKGROUND: Trophoblast cell surface antigen 2 (TROP2) has unclear clinical role in oral squamous cell carcinomas (OSCC). Here, we investigated the association of TROP2 immunoexpression with clinicopathological parameters and survival of OSCC patients. SUBJECTS AND METHODS: Cancer-specific survival (CSS) and disease-free survival (DFS) were assessed in a cohort composed of 266 OSCC. An independent cohort with 88 OSCC samples matched with the normal oral tissue, as well as 17 metastatic lymph nodes, was used for validation. RESULTS: Multivariate analysis showed TROP2 as an independent marker of favorable prognosis for both CSS (HR: 0.60, 95% CI: 0.40-0.90, p = .01) and DFS (HR: 0.57, 95% CI: 0.36-0.89, p = .01). Furthermore, TROP2 protein expression was significantly higher in morphologically normal tissues compared to primary tumors (p < .0001) and lymph node metastases (p = .001), and it was significantly associated with CSS (HR: 0.26, 95% CI: 0.09-0.74, p = .008) in the validation cohort. A pooled mRNA analysis performed on the Oncomine™ database confirmed the underexpression in OSCC compared with normal tissues (p = .014). CONCLUSIONS: In summary, our results point to a favorable prognostic significance of TROP2 overexpression in a large cohort of oral cancer patients, suggesting it as an attractive clinical marker.

Stress induced phosphoprotein 1 overexpression controls proliferation, migration and invasion and is associated with poor survival in oral squamous cell carcinoma.

Objective: Although there have been remarkable achievements in the molecular landscape of oral squamous cell carcinoma (OSCC) in recent years, bringing advances in the understanding of its pathogenesis, development and progression, little has been applied in the prognosis and choosing the optimal treatment. In this study, we explored the influence of the stress induced phosphoprotein 1 (STIP1), which is frequently reported to be highly expressed in many cancers, in OSCCs. Methods: STIP1 expression was assessed in the TCGA database and in two independent cohorts by immunohistochemistry. Knockdown strategy was applied in OSCC cell lines to determine the impact of STIP1 on viability, proliferation, migration and invasion. The zebrafish model was applied for studying tumor formation and metastasis in vivo. The association of STIP1 and miR-218-5p was explored by bioinformatics and mimics transfection. Results: STIP1 was highly expressed in OSCCs and significantly associated with shortened survival and higher risk of recurrence. STIP1 down-regulation decreased proliferation, migration and invasion of tumor cells, and reduced the number of metastases in the Zebrafish model. STIP1 and miR-218-5p were inversely expressed, and the transfection of miR-218-5p mimics into OSCC cells decreased STIP1 levels as well as proliferation, migration and invasion. Conclusion: Our findings show that STIP1 overexpression, which is inversely associated with miR-218-5p levels, contributes to OSCC aggressiveness by controlling proliferation, migration and invasion and is a determinant of poor prognosis.

Eukaryotic translation elongation factor 1δ, N-terminal propeptide of type I collagen and cancer-associated fibroblasts are prognostic markers of oral squamous cell carcinoma patients.

OBJECTIVE: Identifying markers that influence oral squamous cell carcinoma (OSCC) prognosis is a fundamental strategy to improve the overall survival of patients. Markers such as eukaryotic translation elongation factor 1δ (EEF1D), fascin, N-terminal propeptide of type I collagen (PINP), and cancer-associated fibroblasts (CAFs) have been noticed in OSCCs and their levels are closely related to the prognosis of tumors. Our aim was to confirm the role of those markers in OSCC prognosis. STUDY DESIGN: Immunohistochemistry was performed in 90 OSCC specimens. The associations between clinicopathologic features and expression of markers were assessed by χ2 test. Kaplan-Meier curves and univariate and multivariate Cox regression models were used for survival analysis. Markers were analyzed individually and in combination. RESULTS: High expression of EEF1D (P = .017) and PINP (P = .02) and abundant density of CAFs in tumor stroma (P = .005) predicted significantly poor survival in OSCC patients. Multivariate analysis revealed that all 3 parameters are individually independent prognostic factors of OSCC patients, and their combination improved the discrimination of patients at high risk for poor survival. CONCLUSIONS: Our results suggested that the expression of EEF1D and PINP and the density of CAFs might influence the survival of patients with OSCC.

Two rare cases of oral metastasis arising from lung adenocarcinoma and esophageal carcinoma.

Metastasis to the oral cavity are rare, representing only 1% of all oral malignancies, and originate from various sites such as the breast, prostate, lung and kidney. Clinically, they can simulate reactive and inflammatory lesions common in the oral cavity, and the clinical and microscopic diagnosis of these metastasis is a challenge. In this article, we report two new cases of esophageal and lung metastasis to oral tissues, highlighting their clinical characteristics and the process of diagnostic elucidation. We emphasize the importance for clinicians to consider the possibility of metastatic lesions in the oral cavity in patients previously diagnosed with malignant lesions in distant tissues and organs. Key words:Diagnosis, esophageal squamous cell carcinoma, adenocarcinoma of lung, oral cavity, metastasis.

Oral Manifestation of Lymphomatoid Granulomatosis.

Lymphomatoid granulomatosis (LYG) is a rare B-cell lymphoproliferative disorder driven by Esptein-Barr virus (EBV) that most commonly affects the lungs, although extra pulmonary sites like the central nervous system, skin, liver and kidney can also be involved. It is microscopically characterized by an angiocentric and angiodestructive growth pattern, predominantly composed by small T-cells, although a smaller population of atypical large B-cells is considered the true neoplastic component. Oral cavity involvement of LYG has rarely been described and the diagnosis of this neoplasm is very difficult. The aim of this report is to present a rare case of LYG affecting an 86-year-old female patient that was diagnosed due to an extensive, ulcerated and painful oral lesion affecting the hard palate. Detailed microscopic evaluation together with a large immunohistochemical study were necessary to achieve the correct diagnosis of LYG.

Variable expressivity and novel PTEN mutations in Cowden syndrome.

Cowden syndrome (CS) is a phosphatase and tensin homolog gene (PTEN)-associated condition characterized by multiple mucocutaneous hamartomas and an increased risk of malignancies. We reported an isolated case and another of several individuals in one family affected by CS. The isolated case showed typical features, including fibrocystic breast disease, benign thyroid nodules, and multiple papillomatous lesions in the face and oral cavity, and the cause was a novel nonsense mutation-guanine (G) to thymine (T) transition at position 940 (c.940 G>T)-in PTEN. In the family, the proband showed erythema nodosum, duodenal ulcer, intestinal polyps, cervical lipoma, renal cysts, and glaucoma, whereas multiple members of her family were found to have intestinal polyps, and a sister had been diagnosed with breast cancer at early age. An intronic mutation-T>G transition at the +32 position of intron 8 (c.1026+32 T>G)-was found in this family, with in silico analysis revealing the creation of a new donor splice site. This study confirmed the involvement of PTEN in CS and the variable clinical expressivity of disease.

A challenging diagnosis: Case report of oral metastasis from gastric adenocarcinoma mimicking pyogenic granuloma.

RATIONALE: Oral metastases occur more commonly in bone, but can also manifest in soft tissues and eventually resemble a reactive lesion. Few cases of oral metastases mimicking reactive lesions in soft tissues have been reported to date. PATIENT CONCERNS: We report a metastasis of gastric carcinoma (GC) to the oral mucosa without bone involvement in a 43 yom clinically and microscopically mimicking a reactive lesion. The patient related that the lesion had 1 month of evolution, and the ulcerated area suggested the lesion was related to trauma. DIAGNOSES: The histopathological examination of the lesion revealed an exuberant granulation tissue with few neoplastic cells, and the initial diagnosis of pyogenic granuloma was considered. In a second analysis, clusters of clear cells morphologically similar to degenerating mucous cells or macrophages, positive for Cytokeratin (CK)-20, and CDX2 were found. At the moment, it was confirmed the presence of a primary GC in the patient. INTERVENTIONS: A palliative radiotherapy/chemotherapy was started. OUTCOMES: However, the patient died 3 months after the diagnosis of oral metastasis. LESSONS: This report highlights the importance of careful clinical and microscopic examinations in cases of oral metastasis that may mimic a reactive lesion.

Metachronous ameloblastic fibro-odontoma and dentigerous cyst in the posterior mandible.

An ameloblastic fibro-odontoma (AFO) is a rare mixed odontogenic tumor with histologic features of an ameloblastic fibroma in conjunction with the presence of dentin and enamel. It usually appears as a well-circumscribed radiolucency with radiopaque foci and slow growth and is commonly seen in children and young adults. A 13-year-old boy presented with an asymptomatic swelling in the posterior right region of the mandible and the right ascending ramus. The clinical, imaging, and histopathologic findings confirmed the diagnosis of an AFO. After 8 months, a radiolucent lesion involving the unerupted mandibular left third molar was observed; a final diagnosis of a dentigerous cyst (DC) was established for this lesion. Although coincidental events, metachronous odontogenic lesions suggest a possible common genetic origin, since both can be caused by related cellular signaling pathways. Complete enucleation is recommended for both AFOs and DCs; rates of recurrence are low.

Sífilis materna e congênita, subnotificação e difícil controle / Maternal and congenital syphilis, underreported and difficult to control

RESUMO: Objetivo: Identificar e descrever casos de sífilis congênita e materna notificados e não notificados em uma cidade brasileira de médio porte. Métodos: Trata-se de estudo descritivo e retrospectivo que avaliou 214 prontuários de gestantes e recém-nascidos (RNs). Iniciou-se com identificação das fichas de notificação epidemiológica, seguida de busca ativa nas maternidades, avaliando-se todos os prontuários que apresentavam sorologia não treponêmica positiva e prontuários do serviço de referência em infectologia, na cidade de Montes Claros, Minas Gerais, no período de 2007 a 2013. As definições de casos seguiram as recomendações do Ministério da Saúde (MS) no Brasil e as variáveis foram descritas utilizando-se frequências absoluta e relativa. Estudo aprovado pelo Comitê de Ética em Pesquisa (Universidade Estadual de Montes Claros). Resultados: De 214 prontuários avaliados, foram identificados 93 casos de sífilis materna e 54 casos de sífilis congênita. As gestantes analisadas foram, predominantemente, de cor parda, apresentando ensino médio/superior, com faixa etária entre 21 e 30 anos e estado civil solteira. Considerando acompanhamento pré-natal das gestantes com sífilis, observou-se predomínio do diagnóstico tardio, após o parto ou a curetagem; a totalidade dos respectivos tratamentos foi considerada inadequada, segundo o MS. Dos RNs de gestantes com sífilis, a maioria não foi referenciada para acompanhamento pediátrico. Apenas 6,5% dos casos de sífilis em gestantes foram notificados; em relação à forma congênita, esse valor foi de 24,1%. Conclusão: Persistindo a transmissão vertical, verificam-se sinais de que a qualidade da atenção pré-natal e neonatal deve ser reestruturada.

ABSTRACT: Objective: To identify and to describe cases of congenital and maternal syphilis reported and not reported in a Brazilian medium-sized city. Methods: This is a descriptive and retrospective study, which evaluated 214 medical records of pregnant women and newborns. It began with the identification of epidemiological notification records, followed by active search in maternity evaluating all records that did show positive nontreponemal serology and records of the reference service in infectious diseases in Montes Claros, Minas Gerais, from 2007 to 2013. The case definitions followed the Ministry of Health recommendations in Brazil and the variables were described using absolute and relative frequencies. This study was approved by the Ethics in Research Committee (University State of Montes Claros). Results: Of the 214 medical records, we identified 93 cases of maternal syphilis and 54 cases of congenital. The women studied were predominantly mulatto, with Secundary/Higher, aged between 21 and 30 years and single marital status. Considering the prenatal care of pregnant women with syphilis, it was observed predominance of late diagnosis, after parturition or curettage, and all of their treatments were considered inadequate according the Ministry of Health. The newborns of pregnant women with syphilis, most were not referenced for pediatric follow-up. Only 6.5% of syphilis in pregnant women was notified, and in congenital syphilis, 24.1%. Conclusion: Persisting vertical transmission, there are signs that the quality of prenatal and neonatal care should be restructured.

Prevalence of depressive symptoms in patients with cleft lip and palate / Prevalência de sintomas depressivos em pacientes com fissuras labiopalatinas

INTRODUCTION: Cleft lip and/or palate (CL/P) represent the most common congenital anomalies of the face. OBJECTIVE: To evaluate the prevalence of depressive symptoms in children and adolescents with nonsyndromic cleft lip and/or palate (nsCL/P). METHODS: We conducted an observational, case-control study, with a case study group composed of 61 patients with nsCL/P, aged 7-17 years, and a control group of 61clinically normal patients. Both groups were selected at the same institution. RESULTS: Depressive symptoms were observed in the case group (nsCL/P), but there were no statistically significant differences compared to the control group. No association was found between the two groups (case and control) in relation to sociodemographic variables: gender, age and education. CONCLUSIONS: This study identified the prevalence of depressive symptoms in children and adolescents with nsCL/P from a localized geographic population, although the results were not statistically significant when compared to the control group, not justifying the use of CDI (Child Depression Inventory) as a screening instrument for depressive symptoms in the examined population. .

INTRODUÇÃO: Fissuras labiais e/ou palatinas (FL/Ps) representam as anomalias craniofaciais mais comuns. OBJETIVOS: Avaliar a prevalência de sintomas depressivos em crianças e adolescentes não sindrômicos com FL/P (FL/PNS). MÉTODO: Foi realizado um estudo observacional de caso-controle com uma amostra populacional de conveniência, com um grupo caso (61 pacientes com FL/PNS, tendo idades entre 7 a 17 anos) e um grupo controle (61 pacientes clinicamente normais). Ambos os grupos foram selecionados na mesma Instituição. RESULTADOS: Sintomas depressivos foram observados no grupo caso (FL/PNS), mas não houve diferenças estatisticamente significantes quando comparado com o grupo controle. Não foi encontrada associação entre os dois grupos (caso e controle) em relação às variáveis sociodemográficas: gênero, idade e educação. CONCLUSÕES: Este estudo observou a prevalência de sintomas depressivos em crianças e adolescentes com FL/PNS de uma população geográfica localizada, embora os resultados não tenham sido estatisticamente significantes quando comparado com o grupo controle, não justificando assim a utilização de instrumentos rastreadores de sintomas depressivos na população analisada. .

Prevalence of Dental Anomalies in Patients With Nonsyndromic Cleft Lip and/or Palate in a Brazilian Population.

Objective : Many studies have demonstrated a high frequency of dental anomalies in patients with cleft lip and/or palate. Because dental anomalies may complicate dental treatment, we investigated the prevalence of dental anomalies in a group of Brazilian patients with nonsyndromic cleft lip and/or palate. Design, Participants, Setting : Retrospective analysis was performed using clinical records of 296 patients aged between 12 and 30 years with repaired nonsyndromic cleft lip and/or palate without history of tooth extraction and orthodontic treatment. Associations between oral clefts and presence of dental anomalies outside the cleft area were investigated. Results : Dental anomalies were identified in 39.9% of the nonsyndromic cleft lip and/or palate patients, and tooth agenesis (47.5%), impacted tooth (13.1%), and microdontia (12.7%) were the most common anomalies. Cleft lip patients were less affected by dental anomalies compared with cleft palate or cleft lip and palate patients (p  =  .057). Specifically, patients with unilateral cleft lip and palate were significantly more affected by dental anomalies than those with bilateral cleft lip and palate (p  =  .00002), and individuals with unilateral complete cleft lip and palate (p  =  .002) and complete cleft palate (p  =  .01) were significantly more affected by tooth agenesis than other cleft types. Agenesis of the premolars (p  =  .043) and maxillary lateral incisors (p  =  .03) were significantly more frequent in patients with unilateral complete cleft lip and palate. Conclusions : The present study revealed a high frequency of dental anomalies in nonsyndromic cleft lip and/or palate patients and further demonstrated that patients with unilateral cleft lip and palate were frequently more affected by dental anomalies than those with bilateral cleft lip and palate. Moreover, our results demonstrate that dental anomalies should be considered during dental treatment planning for individuals affected by nonsyndromic cleft lip and/or palate.

Profile and scientific production of Brazilian researchers in oral pathology / Perfil e produção científica dos pesquisadores brasileiros em patologia oral

Objective: This study evaluated the profile and scientific production of research­ers in oral pathology who received grants in the area of Dentistry from the Brazilian National Research and Development Council. Material and Method : The standardized online curriculum vitae (Curriculum Lattes) of 34 researchers in oral pathology who received grants in the years 2008-2010 were analyzed. The variables were: gender, affiliation, time from completion of the PhD program, scientific production, and supervision of undergraduate students and Master's and PhD programs. Result: The States of São Paulo (52.94%) and Minas Gerais (26.47%) were responsible for 79.41% of the researchers. Regarding af­filiation, three institutions accounted for approximately 44.11% of the researchers: UNICAMP (17.64%); USP (14.70%); and UFMG (11.76%). The researchers published a total of 906 full-text articles, with a median of 26.64 articles per re­searcher in the triennium and 8.88 articles per year. It was found that of 906 articles published, 366 (40.39%) were published in strata A (qualis-CAPES). Oral pathology researchers supervised 437 scientific initiation and post-graduate students. Of these, 138 (31.57%) were scientific initiation, 169 (38.67%) were Master and 130 (29.74%) were PhD students. Conclusion: An important scientific production of oral pathology researchers in the 2008-2010 triennium was observed. By knowing the profile of researchers in oral pathology, more effective strategies for encouraging scientific production and demanding resources to finance research projects can be defined.

Objetivo: Este estudo objetivou avaliar o perfil e a produção científica de pesquisadores da Odontologia na área da patologia oral que receberam bolsas do Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) no Brasil. Material e Método: O curriculum vitae padronizado (Curriculum Lattes) de 34 pesquisadores da área de patologia oral que receberam bolsas no triênio 2008-2010 foram analisados. As variáveis analisadas foram: sexo, filiação institucional, tempo de conclusão do doutorado, produção científica, e orientação de estudantes de iniciação científica e em programas de mestrado e doutorado. Resultado: Os Estados de São Paulo (18; 52,94%) e Minas Gerais (9; 26,47%) foram responsáveis por 79,41% dos pesquisadores. Quanto à filiação, três instituições foram responsáveis por aproximadamente 44,11% dos pesquisadores: UNICAMP (6 = 17,64%); USP (5 = 14,71%) e UFMG (4 = 11,76%). Os pesquisadores publicaram um total de 906 artigos com texto completo, com mediana de 26,64 artigos por pesquisador no triênio e 8,88 artigos por ano. Verificou-se que de 906 artigos publicados, 366 (40,39%) foram publicados em qualis A (Qualis-CAPES). Os pesquisadores da patologia oral orientaram 437 alunos de graduação e pós graduação. Destes, 138 (31,57%) eram alunos de iniciação científica, 169 (38,67%) eram alunos de mestrado e 130 (29,74%) eram alunos de doutorado. Conclusão: Uma importante produção científica dos pesquisadores da patologia oral no triênio 2008-2010 foi observada. Ao conhecer o perfil dos pesquisadores da Odontologia na área de patologia oral, estratégias mais eficazes para estimular a produção científica e a demanda de recursos para financiar projetos de pesquisa podem ser definidas.

Síndrome de Waardenburg: aspectos oftalmológicos e critérios de diagnóstico: relatos de casos / Waardenburg syndrome: ophthalmic findings and criteria for diagnosis: case reports

OBJETIVO: Descrever as características clínicas e imaginológicas de duas famílias com a síndrome de Waardenburg, sendo uma do tipo I e outra do tipo II, enfatizando as manifestações oftalmológicas, bem como o padrão de herança genética. MÉTODO: Realizou-se um estudo clínico envolvendo as duas famílias afetadas pela síndrome de Waardenburg, sendo, através dos heredogramas, determinado o padrão de herança genética presente. Também foram realizadas análises oftalmológicas abordando a medida da acuidade visual, a presença de distopia cantorum (telecanto), a avaliação da coloração da íris e o mapeamento de retina, além de exames otológicos e dermatológicos. RESULTADOS: O heredograma da família afetada pela síndrome de Waardenburg tipo I revelou um modo autossômico dominante de transmissão. A condição estava presente em 85,71% dos pacientes. A distopia cantorum foi a alteração mais frequente, seguida pela mecha branca na pele da fronte, hipopigmentação da íris e da retina e surdez neurossensorial. A família com síndrome de Waardenburg tipo II apresentou 33,33% dos familiares com a alteração. Nenhum membro apresentou distopia cantorum e hipopigmentação de íris. Três pacientes apresentaram surdez neurossensorial (12,5%), associada ao topete branco e manchas acrômicas confluentes pelo corpo. CONCLUSÃO: O presente estudo mostra a importância do oftalmologista no auxílio do diagnóstico desta rara condição genética, uma vez que inclui alterações oftalmológicas como telecanto, hipopigmentação da íris e retina. A distopia cantorum é o principal critério diagnóstico para diferenciar o tipo I do II e deve ser feita por oftalmologista treinado. As famílias encontram-se em acompanhamento multiprofissional, tendo recebido orientações genéticas e os cuidados referentes à proteção ocular.

PURPOSE: To describe the clinical and imaginological features of two families with Waardenburg syndrome: type I and II, with emphasis on ophthalmic manifestations, as well as the pattern of genetic inheritance. METHODS: We conducted a clinical study involving two families affected by Waardenburg syndrome, and through the pedigree, determined the present pattern of genetic inheritance. Analyses were performed including the measurement of visual acuity, the presence of dystopia cantorum (telecanthus), evaluation of iris color and retinal mapping, as well as dermatological and otological examinations. RESULTS: The pedigree of the family affected by the Waardenburg syndrome type I showed an autosomal dominant mode of transmission. The syndrome was present at 85.71% of patients. The dystopia cantorum was the most frequent feature, followed by the white streak on the skin of the forehead, hypopigmentation of the iris and retina and deafness. The Waardenburg syndrome family type II had 33.33% of family members affected by the syndrome. No member had dystopia cantorum and hypopigmentation of the iris. Three patients had sensorineural hearing loss (12.5%), associated with white forelock and achromatic spots confluent by the body. CONCLUSION: This study shows the importance of the ophthalmologist in aiding the diagnosis of this rare genetic condition, since it includes ocular disorders such as telecanthus, hypopigmentation of the iris and retina. The cantorum dystopia is the main diagnostic criterion to differentiate type I and II syndrome and should be done by a trained ophthalmologist. The families are in medical monitoring, receiving genetic guidelines and care related to eye protection.

Cirurgia combinada de catarata e glaucoma com ponto escleral perilímbico: técnica cirúrgica e resultados a longo prazo / Combined cataract and glaucoma surgery with scleral peri-limbic suture: surgical technique and long-term results

OBJETIVO: Analisar os resultados da cirurgia combinada de catarata e glaucoma (FACO-TREC) e apresentar a técnica com o ponto escleral perilímbico. MÉTODOS: Estudo retrospectivo por levantamento de prontuários com informações sobre a pressão intraocular, acuidade visual, medicação hipotensora antes e depois da cirurgia e descrição do ato cirúrgico combinado (FACO-TREC), com acompanhamento mínimo de seis meses. Foram selecionados 10 pacientes com glaucoma e catarata (15 olhos), acompanhados de janeiro de 2005 a junho de 2007, no Departamento de Glaucoma da Santa Casa Olhos de Montes Claros (MG). A cirurgia de TREC utilizada foi a de base fórnix, sem uso de Mitomicina C, com a incisão principal da cirurgia de catarata realizada no mesmo sítio da TREC. A confecção do ponto escleral perilímbico se dá como uma sutura que se inicia na esclera nua, passa por cima do retalho escleral e é ancorada na esclera do outro lado do retalho. A conjuntiva é suturada com pontos simples por sobre o ponto. RESULTADOS: A acuidade visual, após seis meses da cirurgia mostrou-se melhor em 86,6% (13) dos olhos, inalterada em 6,66% (1 olho) e pior em 6,66%. A pressão intraocular média pré-operatória foi de 18,02 mmHg, a pós-operatória após 6 meses foi de 15,06 mmHg. Cinquenta por cento dos olhos operados ficaram livres dos colírios. CONCLUSÃO: Conclui-se que o ponto escleral perilímbico apresentou resultados favoráveis na obtenção de uma melhora na acuidade visual, redução da pressão intraocular e uma diminuição significativa no uso de drogas hipotensoras à custa de um número muito pequeno de complicações.

PURPOSE: To analyze the results of combined cataract and glaucoma surgery and to present the technique with scleral peri-limbic suture. METHODS: Retrospective study with review of the data about intraocular pressure, visual acuity, antihypertensive medication before and after surgery and description of the combined surgery technique, with follow up of six months. We selected 10 patients with glaucoma and cataract (15 eyes) followed up from January 2005 to June 2007 from Santa Casa Olhos de Montes Claros (MG). The glaucoma surgery was fornix-based, without use of mitomycin C, with the main cataract surgery incision performed on the same site The preparation of the scleral peri-limbic suture is given as a suture that begins on bare sclera, passes over the scleral flap and is anchored in the sclera on the other side of flap. The conjunctiva is sutured over the peri-limbic point. RESULTS: The visual acuity after six months of surgery was better in 86.6% of eyes, unchanged in 6.66% (one eye) and worse in 6.66. The mean preoperative IOP was 18.02 mmHg, after six postoperative months was 15.06 mmHg. Fifty percente of the eyes were free of eye drops. CONCLUSION: We conclude that scleral limbic suture showed favorable results in obtaining an improvement in visual acuity, reduction of intraocular pressure and a significant decrease in the use of hypotensive drugs at the expense of a very small number of complications.

Fatores de risco associados a fissuras orais não sindrômicas numapopulação brasileira: estudo caso-controle / Risk factors associated with nonsyndromic oral clefts in a Brazilian population: a case-control study

Introdução: Fissuras do lábio e/ou palato representam as anomalias congênitas mais comuns da face e, em 70% dos casos, tais anomalias congênitas ocorrem de forma não-sindrômica. Objetivo: Conduzir um estudo caso-controle para detectar fatores de risco associados às fissuras labiais e/ou palatinas não sindrômicas em um grupo de pacientes brasileiros. Material e método: Um questionário foi respondido por 60 mães com filhos apresentando fissuras labiais e/ou palatinas não sindrômicas (grupo caso) e por 51 mães com crianças saudáveis (grupo controle). As seguintes variáveis foram avaliadas: idade materna e paterna, distúrbios maternos, tabagismo e consumo de álcool durante a gravidez, história reprodutiva (aborto espontâneo, gravidez ectópica e natimorto), e uso de medicamentos e de multivitaminas durante a gravidez. Os resultados foram analisados em relação ao risco relativo de cada variável para estimar o odds ratio, com intervalo de confiança de 95%, e em seguida as análises bivariada e multivariada foram realizadas. Resultado: As análises revelaram que o único fator de risco mais relacionado às fissuras labiais e/ou palatinas não sindrômicas foi a variável história de natimorto, com odds ratio = 7,67 (p = 0,05). O uso de drogas lícitas não se correlacionou com as fissuras labiais e/ou palatinas não sindrômicas. Conclusão: Dos principais fatores de risco associados às fissuras labiais e/ou palatinas não sindrômicas descritas na literatura, apenas a história de natimorto mostrou significância estatística na população avaliada.

Background: Cleft lip and/or palate are the most common congenital anomalies of the face. In 70% of cases, such congenital anomalies occur in a nonsyndromic form. Purpose: To conduct a case-control study in order to detect possible risk factors for nonsyndromic cleft lip and/or cleft palate in a group of Brazilian patients. Material and method: A questionnaire was answered by 60 mothers of children with nonsyndromic cleft lip and/or cleft palate (case group), and by 51 mothers of healthy children (control group). The following variables were assessed: maternal and paternal ages, maternal disorders, smoking and alcohol consumption during pregnancy, reproductive history (miscarriage, ectopic pregnancy and stillbirth), medication and multivitamin usage during pregnancy. The results were analyzed in relation to the relative risk of each variable in order to estimate the odds ratio with a confidence interval of 95%. This was followed by bivariate and multivariate analysis. Result: The analyses revealed that the only significantly increased risk factor was a history of stillbirth, with an odds ratio = 7.67 (p = 0.05). The use of licit drugs was not correlated with nonsyndromic oral clefts. Conclusion: Of the main risk factors associated with nonsyndromic oral clefts described in the literature, only a history of stillbirth showed a statistical significance in the population studied.

Region 8q24 is a susceptibility locus for nonsyndromic oral clefting in Brazil.

BACKGROUND: Nonsyndromic cleft lip with or without cleft palate is a relatively common craniofacial defect with multifactorial inheritance. The association of the rs987525 single nucleotide variant, located in a gene desert at 8q24.21 region, has been consistently replicated in European populations. We performed a structured association approach combined with transcriptional analysis of the MYC gene to dissect the role of rs987525 in oral clefting susceptibility in the ethnically admixed Brazilian population. METHODS: We performed the association study conditioned on the individual ancestry proportions in a sample of 563 patients and 336 controls, and in an independent sample of 221 patients and 261 controls. The correlation between rs987525 genotypes and MYC transcriptional levels in orbicularis oris muscle mesenchymal stem cells was also investigated in 42 patients and 4 controls. RESULTS: We found a significant association in the larger sample (p = 0.0016; OR = 1.80 [95% confidence interval {CI}, 1.21-2.69], for heterozygous genotype, and 2.71 [95% CI, 1.47-4.96] for homozygous genotype). We did not find a significant correlation between rs987525 genotypes and MYC transcriptional levels (p = 0.14; r = -0.22, Spearman Correlation). CONCLUSIONS: We present a positive association of rs987525 in the Brazilian population for the first time, and it is likely that the European contribution to our population is driving this association. We also cannot discard a role of rs987515 in MYC regulation, because this locus behaves as an expression quantitative locus of MYC in another tissue.