The effect of folic acid supplementation on dna biomarkers of colorectal cancer risk (uracil misincorporation, global and gene-specific dna hypomethylation) : a randomised intervention study

Background - Alterations in folate status are associated with colorectal carcinogenesis. Folate’s role has been postulated to be either via prevention of changes in DNA methylation or uracil misincorporation.
Objective - To investigate the effect of folic acid supplementation on colonocyte folate status and DNA biomarkers.
Design - Twenty individuals harbouring colonic adenomas were randomised to receive folic acid (600 g daily) or placebo for 6 months post polypectomy. Systemic and colonocyte folate status was determined at baseline and following the intervention. Modified Comet assays were used to determine uracil misincorporation and global DNA hypomethylation at the site adjacent to the polyp and a site distal to the polyp.
Outcomes - Supplementation resulted in increased colonocyte folate, which approached significance, at the site adjacent to the polyp (P= 0.06) but not distal to the polyp (P= 0.36); correspondingly there was a reduction in uracil misincorporation at the site adjacent to the polyp (P = 0.02) and the distal site showed no such trend (P= 0.39). There were no significant changes in global DNA hypomethylation at either site post-intervention.
Conclusions - Folic acid supplementation resulted in increased colonocyte folate and decreased uracil misincorporation at the site of the adenoma but not distal to the adenoma. This supports the hypothesis that localised areas of folate deficiency may exist in human colonic mucosa which respond to folic acid supplementation through increasing colonocyte folate and improving folate-related DNA biomarkers of cancer risk.

Prevalence of hysteroscopic findings and histologic diagnoses in patients with abnormal uterine bleeding

Objective: To describe the prevalence of hysteroscopic findings and histologic diagnoses inpatients with abnormal uterine bleeding (AUB).Design: Retrospective series of consecutive patients.Setting: Tertiary care University hospital and private office.Patient(s): Four thousand fifty-four hysteroscopies with biopsy in patients with AUB evaluated between June 1993 and December 2004.Intervention(S): Hysteroscopies were performed using 2.9-mm or 4-mm telescopes with CO2 or saline as the distension media. Biopsies were (lone with a 5-mm grasper or with a Novak's curette.Main Outcome Measure(s): Prevalence of hysteroscopic findings and histologic analysis of biopsies.Result(S): Endometrial polyp was the most frequent hysteroscopic finding, accounting for 1,374 (33.9%) cases. Normal uterine cavity and cervical canal were found in 814 (20.1%) patients. Submucous fibroids were diagnosed in 302 (7.5%) women. Normal endometrium was the most frequent histologic diagnosis, accounting for 1,888 (46.6%) cases. Endometrial polyp was found in 1, 115 (27.5%) patients. Endometrial hyperplasia was diagnosed in 613 (15.1%) and endometrial cancer in 105 (2.6%) women.Conclusion(s): Endometrial polyps are the most frequent hysteroscopic findings in patients with AUB, whereas normal endometrium is the most frequent histologic diagnosis.

Spatial expression of two anti-inflammatory mediators, annexin 1 and galectin-1, in nasal polyposis

Background There is renewed interest in the role played by specific counter-regulatory mechanisms to control the inflammatory host response, poorly investigated in human pathology. Here, we monitored the expression of two anti-inflammatory mediators, annexin 1 and galectin-1, and assessed their potential link to glucocorticoids' (GCs) effective control of nasal polyposis (NP).Methods Total patterns of mRNA and protein expression were analysed by quantitative real-time PCR (qPCR) and Western blotting analyses, whereas ultrastructural immunocytochemistry was used for spatial localization and quantification of each mediator, focusing on mast cells, eosinophils and epithelial cells.Results Up-regulation of the annexin 1 gene, and down-regulation of galectin-1 gene, was detected in polypoid tissue compared with nasal mucosa. Patient treatment with betamethasone augmented galectin-1 protein expression in polyps. At the cellular level, control mast cells and eosinophils displayed higher annexin 1 expression, whereas marked galectin-1 immunolabelling was detected in the granule matrix of mast cells. Cells of glandular duct epithelium also displayed expression of both annexin 1 and galectin-1, augmented after treatment.Conclusion Mast cells and epithelial cells appeared to be pivotal cell types involved in the expression of both annexin 1 and galectin-1. It is possible that annexin 1 and galectin-1 could be functionally associated with a specific mechanism in NP and that GC exert at least part of their beneficial effects on the airway mucosa by up-regulating, in a specific cell target fashion, these anti-inflammatory agonists.

Expressão dos genes que codificam as proteínas anexina-1 e galectina-1 nos pólipos rinossinusais e sua modulação pelo glicocorticoide

A fisiopatologia da polipose rinossinusal não é totalmente compreendida, apesar de várias hipóteses em relação ao seu processo inflamatório. OBJETIVOS: Estudo prospectivo da expressão dos genes das proteínas, anexina-1 e a galectina-1, que têm ação anti-inflamatória, e sua modulação pelo glicocorticoide. MATERIAL E MÉTODOS: Onze pacientes portadores de polipose rinossinusal tiveram biopsiados seus pólipos em dois momentos: na ausência de glicocorticoide sistêmico, e na sua presença. Nas duas amostras, foi avaliada a expressão desses genes e comparada com a expressão na mucosa nasal normal do meato médio. RESULTADOS: Verificou-se que a média de expressão dos genes que codifica a anexina-1 e galectina-1 estava predominantemente aumentada, independente do uso do glicocorticoide em relação à mucosa nasal controle. Entretanto, nos pólipos sem uso de corticoide, a média de expressão do gene da anexina-1 foi significativamente maior do que nos pólipos que estavam sob uso de glicocorticoide. Com relação à galectina-1 não houve diferença significativa entre as médias de expressão antes e após o uso de glicocorticoide sistêmico. CONCLUSÃO: Os genes apresentaram um aumento da expressão na mucosa nasal polipoide, independente do uso do glicocorticoide, porém a relação destes dois genes das proteínas anti-inflamatórias com o glicocorticoide não ocorreu da mesma maneira.

Gastroesophageal reflux disease and vocal disturbances

CONTEXTO: A doença do refluxo gastroesofágico (DRGE) é uma doença crônica na qual o conteúdo gastroduodenal reflui para o esôfago. O quadro clínico da DRGE é usualmente referido como pirose e regurgitação (manifestações típicas). Manifestações atípicas (distúrbios da voz e asma) podem também ser referidas. OBJETIVO: Analisar os aspectos clínicos, endoscópicos, manométricos e pHmétricos de pacientes portadores da DRGE com distúrbios da voz. MÉTODO: Foram estudados 50 pacientes com a DRGE, sendo 25 com distúrbios da voz (grupo 1 - G1) e 25 sem estes sintomas (controles, grupo 2 - G2). Todos os pacientes foram submetidos a endoscopia, manometria e pHmetria esofágica (dois sensores). Os pacientes do G1 foram submetidos a videolaringoscopia. RESULTADOS: Achados endoscópicos: DRGE não-erosiva foi observada em 95% dos pacientes de G1 e em 88% de G2. Videolaringoscopia: congestão das pregas vocais, assimetria, nódulos e pólipos foram diagnosticados nos pacientes do G1. Manometria esofágica: pressão no esfíncter inferior do esôfago (mm Hg): 11,6 ± 5,2 em G1 e 14,0 ± 6,2 em G2 (P = 0,14); pressão no esfíncter superior do esôfago (mm Hg): 58,4 ± 15,9 em G1 e 69,5 ± 30,7 nos controles. Achados pHmétricos: índice de DeMeester: 34,0 ± 20,9 em G1 e 15,4 ± 9,4 em G2 (P<0,001); número de episódios de refluxo no sensor distal: 43,0 ± 20,4 em G1 e 26, 4 ± 17,2 em G2 (P<0,003); percentagem do tempo com pH esofágico menor que 4 unidades (sensor distal): 9,0% ± 6,4% em G1 e 3,4% ± 2,1% em G2 (P<0,001); número de episódios de refluxo no sensor proximal: 7,5 ± 10,9 em G1 e 5,3 ± 5,7 em G2 (P = 0,38); percentagem de tempo com pH esofágico menor que quatro unidades (sensor proximal): 1,2% ± 2,7% em G1 e 0,5% ± 0,7% em G2 (P = 0,210). CONCLUSÕES: Os aspectos clínicos, endoscópicos e manométricos em pacientes com a DRGE e distúrbios da voz não diferem dos pacientes sem estes sintomas. A intensidade do refluxo gastroesofágico é maior nos pacientes com distúrbios da voz. Os pacientes sem distúrbios da voz podem também apresentar episódios de refluxo gastroesofágico no sensor proximal.

Estudo retrospectivo do resultado anatomopatológico de 100 polipectomias colonoscópicas realizadas na FMB-UNESP

OBJETIVO: Analisar retrospectivamente o resultado do estudo anatomopatológico de polipectomias colonoscópicas realizadas no Setor de Endoscopia da Faculdade de Medicina de Botucatu - UNESP durante os anos de 2002 e 2003. Material e Métodos: Estudamos retrospectivamente, a partir de procedimentos colonoscópicos realizados em nosso serviço, as características dos pólipos retirados: tamanho, localização e distribuição, bem como o motivo da indicação do mesmo e o resultado do estudo anatomopatológico. RESULTADOS: Num total de 100 polipectomias colonoscópicas realizadas em 75 pacientes, observamos que 63% dos pólipos localizava-se em reto e sigmóide e 15,8% no cólon descendente; o estudo anátomopatologico evidenciou que a grande maioria tinha características adenomatosas (54%). A idade dos pacientes variou entre 6 e 92 anos, não havendo predominância quanto ao sexo; a principal indicação para a realização de colonoscopia foi sangramento. CONCLUSÃO: Constatamos o importante papel diagnóstico e terapêutico das colonoscopias no que diz respeito ao câncer colorretal; os achados demonstram que, em nossa casuística, a maioria os pólipos colônicos são adenomatosos, pequenos e de localização distal.

A criança disfônica: diagnóstico, tratamento e evolução clínica

Os nódulos vocais são causas freqüentes de disfonias infantis, porém, através das vídeoendoscopias, outras lesões têm sido diagnosticadas na laringe infantil, como os cistos, sulcos, pontes e micromembranas, denominadas de lesões estruturais mínimas. OBJETIVO: Avaliar, em 71 crianças com disfonia agendadas nos ambulatórios de Foniatria da Faculdade de Medicina de Botucatu (Unesp) nos últimos cinco anos: sexo, idade, diagnósticos, tratamentos e evolução clínica. FORMA DE ESTUDO: Clínico retrospectivo. CASUÍSTICA E MÉTODO: Realizou-se estudo retrospectivo das avaliações otorrinolaringológicas e endoscópicas de 71 crianças com queixas de disfonia e idade entre 3 a 13 anos (45 meninos e 26 meninas). As crianças haviam sido submetidas a exame endoscópico com telescópio rígido ou nasofibroscópio flexível. Foram excluídas as crianças com disfonias funcionais ou com queixas de obstrução respiratória. RESULTADOS: Os principais diagnósticos foram: nódulo vocal (47 casos; 66,2%), cisto epidérmico (7 casos; 9,9%), cisto aberto fistulizado (6 casos; 8,4%), sulco vocal (5 casos; 7,1%), ponte + cisto (2 casos; 2,8%), micromembrana anterior (2 casos; 2,8%) e pólipo vocal (2 casos; 2,8%). As disfonias foram mais freqüentes entre os meninos (63,3%). A fonoterapia isolada foi o tratamento de escolha nos casos de nódulo vocal (evolução favorável), sulco vocal (evolução desfavorável) e micro-membrana (evolução desfavorável). Nas demais lesões (cistos, pontes e pólipos) o tratamento de escolha foi a cirurgia associada à fonoterapia, com resultados satisfatórios, exceto nos casos que recusaram a cirurgia. CONCLUSÃO: Os nódulos vocais são as principais causas de disfonias em crianças, porém as lesões estruturais mínimas mostraram-se também freqüentes, exigindo exame minucioso para o diagnóstico.

Bleomycin sensitivity in patients with familial and sporadic polyposis: a pilot study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Validation of hysteroscopic view in cases of endometrial hyperplasia and cancer in patients with abnormal uterine bleeding

STUDY OBJECTIVE: To validate hysteroscopic view with histology in cases of endometrial hyperplasia and cancer in patients with abnormal uterine bleeding (AUB)DESIGN: Retrospective study.(Canadian Task Force classification II-3).SETTING: University teaching hospitals in Rio de Janeiro and São Paulo, and private office in Rio de Janeiro.PATIENTS: Four thousand and fifty-four patients with AUB in whom hysteroscopic views were complete and the histologic result was conclusive.INTERVENTION: Four thousand and fifty-four office hysteroscopies with complete views and conclusive histologic results. The material for histologic examination was obtained through biopsy of the lesion in an outpatient unit or through the resection of the entire lesion in patients who underwent surgery. Histology was considered the gold standard and compared with the hysteroscopic view.MEASUREMENTS AND MAIN RESULTS: In the histology of the 4054 examinations, 613 (15.2%) were endometrial hyperplasia, and 105 (2.6%) were endometrial cancer. The most frequent hysteroscopic finding was endometrial polyps (31.2%). In endometrial hyperplasia, the sensitivity of the hysteroscopic view was 56.3% (95% CI 52.21-60.2%), specificity was 89.1% (95% CI 88.0%-90.1%), positive predictive value (PPV) was 48.0% (95% CI 44.3%-51.7%), negative predictive value (NPV) was 92.0% (95% Cl 90.1%-92.9%), and accuracy was 72.7% (95% CI 70.7%-74.7%). Accuracy was defined as the proportion of correct results among the hysteroscopic examinations. In endometrial cancer, the sensitivity of the hysteroscopic view was 80.0% (95% Cl 71.1%-87.2%), specificity was 99.5% (95% CI 99.2%-99.7%), PPV was 81.5% (95% Cl 72.7%-88.5%), NPV was 99.5% (95% CI 99.2%-99.7%), and accuracy was 89.8% (95% CI, 85.9%-93.6%). In the 814 patients (20.0%) in whom the hysteroscopic view was normal, there were no false negatives for endometrial cancer; however, there were 37 (4.5%) false negatives for endometrial hyperplasia. In the histologic cases of endometrial cancer, 101 (96.2%) hysteroscopic views were compatible with cancer or hyperplasia (80.0% and 16.2%, respectively). Ninety-seven out of 103 hysteroscopic views with cancer findings (94.2%) had histologic diagnosis of cancer or hyperplasia (81.5% and 12.6%, respectively).CONCLUSION: It seems that even in face of good validity of hysteroscopic view for endometrial hyperplasia and cancer, histologic study is mandatory in the presence of any lesion as the hysteroscopic view cannot completely replace the histologic study in patients with AUB. (C) 2006 AAGL. All rights reserved.

Loss of RKIP expression during the carcinogenic evolution of endometrial cancer

Aims Endometrial cancer is one of the most common cancers in women worldwide, but there is a lack of diagnostic markers for early detection of these tumours. The raf kinase inhibitory protein (RKIP) negatively regulates the Raf/MEK/ERK pathway, and the downregulation of RKIP is associated with tumour progression and metastasis in several human neoplasms. The aim of this study was to assess the expression levels of RKIP in endometrial cancer and determine whether this expression correlates with clinical outcome in these patients.Methods Tissue microarrays constructed using tissue samples from 209 endometrial adenocarcinomas, 49 endometrial polyps and 48 endometrial hyperplasias were analysed for RKIP expression by immunohistochemistry.Results The authors found that RKIP expression decreases significantly during malignant progression of endometrial cancer; it is highly expressed in non-neoplastic tissues (polyps 79.6%; hyperplasias 87.5%) and expressed at very low levels in endometrioid adenocarcinomas (29.7%). No correlations were observed between RKIP expression, clinicopathological data and survival.Conclusion This study demonstrated for the first time that RKIP expression is lost during the carcinogenic evolution of endometrial tumours and that the loss of RKIP expression is associated with a malignant phenotype. Functional studies are needed to address the biological role of RKIP downregulation in endometrial cancer.

Incidência e evolução da polipose nasal em crianças e adolescentes com fibrose cística

Nasal polyps are a clinical sign of alert for investigating Cystic Fibrosis (CF). Aims: To study the incidence of nasal polyps in children and adolescents with cystic fibrosis, its possible association with age, gender, clinical manifestations, genotype and sweat chlorine level, and its evolution with topical steroid therapy. Methods: Clinical symptoms, sweat chlorine level and genotype were studied in 23 cystic fibrosis patients. Nasal polyps were diagnosed by nasal endoscopy and treated with topical steroids during 6 months, followed by a second nasal endoscopy. Fisher test was used for statistical analysis. Results: Nasal polyps were found in 39.1% of the patients (five bilateral, four unilateral), all older than six years, recurrent pneumonia in 82.6%, pancreatic insufficiency in 87% and malnutrition in 74%. No association was seen between nasal polyps and sweat chlorine level, genotype, clinical sings of severity and nasal symptoms. Seven patients improved in their nasal polyps with topical steroids, six showed complete resolution. Conclusion: The study showed a high incidence of nasal polyps in older children, who span the entire range of clinical severity, even in the absence of clinical nasal symptoms. Topical steroid therapy showed good results. An interaction among pediatricians and otolaryngologists is necessary for diagnosis and follow-up. 2008 © Revista Brasileira de Otorrinolaringologia. All Rights reserved.

Avaliação histeroscópica em pacientes com infertilidade

PURPOSE: to describe hysteroscopy findings in infertile patients. METHODS: this was a retrospective series of 953 patients with diagnosis of infertility evaluated by hysteroscopy. A total of 957 patients investigated for infertility were subjected to hysteroscopy, preferentially during the first phase of the menstrual cycle. When necessary, directed biopsies (under direct visualization during the exam) or guided biopsies were obtained using a Novak curette after defining the site to be biopsied during the hysteroscopic examination. Outcome frequencies were determined as percentages, and the χ2 test was used for the correlations. The statistical software EpiInfo 2000 (CDC) was used for data analysis. RESULTS: a normal uterine cavity was detected in 436 cases (45.8%). This was the most frequent diagnosis for women with primary infertility and for women with one or no abortion (p<0.05). Abnormal findings were obtained in 517 of 953 cases (54.2%), including intrauterine synechiae in 185 patients (19.4%), endometrial polyps in 115 (12.1%), endocervical polyps in 66 (6.0%), submucosal myomas in 47 (4.9%), endometrial hyperplasia in 39 (4.1%), adenomyosis in five (0.5%), endometritis (with histopathological confirmation) in four (0.4%), endometrial bone metaplasia in two (0.4%), and cancer of the endometrium in one case (0.1%). Morphological and functional changes of the uterus were detected in 5.6% of the cases, including uterine malformations in 32 (3.4%) and isthmus-cervical incompetence in 21 (2.2%). CONCLUSIONS: intrauterine synechiae were the most frequent abnormal findings in patients evaluated for infertility. Patients with a history of abortion and infertility should be submitted to hysteroscopy in order to rule out intrauterine synechiae as a possible cause of infertility.

Acurácia da histerossonografia versus ultrassonografia transvaginal em mulheres inférteis candidatas às técnicas de reprodução assistida

PURPOSE: To compare the diagnostic accuracy of sonohysterography (HSN) and conventional transvaginal ultrasound (USG) in assessing the uterine cavity of infertile women candidate to assisted reproduction techniques (ART). METHODS: Comparative cross-sectional study with 120 infertile women candidate to ART, assisted at Centro de Reprodução Assistida (CRA) of Hospital Regional da Asa Sul (HRAS), Brasília-DF, from August 2009 to November 2010. Sonohysterography was performed with saline solution infusion in a close system. The sonohysterography finding was compared to previous USG results. The uterine cavity was considered abnormal whenthe endometrium was found to be thicker than expectedduring the menstrual cycle and whenan endometrial polyp, a submucous myoma and an abnormal shape of the uterine cavity were observed. The statistical analysis was doneusing absolute frequencies, percentage values and the χ 2, with the level of significance set at5%. RESULTS:HSN revealed that 92 (76.7%) infertile women candidate to ARThad anormal uterine cavity, while 28 (23.3%) had the following abnormalities: 15 polyps (12.5%).

Correlação ultrassonográfica e histeroscópica no diagnóstico de pólipos endometriais em mulheres na pós-menopausa

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Expressão das proteinas p53, Ki67 e CD31 nos pólipos endometriais em mulheres na pós-menopausa usuárias de tamoxifeno

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB