International cooperation and health policy implementation in a post-conflict situation: the case of East Timor / Cooperação internacional e formulação de políticas de saúde em situação pós-conflito: o caso do Timor-Leste

This study centers on relationships among national and international actors in preparation of the first health policy document for East Timor, under the United Nations transitional administration, between 1999 and 2002. International cooperation support for the health system rehabilitation process during the post-conflict period is analyzed as part of reconstruction of the State in parallel with construction of the country's political and institutional framework. Knowledge, ideas, "ways of doing," and induced and accepted practices permeate an interplay of power relationships that condition both national political alliance-building and the architecture of international aid, pointing to input to a discussion of how these mechanisms interact at different conjunctures and times in different negotiating frameworks. .

Dedica-se, aqui, às relações entre diferentes atores na elaboração do primeiro documento de política de saúde para o Timor-Leste, sob a administração transitória das Nações Unidas, de 1999 a 2002. O apoio da cooperação internacional no processo de reabilitação do sistema de saúde no período pós-conflito é analisado como parte da reconstrução do Estado e concomitante à construção do arcabouço político e institucional no país. Conhecimentos, ideias, "modos de fazer" e práticas induzidas e aceitas entremeiam um jogo de relações de poder que condiciona tanto a articulação política nacional quanto a arquitetura da ajuda externa, apontando elementos para a discussão de como esses mecanismos se organizam em conjunturas diferentes de negociação.

Lesiones gástricas en pacientes infectados con Helicobacter pylori: expresión de RAGE (receptor de productos de glicosilización avanzada) y otros inmunomarcadores / Expression of RAGE in Helicobacter pylori infested gastric biopsies

Background: Inflammation is a common phenomenon present in gastric mucosa of patients infected with H. pylori. Activation of the RAGE/multiligand axis is thought to be a relevant factor in cancer-mediated inflammation. RAGE is a membrane receptor, belonging to the immunoglobulin family, and the over-expression of RAGE has been associated with increased invasiveness and metastasis generation in different types of cancer, including gastric cancer. Furthermore recent experiences show that the use of its soluble form (sRAGE) or silencing of the gene coding for this receptor could provide therapeutic benefits in cancer. Aim: To evaluate the immunohistochemical expression of RAGE, MUC-1, β-Catenin free and phosphorylated, Cyclin-D1 and GSK3 in gastric biopsy specimens infected with H. pylori. Material and Methods: Immunohistochemical analysis was carried out in gastric biopsies from 138 patients: 55 with inflammatory injury (no atrophic gastritis), 42 with pre-cancerous conditions (atrophy or intestinal metaplasia) and 41 with dysplastic lesions or in situ adenocarcinoma. Results: There was a high rate of positive RAGE expression in the three groups of biopsies. Biopsies with dysplasia or in situ carcinoma had a significantly higher percentage of RAGE expression than the other groups of biopsies. Conclusions: The increased RAGE expression reported in both dysplasia and incipient cancer support the role of the multiligand/RAGE axis in gastric carcinogenesis.

Expression of claudin, paxillin and FRA-1 in non-nodular breast lesions in association with microcalcifications / Expressão de claudina, paxilina e FRA-1 em lesões mamárias não nodulares associadas a microcalcificações

CONTEXT AND OBJECTIVE The possible role of adhesion molecules in early breast carcinogenesis has been shown in the literature. We aimed to analyze early adhesion imbalances in non-nodular breast lesions and their association with precursor lesions, in order to ascertain whether these alterations exist and contribute towards early carcinogenesis. DESIGN AND SETTING Retrospective cross-sectional study based on medical records at a private radiological clinic in São Paulo, Brazil. METHODS We retrospectively reviewed the medical records of all consecutive women attended between August 2006 and July 2007 who presented mammographic evidence of breast microcalcifications classified as Breast Imaging Reporting and Data System Atlas (BI-RADS) type 4. These women underwent stereotaxic biopsy. Clinical, radiological and pathological data were collected, and immunohistochemical assays searched for claudin, paxillin, FRA-1 and HER-2. RESULTS Over this period, 127 patients were evaluated. Previous BI-RADS diagnoses showed that 69 cases were in category 4A, 47 in 4B and 11 in 4C. Morphological assessment showed benign entities in 86.5%. Most of the benign lesions showed preserved claudin expression, associated with paxillin (P < 0.001). Paxillin and HER-2 expressions were correlated. FRA-1 expression was also strongly associated with HER-2 expression (P < 0.001). CONCLUSIONS Although already present in smaller amounts, imbalance of adhesion molecules is not necessarily prevalent in non-nodular breast lesions. Since FRA-1 expression reached statistically significant correlations with radiological and morphological diagnoses and HER-2 status, it may have a predictive role in this setting. .

CONTEXTO E OBJETIVO A literatura tem mostrado a importância de moléculas de adesão na carcinogênese precoce de mama. Objetivamos analisar desequilíbrios precoces de adesão em lesões não nodulares da mama e associação com lesões precursoras, a fim de verificar se essas alterações existem e contribuem com a carcinogênese. TIPO DE ESTUDO E LOCAL Estudo retrospectivo baseado em prontuários médicos, numa clínica radiológica privada em São Paulo, Brasil. MÉTODOS Revisamos retrospectivamente prontuários de todas as mulheres consecutivamente atendidas com evidência mamográfica de microcalcificações mamárias, classificadas como tipo 4 do Breast Imaging Reporting and Data System Atlas (BI-RADS) entre agosto de 2006 e julho de 2007. Elas foram submetidas a biópsia estereotáxica. Dados clínicos, radiológicos e histopatológicos foram coletados e ensaios de imunoistoquímica procuraram por claudina, paxilina, HER-2 e FRA-1. RESULTADOS No período, 127 pacientes foram avaliadas. Diagnósticos de BI-RADS anteriores tinham 69 casos na categoria 4A, 47 em 4B, e 11 em 4C. A avaliação morfológica mostrou entidades benignas em 86,5%. A maioria das lesões benignas mostrou expressão preservada de claudina, associada a paxilina (P < 0,001). Expressões de paxilina e HER-2 foram correlacionadas. Expressão de FRA-1 associou-se à de HER-2 (P < 0,001). CONCLUSÕES Embora já presente em menor quantidade, o desequilíbrio de moléculas de adesão não é necessariamente prevalente em lesões mamárias nodulares e talvez a expressão de FRA-1 possa ter um papel preditivo neste cenário, uma vez que atingiu correlações ...

An Inverse Relationship between the Expression of the Gastric Tumor Suppressor RUNX3 and Infection with Helicobacter pylori in Gastric Epithelial Dysplasia

BACKGROUND/AIMS: This study was performed to determine the association between RUNX3 expression and Helicobacter pylori infection in premalignant gastric lesions. METHODS: We examined 107 patients with gastric epithelial dysplasia who had undergone endoscopic mucosal resection or submucosal dissection. All tissue samples were evaluated by RUNX3 staining and subclassified by immunophenotype. H. pylori infection in dysplastic lesions and the normal surrounding tissue was examined by silver staining, and cagA status was assessed by polymerase chain reaction. RESULTS: The loss of RUNX3 expression was observed in 62 cases (57.9%), and an association with H. pylori infection was found in 54 cases (50.5%). The infection rate with the cagA-positive H. pylori strain was 63.0%. In RUNX3-negative lesions, the rate of H. pylori infection (p=0.03) and the frequency of category 4 lesions (according to the revised Vienna classification) were high (p=0.02). In addition, the gastric mucin phenotype was predominant. In RUNX3-negative category 4 lesions, the rate of cagA-positive H. pylori infection rate was high but not significantly increased (p=0.08). CONCLUSIONS: Infection with H. pylori is associated with inactivation of RUNX3 in early gastric carcinogenesis. This mechanism was prominent in gastric cancer with a gastric mucin phenotype.

Diagnostic efficiency of toluidine blue with Lugol's iodine in oral premalignant and malignant lesions.

Background and Objectives: In vivo stains are prompt resources, which have emerged, in the recent years, to aid as clinical diagnostic tools in detecting early premalignant and malignant lesions. The aim of the study was to determine the diagnostic efficiency of toluidine blue with Lugol's iodine in oral premalignancies and malignancies and to evaluate the reliability of in vivo staining with toluidine blue and Lugol's iodine in the lesions at risk of malignancy. Materials and Methods: The study group comprised 30 subjects with clinically suspicious premalignant lesions and 30 subjects with clinically suspicious malignant lesions. All the lesions were stained consecutively with toluidine blue and Lugol's iodine and the dye retention were recorded with photographs. Depending on the retention of the dyes, the biopsy site was determined. The biopsy specimens were sent for histological confirmation and results were statistically analyzed. Results: The overall diagnostic accuracy of Lugol's iodine when used consecutively with toluidine blue stain in distinguishing premalignant lesions and malignant lesions was 90%. As the degree of differentiation of malignant lesions progressed toward more severity, they failed to show the retention of Lugol's iodine and the result was highly significant statistically, with a P value < 0.001. Interpretation and Conclusion: Lugol's iodine when used with toluidine blue helped in delineating the inflammatory lesions and was the mean source in determining clinically the degrees of differentiation of malignant lesions as the poorly differentiated malignant lesions without glycogen content failed to show Lugol's iodine retention. Toluidine blue with Lugol's iodine can be used as a pretherapeutic assessment of the biologic aggressiveness of the disease.

Argyrophilic nucleolar organizer regions in inflammatory, premalignant, and malignant oral lesions: a quantitative and qualitative assessment.

BACKGROUND AND OBJECTIVE: Argyrophilic nucleolar organizer regions (AgNORs) have found widespread application in the past, especially in tumor histopathology. This study was undertaken to evaluate the significance of various AgNOR parameters and to assess their role in differentiating hyperplastic, premalignant, and malignant lesions. MATERIALS AND METHODS: The study sample consisted of archival biopsy specimens of ten squamous cell carcinomas, ten premalignant lesions, and five inflammatory lesions. Two biopsies from normal mucosa acted as control. AgNORs were assessed both quantitatively and qualitatively. The data were analyzed using Student's independent t-test, one-way analysis of variance (ANOVA), and multiple range test (Tukey-HSD). RESULTS: Quantitatively significant difference existed in the number of AgNORs between the normal mucosa, inflammatory lesions, and carcinomas, but the premalignant lesions failed to differ significantly from the normal mucosa. The number of AgNORs was found to be related to epithelial proliferation. Qualitatively, in terms of size, shape, and pattern of distribution, the normal mucosa and inflammatory lesion were alike, but the premalignant and malignant lesions differed significantly from the normal, with a marked degree of AgNOR pleomorphism being observed in carcinomas. CONCLUSIONS: AgNOR quantity is strictly proportional to the proliferative activity of the cell and does not necessarily indicate malignancy. It is the qualitative characteristics of AgNOR that help to differentiate hyperplastic, premalignant, and malignant lesions.

p53 and Ki-67 in Barrett's carcinoma: is there any value to predict recurrence after circumferential endoscopic mucosal resection? / p53 e Ki-67 no carcinoma do esôfago de Barrett: algum valor na predição da recurrência após mucosectomia endoscópica circunferencial?

BACKGROUND: There are situations in which the specimens obtained after endoscopic mucosal resection of superficial adenocarcinoma arising from Barrett's esophagus are not adequate for histopathological assessment of the margins. In these cases, immunohistochemistry might be an useful tool for predicting cancer recurrence. AIM: To evaluate the value of p53 and Ki-67 immunohistochemistry in predicting the cancer recurrence in patients with Barrett's esophagus-related cancer referred to circumferential endoscopic mucosal resection. METHODS: Mucosectomy specimens from 41 patients were analyzed. All endoscopic biopsies prior to endoscopic mucosal resection presented high-grade dysplasia and cancer was detected in 23 of them. Positive reactions were considered the intense coloration in the nuclei of at least 90 percent of the cells in each high-power magnification field, and immunostaining could be classified as superficial or diffuse according to the mucosal distribution of the stained nuclei. RESULTS: Endoscopic mucosal resection samples detected cancer in 21 cases. In these cases, p53 immunohistochemistry revealed a diffuse positivity for the great majority of these cancers (90.5 percent vs. 20 percent), and Ki-67 showed a diffuse pattern for all cases (100 percent vs. 30 percent); conversely, patients without cancer revealed a superficial or negative pattern for p53 (80 percent vs. 9.5 percent) and Ki-67 (70 percent vs. 0 percent). During a mean follow-up of 31.6 months, 5 (12.2 percent) patients developed six episodes of recurrent cancer. Endoscopic mucosal resection specimens did not show any significant difference in the p53 and Ki-67 expression for patients developing cancer after endoscopic treatment. CONCLUSIONS: p53 and Ki-67 immunohistochemistry were useful to confirm the cancer; however, they had not value for predicting the recurrent carcinoma after circumferential endoscopic mucosal resection of Barrett's carcinoma.

RACIONAL: Há situações nas quais o material obtido após mucosectomia endoscópica do adenocarcinoma superficial do esôfago de Barrett é inadequado para avaliação histopatológica de suas margens. Nesses casos, a imunoistoquímica poderia ser de auxílio para predição da recurrência tumoral. OBJETIVO: Avaliar o valor da detecção imunoistoquímica da p53 e do Ki-67 na predição da recurrência tumoral após mucosectomia endoscópica circunferencial do câncer no esôfago de Barrett. MÉTODOS: Foi analisado o material proveniente de mucosectomias de 41 pacientes. Todas as biopsias endoscópicas pré-mucosectomia apresentavam displasia de alto grau e câncer foi detectado em 23 casos. A imunorreatividade foi definida pela coloração de, pelo menos, 90 por cento dos núcleos em cada campo de grande aumento, podendo ser classificada como superficial ou difusa, conforme a distribuição celular dos núcleos corados. RESULTADOS: A mucosectomia detectou o câncer em 21 casos. Nesses casos, a p53 revelou padrão difuso de positividade para a maioria dos casos (90,5 por cento vs. 20 por cento) e o Ki-67 demonstrou padrão difuso para todos os portadores de câncer (100 por cento vs. 30 por cento). Por sua vez, pacientes sem câncer revelaram padrão negativo ou apenas superficial para a p53 (80 por cento vs. 9,5 por cento) e para o Ki-67 (70 por cento vs. 0 por cento). Durante seguimento médio de 31,6 meses, cinco (12,2 por cento) pacientes apresentaram seis episódios de câncer recurrente. Neste grupo, os fragmentos de mucosectomia não demonstraram nenhuma diferença significativa na expressão imunoistoquímica da p53 e do Ki-67 nos pacientes desenvolvendo câncer após o tratamento endoscópico. CONCLUSÕES: A imunoistoquímica da p53 e do Ki-67 é útil na confirmação do câncer; contudo não demonstra nenhum valor na predição da recurrência tumoral após mucosectomia endoscópica circunferencial do esôfago de Barrett com adenocarcinoma.

Expresión antigénica ABH y carácter secretor en pacientes con lesiones orales precancerosas y cancerosas / Secretor status and ABH antigens expression in patients with oral lesion

Los antígenos ABH, productos de la interacción de dos sistemas genéticos Hh y ABO, están sujetos a leyes de herencia y pueden estar localizados no sólo en los eritrocitos sino también en la mayoría de las células humanas. El objetivo del este trabajo fue investigar la relación entre el carácter secretor de pacientes con lesiones orales pre-malignas y malignas y la expresión antigénica ABH en cortes histológicos de dichas lesiones. Se trabajó con muestras incluídas en tacos de parafina de pacientes con lesiones orales. Los pacientes fueron clasificados en 2 grupos a) lesiones pre-malignas y malignas y b) lesiones benignas. Se investigaron los antígenos ABH por la técnica de inmunoadherencia específica modificada. Se utilizó la adherencia al tejido vascular como control positivo y al tejido adiposo como control negativo. Los resultados fueron semicuantificados desde adherencia fuertemente positiva a negativa. El carácter secretor fue determinado por la técnica de inhibición de la hemaglutinación. En 21 de las 34 muestras se observó una débil expresión antigénica en áreas atípicas, y deleción total en las áreas histológicamente afectadas por neoplasia. En 8 muestras hubo pérdida total de los antígenos ABH tanto en áreas normales como patológicas, estos pacientes presentaron un mayor grado de malignidad y metástasis que aquellos que conservaron la antigenicidad. Los pacientes con lesiones orales pre-malignas y malignas presentaron un incremento del carácter no secretor (52,3 por ciento) respecto de la población control (19,5 por ciento) y de aquellos pacientes con lesiones orales benignas (15.4 por ciento). Se observó una importante asociación entre pacientes no secretores y deleción de los antigenos ABH en muestras de lesiones orales. Además, hemos encontrado, en el grupo no secretor, una mayor malignidad de las lesiones orales como así también una mayor presentación de displasia epitelial. El estudio del carácter secretor en los pacientes con lesiones orales...

O critério de positividade para a análise imunoistoquímica da p53 na confirmação da displasia do esôfago de Barrett faz diferença? / Does positive criterium for p53 immunohistochemical analysis in the confirmation of Barrett's dysplasia make difference?

RACIONAL: O esôfago de Barrett é uma complicação da doença do refluxo gastroesofágico com importante potencial de malignização. Relata-se que a expressão do marcador tumoral p53 se acentua com a progressão displasia-adenocarcinoma. OBJETIVO: Avaliar a expressão da p53 no epitélio de Barrett com presença ou não de displasia conforme dois critérios de positividade. MATERIAL E MÉTODOS: O material foi constituído por biopsias endoscópicas de 42 doentes com esôfago de Barrett. Cortes histológicos foram corados pela hematoxilina-eosina, pelo PAS-alcian blue e avaliados quanto à expressão imunoistoquímica da p53. O diagnóstico de displasia foi firmado pela concordância entre três patologistas. Foram utilizados dois critérios de positividade para a p53: 1. a coloração de, pelo menos, metade dos núcleos e 2. o encontro de qualquer núcleo corado. RESULTADOS: O número total de fragmentos foi de 229, com média de 5,4 por paciente. A displasia foi detectada em seis (14,3 por cento) casos. Para diferentes critérios de positividade, a p53 foi detectada, respectivamente, em 5 (13,9 por cento) e 14 (38,9 por cento) com epitélio metaplásico não-displásico. Especificamente nos seis casos displásicos, a p53 foi detectada, conforme o critério de positividade, em um (16,7 por cento) e quatro (66,7 por cento) casos, respectivamente. CONCLUSÕES: Nesta pequena série, a expressão imunoistoquímica da p53, independente do critério de positividade, não foi de auxílio para a confirmação de alterações displásicas no esôfago de Barrett.

Overexpression of Promyelocytic Leukemia Protein and Alteration of PML Nuclear Bodies in Early Stage of Hepatocarcinogenesis

Promyelocytic leukemia protein (PML) is a major component of PML nuclear bodies (PML NBs). Fusion of promyelocytic leukemia gene (PML) with retinoic acid receptor alpha gene with the t (15;17) translocation causes disassembly of PML NBs, leading to development of acute promyelocytic leukemia. In contrast, PML overexpression as well as different morphological changes of PML NBs were described in a few solid tumors. In this study, the expression of PML through the multistep hepatocarcinogenesis was analyzed in 95 cases of human hepatocellular carcinomas (HCCs) for comparison along with dysplastic nodules (DNs) and background liver cirrhosis (LC) or chronic hepatitis by immunohistochemistry and immunoblot. In addition, cases of HCCs were further evaluated according to their histologic grade and etiology. The amount of PML as well as the num-ber and size of PML NBs increased gradually through the progression from LC, DNs to HCCs. The overexpression of PML in HCCs was much more closely associated with HBV infection than HCV infection or alcoholic liver disease. The PML expression, however, was not correlated with histologic grade of HCCs. These results suggest that PML is involved in the early stage of multistep hepatocarcinogenesis, and HBV infection may be associated with the overexpression of PML and the morphological alteration of PML NBs.