Long-Term Recurrence of Nonmelanoma Skin Cancer after Topical Methylaminolevulinate Photodynamic Therapy in a Dermato-Oncology Department

BACKGROUND: Most available studies on the efficacy of topical photodynamic therapy focus on short-to medium-term results. Long-term data are scarce. OBJECTIVE: To evaluate the long-term efficacy of photodynamic therapy with topical methylaminolevulinate to treat Bowen's disease and basal cell carcinoma in the clinical practice setting of a dermato-oncology department. METHODS: The study included patients diagnosed with Bowen's disease or basal cell carcinoma, and who received photodynamic therapy from 2004 to 2008. Treatment protocol and clinical follow-up were standardized. The primary endpoint was clinically observed recurrence in a previous photodynamic therapy-treated area. Descriptive and survival analyses were performed. RESULTS: A total of 31 Bowen's disease lesions and 44 superficial basal cell carcinoma were treated, with a median follow-up of 43.5 months. Recurrence was observed in 14 Bowen's disease lesions (53.8%) and in 11 superficial basal cell carcinoma (33.3%). Significantly higher estimates for recurrence rates were found in patients with Bowen's disease (p=0.0036) or those aged under 58 years (p=0.039). The risk of recurrence was higher in patients with Bowen's disease than in those with superficial basal cell carcinoma and younger patients. CONCLUSIONS: Recurrence should be considered when choosing to treat non-melanoma skin cancer with photodynamic therapy. Younger age and Bowen's disease were independent predictors for long-term recurrence, suggesting the need to establish an extended period of follow-up for this subset of patients.

Predição de Pré-Eclâmpsia no Primeiro Trimestre em Gravidezes de Baixo Risco: Determinação do Cut-Off numa Amostra da População Portuguesa

Objective:We aimed to identify the cut-off for risk of pre-eclampsia (PE) in Portuguese population by applying the first trimester prediction model from Fetal Medicine Foundation (FMF) in a prospective enrolled cohort of low risk pregnant women. Population and methods: A prospective cohort of low risk singleton pregnancies underwent routine first-trimester scree - ning from 2011 through 2013. Maternal characteristics, blood pressure, uterine artery Doppler, levels of pregnancy-associated plasma protein-A (PAPP-A) and free b-human chorionic gonadotropin were evaluated. The prediction of PE in first trimester was calculated through software Astraia, the outcome obtained from medical records and the cutoff value was subse quently calculated. Results:Of the 273 enrolled patients, 7 (2.6%) developed PE. In first trimester women who developed PE presented higher uterine arteries resistance, represented by higher values of lowest and mean uterine pulsatility index, p <0.005. There was no statistical significance among the remaining maternal characteristics, body mass index, blood pressure and PAPP-A. Using the FMF first trimester PE algorithm, an ideal cut-off of 0.045 (1/22) would correctly detect 71% women who developed PE for a 12% false positive rate and a likelihood ratio of 12.98 (area under the curve: 0.69; confidence interval 95%: 0.39-0.99). By applying the reported cutoff to our cohort, we would obtain 71.4% true positives, 88.3% true negatives, 11.4% false positives and 28.6% false negatives. Conclusion: By applying a first trimester PE prediction model to low risk pregnancies derived from a Portuguese population, a significant proportion of patients would have been predicted as high risk. New larger studies are required to confirm the present findings.

Multiple Haemangiomas, Diaphragmatic Eventration and Beckwith-Wiedemann Syndrome: An Unusual Association

A 6-month-old girl with Beckwith-Wiedemann syndrome, multiple haemangiomas (axillary, laryngeal, pulmonary and hepatic) and diaphragmatic eventration was reported. All tumours responded to treatment with propranolol. The surgical correction of diaphragmatic eventration was crucial to a better outcome.

Henoch-Schönlein Purpura Associated with Pulmonary Adenocarcinoma

Introduction: The Henoch-Schönlein purpura (HSP) is an immunoglobulin A (IgA)-mediated smallvessel systemic vasculitis, rare in adults. The association with solid tumours has been described, especially with lung cancer. Case Report: We present the case of a 60-year-old Caucasian male, diagnosed with lung adenocarcinoma that underwent surgical resection without (neo)adjuvant theraphy. Two months latter he was admitted for abdominal pain, purpuric rash on his lower extremities and acute kidney injury, with serum creatinine (Scr) of 2 mg/dl. Urinalysis revealed haematuria and 24h proteinuria (P24h) of 1.5 g. The serum protein electrophoresis, complement components C3 and C4, circulating immune complexes, cryoglobulins, ANCA, ANA, anti-dsDNA and the remaining immunologic study as screening for viral infections (HCV, HBV and HIV) were negative. Renal ultrasound was normal and kidney biopsy revealed mild mesangial proliferation; 2 cellular glomerular crescents and 1 fibrinoid necrosis lesion; large amounts of red blood cell casts; lymphocytic infiltration in the intertubular interstitial capillaries; moderate arteriolar hyalinosis. Immunofluorescence demonstrated mesangial and parietal deposits of IgA. The diagnosis of HSP was assumed, and the patient started prednisolone 1 mg/kg/day. Ten months after diagnosis the patient’s baseline Scr is 1.4 mg/dl with P24h of 0.18g, without haematuria. Conclusion: Although this is a rare association and the exact mechanism behind the disease is yet unknown, physicians should be aware of it. The early recognition and treatment may prevent renal disease progression.

Identification of de Novo Germline Mutations in the HRPT2 Gene in Two Apparently Sporadic Cases with Challenging Parathyroid Tumor Diagnoses

The diagnosis of parathyroid carcinomas is often difficult. HRPT2 mutations have been identified in familial [hyperparathyroidism-jaw tumor (HPT-JT) syndrome] and sporadic parathyroid carcinomas, supporting that HRPT2 mutations may confer a malignant potential to parathyroid tumors. In this study, we report the clinical, histopathological, and genetic investigation of two unrelated cases, whom had apparently sporadic malignant parathyroid tumors, initially diagnosed as adenomas. In one case, the differential diagnosis was complicated by cervical seeding of parathyroid tumor cells. Genetic studies identified de novo HRPT2 germline mutations in cases 1 (c.518_521delTGTC [p.Ser174LysfsX27]) and 2 (c.226 C > T [p.Arg76X]), unveiling the hereditary HPT-JT syndrome in both patients. Furthermore, the identification of somatic mutations in the patients‟ parathyroid tumors provided evidence for complete inactivation of the HRPT2 gene, which was consistent with the tumor malignant features. The sensitivity of parafibromin immunostaining to detect HRPT2 mutations was limited. The present data suggests that patients with apparently sporadic parathyroid carcinomas, or parathyroid tumors with atypical histological features, should undergo molecular genetic testing, as it may detect germline HRPT2 mutations. Establishing the diagnosis of hereditary HPT-JT syndrome is relevant for clinical counseling and management of the carriers and their relatives.

Oral cavity lymphoma as secondary AIDS-defining neoplasm in a patient on HAART with immune reconstitution

Lymphomas of the oral cavity are a rare complication of advanced HIV/AIDS disease. The clinical appearance of these neoplasms includes masses or ulcerative lesions that involve the oral soft tissue and the jaw as the predominant manifestation. We report the case of a patient with AIDS who developed diffuse large B-cell non-Hodgkin’s lymphoma of the oral cavity during highly active antiretroviral therapy, with undetectable plasma viral load and immune reconstitution.

Thomsen-Friedenreich antigens in bladder cancer: evaluation of their prognostic value

RESUMO: Introdução. O cancro de bexiga é uma patologia comum que representa o 6° e o 5° cancro mais incidente em Portugal e na Itália, respetivamente. Em mais de metade dos casos ocorre reincidência durante o primeiro ano, requerendo acompanhamento clínico ao longo da vida. A instilação intravesical de Bacillus Calmette-Guérin (BCG) (uma estirpe atenuada do Mycobacterium bovis) representa uma imunoterapia eficaz no combate ao cancro de bexiga, no entanto, muitos aspetos da interação de BCG com as células tumorais bem como com as células do sistema imunitário permanecem por desvendar. As células tumorais de bexiga expressam frequentemente as formas sialiladas dos antigénios de Thomsen-Friedenreich (TF), i.e., sialil-T (sT) e sialil-Tn (sTn). Contudo ainda se desconhece o significado da sua expressão na malignidade tumoral e se afeta a eficácia da terapêutica BCG. Objetivo do estudo. Investigar o papel dos antigénios sT e sTn no fenótipo maligno de células de cancro de bexiga bem como na resposta mediada pelo sistema imunitário à terapia com BCG. Metodologia. Para tal, foram utilizadas as linhas celulares de cancro da bexiga HT1376 e MCR, geneticamente modificadas por transdução com vetores codificantes para as sialiltransferases ST3GAL1 ou ST6GALNAC1, de forma a expressar homogeneamente os antigénios sT ou sTn respetivamente. Estes modelos celulares foram estudados após confronto com BCG. O nível de BCG internalizado foi avaliado por citometria de fluxo. O perfil global de expressão genética dos modelos celulares antes e após incubação com BCG foi analisado pela tecnologia de microarray. O perfil de citocinas secretadas pelos modelos celulares após incubação com BCG, bem como de macrófagos estimulados pelo secretoma de células de cancro de bexiga que por sua vez foram estimuladas previamente por BCG, foi estudado pelo sistema multiplex de “imuno-esferas”. Resultados. A análise do transcritoma dos modelos celulares revelou que grupos de genes envolvidos em funções específicas foram modulados em paralelo nos dois modelos celulares, após transdução, independentemente da sialiltransferase expressa. Ou seja, em células que expressavam a sialiltransferase ST3GAL1 ou ST6GALNAC1, os genes envolvidos na regulação da segregação cromossómica e na reparação do DNA foram consistentemente regulados negativamente. Genes descritos na literatura como marcadores para o cancro de bexiga foram também modulados. A incubação com BCG resultou numa tendência ao aumento da expressão de genes relevantes na preservação e estabilidade genómica e menor malignidade, no entanto, apenas em células que expressavam sT ou sTn. Entre as dez citocinas testadas, apenas a IL-6 e IL-8 foram expressas pelas linhas celulares de cancro da bexiga, com indução destas após estimulação com BCG, e principalmente em células que expressavam ST3GAL1 ou ST6GALNAC1. Em macrófagos, citocinas inflamatórias, tais como IL-1β, IL-6 e TNFα, e a citocina anti-inflamatória IL-10, foram induzidas apenas pelo secretoma de células de cancro da bexiga confrontadas com BCG, com maior relevância quando estas expressavam ST3GAL1 ou ST6GALNAC1, prevendo a estimulação de macrófagos semelhantes aos de tipo M1 e uma melhor resposta à terapia com BCG. Conclusões. O efeito geral da expressão destas sialiltransferases e dos produtos enzimáticos sT ou sTn nas células de cancro de bexiga conduz a um fenótipo de maior malignidade. Contudo, a maior avidez de estas na produção de citocinas inflamatórias após confronto com BCG, bem como a maior capacidade de estimulação de macrófagos, predirá uma resposta à terapia com BCG mais eficaz em tumores que expressem os antigénios de TF sialilados. Tais conclusões são totalmente concordantes com os nossos mais recentes dados clínicos obtidos em colaboração, que mostram que em doentes com cancro de bexiga que expressam sTn respondem melhor a terapia BCG. ----------ABSTRACT: Background. Bladder cancer is a common malignancy representing the 6th and the 5th most incident cancer in Portugal and in Italy, respectively. More than half of the cases relapse within one year, requiring though a lifelong follow-up. Intravesical instillation of Bacillus Calmette-Guérin (BCG) (an attenuated strain of Mycobacterium bovis) represents an effective immunotherapy of bladder cancer, although many aspects of the interaction of BCG with cancer cells and host immune cells remain obscure. Bladder cancer cells often express the sialylated forms of the Thomsen-Friedenreich (TF), i.e., sialil-T (sT) e sialil-Tn (sTn). However, it’s still unknown the sense of such expression in tumour malignancy and in the BCG therapy efficacy. Aim of the study. To investigate the role of the sT and sTn antigens on the malignant phenotype of bladder cancer cells and the immune mediated response to BCG therapy. Experimental. We have utilized populations of the bladder cancer cell lines HT1376 and MCR, genetically modified by transduction with the sialyltransferases ST3GAL1 or ST6GALNAC1 to express homogeneously sT or sTn antigens. The level of BCG internalized was assessed by flow cytometry. The whole gene expression profile of BCG-challenged or unchallenged bladder cancer cell lines was studied by microarray technology. The profile of cytokines secreted by BCG-challenged bladder cancer cells and that of macrophages challenged by the secretome of BCG-challenged bladder cancer cells was studied by multiplex immune-beads assay. Results. Transcriptome analysis of the sialyltransferase-transduced cells revealed that groups of genes involved in specific functions were regulated in parallel in the two cell lines, regardless the sialyltransferase expressed. Namely, in sialyltransferase-expressing cells, genes involved in the proper chromosomal segregation and in the DNA repair were consistently down-regulated, while genes reported in literature as markers for bladder cancer were modulated. BCG-challenging induced a tendency to up-regulation of the genes preserving genomic stability and reducing malignancy, but only in cells expressing either sT or sTn. Among the ten cytokines tested, only IL-6 and IL-8 were expressed by bladder cancer cell lines and up-regulated by BCG-challenging, mainly in sialyltransferases-expressing cells. In macrophages, inflammatory cytokines, such as IL-1β, IL-6 and TNFα, and the antinflammatory IL-10 were induced only by the secretome of BCG-challenged bladder cancer cells, particularly when expressing either sialyltransferase, predicting the stimulation of M1-like macrophages and a better response to BCG therapy. Conclusions. The general effect of the expression of the two sialyltransferases and their products in the bladder cancer cells is toward a more malignant phenotype. However, the stronger ability of sialyltransferase expressing cells to produce inflammatory cytokines upon BCG-challenging and to stimulate macrophages predicts a more effective response to BCG in tumours expressing the sialylated TF antigens. This is fully consistent with our recent clinical data obtained in collaboration, showing that patients with bladder cancer expressing sTn respond better to BCG therapy.

Immunohistochemical expression of oestrogen and progesterone receptors during experimental acute and chronic murine Schistosomiasis mansoni

INTRODUCTION: The responsibility of Schistosoma mansoni in female infertility is still controversial. This study was conducted to evaluate the effect of acute and chronic schistosomiasis mansoni infection on the endometrium using immunohistochemical analysis of uterine hormone receptor expression. METHODS: Twenty-four nonpregnant swiss albino mice were divided into three groups: control, noninfected; acute; and chronic Schistosoma mansoni infection. Histological sections of uterine specimens were examined by light microscope with an image analyzing system to detect structural histological, estrogen receptor (ER) and progesterone receptor (PR) expression in the endometrium. RESULTS: No secretory phase was detected in the endometrium in acute and chronic Schistosoma infection. Hormone receptor expression (ER and PR) showed statistically significant differences among the groups (p< 0.05), with significant low ER hormone expression in chronic infection, compared to control proliferative, control secretory and acute infection cases, and statistically significant high PR expression in both acute and chronic infection cases compared to the control secretory cases (p< 0.05). CONCLUSIONS: Schistosomiasis mansoni seems to have an important impact on the hormone expression of affected women. Further studies to explore the mechanism of such changes are recommended.

Métodos estatísticos aplicados à modelação de dados oncológicos

RESUMO: A estrutura demográfica portuguesa é marcada por baixas taxas de natalidade e mortalidade, onde a população idosa representa uma fatia cada vez mais representativa, fruto de uma maior longevidade. A incidência do cancro, na sua generalidade, é maior precisamente nessa classe etária. A par de outras doenças igualmente lesivas (e.g. cardiovasculares, degenerativas) cuja incidência aumenta com a idade, o cancro merece relevo. Estudos epidemiológicos apresentam o cancro como líder mundial na mortalidade. Em países desenvolvidos, o seu peso representa 25% do número total de óbitos, percentagem essa que mais que duplica noutros países. A obesidade, a baixa ingestão de frutas e vegetais, o sedentarismo, o consumo de tabaco e a ingestão de álcool, configuram-se como cinco dos fatores de risco presentes em 30% das mortes diagnosticadas por cancro. A nível mundial e, em particular no Sul de Portugal, os cancros do estômago, recto e cólon apresentam elevadas taxas de incidência e de mortalidade. Do ponto de vista estritamente económico, o cancro é a doença que mais recursos consome enquanto que do ponto de vista físico e psicológico é uma doença que não limita o seu raio de ação ao doente. O cancro é, portanto, uma doença sempre atual e cada vez mais presente, pois reflete os hábitos e o ambiente de uma sociedade, não obstante as características intrínsecas a cada indivíduo. A adoção de metodologia estatística aplicada à modelação de dados oncológicos é, sobretudo, valiosa e pertinente quando a informação é oriunda de Registos de Cancro de Base Populacional (RCBP). A pertinência é justificada pelo fato destes registos permitirem aferir numa população específica, o risco desta sofrer e/ou vir a sofrer de uma dada neoplasia. O peso que as neoplasias do estômago, cólon e recto assumem foi um dos elementos que motivou o presente estudo que tem por objetivo analisar tendências, projeções, sobrevivências relativas e a distribuição espacial destas neoplasias. Foram considerados neste estudo todos os casos diagnosticados no período 1998-2006, pelo RCBP da região sul de Portugal (ROR-Sul). O estudo descritivo inicial das taxas de incidência e da tendência em cada uma das referidas neoplasias teve como base uma única variável temporal - o ano de diagnóstico - também designada por período. Todavia, uma metodologia que contemple apenas uma única variável temporal é limitativa. No cancro, para além do período, a idade à data do diagnóstico e a coorte de nascimento, são variáveis temporais que poderão prestar um contributo adicional na caracterização das taxas de incidência. A relevância assumida por estas variáveis temporais justificou a sua inclusão numaclasse de modelos designada por modelos Idade-Período-Coorte (Age-Period-Cohort models - APC), utilizada na modelação das taxas de incidência para as neoplasias em estudo. Os referidos modelos permitem ultrapassar o problema de relações não lineares e/ou de mudanças súbitas na tendência linear das taxas. Nos modelos APC foram consideradas a abordagem clássica e a abordagem com recurso a funções suavizadoras. A modelação das taxas foi estratificada por sexo. Foram ainda estudados os respectivos submodelos (apenas com uma ou duas variáveis temporais). Conhecido o comportamento das taxas de incidência, uma questão subsequente prende-se com a sua projeção em períodos futuros. Porém, o efeito de mudanças estruturais na população, ao qual Portugal não é alheio, altera substancialmente o número esperado de casos futuros com cancro. Estimativas da incidência de cancro a nível mundial obtidas a partir de projeções demográficas apontam para um aumento de 25% dos casos de cancro nas próximas duas décadas. Embora a projeção da incidência esteja associada a alguma incerteza, as projeções auxiliam no planeamento de políticas de saúde para a afetação de recursos e permitem a avaliação de cenários e de intervenções que tenham como objetivo a redução do impacto do cancro. O desconhecimento de projeções da taxa de incidência destas neoplasias na área abrangida pelo ROR-Sul, levou à utilização de modelos de projeção que diferem entre si quanto à sua estrutura, linearidade (ou não) dos seus coeficientes e comportamento das taxas na série histórica de dados (e.g. crescente, decrescente ou estável). Os referidos modelos pautaram-se por duas abordagens: (i)modelos lineares no que concerne ao tempo e (ii) extrapolação de efeitos temporais identificados pelos modelos APC para períodos futuros. Foi feita a projeção das taxas de incidência para os anos de 2007 a 2010 tendo em conta o género, idade e neoplasia. É ainda apresentada uma estimativa do impacto económico destas neoplasias no período de projeção. Uma questão pertinente e habitual no contexto clínico e a que o presente estudo pretende dar resposta, reside em saber qual a contribuição da neoplasia em si para a sobrevivência do doente. Nesse sentido, a mortalidade por causa específica é habitualmente utilizada para estimar a mortalidade atribuível apenas ao cancro em estudo. Porém, existem muitas situações em que a causa de morte é desconhecida e, mesmo que esta informação esteja disponível através dos certificados de óbito, não é fácil distinguir os casos em que a principal causa de morte é devida ao cancro. A sobrevivência relativa surge como uma medida objetiva que não necessita do conhecimento da causa específica da morte para o seu cálculo e dar-nos-á uma estimativa da probabilidade de sobrevivência caso o cancro em análise, num cenário hipotético, seja a única causa de morte. Desconhecida a principal causa de morte nos casos diagnosticados com cancro no registo ROR-Sul, foi determinada a sobrevivência relativa para cada uma das neoplasias em estudo, para um período de follow-up de 5 anos, tendo em conta o sexo, a idade e cada uma das regiões que constituem o registo. Foi adotada uma análise por período e as abordagens convencional e por modelos. No epílogo deste estudo, é analisada a influência da variabilidade espaço-temporal nas taxas de incidência. O longo período de latência das doenças oncológicas, a dificuldade em identificar mudanças súbitas no comportamento das taxas, populações com dimensão e riscos reduzidos, são alguns dos elementos que dificultam a análise da variação temporal das taxas. Nalguns casos, estas variações podem ser reflexo de flutuações aleatórias. O efeito da componente temporal aferida pelos modelos APC dá-nos um retrato incompleto da incidência do cancro. A etiologia desta doença, quando conhecida, está associada com alguma frequência a fatores de risco tais como condições socioeconómicas, hábitos alimentares e estilo de vida, atividade profissional, localização geográfica e componente genética. O “contributo”, dos fatores de risco é, por vezes, determinante e não deve ser ignorado. Surge, assim, a necessidade em complementar o estudo temporal das taxas com uma abordagem de cariz espacial. Assim, procurar-se-á aferir se as variações nas taxas de incidência observadas entre os concelhos inseridos na área do registo ROR-Sul poderiam ser explicadas quer pela variabilidade temporal e geográfica quer por fatores socioeconómicos ou, ainda, pelos desiguais estilos de vida. Foram utilizados os Modelos Bayesianos Hierárquicos Espaço-Temporais com o objetivo de identificar tendências espaço-temporais nas taxas de incidência bem como quantificar alguns fatores de risco ajustados à influência simultânea da região e do tempo. Os resultados obtidos pela implementação de todas estas metodologias considera-se ser uma mais valia para o conhecimento destas neoplasias em Portugal.------------ABSTRACT: mortality rates, with the elderly being an increasingly representative sector of the population, mainly due to greater longevity. The incidence of cancer, in general, is greater precisely in that age group. Alongside with other equally damaging diseases (e.g. cardiovascular,degenerative), whose incidence rates increases with age, cancer is of special note. In epidemiological studies, cancer is the global leader in mortality. In developed countries its weight represents 25% of the total number of deaths, with this percentage being doubled in other countries. Obesity, a reduce consumption of fruit and vegetables, physical inactivity, smoking and alcohol consumption, are the five risk factors present in 30% of deaths due to cancer. Globally, and in particular in the South of Portugal, the stomach, rectum and colon cancer have high incidence and mortality rates. From a strictly economic perspective, cancer is the disease that consumes more resources, while from a physical and psychological point of view, it is a disease that is not limited to the patient. Cancer is therefore na up to date disease and one of increased importance, since it reflects the habits and the environment of a society, regardless the intrinsic characteristics of each individual. The adoption of statistical methodology applied to cancer data modelling is especially valuable and relevant when the information comes from population-based cancer registries (PBCR). In such cases, these registries allow for the assessment of the risk and the suffering associated to a given neoplasm in a specific population. The weight that stomach, colon and rectum cancers assume in Portugal was one of the motivations of the present study, that focus on analyzing trends, projections, relative survival and spatial distribution of these neoplasms. The data considered in this study, are all cases diagnosed between 1998 and 2006, by the PBCR of Portugal, ROR-Sul.Only year of diagnosis, also called period, was the only time variable considered in the initial descriptive analysis of the incidence rates and trends for each of the three neoplasms considered. However, a methodology that only considers one single time variable will probably fall short on the conclusions that could be drawn from the data under study. In cancer, apart from the variable period, the age at diagnosis and the birth cohort are also temporal variables and may provide an additional contribution to the characterization of the incidence. The relevance assumed by these temporal variables justified its inclusion in a class of models called Age-Period-Cohort models (APC). This class of models was used for the analysis of the incidence rates of the three cancers under study. APC models allow to model nonlinearity and/or sudden changes in linear relationships of rate trends. Two approaches of APC models were considered: the classical and the one using smoothing functions. The models were stratified by gender and, when justified, further studies explored other sub-models where only one or two temporal variables were considered. After the analysis of the incidence rates, a subsequent goal is related to their projections in future periods. Although the effect of structural changes in the population, of which Portugal is not oblivious, may substantially change the expected number of future cancer cases, the results of these projections could help planning health policies with the proper allocation of resources, allowing for the evaluation of scenarios and interventions that aim to reduce the impact of cancer in a population. Worth noting that cancer incidence worldwide obtained from demographic projections point out to an increase of 25% of cancer cases in the next two decades. The lack of projections of incidence rates of the three cancers under study in the area covered by ROR-Sul, led us to use a variety of forecasting models that differ in the nature and structure. For example, linearity or nonlinearity in their coefficients and the trend of the incidence rates in historical data series (e.g. increasing, decreasing or stable).The models followed two approaches: (i) linear models regarding time and (ii) extrapolation of temporal effects identified by the APC models for future periods. The study provide incidence rates projections and the numbers of newly diagnosed cases for the year, 2007 to 2010, taking into account gender, age and the type of cancer. In addition, an estimate of the economic impact of these neoplasms is presented for the projection period considered. This research also try to address a relevant and common clinical question in these type of studies, regarding the contribution of the type of cancer to the patient survival. In such studies, the primary cause of death is commonly used to estimate the mortality specifically due to the cancer. However, there are many situations in which the cause of death is unknown, or, even if this information is available through the death certificates, it is not easy to distinguish the cases where the primary cause of death is the cancer. With this in mind, the relative survival is an alternative measure that does not need the knowledge of the specific cause of death to be calculated. This estimate will represent the survival probability in the hypothetical scenario of a certain cancer be the only cause of death. For the patients with unknown cause of death that were diagnosed with cancer in the ROR-Sul, the relative survival was calculated for each of the cancers under study, for a follow-up period of 5 years, considering gender, age and each one of the regions that are part the registry. A period analysis was undertaken, considering both the conventional and the model approaches. In final part of this study, we analyzed the influence of space-time variability in the incidence rates. The long latency period of oncologic diseases, the difficulty in identifying subtle changes in the rates behavior, populations of reduced size and low risk are some of the elements that can be a challenge in the analysis of temporal variations in rates, that, in some cases, can reflect simple random fluctuations. The effect of the temporal component measured by the APC models gives an incomplete picture of the cancer incidence. The etiology of this disease, when known, is frequently associated to risk factors such as socioeconomic conditions, eating habits and lifestyle, occupation, geographic location and genetic component. The "contribution"of such risk factors is sometimes decisive in the evolution of the disease and should not be ignored. Therefore, there was the need to consider an additional approach in this study, one of spatial nature, addressing the fact that changes in incidence rates observed in the ROR-Sul area, could be explained either by temporal and geographical variability or by unequal socio-economic or lifestyle factors. Thus, Bayesian hierarchical space-time models were used with the purpose of identifying space-time trends in incidence rates together with the the analysis of the effect of the risk factors considered in the study. The results obtained and the implementation of all these methodologies are considered to be an added value to the knowledge of these neoplasms in Portugal.

S100, CD68, and MHC class II molecule expression in cervical high- and low-grade HPV-induced lesions

INTRODUCTION: Some human papillomavirus (HPV) types are involved in malignant processes in the cervical epithelium, with 99% of cases attributed to oncogenic HPV infection. This study aimed to detect S100, CD68, and major histocompatibility complex class II (MHC-II) molecules in cervical uterine epithelial samples in patients with high- and low-grade lesions induced by HPV. METHODS: Fifty-eight samples from patients who were confirmed positive or negative for high-risk oncogenic HPV DNA, had histopathological diagnosis of cervical intraepithelial neoplasia (CIN) of grades I, II, or III, or were negative for intraepithelial lesion or malignancy were subjected to immunohistochemistry reaction to S100 protein, CD68, and MHC-II (HLA-DR alpha chain). RESULTS: The presence of MHC-II predominated in samples exhibiting histopathological alterations (p < 0.05). S100 detection was more numerous in carcinoma samples (CIN III) (75%). Presence of this protein correlated significantly (p < 0.05) with histopathological findings and viral load. CONCLUSIONS: A small expression of CD68 was observed, which may be explained by the observation in our study having been made on random microscopic fields and not on specific areas. The findings, such as the presence of S100 protein and MHC-II expression in samples with histological alterations, could suggest that the immune system fails to control HPV replication at the early stages of infection. Further studies with larger prospective data are necessary to confirm this result.

Electrohysterogram signal component cataloging with spectral and time-frequency methods

The Electrohysterogram (EHG) is a new instrument for pregnancy monitoring. It measures the uterine muscle electrical signal, which is closely related with uterine contractions. The EHG is described as a viable alternative and a more precise instrument than the currently most widely used method for the description of uterine contractions: the external tocogram. The EHG has also been indicated as a promising tool in the assessment of preterm delivery risk. This work intends to contribute towards the EHG characterization through the inventory of its components which are: • Contractions; • Labor contractions; • Alvarez waves; • Fetal movements; • Long Duration Low Frequency Waves; The instruments used for cataloging were: Spectral Analysis, parametric and non-parametric, energy estimators, time-frequency methods and the tocogram annotated by expert physicians. The EHG and respective tocograms were obtained from the Icelandic 16-electrode Electrohysterogram Database. 288 components were classified. There is not a component database of this type available for consultation. The spectral analysis module and power estimation was added to Uterine Explorer, an EHG analysis software developed in FCT-UNL. The importance of this component database is related to the need to improve the understanding of the EHG which is a relatively complex signal, as well as contributing towards the detection of preterm birth. Preterm birth accounts for 10% of all births and is one of the most relevant obstetric conditions. Despite the technological and scientific advances in perinatal medicine, in developed countries, prematurity is the major cause of neonatal death. Although various risk factors such as previous preterm births, infection, uterine malformations, multiple gestation and short uterine cervix in second trimester, have been associated with this condition, its etiology remains unknown [1][2][3].

Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

Abstract: Approximately 90% of the world population is infected by Epstein-Barr virus (EBV). Usually, it infects B lymphocytes, predisposing them to malignant transformation. Infection of epithelial cells occurs rarely, and it is estimated that about to 10% of gastric cancer patients harbor EBV in their malignant cells. Given that gastric cancer is the third leading cause of cancer-related mortality worldwide, with a global annual incidence of over 950,000 cases, EBV-positive gastric cancer is the largest group of EBV-associated malignancies. Based on gene expression profile studies, gastric cancer was recently categorized into four subtypes; EBV-positive, microsatellite unstable, genomically stable and chromosomal instability. Together with previous studies, this report provided a more detailed molecular characterization of gastric cancer, demonstrating that EBV-positive gastric cancer is a distinct molecular subtype of the disease, with unique genetic and epigenetic abnormalities, reflected in a specific phenotype. The recognition of characteristic molecular alterations in gastric cancer allows the identification of molecular pathways involved in cell proliferation and survival, with the potential to identify therapeutic targets. These findings highlight the enormous heterogeneity of gastric cancer, and the complex interplay between genetic and epigenetic alterations in the disease, and provide a roadmap to implementation of genome-guided personalized therapy in gastric cancer. The present review discusses the initial studies describing EBV-positive gastric cancer as a distinct clinical entity, presents recently described genetic and epigenetic alterations, and considers potential therapeutic insights derived from the recognition of this new molecular subtype of gastric adenocarcinoma.

Unusual abdominal tumors with intracardiac extension. Two cases with successful surgical resection

Abdominal tumors that can grow through vascular lumen and spread to the right heart are rare. Although these tumors have different histologic aspects, they may cause similar abdominal and cardiac symptoms and are a serious risk factor for pulmonary embolism and sudden death when they reach the right atrium and tricuspid valve. The best treatment is radical surgical resection of the entire tumor using cardiopulmonary bypass with or without deep hypothermia and total circulatory arrest. We report the cases of two patients, the first with leiomyosarcoma of the inferior vena cava and the other with intravenous leiomyomatosis of the uterus that showed intravascular growth up to right atrium and ventricle, who underwent successful radical resection in a one-stage procedure with the use of cardiopulmonary bypass. We discuss the clinical and histologic aspects and imaging diagnosis and review the literature.