Aplicação de técnicas de detecção de apoptose versus proliferação celular no estudo do mastocitoma canino

A apoptose é um mecanismo de morte celular programada que ocorre naturalmente nos tecidos. Alterações neste mecanismo podem resultar na formação de neoplasias. O mastocitoma é uma das neoplasias cutâneas mais frequente em canídeos. O fator de prognóstico mais utilizado é o grau histológico. Porém, devido à imprevisibilidade desta neoplasia é necessário um melhor conhecimento do comportamento da mesma para se melhorarem competências em oncologia. Neste projeto foram estudados 23 amostras de mastocitomas caninos de variadas idades, raça e sexo, que foram submetidas à técnica de imunohistoquímica de modo a analisar a expressão de dois marcadores pró-apoptóticos (TUNEL e Bax), um marcador antiapoptótico (Bcl-2) e um marcador proliferativo (Ki-67). A expressão de TUNEL, Bcl-2 e Ki-67 aumentou do grau I para o grau III do mastocitoma e a de Bax diminuiu. Houve também uma diminuição na expressão de Bax e Bcl-2 no mastocitomas de grau II e um ligeiro aumento na expressão de Ki-67 na mesma classe tumoral. Observou-se assim maior atividade anti-apoptótica e aumento da proliferação celular, associados a um ao prolongamento na sobrevivência das células neoplásicas e, consequentemente, a um pior prognóstico, no grau de malignidade mais severo o grau III.

Fármacos utilizados para controlo da dor em medicina dentária

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Linfomas com expressão na cavidade oral

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Avaliação dos conhecimentos e práticas em medicina dentária na prevenção e detecção precoce do cancro oral

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Intraperitoneal bevacizumab for control of malignant ascites due to advanced-stage gastrointestinal cancers: A multicentre double-blind, placebo-controlled phase II study - AIO SUP-0108

PURPOSE: Malignant ascites is debilitating for patients with advanced cancer. As shown previously, tumour cell production of vascular endothelial growth factor might be a major cause of the formation of malignant ascites. Intraperitoneal bevacizumab could therefore be an option for symptom control in refractory ascites. PATIENTS AND METHODS: Patients with advanced gastrointestinal cancer and malignant ascites who had undergone paracentesis at least twice within the past 4 weeks were randomly assigned in a 2:1 ratio to intraperitoneal bevacizumab (400 mg absolute) or placebo after paracentesis. During the 8-week treatment period, a minimum interval of 14 d was kept between the applications of the study drug. Primary end-point was paracentesis-free survival (ParFS). RESULTS: Fifty-three patients (median age 63 years) were randomised. Forty-nine patients received at least one study drug application and qualified for the main analysis. The proportion of patients with at least one common toxicity criteria grade III-V event was similar with 20/33 (61%) on bevacizumab and 11/16 (69%) on placebo. Median ParFS was 14 d (95% confidence interval [CI]: 11-17) in the bevacizumab arm and 10.5 d (95% CI: 7-21) on placebo (hazard ratio 0.74, 95% CI: 0.40-1.37; P = 0.16). The longest paracentesis-free period was 19 d on bevacizumab (range 6-66 d) and 17.5 d in the placebo arm (range 4-42) (P = 0.85). Median overall survival was 64 d (95% CI: 45-103) on bevacizumab compared to 31.5 d (95% CI: 20-117) on placebo (P = 0.31). CONCLUSION: Intraperitoneal bevacizumab was well tolerated. Overall, treatment did not result in a significantly better symptom control of malignant ascites. However, patients defined by specific immune characteristics may benefit.

Second St. Gallen European Organisation for Research and Treatment of Cancer Gastrointestinal Cancer Conference: consensus recommendations on controversial issues in the primary treatment of rectal cancer

Primary treatment of rectal cancer was the focus of the second St. Gallen European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Cancer Conference. In the context of the conference, a multidisciplinary international expert panel discussed and voted on controversial issues which could not be easily answered using published evidence. Main topics included optimal pretherapeutic imaging, indication and type of neoadjuvant treatment, and the treatment strategies in advanced tumours. Here we report the key recommendations and summarise the related evidence. The treatment strategy for localised rectal cancer varies from local excision in early tumours to neoadjuvant radiochemotherapy (RCT) in combination with extended surgery in locally advanced disease. Optimal pretherapeutic staging is a key to any treatment decision. The panel recommended magnetic resonance imaging (MRI) or MRI + endoscopic ultrasonography (EUS) as mandatory staging modalities, except for early T1 cancers with an option for local excision, where EUS in addition to MRI was considered to be most important because of its superior near-field resolution. Primary surgery with total mesorectal excision was recommended by most panellists for some early tumours with limited risk of recurrence (i.e. cT1-2 or cT3a N0 with clear mesorectal fascia on MRI and clearly above the levator muscles), whereas all other stages were considered for multimodal treatment. The consensus panel recommended long-course RCT over short-course radiotherapy for most clinical situations where neoadjuvant treatment is indicated, with the exception of T3a/b N0 tumours where short-course radiotherapy or even no neoadjuvant therapy were regarded to be an option. In patients with potentially resectable tumours and synchronous liver metastases, most panel members did not see an indication to start with classical fluoropyrimidine-based RCT but rather favoured preoperative short-course radiotherapy with systemic combination chemotherapy or alternatively a liver-first resection approach in resectable metastases, which both allow optimal systemic therapy for the metastatic disease. In general, proper patient selection and discussion in an experienced multidisciplinary team was considered as crucial component of care.

Treatment approach in patients with hyperbilirubinemia secondary to liver metastases in gastrointestinal malignancies: a case series and review of literature

BACKGROUND: Treatment of patients with severe liver dysfunction including hyperbilirubinemia secondary to liver metastases of gastrointestinal (GI) cancer is challenging. Regimen of oxaliplatin and fluoropyrimidine (FP)/folinic acid (FA) ± a monoclonal antibody (moAb), represents a feasible option considering the pharmacokinetics. Clinical data on the respective dosage and tolerability are limited and no recommendations are available. METHODS: Consecutive patients with severe hyperbilirubinemia [>2 × upper limit of the normal range (ULN) and >2.4 mg/dl] due to liver metastases of GI cancer without options for drainage receiving oxaliplatin, FP/FA ± moAb were analyzed. To collect further data a review of the literature was performed. RESULTS: A total of 12 patients were identified between 2011 and 2015. At treatment start, median bilirubin level was 6.1 mg/dl (>5 × ULN, range 2.7-13.6). The majority of patients (n = 11) received dose-reduced regimen with oxaliplatin (60-76%) and FP/FA (0-77%), rapidly escalating to full dose regimen. During treatment, bilirubin levels dropped more than 50% within 8 weeks or normalized within 12 weeks in 6 patients (responders). Median overall survival was 5.75 months (range 1.0-16.0 months) but was significantly prolonged in responders compared to nonresponders [9.7 and 3.0 months, p = 0.026 (two-sided test); 95% confidence interval (CI): 1.10-10.22]. In addition, case reports or series comprising a further 26 patients could be identified. Based on the obtained data a treatment algorithm was developed. CONCLUSION: Treatment with oxaliplatin, FP/FA ± moAb is feasible and may derive relevant benefits in patients with severe liver dysfunction caused by GI cancer liver metastases without further options of drainage.

ESMO consensus guidelines for the management of patients with metastatic colorectal cancer

Colorectal cancer (CRC) is one of the most common malignancies in Western countries. Over the last 20 years, and the last decade in particular, the clinical outcome for patients with metastatic CRC (mCRC) has improved greatly due not only to an increase in the number of patients being referred for and undergoing surgical resection of their localised metastatic disease but also to a more strategic approach to the delivery of systemic therapy and an expansion in the use of ablative techniques. This reflects the increase in the number of patients that are being managed within a multidisciplinary team environment and specialist cancer centres, and the emergence over the same time period not only of improved imaging techniques but also prognostic and predictive molecular markers. Treatment decisions for patients with mCRC must be evidence-based. Thus, these ESMO consensus guidelines have been developed based on the current available evidence to provide a series of evidence-based recommendations to assist in the treatment and management of patients with mCRC in this rapidly evolving treatment setting.

Undiagnosed intracranial lipoma associated with sudden death

Intracranial lipomas represent less than 0.1% of all intracranial tumors. They are usually located in the callus area and often asymptomatic. This paper presents a sudden death case after an episode of convulsions on a 39 years old woman with a history of migraines and seizures since adolescence. The autopsy revealed the presence of an undiagnosed massive brain lipoma (60 × 35 mm) associated with atrophy of the corpus callosum. Although very rare and seldom malignant these may be associated with seizures and sudden death.

Serological diagnosis of echinococcosis: the diagnostic potential of native antigens

PURPOSE: Human alveolar (AE) and cystic echinococcosis (CE) caused by the metacestode stages of Echinococcus multilocularis and E. granulosus, respectively, lack pathognomonic clinical signs. Diagnosis therefore relies on the results of imaging and serological studies. The primary goal of this study was to evaluate the efficacy of several easy-to-produce crude or partially purified E. granulosus and E. multilocularis metacestode-derived antigens as tools for the serological diagnosis and differential diagnosis of patients suspicious for AE or CE. METHODS: The sera of 51 treatment-naïve AE and 32 CE patients, 98 Swiss blood donors and 38 patients who were initially suspicious for echinococcosis but suffering from various other liver diseases (e.g., liver neoplasia, etc.) were analysed. RESULTS: According to the results of enzyme-linked immunosorbent assays (ELISA), metacestode-derived antigens of E. granulosus had sensitivities varying from 81 to 97% and >99.9% for the diagnosis of CE and AE, respectively. Antigens derived from E. multilocularis metacestodes had sensitivities ranging from 84 to 91% and >99.9% for the diagnosis of CE and AE, respectively. Specificities ranged from 92 to >99.9%. Post-test probabilities for the differential diagnosis of AE from liver neoplasias, CE from cystic liver lesions, and screening for AE in Switzerland were around 95, 86 and 2.2%, respectively. Cross-reactions with antibodies in sera of patients with other parasitic affections (fasciolosis, schistosomosis, amebosis, cysticercosis, and filarioses) did occur at variable frequencies, but could be eliminated through the use of confirmatory testing. CONCLUSIONS: Different metacestode-derived antigens of E. granulosus and E. multilocularis are valuable, widely accessible, and cost-efficient tools for the serological diagnosis of echinococcosis. However, confirmatory testing is necessary, due to the lack of species specificity and the occurrence of cross-reactions to other helminthic diseases.

Brain tumour stem cells

The dogma that the genesis of new cells is a negligible event in the adult mammalian brain has long influenced our perception and understanding of the origin and development of CNS tumours. The discovery that new neurons and glia are produced throughout life from neural stem cells provides new possibilities for the candidate cells of origin of CNS neoplasias. The emerging hypothesis is that alterations in the cellular and genetic mechanisms that control adult neurogenesis might contribute to brain tumorigenesis, thereby allowing the identification of new therapeutic strategies.

A VIVÊNCIA DO ONCOLOGISTA NA INFORMAÇÃO DO DIAGNÓSTICO DE CÂNCER À PACIENTE

O presente estudo teve como objetivo, por meio de uma pesquisa qualitativa segundo a abordagem fenomenológica existencial, investigar os pensamentos, sentimentos e atitudes do oncologista na informação do diagnóstico de câncer à paciente. Foram realizadas 5 entrevistas semi-dirigidas com oncologistas que atendem em consultório particular, e foi delimitada a análise compreensiva fenomenológica do conteúdo. Os resultados obtidos mostraram que: A informação do diagnóstico de câncer de mama para pacientes jovens em idade reprodutiva foi considerada a mais marcante para os médicos, lhes causando maior preocupação, medo e tristeza, devido às limitações impostas pela doença aos planos de vida da paciente e às questões da maternidade. Os entrevistados referiram que em qualquer caso, o momento da notícia lhes repercute emocionalmente, pela vivência do sentimento de tristeza, ou por fantasias relacionadas à responsabilidade pela doença. Eles apontaram como mais difícil nesse processo, o confronto com as reações emocionais da paciente e falar sobre o câncer utilizando palavras para amenizar o impacto dessa informação. Diante dessas dificuldades, a evolução da medicina, a possibilidade de cirurgia conservadora e a reconstrução mamária foram consideradas atenuantes. Os médicos afirmaram que informam a paciente de maneira clara, objetiva e gradativa, mas nem todos eles utilizam sempre a palavra câncer . Procuram encorajar a paciente com otimismo e solidariedade, engajando-a no tratamento como participante ativa. Além disso, sentem-se responsáveis por motivar aquela que demonstra desânimo ou que reluta em seguir o tratamento. Eles percebem que a partir da informação do diagnóstico a paciente estabelece um vínculo de confiança e dependência, e identificam que em alguns casos eles também se vinculam à paciente. Entretanto, reconhecem que desse vínculo deriva um desgaste emocional que os leva ao questionamento sobre a escolha de sua especialidade. Constatou-se que alguns oncologistas podem emitir sua opinião sobre determinado diagnóstico, às vezes, a pedido da paciente, mas que ao errarem nesse pré-julgamento, evidenciam sentimentos de impotência, ou fracasso, ou culpa, por não se prepararem, nem à paciente, para o momento da informação. Os casos em que a família interfere com questionamentos ou com o pedido de ocultação da informação não foram vistos por eles de modo negativo, contudo, o pedido de ocultação nem sempre é acatado. Os entrevistados referiram algum tipo de aprendizado através do contato com a paciente oncológica, ou por meio da reavaliação de seus valores morais, ou da reflexão sobre sua própria finitude. Particularmente nos casos de câncer avançado ou terminal, esse aprendizado abrangeu o apoio nos momentos que precedem a morte, ou o reconhecimento da própria impotência. Conclusão: A análise dos resultados revelou os conflitos e as dúvidas do médico como ser ético , que assume os riscos ao escolher quanto, quando e como informar o diagnóstico à paciente, sua consciência de culpabilidade, a ansiedade existencial desencadeada pelas reações emocionais da paciente, a manifestação de sua maneira preocupada de existir no mundo, a busca pelo encontro autêntico e criativo, a subjetividade utilizada como caminho para a compreensão do ser doente e a possibilidade do fracasso de um projeto resultar em frustração e num rebaixamento temporário da confiança em sua própria capacidade. Desse modo, esse trabalho demonstra a inevitável influência dos fatores subjetivos na atitude do médico que informa o diagnóstico de câncer para sua paciente e que esse processo está muito além de qualquer pretensa objetividade.

Obtenção e caracterização de sistemas particulados de quitosana para liberação gástrica de amoxicilina

The infection caused by Helicobacter pylori (H. pylori) is associated with gastroduodenal inflammation can lead to the development of gastritis, gastric or duodenal ulcer and gastric cancer (type 1 carcinogen for stomach cancer). Amoxicillin is used as first-line therapy in the treatment of H. pylori associated to metronidazole or clarithromycin, and a proton pump inhibitor. However, the scheme is not fully effective due to inadequate accumulation of antibiotics in gastric tissue, inadequate efficacy of ecological niche of H. pylori, and other factors. In this context, this study aimed to obtaining and characterization of particulate systems gastrorretentivos chitosan - amoxicillin aiming its use for treatment of H. pylori infections. The particles were obtained by the coacervation method / precipitation using sodium sulfate as precipitating agent and crosslinking and two techniques: addition of amoxicillin during preparation in a single step and the sorption particles prior to amoxycillin prepared by coacervation / precipitation and spray drying. The physicochemical characterization of the particles was performed by SEM, FTIR, DSC, TG and XRD. The in vitro release profile of amoxycillin free and incorporated in the particles was obtained in 0.1 N HCl (pH = 1.2). The particles have higher encapsulation efficiency to 80% spherical shape with interconnected particles or adhered to each other, the nanometric diameter to the systems obtained by coacervation / precipitation and fine for the particles obtained by spray drying. The characterization by FTIR, DSC and XRD showed that the drug was incorporated into the nanoparticles dispersed in the polymeric matrix. Thermal analysis (TG and DSC) indicated that encapsulation provides greater heat stability to the drug. Amoxicillin encapsulated in nanoparticles had slower release compared to free drug. The particles showed release profile with a faster initial stage (burst effect) reaching a maximum at 30 minutes 35% of amoxicillin for the system in 1: 1 ratio relative to the polymer and 80% for the system in the ratio 2: 1. Although simple and provide high encapsulation efficiency of amoxicillin, the process of coacervation, precipitation in one step using sodium sulfate as precipitant / cross-linker must be optimized in order to adjust the release kinetics according to the intended application.

Avaliação da imagem corporal de mulheres submetidas à cirurgia oncológica mamária

Breast cancer is the second type of cancer that affects more women of reproductive age in Brazil. Surgical treatments include: conserving surgery or mastectomy. Aimed to evaluate body image of women undergoing breast cancer surgery, based on the scale Body Image After Breast Cancer Questionnaire. It is a descriptive, exploratory, transversal, with a quantitative approach. Data were collected in Norte-riograndense League Against Cancer, between the months from March to May 2015, after consideration of the Research Ethics Committee of that institution CAEE 35155714.1.0000.5293. The study population consisted of women undergoing breast onco-surgery. To calculate the sample considered the finite population, totaling 120 subjects, collected four guys the most. Data were analyzed by the software Statistical Package for Social Sciences version 20.0. The domain scores of the scale were evaluated using descriptive and inferential statistics. The surgical group mastectomy without reconstruction showed greater impairment of body image in the field "vulnerability", "Care for the body" and "transparency" in relation to other surgical types, and suggests susceptibility to cancer, body appearance and worry that disturb other. The Kruskal-Wallis test showed greater dissatisfaction with body image in the fields "body Stigma" and "transparency" to the radical neoplastic surgery over other surgical types. Dissatisfaction with body image and physical appearance was detected in this study in all six image fields present in scale, with emphasis on the "body Stigma" and "Transparency". This means that the body image disorder is formulated based on the perception of others about themselves and not by perception "self", which justifies the concern with appearance, with body and hide the consequences stemmed cancer. It is expected that the data obtained from the evaluation of body image presented in this study contribute to enable the assistance to oncocirurgiada woman breast integral, essential for the practice of Nursing.