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Introdução: O objetivo deste artigo é rever a experiência do Instituto Português de Oncologia do Porto na terapêutica de tumores neuroendócrinos gastroenteropancreáticos com 177Lu-DOTA-TATE, tendo como principais pontos de análise a segurança e eficácia terapêutica. Material e Métodos: Foi realizada uma análise retrospetiva dos processos clínicos de doentes com tumores neuroendócrinos gastroenteropancreáticos, submetidos a terapêutica com 177Lu-DOTA-TATE entre abril de 2011 e novembro de 2013. Resultados: Dos 36 casos revistos, 30 completaram os três ciclos de 177Lu-DOTA-TATE (83,3%). Nesses doentes foram registados: efeitos colaterais agudos em 8,9% dos ciclos; toxicidade hepática grau 3 CTCAE em 13,3% dos doentes (todos com alterações prévias da função hepática); ausência de toxicidade renal ou hematológica significativa; melhoria sintomática em 71,4% dos doentes; tempo mediano global desde o início da terapêutica até progressão de doença de 25,6 meses; tempo mediano global de sobrevivência desde o diagnóstico de 121,7 meses. Verificou-se um maior tempo livre de progressão de doença e de sobrevivência nos doentes com expressão elevada de recetores da somatostatina (p < 0,05). Discussão: A peptide receptor radionuclide therapy com 177Lu-DOTA-TATE apresenta respostas clínicas favoráveis com segurança e boa tolerabilidade terapêutica, conforme evidenciado no nosso estudo pelos seguintes achados: melhoria dos sintomas na maioria dos doentes e aumento significativo do tempo livre de progressão de doença e da sobrevivência (sobretudo nos doentes com expressão elevada de sstr), com efeitos colaterais agudos e subagudos/crónicos significativos numa minoria de doentes. Conclusão: A peptide receptor radionuclide therapy com 177Lu-DOTA-TATE é uma terapêutica promissora, com benefícios reais em termos de eficácia e segurança nos doentes com tumores neuroendócrinos gastroenteropancreáticos.

The association of well-differentiated gastro-entero-pancreatic neuroendocrine tumors (WD GEP-NETs) with metabolic syndrome (MetS), abdominal obesity, and fasting glucose abnormalities was recently described. The aim of this study was to evaluate whether the presence of MetS or any MetS individual component was also influenced by GEP-NET characteristics at diagnosis. A cohort of patients with WD GEP-NETs (n = 134), classified according to primary tumor location (gastrointestinal or pancreatic), pathological grading (G1 (Ki67 ≤ 2%) and G2 (>3 ≤ 20%) (WHO 2010), disease extension (localized, loco-regional, and metastatic), and presence of hormonal secretion syndrome (functioning/non-functioning), was evaluated for the presence of MetS criteria. After adjustment for age and gender, the odds of having MetS was significantly higher for patients with WD GEP-NET grade G1 (OR 4.35 95%CI 1.30−14.53) and disseminated disease (OR 4.52 95%CI 1.44−14.15). GEP-NET primary tumor location or secretory syndrome did not influence the risk for MetS. None of the tumor characteristics evaluated were associated with body mass index, fasting plasma glucose category, or any of the individual MetS components. Patients with GEP-NET and MetS depicted a higher risk of presenting a lower tumor grade and disseminated disease. The positive association between MetS and GEP-NET characteristics further highlights the potential link between the two conditions.

Background: Lung cancer (LCa) is the most frequently diagnosed and lethal cancer worldwide. Histopathological subtyping, which has important therapeutic and prognostic implications, requires material collection through invasive procedures, which might be insufficient to enable definitive diagnosis. Aberrant DNA methylation is an early event in carcinogenesis, detectable in circulating cell-free DNA (ccfDNA). Herein, we aimed to assess methylation of selected genes in ccfDNA from LCa patients and determine its accuracy for tumor subtyping. Methods: Methylation levels of APC, HOXA9, RARβ2, and RASSF1A were assessed in three independent study groups (study group #1: 152 tissue samples; study group #2: 129 plasma samples; study group #3: 28 benign lesions of lung) using quantitative methylation-specific PCR. Associations between gene promoter methylation levels and LCa subtypes were evaluated using non-parametric tests. Receiver operating characteristic (ROC) curve analysis was performed. Results: In study group #2, HOXA9 and RASSF1A displayed higher methylation levels in small-cell lung cancer (SCLC) than in non-small-cell lung cancer (NSCLC). HOXA9 displayed high sensitivity (63.8%), whereas RASSF1A disclosed high specificity (96.2%) for SCLC detection in ccfDNA. Furthermore, HOXA9 methylation levels showed to be higher in squamous cell carcinoma in comparison with adenocarcinoma in study group #1. Conclusions: Methylation level assessments in ccfDNA may provide a minimally invasive procedure for LCa subtyping, complementing standard diagnostic procedures.

Background: Breast cancer (BrC) is the most frequent neoplasm in women. New biomarkers, including aberrant DNA methylation, may improve BrC management. Herein, we evaluated the detection and prognostic performance of seven genes’ promoter methylation (APC, BRCA1, CCND2, FOXA1, PSAT1, RASSF1A and SCGB3A1). Methods: Methylation levels were assessed in primary BrC tissues by quantitative methylation-specific polymerase chain reaction (QMSP) and in circulating cell-free DNA (ccfDNA) by multiplex QMSP from two independent cohorts of patients (Cohort #1, n = 137; and Cohort #2, n = 44). Receiver operating characteristic (ROC) curves were constructed, and log-rank test and Cox regression were performed to assess the prognostic value of genes’ methylation levels. Results: The gene-panel APC, FOXA1, RASSF1A, SCGB3A1 discriminated normal from cancerous tissue with high accuracy (95.55%). In multivariable analysis, high PSAT1-methylation levels [>percentile 75 (P75)] associated with longer disease-free survival, whereas higher FOXA1-methylation levels (>P75) associated with shorter disease-specific survival. The best performing panel in ccfDNA (APC, FOXA1 and RASSF1A) disclosed a sensitivity, specificity and accuracy over 70%. Conclusions: This approach enables BrC accurate diagnosis and prognostic stratification in tissue samples, and allows for early detection in liquid biopsies, thus suggesting a putative value for patient management.

Introduction: The diagnosis of renal cell carcinoma has been increasing in recent years, especially due to incidental cases, and thus indication for nephron-preserving surgery has also risen. Objectives: To review a series of partial nephrectomies from an oncology institution namely technique features, survival and change in renal function. Material and Methods: A retrospective analysis of all patients with renal tumors that were submitted to partial nephrectomy at our institution between January 2000 and December 2012. Results: A total 156 partial nephrectomies were performed, 85 in men and 71 in women, with mean overall age of 62 ± 15 years. Surgical approach was transperitoneal laparoscopic in 23 cases with the remainder 133 through lumbotomy. Mean ischemic time was < 25 min in all patients and complication rate was 10.9 %, mostly corresponding grade 2 and 3 of the Clavien-Dindo scale. Mean tumor size was 2.9 ± 1.4 cm and the surgical margin was focally affected by tumor in 9.6% of cases. Histologically, 26.2% of cases corresponded to clear cell renal cell carcinoma, with oncocytomas being the most common benign neoplasm with 14.7% of the total. There were 4 cases of recurrence and one case death at follow-up. The mean change in estimated glomerular filtration rate was -5.3 mL/min per 1.73 m2 (p < 0.001). There was no association between warm ischemia time, body mass index, age, ASA score, presence of complications with this decrease in glomerular filtration rate. Discussion: Our positive surgical margins cases were slightly above what is described in literature, however we didn’t find any predictive factor for such finding and ultimately there was no evidence of tumor recurrence or influence in survival in all these cases. Even though there was a significant decrease in estimated glomerular filtration rate, warm ischemia time was very low and only five patients presented with de novo eGFR < 60 mL/min per 1.73 m2, and two patients started hemodialysis. A high volume center seems to be critical for technique optimization and complication management. Conclusion: Our series of partial nephrectomies presents oncological results and preservation of renal function similar to those published in literature. This is a safe technique with good results, justifying its growth.

Objectivos: Avaliação dos resultados obtidos através dos protocolos instituídos no Serviço para despiste de trombofilias e/ou neoplasias em doentes internados ao longo de 5 anos com o diagnóstico de trombose venosa profunda (TVP). Material e métodos: Estudo retrospectivo, através da consulta dos processos hospitalares, de todos os doentes com idade igual ou inferior a 50 anos internados no Serviço entre 01 de Janeiro de 2006 e 31 de Dezembro de 2010 com esse diagnóstico, e análise dos resultados obtidos nos protocolos. Resultados: De um total de 89 doentes, 64 (71,9%) eram do sexo feminino e 25 (28,1%) do masculino, sendo a média de idades de 33,3 ±10,0 anos. 14,6% dos doentes já haviam tido, pelo menos, um episódio prévio de TVP e 78,7% apresentavam, pelo menos, um factor de risco. Em 65 doentes (73,0%) foi aplicado o protocolo de despiste de trombofilias e de neoplasias, tendo sido detectadas trombofilias congénitas em 41 doentes (63,1%), dois casos de síndrome dos anticorpos anti-fosfolipídicos (SAF), um caso de gamapatia monoclonal, um de neoplasia do pulmão e um de cordoma do sacro. 49 dos doentes que realizaram os protocolos (75,4%) foram orientados para a Consulta de Hematologia, sendo que em 40 deles (81,6%) foi sugerido manter a anticoagulação oral por um período superior a 12 meses. Conclusões: Dada a elevada prevalência de polimorfismos genéticos que conferem risco trombótico acrescido e os não raros casos de SAF e de neoplasias ocultas presentes nesta população de doentes, considera-se que, apesar dos elevados custos, se deverá continuar a fazer o despiste deste tipo de patologias.Objectives: Evaluation of the results obtained with the application of specific protocols established in the Department for screening for thrombophilia and malignancy in patients hospitalized during a period of five years with the diagnosis of deep venous thrombosis (DVT). Material and methods: A retrospective study was performed through the review of the clinical files of all patients aged 50 or less hospitalized in our Department between January 1st 2006 and December 31st 2010 with that diagnosis, and the results obtained in the protocols were analysed. Results: From a total of 89 patients, 64 (71,9%) were females and 25 (28,1%) were males, and the mean age was 33,3 ±10,0 years. 14,6% of the patients had already had, at least, one previous episode of deep venous thrombosis and 78,7% had, at least, one risk factor. The protocol for screening for thrombophilia and malignancy was applied to 65 patients (73,0%), being detected congenital thrombophilias in 41 patients (63,1%), two cases of antiphospholipid antibody syndrome (APS), one case of monoclonal gammopathy, one of lung cancer and one of sacral chordoma. 49 of the patients subjected to the protocols (75,4%) were referred to the Hematology Clinic for evaluation and in 40 of those patients (81,6%) was suggested keeping oral anticoagulation for more than 12 months. Conclusions: Given the high prevalence of genetic polimorphisms that confer a higher thrombotic risk and the not rare cases of APS and of occult malignancies present in this population, it is considered that, despiste its elevated costs, the screening for these kind of pathologies should continue to be done.

Doente de 19 anos com quadro de febre com 8 dias de evolução e posterior instalação súbita de afasia, hemiparésia esquerda e alterações do comportamento. Aumento das proteínas de fase aguda no estudo analítico. TAC e RMN crânio-encefálicas revelaram lesão isquémica temporo-parietal direita. Ecocardiograma excluiu endocardite. Eco-döppler e angio-TAC carotídeo-vertebrais mostraram formação vegetante, móvel com a pulsação cardíaca, na artéria carótida comum direita. Submetido, de urgência, a cirurgia carotídea. Intraoperatoriamente constatou-se a presença de trombo ligeiramente aderente à artéria carótida comum e na dependência de lesão da íntima subjacente, tendo-se procedido à sua exérese e a arteriorrafia primária. Aponta-se como etiologia mais provável do quadro, uma vasculite secundária a infecção por HSV1 (infecção activa) ou por Rickettsia conorii.19 years old patient with fever for 8 days associated with sudden aphasia, left hemiparesis and abnormal behavior. Increased acute phase proteins in the analytical study. Head CT scan and MRI revealed a right temporo-parietal ischemic lesion. An echocardiogram excluded endocarditis. Ultrasound and CT angiography scanning of the extracranial cerebral circulation showed a vegetative formation, mobile with the heartbeat, in the right common carotid artery. Submitted, urgently, to carotid surgery. Intraoperatively, a slightly adherent thrombus to the common carotid artery was found and in the dependence of an underlying injury to the intima. The thrombus was ressected and a primary arteriorrhaphy performed. It is pointed out a vasculitis secondary to HSV1 (active infection) or to Rickettsia conorii infection as the most likely etiology of the clinic.

Apresenta-se o caso clínico de um doente com volumoso aneurisma da artéria renal esquerda. Do sexo masculino, de 22 anos de idade, com lombalgia à esquerda com algumas semanas de evolução. Recorreu ao médico assistente que solicitou estudo imagiológico por ecografia abdominal. Detectada imagem sugestiva de aneurisma da aorta abdominal. Este achado motivou a transferência para o nosso Hospital onde foi admitido consciente e orientado, hemodinamicamente estável, apresentando uma massa pulsátil epigástrica, com frémito e sopro sistólico à auscultação. Angio-TC revelou um aneurisma da artéria renal esquerda com 16 cm de diâmetro. Dada a estabilidade clínica e topografia lesional optou-se por tentar embolizar, sem sucesso, o tronco da artéria renal esquerda antes da abordagem cirúrgica. O doente foi então submetido a Nefrectomia total esquerda por via toraco-abdominal. Pós-operatório sem complicações, locais ou sistémicas. Alta ao 8ºdia, mantendo boa função renal e com níveis normais de hemoglobina. Diagnóstico de aneurisma da artéria renal confirmado por estudo anátomo-patológico da peça operatória.One case of a large left renal artery aneurysm in a young patient 22 years old is presented. He appealed to his assistant physician a few weeks after development of left back pain. Abdominal ultrasound imaging study has been requested. Suggestive abdominal aortic aneurysm was detected. This finding led to the transfer to our hospital where he was admitted conscious and hemodynamically stable. A pulsatile epigastric mass with a systolic murmur on auscultation and thrill were detected. Angio-CT scan revealed a left renal artery aneurysm, 16 cm in diameter. Given the clinical stability and lesional topography we decide a previous embolization of left renal artery, unsuccessfully. The patient underwent then left total nephrectomy, through thoraco-abdominal incision. No local or systemic complications in the postoperative period. Discharged at 8th day maintaining normal renal function and hemoglobin levels. Renal artery aneurysm was confirmed in a pathological study of the surgical specimen.

Apresenta-se caso clínico de doente com quadro de hipertensão portal pela presença de fístula artério-venosa entre a artéria gastroduodenal e a veia porta. Indivíduo do sexo masculino, de 77 anos, previamente saudável, com ascite volumosa de instalação recente. Hemorragia digestiva alta por rotura de varizes esofágicas. TAC abdominal revelando acentuada dilatação da veia porta (30 mm), envolvida em fístula artério-venosa com origem na artéria gastroduodenal; fígado sem estigmas de hepatopatia crónica e sem nódulos; ascite volumosa. Procedeu-se à laparotomia com drenagem de ascite, isolamento e laqueação do trajecto fístuloso entre a artéria gastroduodenal e a veia porta. Sem complicações intra-operatórias. Ao 18º dia, após regressão da ascite, teve alta medicado com diuréticos.A case report of a patient with a framework for portal hypertension due to the presence of arteriovenous fistula between the gastroduodenal artery and portal vein is presented. A 77 years male previously healthy with a recent ascites appeared with a digestive hemorrhage caused by rupture of esophageal varices. Abdominal CT scan revealed marked dilatation of the portal vein (30 mm) related with an arteriovenous fistula between this vein and the gastroduodenal artery, liver without chronic liver disease stigmata and without nodules; remarkable ascites. Laparotomy, drainage of ascites, isolation and ligation of the journey fistula between the gastroduodenal artery and portal vein was performed. No intraoperative complications. Discharged the 18th postoperative day after regression of ascites, treated with diuretics.

Kolmogorov complexity and Shannon entropy are conceptually different measures. However, for any recursive probability distribution, the expected value of Kolmogorov complexity equals its Shannon entropy, up to a constant. We study if a similar relationship holds for R´enyi and Tsallis entropies of order α, showing that it only holds for α = 1. Regarding a time-bounded analogue relationship, we show that, for some distributions we have a similar result. We prove that, for universal time-bounded distribution mt(x), Tsallis and Rényi entropies converge if and only if α is greater than 1. We also establish the uniform continuity of these entropies.

Introdução: Os autores elaboraram um estudo retrospectivo de todos os casos clínicos admitidos no seu Serviço com o diagnóstico de aneurisma poplíteo ao longo de 5 anos. Material e Métodos: Para atingir esse objectivo, procederam à consulta dos processos hospitalares de todos os doentes admitidos com o diagnóstico de aneurisma poplíteo entre 01 de Janeiro de 2004 e 31 de Dezembro de 2008. Resultados: De um total de 61 doentes, 37 (60,7%) apresentavam aneurismas bilaterais. Desses 61 doentes, 58 eram do sexo masculino e 3 do feminino, sendo a média de idades de 66,9 ± 11,6 anos. 36,1% dos doentes apresentavam também aneurismas noutras localizações. Os aneurismas eram, na sua maioria, assintomáticos. Quando sintomáticos, a forma de apresentação mais frequente foi a isquémia aguda por trombose do aneurisma. Dentro da totalidade dos aneurismas poplíteos (n=98), 37 foram operados electivamente, 29 de urgência e 32 não foram operados. As intervenções cirúrgicas de eleição foram a exclusão do aneurisma através de bypass femoro-poplíteo distal com veia safena interna (n=48) ou com prótese (n=16). As taxas de patência primária aos 30 dias foram de 98% com o uso de veia e de 68,8% com prótese, tendo motivado 3 amputações supracondilianas. Conclusões: Os aneurismas poplíteos são mais prevalentes no sexo masculino, frequentemente bilaterais, e existe uma forte relação entre estes e aneurismas noutras localizações/megadistrofia arterial generalizada. O tratamento cirúrgico ideal é o realizado electivamente com material autólogo, sendo as taxas de patência com o recurso a material protésico bastante inferiores.Introduction: The authors performed a 5-year retrospective study of all the case reports admitted in their Department with the diagnosis of popliteal aneurysm. Material and Methods: To achieve that purpose, the clinical files of all the patients admitted with the diagnosis of popliteal aneurysm between January 1st 2004 and December 31st 2008 were reviewed. Results: From a total of 61 patients, 37 (60,7%) had bilateral aneurysms. Of those 61 patients, 58 were males and 3 were females. The mean age was 66,9 ± 11,6 years. 36,1% of the patients had also aneurysms in other locations. The majority of the aneurysms were asymptomatic. When symptomatic, the most frequent presentation was acute ischemia caused by thrombosis of the aneurysm. Of all the popliteal aneurysms (n=98), 37 were repaired electively, 29 urgently and 32 were not repaired. The most used surgical interventions were the exclusion of the aneurysm by distal femoropopliteal bypass with greater saphenous vein (n=48) or with prosthesis (n=16). Primary patency rates at 30 days were of 98% with vein and of 68,8% with prosthesis, which caused 3 transfemoral amputations. Conclusions: Popliteal aneurysms are more prevalent in males, frequently bilateral and there is a strong connection between them and aneurysms in other locations/arteriomegaly. The ideal surgical treatment is the elective repair with autologous material, being the patency rates with prosthesis inferior to the ones with vein.

Background: Breast (BrC), colorectal (CRC) and lung (LC) cancers are the three most common and deadly cancers in women. Cancer screening entails an increase in early stage disease detection but is hampered by high false-positive rates and overdiagnosis/overtreatment. Aberrant DNA methylation occurs early in cancer and may be detected in circulating cell-free DNA (ccfDNA), constituting a valuable biomarker and enabling non-invasive testing for cancer detection. We aimed to develop a ccfDNA methylation-based test for simultaneous detection of BrC, CRC and LC. Methods: CcfDNA from BrC, CRC and LC patients and asymptomatic controls were extracted from plasma, sodium-bisulfite modified and whole-genome amplified. APC, FOXA1, MGMT, RARβ2, RASSF1A, SCGB3A1, SEPT9, SHOX2 and SOX17 promoter methylation levels were determined by multiplex quantitative methylation-specific PCR. Associations between methylation and standard clinicopathological parameters were assessed. Biomarkers’ diagnostic performance was also evaluated. Results: A “PanCancer” panel (APC, FOXA1, RASSF1A) detected the three major cancers with 72% sensitivity and 74% specificity, whereas a “CancerType” panel (SCGB3A1, SEPT9 and SOX17) indicated the most likely cancer topography, with over 80% specificity, although with limited sensitivity. Conclusions: CcfDNA’s methylation assessment allows for simultaneous screening of BrC, CRC and LC, complementing current modalities, perfecting cancer suspects’ triage, increasing compliance and cost-effectiveness.

Entropy and compression have been used to distinguish fetuses at risk of hypoxia from their healthy counterparts through the analysis of Fetal Heart Rate (FHR). Low correlation that was observed between these two approaches suggests that they capture different complexity features. This study aims at characterizing the complexity of FHR features captured by entropy and compression, using as reference international guidelines. Single and multi-scale approaches were considered in the computation of entropy and compression. The following physiologic-based features were considered: FHR baseline; percentage of abnormal long (%abLTV) and short (%abSTV) term variability; average short term variability; and, number of acceleration and decelerations. All of the features were computed on a set of 68 intrapartum FHR tracings, divided as normal, mildly, and moderately-severely acidemic born fetuses. The correlation between entropy/compression features and the physiologic-based features was assessed. There were correlations between compressions and accelerations and decelerations, but neither accelerations nor decelerations were significantly correlated with entropies. The %abSTV was significantly correlated with entropies (ranging between −0.54 and −0.62), and to a higher extent with compression (ranging between −0.80 and −0.94). Distinction between groups was clearer in the lower scales using entropy and in the higher scales using compression. Entropy and compression are complementary complexity measures.

The ability to effectively modify behaviours is increasingly relevant to attain and maintain a good health status. Current behaviour-change models and theories present two main approaches for (healthier) decision-making: one analytical/logical, and one experiential/emotional/intuitive. Therefore, to achieve an integral and dynamic understanding of the public perceptions both approaches should be considered: community surveys should measure cognitive understanding of health-risk contexts, and also explore how past experiences affect this understanding. In 2011, community perceptions regarding domestic source reduction were assessed in Madeira Island͘. After Madeira's first dengue outbreak (2012) a unique opportunity to compare perceptions before and after the outbreak-experience occurred. This was the aim of this study, which constituted the first report on the effect of an outbreak experience on community perceptions regarding a specific vector-borne disease. A cross-sectional survey was performed within female residents at the most aegypti-infested areas. Perceptions regarding domestic source reduction were assessed according to the Essential Perception (EP)-analysis tool. A matching process paired individuals from studies performed before and after the outbreak, ensuring homogeneity in six determinant variables. After the outbreak, there were more female residents who assimilated the concepts considered to be essential to understand the proposed behaviour. Nevertheless, no significant difference was observed in the number of female residents who achieved the defined 'minimal understanding''. Moreover, most of the population (95.5%) still believed at least in one of the identified myths. After the outbreak some myths disappeared and others appeared. The present study quantified and explored how the experience of an outbreak influenced the perception regarding a dengue-preventive behaviour. The outbreak experience surprisingly led to the appearance of new myths within the population, apart from the expected increase of relevant concepts' assimilation. Monitoring public perceptions is therefore crucial to make preventing dengue campaigns updated and worthy.

ABSTRACT Tibiofemoral unilateral knee dislocations are uncommon, making bilateral dislocations even rarer injuries. Knee dislocation is considered one of the most serious injuries that can affect this joint. Associated complications such as popliteal artery injury are responsible for the important morbidity in these patients. The authors report the case of a 52-year-old man with a traumatic bilateral knee dislocation with associated bilateral popliteal arterial injury. His clinical presentation along with radiographic and angiographic findings are described. Surgical and non-surgical treatment and functional outcomes are also reported.