Browsing by Author "Lopes, C."
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- 17-Week Delay Surgery after Chemoradiation in Rectal Cancer with Complete Pathological ResponsePublication . Santos, M.; Gomes, M.; Moreno, F.; Rocha, A.; Lopes, C.Neoadjuvant chemoradiation (CRT) followed by curative surgery still remains the standard of care for locally advanced rectal cancer (LARC). The main purpose of this multimodal treatment is to achieve a complete pathological tumor response (ypCR), with better survival. The surgery delay after CRT completion seems to increase tumor response and ypCR rate. Usually, time intervals range from 8 to 12 weeks, but the maximum tumor regression may not be seen in rectal adenocarcinomas until several months after CRT. About this issue, we report a case of a 52-year-old man with LARC treated with neoadjuvant CRT who developed, one month after RT completion, an acute myocardial infarction. The need to increase the interval between CRT and surgery for 17 weeks allowed a curative surgery without morbidity and an unexpected complete tumor response in the resected specimen (given the parameters presented in pelvic magnetic resonance imaging (MRI) performed 11 weeks after radiotherapy completion).
- Avaliação e tratamento do doente com acne – Parte I: Epidemiologia, etiopatogenia, clínica, classificação, impacto psicossocial, mitos e realidades, diagnóstico diferencial e estudos complementaresPublication . Figueiredo, A.; Massa, A.; Picoto, A.; Soares, A.; Basto, A.; Lopes, C.; Resende, C.; Rebelo, C.; Brandão, F.; Pinto, G.; Oliveira, H.; Selores, M.; Gonçalo, M.; Bello, R.O Portuguese Acne Advisory Board (PAAB), grupo de dermatologistas portugueses que, à semelhança de grupos congéneres internacionais, tem dedicado particular atenção à definição de linhas de orientação para o tratamento da acne, pretende que o presente documento constitua uma ferramenta útil na abordagem dos doentes com esta patologia. Elaborou-se um dossier, para educação médica contínua, subdividido em 2 partes: Parte I – etiopatogenia e clínica; Parte II – abordagem terapêutica. Nesta Parte I, revêem-se os principais aspectos da clínica e da fisiopatogenia da acne à luz dos conhecimentos actuais. Discute-se a importância do impacto psicológico e social desta entidade e analisam-se os principais mitos e realidades com ela relacionados. Descrevem-se, sucintamente, as patologias mais relevantes no diagnóstico diferencial das lesões de acne. Enumeram-se as indicações para estudo hormonal, bem como os exames a efectuar nos doentes com esta patologia.
- Avaliação e tratamento do doente com acne – Parte II: Tratamento tópico, sistémico e cirúrgico, tratamento da acne na grávida, algoritmo terapêuticoPublication . Figueiredo, A.; Massa, A.; Picoto, A.; Soares, A.; Basto, A.; Lopes, C.; Resende, C.; Rebelo, C.; Brandão, F.; Pinto, G.; Oliveira, H.; Selores, M.; Gonçalo, M.; Bello, R.O Portuguese Acne Advisory Board (PAAB), grupo de dermatologistas portugueses que, à semelhança de grupos congéneres internacionais, tem dedicado particular atenção à definição de linhas de orientação para o tratamento da acne, pretende que o presente documento constitua uma ferramenta útil na abordagem dos doentes com esta patologia. Elaborou-se um dossier, para educação médica contínua, subdividido em 2 partes: Parte I – etiopatogenia e clínica; Parte II – abordagem terapêutica. Nesta Parte II discute-se a abordagem terapêutica – tópica e sistémica – em cada forma clínica de acne, dando particular ênfase aos retinóides e aos antimicrobianos, e salientam-se as estratégias a adoptar para limitar a crescente resistência bacteriana aos antibióticos. Referem-se as indicações específicas para terapêutica hormonal e analisam-se as particularidades do tratamento da acne na grávida e lactante. Descrevem-se algumas técnicas para correcção das cicatrizes da acne. Por último, publica-se um algoritmo que pretende ilustrar a classificação da acne e definir, para cada tipo clínico, a abordagem terapêutica consensualmente recomendada.
- A clinical-pathological and survival study of oral squamous cell carcinomas from a population of the North of PortugalPublication . Monteiro, L.; Barbas-Amaral, J.; Vizcaíno, J.; Lopes, C.; Torres, F.OBJECTIVES: Our aim was to analyze the clinical, pathological, and outcome characteristics of oral squamous cell carcinomas (OSCC) from a population of the North of Portugal. MATERIAL AND METHODS: We conducted a descriptive study of 128 OSCC diagnosed between the years of 2000 and 2010 in the Centro Hospitalar do Porto. Through of the review of the clinical records we studied several clinical, pathological, and outcome variables. The overall survival (OS) and disease-free survival (DFS) were analyzed by Kaplan-Meier method and log-rank test. Cox regression method was used for multivariate analysis. RESULTS: Of 128 patients with OSCC, 83 (64.8%) were male and 45 (35.2%) were female, (mean age of 62.13±15.57 years). The most affected location was the tongue (n=52; 40.6%). The most common cause of reference was a non-healing ulcer (n=35; 28.9%) followed by oral pain (n=27; 22.3%). Sixty (60.6%) patients were tobacco consumers and 55 (57.3%) alcohol consumers. The cumulative 3-years OS rate was 58.6% and DFS was 55.4%. In multivariable analysis for OS, we found an adverse independent prognostic value for advanced tumour size (p<0.001) and for the presence of perineural permeation (p=0.012). For DFS, advanced stage tumours presented adverse independent prognostic value (p<0.001). CONCLUSION: OSCC occurred most frequently in males, in older patients, and in patients with tobacco and/or alcohol habits. TNM and tumour stage additionally to the perineural permeation were the most important prognostic factor for the survival of these patients, contributing to identify high-risk subgroups and to guide therapy.
- Duodenal gastrointestinal stromal tumor and endoscopic ultrasoundPublication . Castro-Poças, F.; Araújo, T.; Silva, J.; Lopes, C.; M Saraiva, M.Duodenal gastrointestinal stromal tumors (GISTs) are a very rare condition. The pre-operative diagnosis can be a challenge but it is very important because GISTs have singularities that differ from other tumors and their location in the duodenum itself can have a major role in the choice of the surgical approach. We present two cases of duodenal GISTs where endoscopic ultrasound had a single role in their management, namely allowing the possibility to obtain material for immunocytochemical pre-operative diagnosis and regarding the precise relation to the papilla of Vater. The patients were operated and histological examination confirmed the diagnosis in both cases.
- EMMPRIN expression in oral squamous cell carcinomas: correlation with tumor proliferation and patient survivalPublication . Monteiro, L.; Delgado, M.; Ricardo, S.; Garcez, F.; Barbas-Amaral, J.; Pacheco, J.; Lopes, C.; Bousbaa, H.The aim of our study was to explore the clinicopathological and prognostic significance of extracellular matrix metalloproteinase inducer (EMMPRIN) expression in oral squamous cell carcinomas (OSCC), and its relation with the proliferative tumor status of OSCC. We examined EMMPRIN and Ki-67 proteins expression by immunohistochemistry in 74 cases with OSCC. Statistical analysis was conducted to examine their clinicopathological and prognostic significance in OSCC. EMMPRIN membrane expression was observed in all cases, with both membrane and cytoplasmic tumor expression in 61 cases (82.4%). EMMPRIN overexpression was observed in 56 cases (75.7%). Moderately or poorly differentiated tumors showed EMMPRIN overexpression more frequently than well-differentiated tumors (P = 0.002). Overexpression of EMMPRIN was correlated with high Ki-67 expression (P = 0.004). In the multivariate analysis, EMMPRIN overexpression reveals an adverse independent prognostic value for cancer-specific survival (CSS) (P = 0.034). Our results reveal that EMMPRIN protein is overexpressed in more than two-thirds of OSCC cases, especially in high proliferative and less differentiated tumors. The independent value of EMMPRIN overexpression in CSS suggests that this protein could be used as an important biological prognostic marker for patients with OSCC. Moreover, the high expression of EMMPRIN makes it a possible therapeutic target in OSCC patients.
- Expansão de células estaminais em carcinoma ductal in situ da mamaPublication . Arnaud, P.; Marques, O.; Rosa, A.; Carvalho, F.; Rema, A.; Lopes, C.
- Genetic polymorphisms in key hypoxia-regulated downstream molecules and phenotypic correlation in prostate cancerPublication . Fraga, A.; Ribeiro, R.; Coelho, A.; Vizcaíno, J.; Coutinho, H.; Lopes, J.; Príncipe, P.; Lobato, C.; Lopes, C.; Medeiros, R.Background In this study we sought if, in their quest to handle hypoxia, prostate tumors express target hypoxia-associated molecules and their correlation with putative functional genetic polymorphisms. Methods Representative areas of prostate carcinoma (n = 51) and of nodular prostate hyperplasia (n = 20) were analysed for hypoxia-inducible factor 1 alpha (HIF-1α), carbonic anhydrase IX (CAIX), lysyl oxidase (LOX) and vascular endothelial growth factor (VEGFR2) immunohistochemistry expression using a tissue microarray. DNA was isolated from peripheral blood and used to genotype functional polymorphisms at the corresponding genes (HIF1A +1772 C > T, rs11549465; CA9 + 201 A > G; rs2071676; LOX +473 G > A, rs1800449; KDR – 604 T > C, rs2071559). Results Immunohistochemistry analyses disclosed predominance of positive CAIX and VEGFR2 expression in epithelial cells of prostate carcinomas compared to nodular prostate hyperplasia (P = 0.043 and P = 0.035, respectively). In addition, the VEGFR2 expression score in prostate epithelial cells was higher in organ-confined and extra prostatic carcinoma compared to nodular prostate hyperplasia (P = 0.031 and P = 0.004, respectively). Notably, for LOX protein the immunoreactivity score was significantly higher in organ-confined carcinomas compared to nodular prostate hyperplasia (P = 0.015). The genotype-phenotype analyses showed higher LOX staining intensity for carriers of the homozygous LOX +473 G-allele (P = 0.011). Still, carriers of the KDR−604 T-allele were more prone to have higher VEGFR2 expression in prostate epithelial cells (P < 0.006). Conclusions Protein expression of hypoxia markers (VEGFR2, CAIX and LOX) on prostate epithelial cells was different between malignant and benign prostate disease. Two genetic polymorphisms (LOX +473 G > A and KDR−604 T > C) were correlated with protein level, accounting for a potential gene-environment effect in the activation of hypoxia-driven pathways in prostate carcinoma. Further research in larger series is warranted to validate present findings.
- Hipersensibilidade aos AINES na criança: aspectos clínicos e diagnósticoPublication . Lopes, C.; Gomes, E.Objectivos e concepção do estudo: Os anti-inflamatórios não esteróides (AINES) são a segunda causa mais frequente de reacções de hipersensibilidade a fármacos tanto em adultos como em crianças. A suspeita diagnóstica baseia-se numa relação temporal próxima entre a administração do fármaco e o aparecimento de sintomatologia sugestiva, sobretudo respiratória e/ou cutânea. O esclarecimento do diagnóstico é de grande importância pois evita situações de ansiedade nos doentes e a utilização desnecessária de fármacos alternativos menos adequados e mais dispendiosos. É frequente o recurso à prova de provocação oral (PPO) com carácter diagnóstico, devido à ausência de outros meios auxiliares diagnósticos devidamente padronizados e validados. Este trabalho pretende avaliar os resultados e a importância da PPO diagnóstica no estudo de doentes pediátricos enviados a uma consulta de Imunoalergologia por suspeita de hipersensibilidade a AINES. Material e métodos: Investigámos 24 doentes referenciados à consulta durante 2005-06 por suspeita de hipersensibilidade a AINES e avaliámos os resultados das PPO realizadas e a sua importância para o esclarecimento diagnóstico. Resultados e conclusões: Os fármacos mais frequentemente implicados foram o ibuprofeno (71%) e o paracetamol (24%) sendo as reacções cutâneas as mais frequentes. Quatro doentes não realizaram PPO, um por recusa, um por história não sugestiva de hipersensibilidade e dois por comprovada tolerância posterior ao fármaco suspeito. Entre os 20 que realizaram PPO com o fármaco suspeito apenas em dois se confirmou o diagnóstico inicial de hipersensibilidade (um caso ao ibuprofeno e paracetamol e noutro ao ácido acetilsalicílico). Estes doentes realizaram posteriormente testes de provocação para pesquisa de alternativas terapêuticas. A PPO teve um papel fundamental na avaliação deste grupo de doentes com suspeita de hipersensibilidade a AINEs tendo permitido diagnosticar dois casos de hipersensibilidade (10%) e excluir a suspeita inicial nos restantes. ABSTRACT Aim and study concept: Non steroid anti-inflammatory drugs (NSAID) are the second most important cause of drug hypersensitivity reactions in adults and in children. Symptoms are mostly cutaneous and/or respiratory and a close temporal relation with drug administration is suggestive of an etiological association. An accurate diagnosis is of great importance since it avoids patient’s anxiety and unnecessary use of less suitable and more expensive drugs. An oral provocation test (OPT) is often used to establish the diagnosis since other validated and well standardized diagnostic tests are still lacking. This study aims to assess the results and importance of OPT in paediatric patients with suspected NSAID hypersensitivity referred to a specialized allergy clinic. Material and Methods: Twenty four patients referred during 2005-06 with suspected NSAID hypersensitivity reaction were investigated. OPT results and its importance in establishing a diagnosis were evaluated. Results and conclusions: The drugs most often implicated were ibuprofen (71%), and paracetamol (24%); cutaneous reactions were the most frequently found. Four patients were not submitted to OPT for the following reasons: one refused, one had a non-suggestive history, and two had already tolerated the suspected drug. From the 20 who underwent OPTs only in two we confirmed the initial suspicion of drug hypersensitivity (one to ibuprofen and paracetamol, the other to acetyl salicylic acid). These patients were submitted to further OPTs to find alternative therapeutic options. Oral provocation testing was very useful in the assessment of suspected NSAID hypersensitivity confirming the diagnosis in two cases (10%) and excluding the initial suspicion in the remaining patients.
- A lactate shuttle system between tumour and stromal cells is associated with poor prognosis in prostate cancerPublication . Pértega-Gomes, N.; Vizcaíno, J.; Attig, J.; Jurmeister, S.; Lopes, C.; Baltazar, F.BACKGROUND: In a malignant tumour, cancer cells are embedded in stromal cells, namely cancer-associated fibroblasts (CAFs). These CAFs are now accepted as important players in cancer dynamics, being involved in tumour growth and progression. Although there are various reports on the interaction between tumour and stromal cells, the clinico-pathological significance of this cross-talk is still largely unknown. In this study, we aimed to characterise the expression of key metabolic proteins involved in glucose transport, pyruvate/lactate shuttle system, glycolytic metabolism and fatty acid oxidation in CAFs and tumour cells in different stages of malignant transformation. We further aimed to contextualise the clinico-pathological significance of these protein expression profiles with reference to known prognostic indicators, including biochemical recurrence in pT stage. METHODS: Prostate tissues were obtained from 480 patients with a median age of 64 years following radical prostatectomy with no previous hormonal therapy. Tissues were analysed for the expression of several key metabolism-related proteins in glands and surrounding fibroblasts by immunohistochemistry. Reliable markers of prognosis such as pT stage and biochemical recurrence were assessed for each case. RESULTS: We observed that prostate cancer cells did not rely mainly on glycolytic metabolism, while there was a high expression of MCT4 and CAIX - in CAFs. This corroborates the hypothesis of the "Reverse Warburg effect" in prostate cancer, in which fibroblasts are under oxidative stress and express CAIX, an established hypoxia marker. We found that alterations in the expression of metabolism-related proteins were already evident in the early stages of malignant transformation, suggesting the continuing alteration of CAFs from an early stage. Additionally, and for the first time, we show that cases showing high MCT4 expression in CAFs with concomitant strong MCT1 expression in prostate cancer (PCa) cells are associated with poor clinical outcome, namely pT3 stage of the tumour. CONCLUSIONS: In summary, this work demonstrates for the first time the clinico-pathological significance of the lactate shuttle in prostate cancer. It also suggests that other alterations in CAFs may be useful prognostic factors, and further supports the use of MCT1/MCT4 as targets for PCa therapy.