Profilaxia antibiótica

Antibiotic prophylaxis takes the prevention of the infection as an objective, through the administration of antimicrobians. There are benefits and potential damages in this medical attitude obligating to a cost - benefits analysis, which must take into account factors as the gravity of the disease to prevent, activity of the microbial agent, induction of resistances, toxicity, etc. This text is about antibiotic prophylaxis in endocarditis and in surgery procedures reporting the experience of the Hospital Santo António (HSA). The international recommendations for antibiotics administration in endocarditis made it more selective, taking into account that the bacteriemia resultant of the daily activities has bigger probability of causing infectious endocarditis than the bacteriemia associated to odontologic proceedings and that, only a scarce number of cases might be prevented even that the antibiotic prophylaxis is 100 % effective. Surgical site infection (SSI) it is an important problem, occupying in the HSA the third place of the nosocomial infections (NI), after UTI and respiratory infections. In a series of 15000 surgical procedures the rate of NI was 3,36 %, with a highly probable subnotification. The most frequent type of SSI is superficial incision and the commonest microbial agents were the methicilin-resistant Staphylococus aureus and the Escherichia coli. Appendicectomy and the wound desbridment / abscesses were the surgical procedures that more contributed to SSI. The strategy followed, in 1995, by the HSA for antibiotic prophylaxis in surgery was based on the Recommendations of “Surgical Wound Task Force Guidelines for the prevention of Surgical Wound Infection” and of “Center for Disease Control”, in an initiative of the group of antimicrobial - committee of pharmacy and therapeutics, with the support of the Administration and the involvement of several specialists. In a global evaluation of the adhesion to the published recommendations we note that the correct use exceeded 60% in clean surgery without use of prothesis. Of the remainder, nearly 30 % did not do prophylactic antibiotic and only 6 % did it wrongly as therapeutic intention. This last percentage increases for the double in the clean-contaminated, contaminated and dirty, as well as in the emergency surgery. The experience of the HSA allows us to affirm that the fulfillment of a protocol of antibiotic prophylaxis in surgery can be got with the involvement from the beginning, in the process, of the responsible persons and with efficient measures of control and of easy application.  A antibioterapia profiláctica tem como objectivo a prevenção da infecção através da administração de antimicrobianos. Há benefícios e prejuízos potenciais nesta atitude médica pelo que é imperiosa uma análise dos custos-benefícios envolvidos, que deve ter em conta factores como a gravidade da doença a prevenir, espectro de actividade do agente microbiano, indução de resistências, toxicidade, etc. Nesta exposição vamos debruçar-nos sobre a antibioterapia profiláctica da endocardite e em cirurgia relatando a experiência do Hospital de Santo António (HSA). Na endocardite as recomendações internacionais para administração de antibióticos tornaram-se mais selectivas tendo em conta que a bacteriemia resultante das actividades diárias tem maior probabilidade de causar endocardite infecciosa que a bacteriemia associada a procedimentos odontológicos e que apenas um número escasso de casos poderia ser prevenida pela profilaxia antibiótica mesmo que a profilaxia seja 100% efectiva. Quanto à infecção do local cirúrgico (ILC) trata-se de um problema importante, ocupando no HSA o terceiro lugar das infecções nosocomiais, a seguir à ITU e infecções respiratórias. Numa série de 15 000 intervenções registadas, a taxa de ILC registada até à data da alta hospitalar é de 3,36 %, sendo altamente provável a existência de subnotificação. O tipo de ILC mais frequente é superficial e os agentes microbianos mais comuns foram Staphylococus aureus meticilina resistente e Escherichia coli. A apendicectomia e o desbridamento de feridas / abcessos foram os actos cirúrgicos que mais contribuíram para a ILC. A estratégia seguida, em 1995, pelo HSA para antibioprofilaxia cirúrgica foi a de seguir as Recomendações da “Surgical Wound Task Force Guidelines for Prevention of Surgical Wound Infeccion” e do “Center Disease Control”, numa iniciativa do grupo de antimicrobianos da Comissão de Farmácia e Terapêutica, com o apoio da Administração e o envolvimento de vários especialistas. Numa avaliação global da adesão às recomendações publicadas constatamos que ultrapassou os 60 % a sua utilização correcta, em cirurgia limpa sem uso de próteses. Dos restantes, cerca de 30 % não fez antibiótico profiláctico e apenas 6 % o fez inadequadamente sendo registada a intenção terapêutica. Esta última percentagem aumenta para o dobro nas cirurgias limpo-contaminadas, contaminadas e conspurcadas, assim como na cirurgia de urgência. A experiência do HSA permite-nos afirmar que o cumprimento de um protocolo de antibioprofilaxia em cirurgia pode ser conseguido com o envolvimento desde o início, no processo, das pessoas responsáveis e com medidas de controlo eficazes e de fácil aplicação

Neuroendocrine breast carcinoma

Neuroendocrine breast cancer (NEBC) is a rare and heterogeneous entity. It most commonly presents a luminal phenotype and a worse prognosis. When diagnosed in an advanced stage, metastasis from another neuroendocrine tumor should be excluded.This case features a premenopausal woman with an oligometastatic breast large cell neuroendocrine carcinoma, estrogen receptor (ER) positive, and human epidermal growth factor receptor 2 (HER2) negative. Since the patient was very symptomatic at the presentation of the disease, chemotherapy was started. Complete radiological response of the metastatic disease was achieved, and the patient was then submitted to radical breast surgery and bilateral oophorectomy. She subsequently underwent radiation therapy. Since then and to date, she has been under endocrine therapy (ET) and a CDK4/6 inhibitor (CDK4/6i), with no evidence of malignant disease. Evidence to guide the choice of treatment for these tumors is currently scarce. In cases with oligometastatic disease, radical treatment should be considered. Given that this entity is rare, its reporting should be encouraged

SRC inhibition prevents P-cadherin mediated signaling and function in basallike breast cancer cells

© The Author(s). 2018. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.BACKGROUND: Basal-like breast cancer (BLBC) is a poor prognosis subgroup of triple-negative carcinomas that still lack specific target therapies and accurate biomarkers for treatment selection. P-cadherin is frequently overexpressed in these tumors, promoting cell invasion, stem cell activity and tumorigenesis by the activation of Src-Family kinase (SRC) signaling. Therefore, our aim was to evaluate if the treatment of BLBC cells with dasatinib, the FDA approved SRC inhibitor, would impact on P-cadherin induced tumor aggressive behavior. METHODS: P-cadherin and SRC expression was evaluated in a series of invasive Breast Cancer and contingency tables and chi-square tests were performed. Cell-cell adhesion measurements were performed by Atomic Force Microscopy, where frequency histograms and Gaussian curves were applied. 2D and 3D cell migration and invasion, proteases secretion and self-renew potential were evaluated in vitro. Student's t-tests were used to determine statistically significant differences. The cadherin/catenin complex interactions were evaluated by in situ proximity-ligation assay, and statistically significant results were determined by using Mann-Whitney test with a Bonferroni correction. In vivo xenograft mouse models were used to evaluate the impact of dasatinib on tumor growth and survival. ANOVA test was used to evaluate the differences in tumor size, considering a confidence interval of 95%. Survival curves were estimated by the Kaplan-Meier's method, using the log-rank test to assess significant differences for mice overall survival. RESULTS: Our data demonstrated that P-cadherin overexpression is significantly associated with SRC activation in breast cancer cells, which was also validated in a large series of primary tumor samples. SRC activity suppression with dasatinib significantly prevented the in vitro functional effects of P-cadherin overexpressing cells, as well as their in vivo tumorigenic and metastatic ability, by increasing mice overall survival. Mechanistically, SRC inhibition affects P-cadherin downstream signaling, rescues the E-cadherin/p120-catenin complex to the cell membrane, recovering cell-cell adhesion function. CONCLUSIONS: In conclusion our findings show that targeting P-cadherin/SRC signaling and functional activity may open novel therapeutic opportunities for highly aggressive and poor prognostic basal-like breast cancer.This work was funded by Laço Grant 2014, by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 – Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by FCT - Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia e Ensino Superior under the projects PTDC/SAU-GMG/120049/2010-FCOMP-01-0124-FEDER-021209, PEst-C/SAU/LA0003/2013, NORTE-01-0145-FEDER-000029 and POCI-01-0145-FEDER-016390. FCT funded the research grants of ASR (SFRH/BPD/75705/2011), ARN (SFRH/BD/100380/2014), BS (SFRH/BPD/104208/2014), AFV (SFRH/BPD/90303/2012), as well as JP with Programa IFCT 2013 (FCT Investigator). IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274)info:eu-repo/semantics/publishedVersio

Actin stress fiber organization promotes cell stiffening and proliferation of pre-invasive breast cancer cells

This deposit is composed by the main article and supplementary files of the publication.Studies of the role of actin in tumour progression have highlighted its key contribution in cell softening associated with cell invasion. Here, using a human breast cell line with conditional Src induction, we demonstrate that cells undergo a stiffening state prior to acquiring malignant features. This state is characterized by the transient accumulation of stress fibres and upregulation of Ena/VASP-like (EVL). EVL, in turn, organizes stress fibres leading to transient cell stiffening, ERK-dependent cell proliferation, as well as enhancement of Src activation and progression towards a fully transformed state. Accordingly, EVL accumulates predominantly in premalignant breast lesions and is required for Src-induced epithelial overgrowth in Drosophila. While cell softening allows for cancer cell invasion, our work reveals that stress fibre-mediated cell stiffening could drive tumour growth during premalignant stages. A careful consideration of the mechanical properties of tumour cells could therefore offer new avenues of exploration when designing cancer-targeting therapies.Bloomington Drosophila Stock Centre; Vienna Drosophila Research Center (VDRC); Developmental Studies Hybridoma Bank (DSHB); Fundação para a Ciência e Tecnologia (FCT) grant: (IF/01031/2012); Laço Grant in breast cancer 2015; Alexander von Humboldt Foundation grant: (Alexander von Humboldt Professorship); Liga Portuguesa contra o Cancro/Pfizer.info:eu-repo/semantics/publishedVersio

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Squamous cell carcinoma with sarcomatous transformation of the penis

Malignant tumors of the penis are rare, most of them being squamous cell carcinomas (SCCs). We report the case of a 75-year-old man with a large penile mass submitted to partial penectomy. The specimen showed an exophytic mass involving the glans, coronal sulcus, and prepuce. Microscopic examination showed a carcinoma with two distinct areas: a mixed SCC and a sarcomatoid carcinoma. The SCC component had areas of verrucous carcinoma and areas of classical invasive SCC. The tumor cells expressed p63 with the absence of p16 expression. Vimentin and p53 were positive in the sarcomatous component. The morphology and immunohistochemistry were compatible with mixed SCC (verrucous hybrid-sarcomatoid carcinoma). Additionally, the tumor cells also expressed 3 different clones of PDL1 (22C3, SP263, and SP142). Two months later, the patient presented local recurrence with multiple lymph nodes and lung metastases, dying 7 weeks later. Mixed tumors represent diagnostic challenges. The correct identification of adverse prognostic factors can be the first step to implement the treatment with a higher probability of success