604 research outputs found

    Linking surgical specimen length and examined lymph nodes in colorectal cancer patients.

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    AbstractAimThe number of examined lymph nodes (NLN) was associated with survival of stages II and III colorectal cancer (CRC) patients. Guidelines recommend examining at least 12 lymph nodes. This study investigated the influence of surgical specimen length on lymph node harvest and compliance with international guidelines.Materials and methodsThis population-based study included 4,724 cases of surgically treated CRC that were diagnosed from 2002 to 2008. Multivariate analyses were performed for the main study variables (age, gender, diagnosis at screening or in symptomatic patients, cancer site, staging, grading, number of positive nodes, neo-adjuvant treatment for rectal cancer, hospital were surgery was performed). Fractional polynomial models investigated the relationship between continuous variables and outcomes.ResultsThe NLN increased over time reaching ≥12 NLN in 64% of cases at the end of the study period. More NLN were associated with young age, right colon cancer, pT3–T4 disease, stages II and III and high grade. Fewer NLN were associated with short surgical specimen length and neo-adjuvant treatment in rectal cancer patients. Use of laparoscopy increased sharply over time.ConclusionsNLN increased over time in accordance with international guidelines. Surgical specimen length correlated with NLN which may determine therapeutic choices, particularly in stage II colon cancer. When harvested lymph nodes are under 10 in number and all are negative, chemotherapy is always recommended. As specimen lengths <20 cm were associated with a high risk of inadequate NLN counts, patients are at risk of over-treatment

    Ativação de neutrófilos de indivíduos saudáveis e imunocomprometidos por promastigotas de Leishmania spp.

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    Os neutrófilos são as primeiras células polimorfonucleares do sistema imunitário inato a chegar ao local de infeção, constituindo a primeira linha de defesa contra agentes invasores, como no caso do parasita Leishmania. Este parasita é causador da leishmaniose que tem sido reportada em mais de 98 países e que pode afetar animais e seres humanos. As diferentes espécies do parasita podem causar leishmaniose com diferentes apresentações clinicas, das quais salientamos a leishmaniose visceral e a leishmaniose cutânea. O presente trabalho teve como objetivo analisar a resposta imunitária de células polimórficas nucleares (PMN) de indivíduos com diferentes competências imunitárias quando expostas a parasitas de espécies viscerais (L. infantum) e cutâneas (L. amazonensis, L. shawi e L. guyanensis). A internalização parasitária foi confirmada por microscopia optica. A ativação celular foi avaliada através de técnicas laboratoriais que permitaram analisar os mecanismos oxidativos, nomeadamente a produção de ião superóxido, a exocitose de grânulos ricos em enzimas proteolíticas, como é o caso específico da elastase neutrofilica (NE) e da catepsina G (CatG) e a libertação de armadilhas extracelulares (NET). Verificou-se que as espécies de Leishmania induzem a exocitose de CatG e a libertação de NET, independentemente da competência imunitária dos indivíduos estudados. Contudo, idêntica situação não se verifica no caso do stress oxidativo ou da libertação de NE. Leishmania spp. estimulou o stress oxidativo, com produção do ião superóxido, nos PMN de indivíduos saudáveis enquanto os PMN de indivíduos imunocomprometidos apenas parece ficar ativado na presença de L. infantum e de L. amazonensis apontando para mecanismos de ativação diversos decorrentes quer da espécie do parasita quer do nível imunitário do hospedeiro. Situação similar ocorreu na exocitose de grânulos ricos em NE. L. infantum e L. shawi estimularam a libertação de NE por PMN de indivíduos saudáveis e imunocomprometidos. Porém, os PMN de indivíduos com comprometimento da imunidade também responderam aos parasitas da espécie L. amazonensis enquanto que L. guyanensis unicamente induziu a exocitose de NE nos PMN de indivíduos saudáveis. Estes resultados apontam para a existência de especificidades próprias na ativação destes mecanismos relativamente às espécies de Leishmania e ao estado imunitário do hospedeiro. Estudos complementares são necessários para esclarecer o processo de ativação, bem como identificar os eventuais antigénios parasitários (ou até ilhas CpG) que conduzem a ativação de PMN humanos.Neutrophils are the first polymorphonuclear cells of the innate immune system to reach the infection site, providing the first line of defense against invading pathogens, such as the Leishmania parasite. This parasite causes leishmaniasis that has been reported over 98 countries, affecting both animals and human beings. Different species of the parasite can cause leishmaniasis with diverse clinical presentations, as is the case of visceral leishmaniasis and cutaneous leishmaniasis. The present study aimed to evaluate the immune response of polymorphic nuclear cells (PMN) of individuals with different immune competence when exposed to visceral (L. infantum) and cutaneous parasitic species (L. amazonensis, L. guyanensis and L. shawi). Uptake of parasites by PMN was confirmed by optical microscopy. Laboratory techniques were used to evaluate the PMN activation by assessing oxidative mechanisms, namely the production of ion superoxide exocytosis, exocytosis of granules rich in proteolytic enzymes, as is the specific case of neutrophil elastase (NE) and cathepsin G (CatG) and the release of extracellular traps (NET). It was found that the species of Leishmania induce CatG exocytosis and NET release, regardless of the immune competence of the studied subjects. On the contrary, in the case of oxidative stress or the release of NE some differences were observed between PMN from healthy and immuncompromised individuals. All species of Leishmania induced oxidative stress, with production of superoxide ion in PMN of healthy individuals. However, PMN of immunocompromised individuals just seems to be activated in the presence of L. infantum and L. amazonensis parasites, pointing to the possible existence of more than one activation mechanism in association with the immune competence of the host that can be specifically primed by a particular parasite species. A similar situation was observed in the exocytosis of granules rich in NE. L. infantum and L. shawi stimulated the release of NE by PMN isolated from healthy and immunocompromised individuals. However, PMN from individuals with impaired immunity also appeared to respond to L. amazonensis parasites while L. guyanensis only induced PMN from healthy individuals to exocytosis NE. These findings suggest that the presence of specific features in the activation of these particular mechanisms might be related to the species of Leishmania and also to the immune status of the host. Additional studies are needed to clarify the activation process and identify parasitic antigens (or even CpG islands) that direct cell activation

    Clinical translation and implementation of optical imaging agents for precision image-guided cancer surgery

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    Introduction The field of tumor-specific fluorescence-guided surgery has seen a significant increase in the development of novel tumor-targeted imaging agents. Studying patient benefit using intraoperative fluorescence-guided imaging for cancer surgery is the final step needed for implementation in standard treatment protocols. Translation into phase III clinical trials can be challenging and time consuming. Recent studies have helped to identify certain waypoints in this transition phase between studying imaging agent efficacy (phase I-II) and proving patient benefit (phase III). Trial initiation Performing these trials outside centers of expertise, thus involving motivated clinicians, training them, and providing feedback on data quality, increases the translatability of imaging agents and the surgical technique. Furthermore, timely formation of a trial team which oversees the translational process is vital. They are responsible for establishing an imaging framework (camera system, imaging protocol, surgical workflow) and clinical framework (disease stage, procedure type, clinical research question) in which the trial is executed. Providing participating clinicians with well-defined protocols with the aim to answer clinically relevant research questions within the context of care is the pinnacle in gathering reliable trial data. Outlook If all these aspects are taken into consideration, tumor-specific fluorescence-guided surgery is expected be of significant value when integrated into the diagnostic work-up, surgical procedure, and follow-up of cancer patients. It is only by involving and collaborating with all stakeholders involved in this process that successful clinical translation can occur. Aim Here, we discuss the challenges faced during this important translational phase and present potential solutions to enable final clinical translation and implementation of imaging agents for image-guided cancer surgery.Surgical oncolog
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