RESUMO
PURPOSE: The administration of a dose boost to the tumor bed after breast-conserving surgery has proven to reduce local recurrence. Intra-operative electron radiotherapy (IOERT) offers an alternative method to deliver a boost with several advantages, such as direct visualization of the tumor bed, less inter- and intrafraction motion and a reduction in the number of medical appointments. The objective of our study is to assess chronic toxicity and long-term outcome for our patients after IOERT boost. MATERIAL AND METHODS: Forty-six patients treated at our institution between July 2013 and June 2020 with IOERT boost during Breast-Conserving Surgery and consecutive whole breast irradiation were prospectively analyzed. A 10-12 Gy boost was prescribed to 42 patients and 4 patients received a 20 Gy boost. An analysis for overall survival, local relapse and distant progression was performed. Acute and chronic toxicity was assessed by CTCAE 4.0. RESULTS: The median age was 64.5 years (40-90). The median follow-up was 62 months (4-86). We had no local recurrences but 2 patients (4.3%) presented a distant recurrence. Mean pathological tumor size was 16 mm (6-52). 84.8% (39) of the patients had invasive ductal carcinoma. 52.2% (24) presented histological grade II. 52.2% (24) were Luminal A like, 21.7% (10) Luminal B like, 13% (6) HER2 positive, 13% (6) triple negative. No Grade 3-4 chronic toxicity was observed. Grade 1-2 fibrosis was evidenced in 13% (6) of the patients, 4.3% (2) patients presented fat necrosis, 6.5% (3) presented seroma, 4.3% (2) had localized pain, 2.2% (1) presented localized hematoma and 2.2% (1) presented localized edema. CONCLUSIONS: IOERT boost in breast cancer treatment during BCS is a safe option with low chronic toxicity. The recurrence rates are comparable to published data and emphasize that IOERT as boost is an effective treatment.
Assuntos
Neoplasias da Mama/radioterapia , Mama/efeitos da radiação , Carcinoma Ductal de Mama/radioterapia , Elétrons/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/secundário , Carcinoma Ductal de Mama/cirurgia , Feminino , Fibrose/patologia , Humanos , Período Intraoperatório , Mastectomia Segmentar , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Complicações Pós-Operatórias , Estudos Prospectivos , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Resultado do TratamentoRESUMO
Anaplastic thyroid cancer (ATC) is the most aggressive solid tumor and almost uniformly lethal in humans. The Boards of the Thyroid Cancer Group of the Spanish Society of Endocrinology and Nutrition and the Grupo Español de Enfermedades Huérfanas e Infrecuentes of the Spanish Society of Oncology requested that an independent task force draft a more comprehensive consensus statement regarding ATC. All relevant literature was reviewed, including serial PubMed searches together with additional articles. This is the first, comprehensive Spanish consensus statement for ATC and includes the characteristics, diagnosis, initial evaluation, treatment goals, recommendations and modalities for locoregional and advanced disease, palliative care options, surveillance, and long-term monitoring. Newer systemic therapies are being investigated, but more effective combinations are needed to improve patient outcomes. Though more aggressive radiotherapy has reduced locoregional recurrences, median overall survival has not improved in more than 50 years.
Assuntos
Carcinoma Anaplásico da Tireoide/terapia , Neoplasias da Glândula Tireoide/terapia , Algoritmos , Terapia Combinada , Consenso , Humanos , EspanhaRESUMO
Thyroid cancer is the single most prevalent endocrine malignancy; differentiated thyroid cancer (DTC) accounts for more than 90 % of all malignancies and its incidence has been rising steadily. For more patients, surgical treatment, radioactive iodine (RAI) ablation, and thyroid-stimulating hormone (TSH) suppressive therapy achieve an overall survival (OS) rate of 97.7 % at 5 years. Nevertheless, locoregional recurrence occurs in up to 20 % and distant metastases in approximately 10 % at 10 years. Two-thirds of these patients will never be cured with radioactive iodine therapy and will become RAI-refractory, with a 3-year OS rate of less than 50 %. Over the last decade, substantial progress has been made in the management of RAI-refractory DTC. Given the controversy in some areas, the Spanish Task Force for Thyroid Cancer on behalf of Spanish Society of Endocrinology Thyroid Cancer Working Group (GTSEEN) and the Spanish Rare Cancer Working Group (GETHI) have created a national joint task force to reach a consensus addressing the most challenging aspects of management in these patients. In this way, multidisciplinary management should be mandatory and nuclear medicine targeted therapy, novel molecular targeted agents, and combinations are currently changing the natural history of RAI-refractory DTC.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Radioisótopos do Iodo , Guias de Prática Clínica como Assunto/normas , Inibidores de Proteínas Quinases/uso terapêutico , Tolerância a Radiação/efeitos dos fármacos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Diferenciação Celular/efeitos da radiação , Consenso , Gerenciamento Clínico , Humanos , Terapia de Alvo MolecularRESUMO
BACKGROUND: Of all thyroid cancers, <5 % are medullary (MTC). It is a well-characterized neuroendocrine tumor arising from calcitonin-secreting C cells, and RET gene plays a central role on its pathogeny. METHODS: The electronic search was conducted using MEDLINE (PubMed), EMBASE and Cochrane Central Register of Controlled Trials. Quality assessments of selected current articles, guidelines and reviews of MTC were performed. RESULTS: This consensus updates and summarizes biology, treatment and prognostic considerations of MTC. CONCLUSIONS: Multidisciplinary teams and specialized centers are recommended for the management of MTC patients. In the metastatic setting, those patients with large volume of disease are candidates to start systemic treatment mainly if they are symptomatic and the tumor has progressed in the last 12-14 months. Wait and see strategy should be offered to patients with: disseminated disease with only high levels of calcitonin and no macroscopic structural disease, low burden and absence of progression.
Assuntos
Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/terapia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , HumanosRESUMO
HIV is a major public health issue, and infection of CD4(+) T lymphocytes is one of its key features. Whereas several cellular proteins have been identified that facilitate viral infection and replication, the role of hemichannels in these processes has not been fully characterized. We now show that the HIV isolates, R5 and X4, induced a transient-early (5-30 min) and a later, persistent (48-120 h) opening of Panx1 hemichannels, which was dependent on the binding of HIV to CD4 and CCR5/CXCR4 receptors. Blocking Panx1 hemichannels by reducing their opening or protein expression inhibited HIV replication in CD4(+) T lymphocytes. Thus, our findings demonstrate that Panx1 hemichannels play an essential role in HIV infection.
Assuntos
Linfócitos T CD4-Positivos/virologia , Conexinas/fisiologia , HIV/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Conexina 43/fisiologia , Humanos , Receptores CCR5/fisiologia , Receptores CXCR4/fisiologia , Replicação ViralRESUMO
AIMS: Dekkera bruxellensis and Pichia guilliermondii are contaminating yeasts in wine due to the production of phenolic aromas. Although the degradation pathway of cinnamic acids, precursors of these phenolic compounds has been described in D. bruxellensis, no such pathway has been described in P. guilliermondii. METHODS AND RESULTS: A molecular and physiological characterization of 14 D. bruxellensis and 15 P. guilliermondii phenol-producing strains was carried out. Both p-coumarate decarboxylase (CD) and vinyl reductase (VR) activities, responsible for the production of volatile phenols, were quantified and the production of 4-vinylphenol and 4-ethylphenol were measured. All D. bruxellensis and some P. guilliermondii strains showed the two enzymatic activities, whilst 11 of the 15 strains of this latter species showed only CD activity and did not produce 4-EP in the assay conditions. Furthermore, PCR products obtained with degenerated primers showed a low homology with the sequence of the gene for a phenyl acrylic acid decarboxylase activity described in Saccharomyces cerevisiae. CONCLUSIONS: D. bruxellensis and P. guilliermondii may share a similar metabolic pathway for the degradation of cinnamic acids. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first work that analyses the CD and VR activities in P. guilliermondii, and the results suggest that within this species, there are differences in the metabolization of cinnamic acids.
Assuntos
Cinamatos/metabolismo , Dekkera/metabolismo , Pichia/metabolismo , Vinho/microbiologia , Carboxiliases/metabolismo , Dekkera/genética , Contaminação de Alimentos , Oxirredutases/metabolismo , Fenóis/análise , Pichia/genética , Reação em Cadeia da Polimerase , Técnica de Amplificação ao Acaso de DNA PolimórficoRESUMO
We report a case of bilateral reversed palmaris longus muscle (PLM). The muscle was tendinous in its upper portion and muscular in its lower portion in both arms. This rare variation has been mentioned only once in the literature as a surgical finding. According to the literature, a reversed PLM may cause a compartment syndrome in the wrist area, carpal tunnel, and Guyon's syndrome. The described variation is also useful to the hand surgeon as a tendon graft, a tendon for transfer, or as an anatomical landmark for operations at this area.
Assuntos
Antebraço/anormalidades , Músculo Esquelético/anormalidades , Anormalidades Musculoesqueléticas/patologia , Tendões/anormalidades , Idoso , Síndrome do Túnel Carpal/etiologia , Síndrome do Túnel Carpal/cirurgia , Antebraço/cirurgia , Humanos , Úmero/anormalidades , Masculino , Músculo Esquelético/cirurgia , Transferência Tendinosa/efeitos adversos , Transferência Tendinosa/normas , Tendões/cirurgia , Punho/anormalidades , Punho/fisiologia , Punho/cirurgiaRESUMO
Traumatic brain injury (TBI) is a worldwide health problem that is especially prevalent in young adults. It is characterized by one or more primary injury foci, with secondary spread to initially not compromised areas via cascades of inflammatory response, excitotoxicity, energy failure conditions, and amplification of the original tissue injury by glia. In theory, such progression of injury should be amenable to management. However, all neuroprotective drug trials have failed, and specific treatments remain lacking. These negative results can be explained by a neuron centered approach, excluding the participation of other cell types and pathogenic mechanisms. To change this situation, it is necessary to secure a better understanding of the biological mechanisms determining damage progression or spread. We discuss the biological mechanisms involved in the progression of post-trauma tissue damage, including the general physiopathology of TBI and cellular mechanisms of secondary damage such as inflammation, apoptosis, cell tumefaction, excitotoxicity, and the role of glia in damage propagation. We highlight the role of glia in each cellular mechanism discussed. Therapeutic approaches related to the described mechanisms have been included. The discussion is completed with a working model showing the convergence of the main topics.
Assuntos
Lesões Encefálicas/fisiopatologia , Animais , Apoptose , Morte Encefálica , Edema Encefálico/etiologia , Lesões Encefálicas/complicações , Lesões Encefálicas/metabolismo , Tamanho Celular , Lesão Axonal Difusa/etiologia , Lesão Axonal Difusa/patologia , Lesão Axonal Difusa/fisiopatologia , Ácido Glutâmico/metabolismo , Humanos , Hiperglicemia/etiologia , Inflamação , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/fisiopatologia , Transporte de Íons , Modelos Neurológicos , Neuroglia/fisiologia , Neurônios/patologiaRESUMO
Bovine mastitis is one of the most economically deleterious diseases affecting dairy herds and results from an infection of the udder by pathogenic microorganisms such as Staphylococcus aureus, Streptococcus uberis, and Escherichia coli. The mammary gland is capable of preventing and combating bacterial infection by means of a complex network of innate and adaptive immune mechanisms. Lactoferrin is an 86-kDa protein with antibacterial activity that plays a role in the mammary gland's defense against infection. ß-Lactoglobulin (ß-LG) is an 18-kDa protein that is present in most mammals but is notably absent in humans, rodents, and lagomorphs. Different genetic variants of this protein exist, with ß-LG A and ß-LG B being the most common. In spite of being well studied, the biological function of ß-LG is not thoroughly understood, and most noticeably, no reports exist on the effects of the native protein on bacterial growth. Hence, the objective of this study was to assess the potential antibacterial activity of ß-LG against mastitis agents. To do this, we purified ß-LG from normal bovine milk using a mild, nondenaturing method and performed in vitro growth inhibition assays with Staph. aureus, E. coli, and Strep. uberis. ß-Lactoglobulin inhibited the growth of Staph. aureus and Strep. uberis but had no effect on E. coli. The antimicrobial activity against Staph. aureus and Strep. uberis was concentration dependent and was elicited by the intact protein because Tricine-sodium dodecyl sulfate-PAGE and analytical gel filtration chromatography did not reveal the presence of short degradation peptides. Analysis of the genetic variants of ß-LG showed that ß-LG A has higher inhibitory activity against Staph. aureus and Strep. uberis than ß-LG B. Coincubation of ß-LG and lactoferrin resulted in an augmented antibacterial activity against Staph. aureus, suggesting an additive effect of the proteins. This result, along with the proteins' complementary spectrum of action, suggests that ß-LG and lactoferrin may complement each other in the mammary gland's defenses against bacterial infection.
Assuntos
Anti-Infecciosos/farmacologia , Lactoglobulinas/farmacologia , Mastite Bovina/prevenção & controle , Animais , Bovinos , Contagem de Colônia Microbiana/veterinária , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Feminino , Lactoglobulinas/genética , Mastite Bovina/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Streptococcus/classificação , Streptococcus/efeitos dos fármacos , Streptococcus/crescimento & desenvolvimentoRESUMO
AIMS: To investigate whether the presence of Pichia guilliermondii impacts on the production of volatile phenols from mixed wine fermentations with Dekkera bruxellensis and Saccharomyces cerevisiae. METHODS AND RESULTS: Four inoculation strategies were performed in small-scale fermentations involving P. guilliermondii, D. bruxellensis and S. cerevisiae using Syrah grape juice supplemented with 100 mg l(-1) of p-coumaric acid. High pressure liquid chromatography was used for the quantification or volatile phenols. Significant high levels of 4-ethylphenol and 4-ethylguaicol (720 and 545 microg l(-1), respectively), as well as the highest levels of 4-vinylphenol (>4500 microg l(-1)), were observed when P. guilliermondii species was inoculated from the beginning of the fermentation. CONCLUSIONS: The metabolic interaction occurring between the high vinylphenol producer species P. guilliermondii and D. bruxellensis exhibiting a high vinylphenol reductase activity resulted in an increased production of volatile phenols in wine. SIGNIFICANCE AND IMPACT OF THE STUDY: Pichia guilliermondii must be considered a very important spoilage yeast in the wine industry capable of producing large amounts of volatile phenols.