Metástase em polegar de carcinoma de pequenas células de pulmão tratada com radioterapia

A rare case of thumb metastasis from small cell lung cancer is presented. The patient underwent local radiotherapy with complete palliation of symptoms. She died 4 months later with disseminated disease. Considerations about incidence, treatment, and physiopathology of this kind of dissemination are made. Conservative treatment of finger metastasis with radiation may be considered due to the poor outcome of these patients.Apresentamos um caso raro de metástase em polegar de carcinoma de pequenas células de pulmão. A paciente foi submetida a radioterapia local com alívio completo dos sintomas. Quatro meses após o término do tratamento evoluiu a óbito com doença disseminada. São feitas considerações sobre incidência, tratamento e fisiopatologia desse tipo de disseminação. O tratamento conservador com radioterapia de metástases em dedos deve ser considerado, principalmente devido ao prognóstico reservado desses pacientes

Panbronquiolite difusa: uma doença subdiagnosticada? Estudo de quatro casos no Brasil

BACKGROUND: Diffuse panbronchiolitis is a clinical pathologic condition characterized by chronic inflammation of respiratory bronchioles, with clinical features that position it as a differential diagnosis among the sinopulmonary syndromes. METHODS AND RESULTS: We present 4 cases (1 Black, 2 Japanese descendants, and 1 Japanese), living in Brazil, in which the diagnosis was made by the clinical and radiological features and confirmed by transbronchial biopsy. The clinical findings included chronic sinusitis, productive cough, rhonchi, and wheezes. The pulmonary function tests showed an obstructive pattern. High resolution computerized tomography showed a diffuse nodular pattern, airway ectasia, and airway wall thickening. The biopsy showed interstitial accumulation of foam cells and lymphoid cells in the walls of respiratory bronchioles: 2 of our cases had bronchus-associated lymphoid tissue hyperplasia. We searched for the HLA Bw54 in all of our patients, but only 1 was positive. A low dose macrolide treatment was introduced, resulting in with clinical and functional improvement. A score that rated the extent of nodules, airway ectasia, mucus plugging, and airway wall thickening was applied on pre- and post-treatment High resolution computerized tomography results, revealing an improvement in tomographic pattern related to that observed in the pulmonary function tests. CONCLUSION: We conclude that diffuse panbronchiolitis is a systemic disease that is not exclusive to the Asian population, whose clinical and radiological features should be better known by occidental pulmonary physicians.INTRODUÇÃO: A Panbronquiolite Difusa é uma entidade clínico-patológica caracterizada pela inflamação crônica dos bronquíolos respiratórios e que, clinicamente, apresenta-se como diagnóstico diferencial das síndromes sino-pulmonares. MÉTODOS E RESULTADOS: Apresentamos 4 casos (um negro, dois descendentes de japoneses e um japonês), que moram no Brasil, nos quais a suspeita diagnóstica se baseou nos aspectos clínicos e radiológicos e foi confirmada através da biópsia transbrônquica. As principais características clínicas eram sinusite crônica, tosse produtiva, além da presença de roncos e sibilos. Os testes de função pulmonar evidenciaram um padrão obstrutivo. A tomografia de tórax de alta resolução demonstrou um padrão nodular difuso, além de ectasia e espessamento das paredes das vias aéreas. O exame histológico evidenciou acúmulo intersticial de macrófagos xantomatosos e infiltração de linfócitos na região dos bronquíolos respiratórios, sendo que 2 de nossos casos ainda apresentaram hiperplasia de tecido linfocitário associado aos brônquios. Investigamos a presença do HLA Bw54 nos quatro casos, sendo apenas um positivo. Após o diagnóstico, instituiu-se o tratamento com macrolídeos em dose baixa, tendo como resultado melhora clínica e funcional. Um escore que avalia a extensão do padrão nodular, a ectasia e o espessamento das vias aéreas e ainda o grau de impactação mucóide visíveis à tomografia foi utilizado pré e pós tratamento evidenciando uma melhora compatível com a observada à função pulmonar. CONCLUSÃO: Concluímos que a Panbronquiolite Difusa é uma doença sistêmica, não exclusiva da população oriental, cujas características clínicas e radiológicas devem ser melhor conhecidas pelos médicos ocidentais

Mesothelin expression remodeled the immune-matrix tumor microenvironment predicting the risk of death in patients with malignant pleural mesothelioma

BackgroundThe combination of immunobiological agents with immune checkpoint proteins is a promising treatment for malignant pleural mesothelioma (MPM). Mesothelin and anti-PD-L1 antibody-drug conjugates specifically target malignant neoplastic cells, inhibit the migration and invasion of neoplastic cells, and restore the immune landscape. In this study, we confirmed the importance of mesothelin and examined the relationship between mesothelin and the immune landscape of the tumor microenvironment (TME) in two MPM cohorts.MethodsThe discovery cohort included 82 MPM cases. Tissue microarray slides were generated, and samples were processed for hematoxylin & eosin staining, immunohistochemistry, and immunofluorescence assays. The relationship between mesothelin, biomarkers of histogenesis, histological aggressiveness, PD-L1, immune cells (CD4, CD8, CD20, CD68), and collagen type I and type V fibers was evaluated by quantitative digital analyses. The outcome was the survival time until death from disease recurrence. The exploratory cohort included 87 malignant mesothelioma (MESO) patients from The Cancer Genome Atlas database.ResultsMost patients were male (70.7%) with a history of asbestos exposure (53.7%) and with the epithelioid subtype (89%). Surgical resection was performed in 85.4% of patients, and 14.6% received chemotherapy; 59.8% of patients died from disease extension to the mediastinum. Low tumor mesothelin expression was associated with tumor necrosis and nuclear grade 1, whereas high mesothelin expression was significantly associated with the epithelioid histotype and high density of T cells CD8+, macrophages CD68+, and collagen type I fibers. Cox multivariate analysis showed a high risk of death for non-operated patients [hazard ratio (HR), 3.42 (1.15–10.16)] with low tumor mesothelin levels [HR, 2.58 (1.09–6.10)] and high PD-L1 and low infiltration of T cells CD4+ [HR, 3.81 (1.58–9.18)]. In the exploratory cohort, low mesothelin and high COL1A1 and COL5A1 expression were associated with poor overall survival.ConclusionTumor mesothelin expression associated with the TME immune landscape predicts the risk of death for patients with MPM and could be a new target for immunotherapy in MPM

Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols

(Poly)phenols are a large group of compounds, found in food, beverages, dietary supplements and herbal medicines. Owing to their biological activities, absorption and metabolism of the most abundant compounds in humans are well understood. Both the chemical structure of the phenolic moiety and any attached chemical groups define whether the polyphenol is absorbed in the small intestine, or reaches the colon and is subject to extensive catabolism by colonic microbiota. Untransformed substrates may be absorbed, appearing in plasma primarily as methylated, sulfated and glucuronidated derivatives, with in some cases the unchanged substrate. Many of the catabolites are well absorbed from the colon and appear in the plasma either similarly conjugated, or as glycine conjugates, or in some cases unchanged. Although many (poly)phenol catabolites have been identified in human plasma and / or urine, the pathways from substrate to final catabolite, and the species of bacteria and enzymes involved, are still scarcely reported. While it is clear that the composition of the human gut microbiota can be modulated in vivo by supplementation with some (poly)phenol-rich commodities, such modulation is definitely not an inevitable consequence of supplementation, it depends on the treatment, length of time and on the individual metabotype, and it is not clear whether the modulation is sustained when supplementation ceases. Some catabolites have been recorded in plasma of volunteers at concentrations similar to those shown to be effective in in vitro studies suggesting that some benefit may be achieved in vivo by diets yielding such catabolites

Hipercoagulabilidade e câncer de pulmão

A relação entre câncer e alteração na coagulação já havia sido sugerida há quase 150 anos por Trousseau e, subseqüentemente, ficou claro o maior risco que os pacientes oncológicos têm de desenvolverem fenômenos tromboembólicos. Isto pode ser conseqüência da ativação do sistema de coagulação pelas células neoplásicas ou pelas terapias empregadas (quimioterapias e cirurgias). Tais fenômenos podem, ainda, ser a primeira manifestação do câncer e a sua recorrência, mesmo com anticoagulação adequada, foi descrita. O sistema de coagulação é ativado, normalmente, com finalidade reparativa. Na presença de neoplasias, este complexo sistema está atuante frente a variados estímulos e parece contribuir para a progressão tumoral. Este efeito é mais importante para os focos metastáticos que para o próprio tumor primário. Contudo, a maior parte das vítimas de neoplasias morre das complicações das metástases, revelando a importância deste tema. Nesta área, vários mecanismos já são conhecidos e geram interessantes perspectivas para tratamentos futuros. Atualmente, o sucesso obtido com as heparinas de baixo peso molecular no carcinoma de pequenas células de pulmão é animador. Embora o conhecimento sobre esses mecanismos sejam relativamente recentes, os campos de pesquisa e tratamento estão amplamente abertos