Chemotherapy-induced fatigue is associated with changes in gene expression in the peripheral blood mononuclear cell fraction of patients with locoregional breast cancer.

PURPOSE: Chemotherapy-induced fatigue (CIF) is a frequent symptom that impairs patient functioning and quality of life. We aimed to evaluate whether systemic chemotherapy can induce a specific gene expression profile in peripheral blood mononuclear cells (PBMNC) of patients with locoregional breast cancer (LRBC) who develop CIF. METHODS: PBMNC were collected from 3 patients who developed CIF before and after their initial cycle of chemotherapy, and RNA-seq was performed in an Ion Torrent™ System. A total of 12.345 transcripts were sequenced, of which 26 were selected out of 71 that had significantly different expression before and after chemotherapy. The RNA-seq results were validated by RT-qPCR in a different group of 28 patients with LRBC who developed CIF after their first cycle of chemotherapy and in six patients who also received chemotherapy but did not develop CIF (controls). We assessed CIF according the BFI and Chalder Questionnaires. RESULTS: We observed a significant increase in expression of DUSP18 and RHOBTB1 and decreased expression of NCAN and RAET1G in patients who developed CIF after chemotherapy. Control patients only exhibited a significant decrease in NCAN expression. CONCLUSION: CIF induces specific changes in gene expression in the PBMNC of LRBC patients. Some of these changes, such as downregulation of NCAN expression, may reflect direct effects of chemotherapy since they are also observed in the controls. Furthermore, CIF may involve downregulation of skeletal muscle genes (RHOBT1, DUSP18) and immune systems (RAETG1), whereas NCAN downregulation may underlie the adverse cognitive effects of chemotherapy.

Purified Dry Paullinia cupana (PC-18) Extract for Chemotherapy-Induced Fatigue: Results of Two Double-Blind Randomized Clinical Trials.

Fatigue is frequent among oncologic patients. Unpurified Paullinia cupana dry extract showed encouraging results for chemotherapy-induced fatigue in our previous studies. We report two randomized, double-blind studies with a standardized dry purified Paullinia cupana extract named PC-18. For both studies, we recruited early breast cancer patients who had an increase in their fatigue scores after their first cycle of adjuvant chemotherapy. In the first study, we compared an oral dose of 37.5 mg of PC-18 twice daily with placebo. In the second study, we examined PC-18 at either 7.5 or 12.5 mg orally twice daily versus placebo. In both studies, PC-18 was not superior to placebo as assessed by both Chalder and Brief Fatigue Inventory (BFI) fatigue questionnaires, probably reflecting unexpectedly good placebo antifatigue activity. Since all capsules employed in both studies contained about 100 mg of magnesium silicate as an excipient, we retrospectively evaluated frozen serum samples from the second study and found a significant increase in magnesium levels after patients received placebo. By multivariate analysis, higher prerandomization magnesium levels and higher BFI scores together with the use of a 12.5 mg dose of PC-18 all correlated significantly with higher posttreatment BFI scores. We observed no significant toxicities in any of the trials. We conclude that the absence of differences between PC-18 and placebo may be due to the unexpectedly high antifatigue activity of the placebo in these studies. Further studies evaluating the role of magnesium supplementation for chemotherapy-induced fatigue are needed.

Linfoma anaplásico diagnosticado de forma incidental após trauma / Anaplastic lymphoma diagnosed out of a incidental form after trauma

O linfoma não Hodgkin de células T periféricas possui um subtipo denominado linfoma anaplásico de células grandes (LACG) que pode apresentar-se sob duas formas variantes que distinguem entre si na apresentação clínica e prognóstico. O artigo a seguir relata o caso de um paciente que teve o diagnóstico desta neoplasia após trauma no pé sofrido por acidente de moto. Relatos de casos publicados previamente na literatura descrevem a associação do surgimento desta entidade em partes do corpo que sofreram traumas locais de origens diversas, sugerindo uma relação direta entre eles através no influxo de células T na carcinogênese desta neoplasia linfoproliferativa.

Carcinoma tímico metastático com resposta prolongada a pemetrexed e octreotide / Metastatic thymic carcinoma with prolonged response to pemetrexed and octreotide

Em adultos os carcinomas tímicos representam cerca de 20% das neoplasias mediastinais. A maioria dos pacientes tem entre 40 e 60 anos de idade e há ligeira predominância do sexo masculino. Em função da raridade da doença não há ensaios clínicos randomizados realizados para orientar a escolha do tratamento na doença metastática refratária ou recorrente. Alguns regimes de segunda linha têm sido usados, a maioria baseada em cisplatina. Como linhas alternativas as opções são pemetrexed, 5-flourouracil associado a leucovorin, gemcitabina, capecitabina e paclitaxel, todas com taxas de resposta pequenas. Relatamos neste artigo um caso de carcinoma tímico tratado com pemetrexed e octreotide com resposta prolongada ao tratamento.

Late favorable results of duroplasty with biocellulose: clinical retrospective study of 20 cases / Resultados tardios favoráveis de duraplastia com biocelulose: estudo clínico retrospectivo de 20 casos

Objective: Considering the importance of dural replacement in neurosurgery, mainly in times of advanced endoscopic skull base approaches, the authors report the late results after implanting of pure biocellulose membrane in 20 patients harboring different types of lesion, from 1996 to 1999, with objective of demonstrate its use in neurosurgery. Method: The casuistic was followed clinically and image studies were indicated when necessary. Dural substitution was achieved by continuous 4:0 prolene suture without additional glue. Results: The casuistic is constituted by four convexity or parasagittal meningiomas, three single cortical metastasis (melanoma, lung and renal carcinomas), two cerebellar gliomas (one multicentric GBM, one pilocytic cerebellar astrocytoma), one decompressive craniectomy for brain edema due to vasosespasm after aneurysm clipping one decompressive craniotomy for cerebral edema after hemorrhage of a giant fronto-parietal AVM, two mirror MCA aneurysms, one pineal and mesencephalic astrocitoma, one quadrigeminal cistern cyst, one accoustic schwanoma, one spontaneous cerebellar hematoma, one decompressive neurovascular operation for trigeminal neuralgia; 1 cauda equina ependimoma, one lombar myelomeningocele. Currently nine patients are alive, none had direct complication of implant. Recent NMR images of survivors do not show the membrane. Three wound infections could not be definitively attributed to patch. Conclusion: The material was considered safe for dural replacement. Due to inadequate elasticity of pure cellulose, the research was interrupted, waiting for a better product, which is currently being tested.

Objetivo: Tendo em vista a importância da substituição da dura-máter em tempos atuais, em que a cirurgia de base de crânio apresenta grande demanda, os autores reportam os resultados tardios após implante da membrana de biocelulose pura em 20 pacientes portadores de diversos tipos de lesões neurológicas, entre os anos 1996 e 1999, com a finalidade de demonstrar a viabilidade de seu uso em neurocirurgia. Método: A casuística foi acompanhada com avaliações clínicas periódicas, aleatoriamente realizadas, além de estudos de imagem, indicados quando necessários. A substituição dural foi realizada por sutura contínua de fio prolene 4:0, sem cola de fibrina adicional. Resultados: Foram operados quatro meningiomas parassagitais, três metástases corticais únicas (melanoma, pulmão e carcinoma renal), dois gliomas cerebelares (um GBM multicêntrico e um astrocitoma pilocítico), uma craniectomia descompressiva por edema cerebral hemisférico devido a vasoespasmo após clipagem de aneurisma, uma craniectomia descompressiva por edema após cirurgia de MAV frontoparietal, dois aneurismas de ACM em espelho, um astrocitoma de mesencéfalo e pineal, um cisto aracnóideo de cisterna quadrigeminal, um schwanoma de vestibulococlear, um hematoma cerebelar espontâneo, uma descompressiva neurovascular de trigêmeo, um ependimoma de cauda equina e um mielomeningocele lombar. Atualmente nove pacientes estão vivos e nenhum apresentou complicação relativa ao implante. Exames de RNM recentes dos sobreviventes não mostrou alteração especial no local do implante, não sendo possível reconhecer a membrana. Três infecções de ferida não foram definitivamente relacionadas ao implante. Conclusão: O material foi considerado seguro para substituir a dura-máter. Por causa da inadequada elasticidade e tendência a rasgar da celulose pura, a pesquisa foi interrompida, aguardando material mais adequado, que está atualmente sendo testado.