Adjuvant radiotherapy for gastric carcinoma: 10 years follow-up of 244 cases from a single institution.

BACKGROUND: Postoperative chemoradiotherapy (CRT) of gastric carcinoma improves survival among high- risk patients. This study was undertaken to analyse long-term survival probability and the impact of certain covariates on the survival outcome in affected individuals. MATERIALS AND METHODS: Between January 2000 and December 2005, 244 patients with gastric cancer underwent adjuvant radiotherapy (RT) in our institution. Data were retrieved retrospectively from patient files and analysed with SPSS version 21.0. RESULTS: A total of 244 cases, with a male to female ratio of 2.2:1, were enrolled in the study. The median age of the patients was 52 years (range, 20-78 years). Surgical margin status was positive or close in 72 (33%) out of 220 patients. Postoperative adjuvant RT dose was 46 Gy. Median follow-up was 99 months (range, 79-132 months) and 23 months (range, 2-155 months) for surviving patients and all patients, respectively. Actuarial overall survival (OS) probability for 1-, 3-, 5- and 10-year was 79%, 37%, 24% and 16%, respectively. Actuarial progression free survival (PFS) probability was 69%, 34%, 23% and 16% in the same consecutive order. AJCC Stage I-II disease, subtotal gastrectomy and adjuvant CRT were significantly associated with improved OS and PFS in multivariate analyses. Surgical margin status or lymph node dissection type were not prognostic for survival. CONCLUSIONS: Postoperative CRT should be considered for all patients with high risk of recurrence after gastrectomy. Beside well-known prognostic factors such as stage, lymph node status and concurrent chemotherapy, the type of gastrectomy was an important prognostic factor in our series. With our findings we add to the discussion on the definition of required surgical margin for subtotal gastrectomy. We consider that our observations in gastric cancer patients in our clinic can be useful in the future randomised trials to point the way to improved outcomes.

Ewing sarcoma cancer stem cells : from mechanisms to therapeutic targeting

Le sarcome d'Ewing (SE) est la 2ème tumeur des os la plus fréquente chez les enfants, et le pronostic est sombre au stade métastatique. La pathogenèse du SE repose sur une translocation, provocant la fusion du domaine activateur du facteur de transcription EWS, avec la partie liant l'ADN de la protéine FLI-1. Les cellules souches cancéreuses (CSC) sont supposées être les moteurs de la croissance tumorale, et représente de ce fait des cibles thérapeutiques préférentielles. Dans ce travail nous nous sommes efforcés de comprendre, ainsi que de cibler les mécanismes liés à l'émergence des CSC dans le sarcome d'Ewing. La formation des CSC du ES est liée à un défaut de maturation des miRNAs provoqué par une sous-expression d'un gène, TARBP2, dans les CSC. Ce défaut de maturation peut être corrigé par un traitement des cellules avec de l'enoxacine, une fluoroquinolone utilisée pour traiter les infections urinaires. L'enoxacine seule n'étant pas suffisante pour éradiquer les tumeurs in vivo, nous avons testé la combinaison d'une thérapie ciblée sur les CSC avec une chimiothérapie classique, la doxorubicine, ciblant les cellules différentiées. In vitro l'enoxacine induit l'apoptose dans les CCS sans affecter les cellules différentiées, alors que à l'inverse, la doxorubicine n'affecte que les cellules de la « masse » tumorale. In vivo la combinaison de ces deux drogues inhibe la croissance de tumeurs provenant de cellules primaires xenotranplantées et éradique les CSCs. Nos résultats mettent en lumière une nouvelle approche thérapeutique directement applicable pour le sarcome d'Ewing, et pourraient ainsi rapidement déboucher sur des essais cliniques. Dans la deuxième partie de ce travail nous avons essayé de comprendre comment EWS-FLI1, la protéine de fusion issue de la translocation chromosomique du sarcome d'Ewing conduit à la génération des CSC. Pour cela nous avons effectué des ChIPseq (immunoprecipitation de la chromatine suivi de séquençage) pour EWS-FLI1 ainsi que pour certaines modifications histoniques. -- Ewing sarcoma family tumors (ESFT) are the second most frequent bone tumors in children and have a high rate of recurrence when metastatic at presentation. The pathogenesis of Ewing sarcoma is underlayed by a translocation, leading to the fusion of the trans-activating domain of EWS with the FLU DNA binding domain. Cancer stem cells (CSCs) are thought to be the driving force of tumor growth. In this work we focused on understanding the mechanisms underlying ESFT CSC emergence as well as defining targeted therapeutic strategies. Emergence of CSCs in ESFT has been shown to arise from a defect in TARBP2-dependent microRNA maturation, which can be corrected by exposure to the fluoroquinolone enoxacin. As enoxacin alone is not sufficient to reverse tumor growth in vivo, we assessed the effect of combining a drug that abrogates CSC properties with doxorubicin, a standard-of-care therapy in ESFT. Primary ESFT CSCs and bulk tumor cells were treated with different concentration of drugs and displayed divergent responses to doxorubicin and enoxacin. Doxorubicin, which targets the tumor bulk, displayed toxicity toward primary adherent ESFT cells in culture but not to CSC-enriched ESFT spheres. Conversely, enoxacin induced apoptosis but only in ESFT spheres and specifically on the CD133+ population. In combination, the two drugs markedly depleted CSC and strongly reduced primary growth in xenograft assays of two primary ESFT. Our results identify a potentially attractive therapeutic strategy for ESFT that combines mechanism-based targeting of CSC using a low toxicity antibiotic with a standard-of-care cytotoxic drug, offering immediate applications for clinical evaluation. In the second part of this work we performed chromatin immunopercipitation on CSCs and bulk cells for EWS-FLI1 binding as well as some chromatin modifications, and concluded that EWS-FLI1 shows cell context dependent binding.

The Human Mesenchymal Stromal Cell-Derived Osteocyte Capacity to Modulate Dendritic Cell Functions Is Strictly Dependent on the Culture System.

In vitro differentiation of mesenchymal stromal cells (MSC) into osteocytes (human differentiated osteogenic cells, hDOC) before implantation has been proposed to optimize bone regeneration. However, a deep characterization of the immunological properties of DOC, including their effect on dendritic cell (DC) function, is not available. DOC can be used either as cellular suspension (detached, Det-DOC) or as adherent cells implanted on scaffolds (adherent, Adh-DOC). By mimicking in vitro these two different routes of administration, we show that both Det-DOC and Adh-DOC can modulate DC functions. Specifically, the weak downregulation of CD80 and CD86 caused by Det-DOC on DC surface results in a weak modulation of DC functions, which indeed retain a high capacity to induce T-cell proliferation and to generate CD4(+)CD25(+)Foxp3(+) T cells. Moreover, Det-DOC enhance the DC capacity to differentiate CD4(+)CD161(+)CD196(+) Th17-cells by upregulating IL-6 secretion. Conversely, Adh-DOC strongly suppress DC functions by a profound downregulation of CD80 and CD86 on DC as well as by the inhibition of TGF-β production. In conclusion, we demonstrate that different types of DOC cell preparation may have a different impact on the modulation of the host immune system. This finding may have relevant implications for the design of cell-based tissue-engineering strategies.

Long-term effects of Roux-en-Y gastric bypass on postprandial plasma lipid and bile acids kinetics in female non diabetic subjects: A cross-sectional pilot study.

BACKGROUND AND AIMS: Formerly obese patients having undergone Roux-en-Y gastric bypass (RYGB) display both an accelerated digestion and absorption of carbohydrate and an increased plasma glucose clearance rate after meal ingestion. How RYGB effects postprandial kinetics of dietary lipids has yet not been investigated. METHODS: Plasma triglyceride (TG), apoB48, total apoB, bile acids (BA), fibroblast growth factor 19 (FGF19), and cholecystokinin (CCK) were measured in post-absorptive conditions and over 4-h following the ingestion of a mixed test meal in a cross-sectional, pilot study involving 11 formerly obese female patients 33.8 ± 16.4 months after RYGB surgery and in 11 weight- and age-matched female control participants. RESULTS: Compared to controls, RYGB patients had faster (254 ± 14 vs. 327 ± 7 min, p < 0.05) and lower (0.14 ± 0.04 vs. 0.35 ± 0.07 mM, p < 0.05) peak TG responses, but their peak apoB48 responses tended to be higher (2692 ± 336 vs. 1841 ± 228 ng/ml, p = 0.09). Their postprandial total BA concentrations were significantly increased and peaked earlier after meal ingestion than in controls. Their FGF19 and CCK concentrations also peaked earlier and to a higher value. CONCLUSIONS: The early postprandial apoB48 and BA responses indicate that RYGB accelerated the rate of dietary lipid absorption. The lower postprandial peak TG strongly suggests that the RYGB simultaneously increased the clearance of TG-rich lipoproteins. CLINICAL TRIAL REGISTRATION: NCT01891591.

Sarcoma embrionário indiferenciado do fígado: relato de caso

O sarcoma embrionário indiferenciado do fígado é uma entidade rara que acomete, principalmente, crianças acima dos cinco anos de idade. O aspecto macroscópico consiste, caracteristicamente, de grande massa hepática com maior componente sólido, porém apresenta algumas áreas císticas. Curiosamente, a tomografia computadorizada superestima o componente cístico da lesão, sendo a ultra-sonografia um método mais fidedigno na demonstração da consistência do tumor. Os estudos por imagem ajudam a afastar enfermidades não-neoplásicas, como abscessos e hematomas hepáticos, e avaliam a extensão das lesões. O diagnóstico de sarcoma embrionário indiferenciado pode ser corretamente presumido quando se consideram os achados de imagem em conjunto com a idade do paciente e o nível de alfa-fetoproteína. Os autores descrevem um caso de sarcoma embrionário indiferenciado no fígado de uma criança do sexo feminino de dez anos de idade, enfatizando seus aspectos imagenológicos e o diagnóstico diferencial.

SARCOMA SINOVIAL FIBROSO DO PÉ: RELATO DE CASO

Os autores relatam o caso de uma paciente de 24 anos de idade, que apresentou dor e aumento do volume do hálux esquerdo há três meses. A ultra-sonografia mostrou massa sólida, hipoecóide, heterogênea, com áreas císticas e calcificação, no dorso do hálux esquerdo, em partes moles, com estrutura tendínea no seu interior, sem aparente comprometimento de estruturas ósseas. O estudo com Doppler colorido mostrou hipervascularização central e periférica na lesão. A ressonância magnética evidenciou massa sólida, de partes moles, com estrutura tendínea no seu interior, com médio sinal em T1 e alto sinal em T2, com realce intenso e heterogêneo pelo meio de contraste paramagnético, sem acometimento de estruturas ósseas. A paciente foi submetida a procedimento cirúrgico, com ressecção da lesão descrita, no dorso do hálux esquerdo, e o exame anatomopatológico demonstrou tratar-se de sarcoma sinovial fibroso monofásico.

Tumores ósseos raros da calota craniana: sarcoma de Ewing e tumor de Triton

O sarcoma de Ewing e o tumor de Triton representam dois tumores ósseos raros da calota craniana, os quais possuem clínica e aspecto imagenológico inespecíficos. Entretanto, os métodos de imagem são importantes para a detecção das lesões durante a investigação diagnóstica, para a avaliação da extensão das lesões ósseas, do possível acometimento de partes moles e do parênquima encefálico, e avaliação de recorrência local e/ou metástases a distância. A confirmação diagnóstica é determinada pela histologia e auxiliada pela imuno-histoquímica. Os autores relatam dois casos desses tumores e seus achados pelos métodos de imagem.

Sarcoma de Ewing: aspectos clínicos e radiográficos de 226 casos

OBJETIVO: Avaliar os aspectos radiográficos e clínicos presentes em pacientes com o diagnóstico de sarcoma de Ewing confirmado por histopatologia. MATERIAIS E MÉTODOS: Foram analisados, neste trabalho, os dados clínicos e radiográficos (quando disponíveis) de 226 pacientes com o diagnóstico de sarcoma de Ewing ósseo. RESULTADOS: Dos casos avaliados, 61,5% (139) eram do sexo masculino e 83,7% (189) eram brancos. A mediana de idade dos pacientes foi de 14 anos e a topografia mais freqüente das lesões foi o osso ilíaco, em 13,7% (31) dos casos. O aspecto radiográfico mais comum foi o de lesão lítica com reação periosteal (padrões variados), em 32,7% (74) dos casos. CONCLUSÃO: O sarcoma de Ewing ósseo é uma neoplasia bastante agressiva, ocorrendo mais comumente em indivíduos na segunda década de vida e cujo aspecto radiográfico mais comum é o de lesão lítica com reação periosteal típica de lesão agressiva.

Sarcoma fibromixóide de baixo grau da parede torácica: relato de caso

Este relato descreve um caso de sarcoma fibromixóide de baixo grau na parede torácica em uma paciente feminina de 23 anos de idade. A radiografia de tórax e a tomografia computadorizada demonstraram massa heterogênea na região inferior do hemitórax direito, com necrose e focos de calcificação. O exame histológico foi sugestivo de leiomioma, mas a imuno-histoquímica definiu o diagnóstico de sarcoma fibromixóide de baixo grau. A evolução clínica do caso foi boa, apesar dos aspectos de malignidade demonstrados na tomografia computadorizada.

Oxidative stress in gastric mucosa of asymptomatic humans infected with Helicobacter pylori: effect of bacterial eradication.

BACKGROUND: Inducible nitric oxide synthase (iNOS) and interleukin 8 (IL-8) are positive in approximately 50% of Helicobacter pylori-related diseases but it is not clear whether oxidative stress is also present in H. pylori asymptomatic humans. Our aim was to study the expression of iNOS, superoxide dismutase, catalase and IL-8 production in H. pylori-infected asymptomatic humans, and to investigate the effect of eradication of H. pylori. MATERIALS AND METHODS: Biopsies of corpus and antrum of asymptomatic H. pylori positive and negative humans served for determination of the gastritis score and H. pylori status; iNOS was measured by reverse transcriptase polymerase chain reaction and immunohistochemistry and superoxide dismutase and catalase by immunohistochemistry. IL-8 in biopsies was assessed by enzyme-linked immunosorbent assay. RESULTS: Immunostaining of iNOS, catalase and superoxide dismutase was significantly associated with H. pylori infection and was localized to inflammatory cells. IL-8 concentrations were greater in the H. pylori positive than H. pylori negative group and decreased after bacterial eradication. A decrease in staining for iNOS and catalase was observed after H. pylori eradication. CONCLUSIONS: INOS and antioxidant enzymes are present in gastric biopsies of asymptomatic H. pylori positive humans. Eradication caused a significant decrease in staining for iNOS and catalase. These results indicate that oxidative stress occurs in asymptomatic patients and can be modulated by H. pylori eradication.

Sarcoma de Kaposi relacionado à síndrome da imunodeficiência adquirida: características do comprometimento hepático na tomografia computadorizada e na ressonância magnética

Sarcoma de Kaposi é uma neoplasia associada a condições de imunossupressão que acomete os vasos linfáticos e sanguíneos. É a neoplasia intra-hepática mais comum na síndrome da imunodeficiência adquirida. A tomografia computadorizada e a ressonância magnética revelam múltiplos pequenos nódulos, proeminência e realce dos planos periportais, devido à presença de tecido neoplásico. Os autores descrevem um caso de paciente masculino, de 47 anos de idade, com síndrome da imunodeficiência adquirida e sarcoma de Kaposi disseminado.