Valoración de la capacidad funcional de niños con tumores sólidos / Assessment of the exercise capacity of children with solid tumors

Introducción: El ejercicio físico podría ser una herramienta eficaz para mantener alta la capacidad funcional en los pacientes con tumores sólidos (TS), pero antes de comenzar a analizar su efecto, debemos establecer si dicha capacidad funcional está disminuida en la población que padece esta enfermedad. El objetivo de este trabajo fue comparar la capacidad funcional y la agilidad de las tareas de la vida diaria en niños que padecen TS respecto a niños sanos controles (NS). Material/métodos: Se seleccionaron 52 niños, 24 pacientes de TS del HIUNJ (edad (años) 10±4,2; altura (cm) 146±21,9; peso (kg) 41,3±20,2; IMC (kg/m2) 18,1±4,9) y 28 niños sanos pareados en edad(años) 8 ±3,4; altura (cm) 137±21,4; peso (kg) 33,6±13,7; IMC (kg/m2) 17,1±2,1. Las variables analizadas fueron: capacidad funcional (VO2pico, VO2VT1) medida a través de prueba de esfuerzo con análisis de gases y agilidad (tiempo utilizado en los test funcionales «Test Up and Go 3m» (TUG-3) y «Test Up and Down Stairs12» (TUDS-12). Para el análisis de datos, se utilizó la prueba estadística T-student (SPSS.20). Resultados: La capacidad funcional, medida a través de VO2pico, en niños con TS fue significativamente más baja que en NS (25±8,8 ml·kg-1·min-1 vs 40,9±8,9 ml·kg-1·min-1 respectivamente), el VO2VT1 fue también menor para el grupo de niños de TS (17,1±6 ml·kg-1·min-1 vs 25,7±4,9 ml·kg-1·min-1). No se encontraron diferencias significativas en la FCpico. Los test funcionales no mostraron diferencias entre ambos grupos. Discusión/Conclusión: Los niños que padecen TS tienen un descenso de un 38,8% en su capacidad funcional. Según Myers et al. 2002 (N Engl J Med 2002; 4:793-801), un descenso de 3,5 ml/kg/min de la capacidad funcional se asocia con una reducción de un 12% en la tasa de longevidad en poblaciones enfermas. La capacidad funcional más baja de los niños con TS afecta al proceso evolutivo de su enfermedad, sugiriendo el ejercicio como herramienta capaz de incrementar dicha capacidad funcional

Introduction: Physical exercise would be an efficient tool in order to maintain a high exercise capacity in solid tumors patients (ST), but before to analyze its effects, we must establish whether this exercise capacity is reduced in the population who suffer this illness. The aim of this study was to assess and compare the exercise capacity and agility (functional mobility) of the day live tasks in children who suffer TS respect those healthy matched (HC). Materials and methods: We studied a total of 52 children, 24 patients of ST from HIUNJ (age (years old) 10±4,2; height (cm) 146±21,9; weight (kg) 41,3±20,2; BMI (kg/m2) 18,1±4,9) and 28 healthy control children matched in age (years old) 8 ±3,4; height (cm) 137±21,4; weight (kg) 33,6±13,7; BMI (kg/m2) 17,1±2,1. The studied outcomes included: exercise capacity (VO2peak, VO2VT1) measured by a treadmill exercise testing using a metabolic chart «breath by breath»; and agility or functional mobility (seconds), time to finish the «Test Up and Go 3m» (TUG-3) and «Test Up and Down Stairs 12» (TUDS-12). T-student (SPSS.20) statistical test was used to data analysis. Results: Exercise capacity, measured by VO2peak, was significantly lower in children with ST than in HC (25±8,8 ml·kg-1·min-1 vs 40,9±8,9 ml·kg-1·min-1 respectively) and the VO2VT1 was also lower in ST group (17,1±6 ml·kg-1·min-1 vs 25,7±4,9 ml·kg-1·min-1). We did not found significantly differences in the peak heart rate neither in the agility or functional mobility between both groups. Conclusions: Solid tumors children have a 38,8% reduced their exercise capacity. According to Myers et al. 2002 (N Engl JMed 2002; 4:793-801), an exercise capacity decrease of 3,5 ml·kg-1·min-1 is associated with a risk of longevity reduction of a 12%. A lower exercise capacity in the ST group concerns the illness evolutionary process, and they suggest the exercise as a tool be capable to increase this capacity

Initial surgical experience in laparoscopic total mesorectal excision for middle and lower third rectal cancer: short-term results.

INTRODUCTION: Total mesorectal excision (TME) of the rectum has been advocated as the gold standard surgical treatment of middle and lower third rectal cancer. Laparoscopy has gained acceptance among surgeons in the treatment of colon malignancies, while scepticism exists about laparoscopic TME in terms of safety and its oncological adequacy. OBJECTIVE: To evaluate the impact of laparoscopic TME on surgical and oncological outcome in a group of consecutive unselected patients. METHODS: One hundred and thirty-two patients with middle or inferior rectal cancer were admitted to our unit and underwent TME from December 1998 to February 2008. Eighty-nine patients were approached with laparoscopy. Patients staged cT3/4 cTxN+ or uTxN+ were submitted to neoadjuvant treatment. Postoperative complications and oncological outcomes were registered. RESULTS: In the laparoscopic group 80 anterior resections (including 4 intersphincteric resections and manual colo- anal anastomosis) and 9 abdominal-perineal resections were performed. 33.3% of patients were enrolled in "long-course" neoadjuvant chemo-radiotherapy (partial and complete response rates 88.2% and 11.8%, respectively). Protective lateral ileostomy was performed in 72% of patients. Mean operative time was 254.3+/-38.3 min and mean blood loss was 215+/-180 ml. Conversion rate was 12.7%. Morbidity rate was 39.3% without mortality. The rate of anastomotic leaks was 13.48%, reoperation rate 13.48%, recovery rate 3.1+/-1.4 days and hospital stay 10.4+/-4.6 days. Concerning adequacy of oncologic resection, mean distance of the tumour from the anal verge was 4.3+/-2.2 cm. Nodal sampling of 12.4+/-4.8 were obtained. Six patients (6/89, 6.74%) had a R1 margin: 3 distal and 3 circumferential. Median follow-up was 29 months and local recurrence rate was 5.79%. Four-year cumulative overall survival was 78% and disease-free survival was 63% (Kaplan-Meier method). CONCLUSIONS: Laparoscopic approach for rectal tumour is a technically demanding procedure, but it is oncologically safe.

Tolerization with BLP down-regulates HMGB1 a critical mediator of sepsis-related lethality.

Tolerization with bacterial lipoprotein (BLP) affords a significant survival benefit in sepsis. Given that high mobility group box protein-1 (HMGB1) is a recognized mediator of sepsis-related lethality, we determined if tolerization with BLP leads to alterations in HMGB1. In vitro, BLP tolerization led to a reduction in HMGB1 gene transcription. This was mirrored at the protein level, as HMGB1 protein expression and release were reduced significantly in BLP-tolerized human THP-1 monocytic cells. BLP tolerance in vivo led to a highly significant, long-term survival benefit following challenge with lethal dose BLP in C57BL/6 mice. This was associated with an attenuation of HMGB1 release into the circulation, as evidenced by negligible serum HMGB1 levels in BLP-tolerized mice. Moreover, HMGB1 levels in peritoneal macrophages from BLP-tolerized mice were reduced significantly. Hence, tolerization with BLP leads to a down-regulation of HMGB1 protein synthesis and release. The improved survival associated with BLP tolerance could thus be explained by a reduction in HMGB1, were the latter associated with lethality in BLP-related sepsis. In testing this hypothesis, it was noted that neutralization of HMGB1, using anti-HMGB1 antibodies, abrogated BLP-associated lethality almost completely. To conclude, tolerization with BLP leads to a down-regulation of HMGB1, thus offering a novel means of targeting the latter. HMGB1 is also a mediator of lethality in BLP-related sepsis.

Gene expression profiles of peripheral blood leukocytes after endotoxin challenge in humans.

To define gene expression profiles that occur during the initial activation of human innate immunity, we administered intravenous endotoxin (n = 8) or saline (n = 4) to healthy subjects and hybridized RNA from blood mononuclear cells (0, 0.5, 6, 24, 168 h) or whole blood (0, 3, 6, 24, 168 h) to oligonucleotide probe arrays. The greatest change in mononuclear cell gene expression occurred at 6 h (439 induced and 428 repressed genes, 1% false discovery rate, and 50% fold change) including increased expression of genes associated with pathogen recognition molecules and signaling cascades linked to receptors associated with cell mobility and activation. Induced defense response genes included cytokines, chemokines, and their respective receptors, acute-phase transcription factors, proteases, arachidonate metabolites, and oxidases. Repressed defense response genes included those associated with co-stimulatory molecules, T and cytotoxic lymphocytes, natural killer (NK) cells, and protein synthesis. Gene expression profiles of whole blood had similar biological themes. Over 100 genes not typically associated with acute inflammation were differentially regulated after endotoxin. By 24 h, gene expression had returned to baseline values. Thus the inflammatory response of circulating leukocytes to endotoxin in humans is characterized by a rapid amplification and subsidence of gene expression. These results indicate that a single intravascular exposure to endotoxin produces a large but temporally short perturbation of the blood transcriptome.

Inflammation-promoting activity of HMGB1 on human microvascular endothelial cells.

Systemic inflammation because of sepsis results in endothelial cell activation and microvascular injury. High-mobility group protein-1 (HMGB1), a novel inflammatory molecule, is a late mediator of endotoxin shock and is present in the blood of septic patients. The receptor for advanced glycation end products (RAGE) is expressed on endothelium and is a receptor for HMGB1. Here we examine the effects of HMGB1 on human endothelial cell function. Recombinant human HMGB1 (rhHMGB1) was cloned and expressed in Escherichia coli and incubated with human microvascular endothelium. rhHMGB1 caused a dose- and time-dependent increase in the expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and RAGE. rhHMGB1 induced the secretion of tumor necrosis factor-alpha (TNFalpha), interleukin 8 (IL-8), monocyte chemotactic protein-1 (MCP-1), plasminogen activator inhibitor 1 (PAI-1), and tissue plasminogen activator (tPA) (P <.01). rhHMGB1 stimulation resulted in transient phosphorylation of mitogen-activated protein (MAP) kinases, extracellular signal-related kinase (ERK), Jun N-terminal kinase (JNK), and p38, and in nuclear translocation of transcription factors NF-kappaB and Sp1. These effects are partially mediated by TNFalpha autocrine stimulation, as anti-TNFalpha antibodies significantly decrease chemokine and adhesion molecule responses (P

Granulocyte colony-stimulating factor improves deficient in vitro neutrophil transendothelial migration in patients with advanced liver disease.

Bacterial infections are frequent complications in patients with liver cirrhosis. Cirrhotic patients present abnormalities in both innate and adaptive immune responses, including a deficient neutrophil recruitment to infected sites. The purpose of this study was to assess neutrophil-endothelium interactions in cirrhotic patients and evaluate the effects of G-CSF on this process. We studied neutrophil adhesion and transendothelial migration in 14 cirrhotic patients and 14 healthy controls. We also analyzed neutrophil expression of the adhesion molecules CD62L and CD11b in whole blood by flow cytometry. Cirrhotic patients expressed higher levels of CD11b than healthy controls, whereas CD62L expression was significantly lower, suggesting exposure of neutrophils to activating agents within the bloodstream. Neutrophils from cirrhotic patients showed increased adhesion to both resting and tumor necrosis factor alpha-stimulated microvascular endothelial cells and decreased transendothelial migration. Granulocyte colony-stimulating factor (G-CSF) (100 ng/ml) significantly enhanced neutrophil adhesion to microvascular endothelial cells in healthy controls but not in cirrhotic patients. G-CSF also significantly improved neutrophil transmigration in cirrhotic patients and healthy controls. In conclusion, cirrhotic patients exhibit increased neutrophil adhesion to microvascular endothelium and deficient transendothelial migration. G-CSF enhances neutrophil transendothelial migration in cirrhotic patients despite having no effect on neutrophil adhesion. Therefore, G-CSF may be able to increase neutrophil recruitment into infected sites in these patients.