[Resected non-small cell bronchogenic carcinoma stage pIIIA-N2. Which patients will benefit most from adjuvant therapy?]. / Carcinoma broncogénico no microcítico resecado, estadio pIIIA-N2. ¿En qué pacientes la adyuvancia ofrece mayor beneficio?

BACKGROUND: Controversy persists as regards the indications and results of surgery in the treatment of patients with stage pIIIA-N2 non-small cell lung cancer (NSCLC). The objective of this study was to analyze the overall survival of a multicentre series of these patients and the role of adjuvant treatment, looking for factors that may define subgroups of patients with an increased benefit from this treatment. METHODS: A retrospective study was conducted on 287 patients, with stage pIIIA-N2 NSCLC subjected to complete resection, taken from a multi-institutional database of 2.994 prospectively collected consecutive patients who underwent surgery for lung cancer. Adjuvant treatment was administered in 238 cases (82.9%). Analyses were made of the age, gender, histological type, administration of induction and adjuvant chemotherapy and/or radiation therapy treatments. RESULTS: The 5-year survival was 24%, with a median survival of 22 months. Survival was 26.5% among patients receiving with adjuvant treatment, versus 10.7% for those without it (P=.069). Age modified the effect of adjuvant treatment on survival (interaction P=.049). In patients under 70 years of age with squamous cell carcinoma, adjuvant treatment reduced the mortality rate by 37% (hazard ratio: 0,63; 95% CI; 0,42-0,95; P=.036). CONCLUSIONS: Completely resected patients with stage pIIIA-N2 NSCLC receiving adjuvant treatment reached higher survival rates than those who did not. Maximum benefit was achieved by the subgroup of patients under 70 years of age with squamous cell carcinoma.

The differential tissue expression of inflammatory, oxidative stress, and apoptosis markers in human uncontrolled non-heart-beating donors.

BACKGROUND: Uncontrolled non-heart-beating donor (UNHBD) transplantation offers a major opportunity to ameliorate the effects of the donor shortage. However, little is known about the true status of the organs obtained from these donors. UNHBD transplantation is performed under unfavorable conditions and involves exposure to several harmful stimuli that have been identified as triggers for immediate inflammatory response, oxidative stress, and apoptotic phenomena. This adverse scenario could explain the higher rates of graft dysfunction due to primary nonfunction traditionally observed in NHBD. Our aim was to assess the expression of proinflammatory, oxidative, and apoptotic markers in liver, lung, and pancreas tissue samples obtained from UNHBD and to compare these expression levels with those observed in brain-dead donors (BDD). METHODS: Samples from human type 2 NHBD and BDD were obtained at the end of cold storage. Interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, IL-10, endothelial nitric oxide synthase, inducible nitric oxide synthase, type 1 heme oxygenase, type 2 heme oxygenase, Bax, and Bcl-2 protein and mRNA expression, as well as catalase, glutathione peroxidase, and glutathione reductase tissue activity, were determined. RESULTS: UNHBD showed similar or lower expression of proinflammatory mediators and apoptosis markers in all three organs without modifications to the anti-inflammatory cytokines. Although the major oxidative stress marker levels were also comparable in both types of donors, the type 1 heme oxygenase mRNA expression and antioxidant enzyme activity were slightly diminished in UNHBD. CONCLUSIONS: The initial tissue damage generated during the UNHB donation process is at least comparable with that observed in BDD. However, although the expression of the immediate immune response and apoptosis markers is similar, a mild impairment of the local antioxidant activity was observed.

Tacrolimus modulates liver and pancreas nitric oxide synthetase and heme-oxygenase isoforms and cytokine production after endotoxemia.

Cytoprotective effects of tacrolimus are due to its unspecific anti-inflammatory and anti-oxidant properties. Neither the exact mechanisms nor if there is any organ-specificity or dose-dependent response have not been yet elucidated. Our aim was to evaluate the effect of tacrolimus on oxidative stress and mediator production in liver and pancreatic tissue secondary to endotoxemia. Wistar rats were pretreated with intraperitoneal injection of tacrolimus (0.07, 0.15, and 0.3mg/kg) 24h before Escherichia coli LPS was administrated. Animals were sacrificed 24h after LPS administration and iNOS, eNOS, and nNOS and type 1 and 2 heme-oxygenase (HO) expression were measured. TNF-α and IL-1 tissue expression and plasmatic NO, CO, TNF-α, and IL-1 were also determined. LPS exposure increased iNOS expression in both organs, eNOS did not show variations and liver nNOS expression was significantly lower. Tacrolimus diminished both pancreas and liver iNOS and nNOS expression. Both liver and pancreatic eNOS expression augmented when tacrolimus was administrated. High doses of tacrolimus were correlated with ameliorated liver HO-1 plus HO-2 and pancreas HO-1 expression after LPS stimulation. Tacrolimus treatment diminished TNF-α but not IL-1 expression increase after LPS challenge in hepatic tissue. Pancreatic TNF-α and IL-1 values diminished partially when high doses were employed. Plasmatic NO, CO, TNF-α, and IL-1 concentrations increase after LPS challenge was diminished when highest doses of tacrolimus were given. In conclusion, tacrolimus exerts a protective effect on commonly observed harmful phenomena after LPS stimulation by modulating liver and pancreas oxidative enzyme expression and cytokine production.

Glucose intolerance modifies the inflammatory response after intestinal ischemia-reperfusion.

Streptozotocin administration in newborn rats (nSTZ-rats) leads to adults with mild insulin deficiency and normoglycemia, and is accepted as a model of type 2 diabetes. We examined possible differences in the production of inflammatory mediators between healthy and nSTZ-rats after ischemia-reperfusion (I-R). Two-month-old control and nSTZ-rats were randomly separated into control and intestinal I-R groups. After reperfusion, samples were obtained from the portal vein (PV) infrahepatic cava vein (ICV), suprahepatic cava vein (SCV), jejunal wall, and pancreas. Nitric oxide (NO), lipid hydroperoxides (LPO), tumor necrosis factor alpha (TNF-alpha), 60 kDa receptor (sTNF-R1), 80 kDa (sTNF-R2), and intercellular adhesion molecule-1 (ICAM-1), were determined. After I-R, nSTZ-rats showed increased plasma concentrations of LPO, NO, ICAM-1 (0.5141 +/- 0.083 vs 0.024 +/- 0.003, ICV; 0.574 +/- 0.075 vs 0.023 +/- 0.003, SCV; 0.528 +/- 0.067 vs 0.027 +/- 0.003 PV; ng/ml), TNF-alpha (42.4 +/- 5.7 ICV, 248.4 +/- 28.2 SCV, and 33.6 +/- 4.0 PV. In n STZ-rats, vs 4.36 +/- 0.57, 4.74 +/- 0.77, and 3.16 +/- 0.32, respectively, in control rats; pg/ml), and sTNF-R1. Both TNF-alpha and NO plasma levels were higher in SCV than in ICV and PV after I-R. In addition, after I-R, jejunal wall of nSTZ-rats showed an increase of TNF-alpha IL-1, and IL-10 levels. A pre-existing state of glucose intolerance intensifies the inflammatory response after intestinal I-R.

Prótesis de Angelchik: estudio funcional a más de 10 años / Angelchik prosthesis: functional results after a ten-year follow-up

Objetivo. Valorar la utilidad de la prótesis de Angelchik en el control del reflujo gastroesofágico y su repercusión en la función del esófago a largo plazo.Métodos. Se llevó a cabo un seguimiento prospectivo (74-180 meses, mediana 138) de 26 enfermos a los que se implantó la prótesis de Angelchik entre marzo de 1983 y junio de 1988, mediante cuestionario, tránsito, endoscopia y manometría. Agrupamos los resultados en tres períodos: primer año, segundo a tercer año y a partir del sexto año. En la tercera revisión se incorporaron la pH-metría de 24 h y una prueba de aclaramiento isotópico esofágico.Resultados. Tras la cirugía aumentó la presión espiratoria máxima del esfínter esofágico inferior (11,3 ñ 0,8 en la primera; 12, 2 ñ 0,8 en la segunda, y 14,3 ñ 1,3 mmHg en la tercera revisión postoperatoria [en todos los casos p < 0,01] frente a 4,8 ñ 0,5 en el preoperatorio).Asimismo, se incrementaron la longitud total (2,7 ñ 0,1 cm en la primera; 2,9 ñ 0,1 en la segunda, y 3,1 ñ 0,2 en la tercera revisión postoperatoria frente a 2,3 ñ 0,1 cm en el preoperatorio; p < 0,05) y abdominal (1,3 ñ 0,1 cm en todas las revisiones postoperatorias frente a 0,8 ñ 0,1 cm en el preoperatorio; p < 0,05) del esfínter esofágico inferior. En el cuerpo esofágico destaca una disminución de las ondas terciarias en la evaluación más tardía respecto al preoperatorio. De 15 enfermos en que se realizó pH-metría, sólo uno presentaba reflujo.Conclusiones. La prótesis de Angelchik produce una mejoría estable a largo plazo de la competencia funcional del esfínter esofágico inferior, con escasa repercusión adversa en la dinámica del cuerpo esofágico, y sin afección significativa de la función del esfínter esofágico superior. Igualmente es eficaz en el control del reflujo gastroesofágico (AU)

Acute respiratory distress syndrome in the septic surgical patient.

The acute respiratory distress syndrome (ARDS) is a process of acute inflammatory lung injury that affects a diverse array of surgical and medical patients. The syndrome is mediated by a complex and interacting system of chemical mediators produced by several types of pulmonary cells. Regardless of the predisposing causes, activation of the nuclear factor kappa B seems to be, at the molecular level, a signature event of ARDS, leading to the rapid activation of intracellular signaling pathways, which coordinate the induction of multiple genes encoding inflammatory mediators. There are at least two compelling reasons for promoting an understanding of these interactions and their molecular mediators and second messengers: new therapies intended to modulate these factors continue to be developed, and the levels of some of these molecules, most notably cytokines, may serve as early indicators of the onset of ARDS.

3p21, 5q21, 9p21 and 17p13.1 allelic deletions are potential markers of individuals with a high risk of developing adenocarcinoma in Barrett's epithelium without dysplasia.

BACKGROUND/AIMS: A common genetic abnormality detected in Barrett's adenocarcinoma is LOH (loss of heterozygosity) at the sites of known or putative tumor suppressor genes. Thus, some deletions have also been determined in peritumoral Barrett's epithelium. These findings suggest that a tissue field of somatic genetic alterations precede the histopathological phenotypic changes of carcinoma. We investigated 32 cases of Barrett's esophagus with no evidence of dysplasia for LOH at 5q21 (APC), 3p21, 9p21 (p16) and 17p13.1 (p53) chromosomal regions. METHODOLOGY: Two groups were randomly selected and compared: 16 cases of Barrett's epithelium adjacent to adenocarcinoma and 16 cases of Barrett's epithelium with no evidence of malignant transformation in a 5-10 years follow-up period. In three adenocarcinomas cases several previous endoscopic biopsies of Barrett's esophagus were available. RESULTS: We determined frequent allelic losses in adenocarcinomas at p53 (54%), p16 (50%), 3p21 (40%) and 5q21 (33%). Identical LOH was present in most cases in the Barrett's epithelium adjacent to adenocarcinoma. LOH at these loci was unusual in Barrett's epithelium with no evidence of malignant transformation. However, in cases where sequential endoscopic biopsies were performed in advance to the adenocarcinoma diagnosis LOH was already present in the Barrett's epithelium. CONCLUSIONS: We suggest that LOH at these loci may be present before the onset of the malignant growth and LOH studies may supplement the histopathological evaluation of Barrett's epithelium. LOH at 3p21, 5q21, 9p21 and 17p13 chromosomal regions in cells of Barrett's epithelium without dysplasia may have a role as a potential marker for individuals with a high risk of developing adenocarcinoma.

Surfactant strengthens the inhibitory effect of C-reactive protein on human lung macrophage cytokine release.

In this study we investigated the effect of acute-phase levels of C-reactive protein (CRP) on cytokine production by pulmonary macrophages in the presence or absence of pulmonary surfactant. Both human alveolar and interstitial macrophages as well as human surfactant were obtained from multiple organ donor lungs. Precultured macrophages were stimulated with LPS alone or together with IFN-gamma in the presence or absence of CRP, surfactant, and combinations. Releases of TNF-alpha and of IL-1beta to the medium were determined. We found that CRP could modulate lung inflammation in humans by decreasing the production of proinflammatory cytokines by both alveolar and interstitial macrophages stimulated with LPS alone or together with IFN-gamma. The potential interaction between CRP and surfactant phospholipids did not overcome the effect of either CRP or surfactant on TNF-alpha and IL-1beta release by lung macrophages. On the contrary, CRP and pulmonary surfactant together had a greater inhibitory effect than either alone on the release of proinflammatory cytokines by lung macrophages.