The neural cell adhesion molecule is involved in the metastatic capacity in a murine model of lung cancer.

Neural cell adhesion molecule (NCAM) is involved in cell growth, migration, and differentiation. Its expression and/or polysialylation appear to be deregulated in many different cancer types. We employed the lung tumor cell line LP07, syngeneic in BALB/c mice to investigate the role of NCAM in malignant progression. LP07 cells express the three main NCAM isoforms, all of them polysialylated. This cells line, pretreated with an anti-NCAM antibody and inoculated intravenously (i.v.) into syngeneic mice, developed less and smaller lung metastases. In vitro studies showed that NCAM bound antibody inhibited cell growth, mainly due to an increase in apoptosis, associated with a decrease of cyclin D1 and enhanced expression of active caspase 3 and caspase 9. Anti-NCAM-treated LP07 cells showed impairment in their ability to migrate and adhere to several extracellular matrix components. Secreted uPA activity was also reduced. NCAM-140 knocked-down by siRNA in LP07 cells pretreated or not with anti-NCAM showed an impaired metastasizing ability upon i.v. inoculation into mice. These results suggest that anti-NCAM treatment could be mimicking homophilic trans-interactions and NCAM-140 knocked-down impairs heterophilic interactions, both leading to inhibition of metastatic dissemination. The involvement of NCAM in lung tumor progression was confirmed in human NSCLC tumors. Sixty percent of the cases expressed NCAM at tumor cell level. A multivariate analysis indicated that NCAM expression was associated with a shorter overall survival in this homogeneous series of Stages I and II NSCLC patients. NCAM may be able to modulate mechanisms involved in lung carcinoma progression and represents an attractive target to control metastatic progression.

Pneumo-PET-CT: Initial Results of This Novel Technique on the Evaluation of Esophageal and Gastric Tumors with Anatomic-Surgical Correlation.

We present the initial results of a novel hybrid scanning-based technique that combines pneumo-computed tomography (PNCT) with positron emission tomography (PET) using 2-(fluorine-18) fluoro-2-deoxy-D-glucose (FDG). We denominate it pneumo-PET-CT. The focus of our discussion will be on the description of the pneumo-PET-CT technique and the interpretation criteria with emphasis on its benefits and applications in the presurgical and postneoadjuvant therapy evaluation of esophageal, esophagogastric junction (EGJ), and gastric tumors.

[Predictive response variables to recombinant human erythropoietin treatment in patients with anemia and cancer]. / Variables predictivas de respuesta a la eritropoyetina recombinante humana en pacientes con anemia y cáncer.

The use of human recombinant erythropoietin (rHuEpo) has been approved by the Food and Drug Administration (FDA) in patients with anemia and cancer. Although good results have been obtained, it is too expensive to permit its use massively. For the purpose of evaluating the therapeutic effect of rHuEpo, including toxicity, predictive response variables and quality of life parameters, a prospective trial was carried out in patients with anemia and cancer. Hematimetric parameters, ferritin, Epo, cytokines, transfusions and quality of life were registered. A total of 36 patients were treated in the protocol (34 were evaluable): 16 men and 20 women, with a medium age 56.4 years; 27 patients were treated with chemotherapy (16 with cisplatinum); 15 patients presented medullar infiltration. In 73.5% patients an increase in the level of hemoglobin was registered, and in 64.7% its normalisation was attained. Transfusional requirements were reduced by 50%. The hemoglobin increase greater than 0.5 g/dl at the second week of treatment was the most significant variable of early response. Patients treated with cisplatinum, seric ferritin lower than 1,100 ng/dl and those without medullar tumoral infiltration responded best. Serum Epo, cytokines (IL-1, IL-6 and TNF) and reticulocyte count at the second week did not correlate with response. Quality of life parameters were better in patients with good response to rHuEpo. It can be concluded that good results in the treatment of patients with anemia and cancer are obtained with rHuEpo.

Colorectal cancer staging: reappraisal of N/PN classification.

PURPOSE: Current American Joint Committee on Cancer and the Union Internationale Contre le Cancer TNM classification disregards location of positive nodes, discontinuing N3 category, which constitutes a major modification to 1987 version. This study was designed to assess the impact of the recategorization of former N3 cases and the reliability of the current N1-N2 subcategorization of Stage III patients. METHODS: Prospectively collected data from 1,391 patients (55.8 percent males; median age, 64 (range, 21-97) years), operated on with curative intent between 1980 and 1999, were analyzed. The median follow-up was 60 (interquartile range, 27-97) months with 129 cases lost to follow-up. RESULTS: Of positive node cases, 25.3 percent were former N3. Among them, 30.5 percent migrated to the N1 group and 69.5 percent to the N2 group. The proportions of former N3 cases in N1 and N2 groups were 12.5 percent and 46.1 percent, respectively (P<0.001). Node-positive patients had an actuarial five-year survival rate of 56.7 percent (95 percent confidence interval, 53-59), with a significant difference between N1/N2 categories (63.6 vs. 44.1 percent, respectively; P<0.001). Although apical node involvement and more than three positive nodes were associated with poorer outcomes in univariate analysis, only the number of positive nodes had independent association (hazard ratio, 1.6 (range, 1.2-2.2); P<0.001). Integration of former N3 cases did not modify outcomes. CONCLUSIONS: The recategorization of former N3 involved a high proportion of positive node cases. Current N1/N2 categories clearly defined different outcomes and were not modified by the integration of former N3.

Ferritina urinaria: un nuevo indicador de nefrotoxicidad por cisplatino? / Urinary ferritin: a new marker of cisplatin nephrotoxicity?

Con el objetivo de relacionar las variaciones de ferritina urinaria (FU) con diversos indicadores de nefrotoxicidad por cisplatino (cisP), 26 pacientes recibieron 6 ciclos de quimioterapia que incluían CisP (sin otras drogas nefrotóxicas). El grupo control (CONT, N = 20) fue tratado con seis ciclos de quimioterapia sin drogas nefrotóxicas. Las edades fueron similares en ambos grupos (50,2 ñ 2,6 y 47,7 ñ 2,8 años). En el grupo CisP la FU (ng/mL) basal (B) fue 2,05 ñ 0,19 y luego del 2do ciclo (2C) 50,37 ñ 8,94 (p < 0,001); los valores de ß sub2 microglobulina (ßµG, ng/mL) fueron 248 ñ 10 (B) y 295 ñ 44 (2C; p < 0,01); los de magnesio sérico (MgS, meq/L), 2,03 ñ 0,03 (B) y 1,67 ñ 0,04 (2C; p < 0,001) y los clearances de creatinina (CLCr, mL/min), 109 ñ 3,6 (B) y 94,8 ñ 3,4 (2C; p < 0,001). FU se correlacionó significativamente (p < 0,0001; N = 208) con ßµG (r = 0,550), MgS (r = 0,465) y CLCr (r = 0,375), pero no con la ferritina sérica. En CONT no hubo modificaciones de FU. ßµG, MgS ni CLCr. Los resultados sugieren que el incremento de FU podría ser un indicador de nefrotoxicidad por cisP, cuya utilidad clínica es necesario evaluar

Variables predictivas de respuesta a la eritropoyetina recombinante humana en pacientes con anemia y cancer / Predictive response variables to recombinant human erythropoietin treatment in patients with anemia and cancer

The use of human recombinant erythropoietin (rHuEpo) has been approved by the Food and Drug Administration (FDA) in patients with anemia and cancer. Although good results have been obtained, it is too expensive to permit its use massively. For the purpose of evaluating the therapeutic effect of rHuEpo, including toxicity, predictive response variables and quality of life parameters, a prospective trial was carried out in patients with anemia and cancer. Hematimetric parameters, ferritin, Epo, cytokines, transfusions and quality of life were registered. A total of 36 patients were treated in the protocol (34 were evaluable): 16 men and 20 women, with a medium age 56.4 years; 27 patients were treated with chemotherapy (16 with cisplatinum); 15 patients presented medullar infiltration. In 73.5 percent patients an increase in the level of hemoglobin was registered, and in 64.7 percent its normalisation was attained. Transfusional requirements were reduced by 50 percent. The hemoglobin increase greater than 0.5 g/dl at the second week of treatment was the most significant variable of early response. Patients treated with cisplatinum, seric ferritin lower than 1,100 ng/dl and those without medullar tumoral infiltration responded best. Serum Epo, cytokines (IL-1, IL-6 and TNF) and reticulocyte count at the second week did not correlate with response. Quality of life parameters were better in patients with good response to rHuEpo. It can be concluded that good results in the treatment of patients with anemia and cancer are obtained with rHuEpo.

Quistes y tumores del timo: enfoque multidisciplinario de diagnóstico y tratamiento / Thymic cysts and tumors: multispeciality diagnostic methods and treatment

Objetivo: Analizar los resultados de una serie de tumores de timo. Población: 43 pacientes asistidos en el período de 1977-97, sobre un total de 114 tumores de mediastino (37,7 por ciento). Método: Se analizó específicamente la sintomatología, metodología de diagnóstico, características tumorales locales (grado de invasión en los timomas), tratamiento instituido, mortalidad, supervivencia y causa de muerte. Resultados: Los 43 tumores se presentaron en 25 mujeres y 18 hombres, edad promedio 48 años. El timoma (28 casos) fue la variedad más frecuente (65 por ciento). Quince pacientes no tuvieron síntomas (34,9 por ciento), la Miastenia Gravis (MG) con 10 casos fue la sintomatología más común. La Rx y la TAC de tórax fueron estudios suficientes para la detección y evaluación general de los tumores. En 12 tumores malignos/invasores se obtuvo diagnóstico preoperatorio, 7 por punción percutánea y 5 por mediastinoscopía, mediastinotomía o biopsia cervical. Hubo 12 timomas no invasores y 16 invasores (9 Estadio II, 5 Estadio III y 2 Estadio IV). Se operaron 42 pacientes, el abordaje más frecuente fue la esternotomía mediana (23 casos), todos fueron resecados, 30 con resección simple y 12 ampliadas. Un paciente (linfoma de timo) sólo recibió irradiación y quimioterapia (QMT), 21 recibieron irradiación P.O., 13 timomas, 5 linfomas y 3 carcinomas. Tres pacientes recibieron QTM neoadyuvante con resultados favorables, y 9 adyuvante. Fallecieron 2 pacientes en el P.O. inmediato, ambos portadores de MG, y 6 en el P.O. alejado, 3 por progresión tumoral, los restantes por crisis de MG tromboembolismo pulmonar y complicación de la QMT. La supervivencia actuarial global posoperatoria (P.O.) de los 28 timomas fue a 5 y 10 años del 73 por ciento, 3 de los 5 carcinomas fallecieron por progresión tumoral entre los 2 y 27 meses. Conclusiones: El 34,9 por ciento de los tumores del timo fueron asintomáticos. El timoma fue la variedad más frecuente (65 por ciento), su malignidad se determinó por el grado de invasión, siendo el 43 por ciento no invasivos. Para los tumores invasivos/malignos la punción percutánea fue un método de diagnóstico muy efectivo. El tratamiento de elección de ser la resección quirúrgica con criterio agresivo, y de ser necesaria localmente extendida. La irradiación P.O. fue efectiva en los timomas invasores, la QMT neoadyuvante presentó buen índice de respuesta favorable. Se observó peor evolución P.O. inmediata en los pacientes portadores de M.G...