Pulmonary neuroendocrine carcinoid tumors: Is there a predictive role to the Ki 67 index?

INTRODUCTION: There are several factors predicting evolution in carcinoid tumors (CT) to date including the Ki67 role. AIMS: The aim of this study is to identify a KI67 cut-off point for a population of CT and determine its prognostic implication in global and disease-free survival. METHODS: Hematoxylin-eosin slides of 102 CT were revised. The percentage of cells expressing Ki 67 was determined manually. STATISTICAL ANALYSIS: The variables were compared with the t-test or the Wilcoxon test according to their distribution, the categorical ones with Chi-square or Fisher's test. The best cut-off point was established by constructing receiver operating characteristic curves, then using that value as a dichotomous variable. RESULTS: 72 typical carcinoids (TC) and 30 atypical carcinoids (AC) were analyzed; 66% were female. Median age (TC 38 vs. AC 51, P = 0.001), Ki67 expression (TC 0.63 vs. AC 2, P = 0.003), tumor size (TC 2.5 vs. AC 2.6, P = 0.001), the percentage relapse (TC 3.4% vs. AC 23%, P = 0.006), and the number of deaths (TC 1 vs. AC 4, P = 0.042) were significantly higher in the AC subgroup. The best cut-off point for Ki 67 was 0.755 (area under the curve AUC 0.564, 95% confidence interval 0.270-0.857), with no significant differences found in the disease-free and overall survival curves when considering values < or ≥ at the established cut-off point. The best cut-off point of the Ki-67 when exclusively analyzing AC was 1.18. When using this value as a predictive variable, a marginal statistical association was observed between Ki-67 expression, mortality (P = 0.077), and the frequency of relapses (P = 0.054). CONCLUSIONS: Histological type is the best predictor of prognosis in the carcinoid tumor group. In the AC subgroup, the marginal association between mortality, frequency of relapses and Ki values 67 ≥ 1.18 has clinical relevance future analyses are required to determine the real predictive value of this variable.

Mediastinal germ cell tumors: cohort of patients with this rare entity.

BACKGROUND: Extragonadal germ cell tumors are infrequent and represent between 1-10% of all mediastinal tumors. It presents differences to those of gonadal location in terms of clinical presentation, behavior and prognosis which is poor even with treatment. METHODS: Retrospective and descriptive cohort study on 16 patients with diagnosis of mediastinal germ cell tumor surgically treated at Maria Ferrer Respiratory Rehabilitation Hospital and Alexander Fleming Specialized Medical Institute. RESULTS: Nine men and 7 women were analyzed over a period of 10 years. The median age was significantly lower among men (22 vs. 38 years, P<0.01). The most common initial symptom was pain in 43.75%. Chest tomography was the diagnostic method used in 13 patients (81.25%). Tumor marker levels were raised in 7 patients (43.75%), and decreased after surgery. All women had a mature teratoma, however, no statistically significant difference was found at the histological distribution by gender (P=0.336). The median tumor size was 9.50 centimeters. The most frequent surgical approach was sternotomy. No woman in the series received treatment before or after surgery, while 88.90% of men received neoadjuvant treatment for invasion or intimate contact with neighboring structures (P=0.001). Chemotherapy was indicated in 33.30% of the male population due to relapse. The median follow-up was 36 months (range, 1-95 months). No statistically significant differences were observed in the median follow-up (P=0.950), the percentage of relapses (P=0.091) and overall survival by gender (P=0.335). Overall survival was 75%. CONCLUSIONS: Tumors were predominantly primary and not seminomatous. Multimodal treatment was a useful tool to improve the chances of resection and overall survival. There was a percentage of women higher than the published literature, teratomas predominated in them, and surgery was the only necessary treatment.

Tumores carcinoides pulmonares tratados quirúrgicamente valor pronóstico de la 7ª estadificación TNM

Con el objetivo de evaluar el valor pronóstico de la 7a estadificación TNM se analizaron 43 mujeres (61%) y 28 hombres (39%) con diagnóstico de tumor carcinoide tratados quirúrgicamente desde enero/1975 hasta diciembre/2011. Mediana de edad: 38 años (13-67). Presentaron carcinoide típico (CT) 63 (89%) pacientes y 8 (11%) carcinoide atípico (CA). Mediana de seguimiento: 4 años (1 - 24 años). Los estadios correspondientes a CT fueron: IA = 33 (52%), IB = 10 (16%), IIA = 2 (3%), IIB = 2 (3%), IIIA = 12 (19%) y IIIB = 2 (3%); para los CA fueron: IA = 1 (12.5%), IIB = 1 (12.5%), IIIA = 2 (25%) y IIIB = 4 (50%). No hubo diferencia estadísticamente significativa en la supervivencia global a cinco años en el análisis estratificando por estadios (p = 0.689), ni analizando separadamente cada tipo histológico (CT p = 0.547; CA p = 0.592). El intervalo libre de enfermedad fue significativamente menor (CT: 3 años vs CA: 2 años, p = 0.000) y las recaídas más frecuentes en el grupo de carcinoides atípicos (CA: 50% vs CT: 2%, p = 0.000). Los pacientes con CT presentaron buena evolución aun en estadios avanzados, mientras que los que tuvieron CA presentaron menor tiempo de supervivencia e intervalo libre de enfermedad, y mayor frecuencia de recurrencia. El subtipo histológico resultó un factor significativo de pronóstico, mientras que la 7ª estadificación TNM no contribuyó en predecir la supervivencia en los tumores carcinoides.

We analyzed 43 women (61%) and 28 men (39%) surgically treated for carcinoid tumors from Jan/1975 to Dec/2011. Median age: 38 years (13-67). Typical carcinoid (TC) appeared in 63 (89%) patients, 8 (11%) suffered from atypical carcinoid (AC). Median follow-up: 4 years (1-24). TC stages were: IA = 33 (52%), IB = 10 (16%), IIA = 2 (3%), IIB = 2 (3%), IIIA = 12 (19%) and IIIB = 2 (3%); AC stages were: IA = 1 (12.5%), IIB = 1 (12.5%), IIIA = 2 (25%) and IIIB = 4 (50%). TNM classification did not show significant differences on 5-years survival period by stage (p = 0.689), even according to histological type (TC: p = 0.547; AC: p = 0.592). The disease-free survival rate was significantly lower (TC: 3 years vs. AC: 2 years, p = 0.000) and relapses were more frequent in AC (AC: 50% vs. TC: 2%, p = 0.000). The 7th TNM staging was not influential in estimating survival from carcinoid tumours in our population. The histological subtype was a better prognostic factor.

Observational study of patients with gastroenteropancreatic and bronchial neuroendocrine tumors in Argentina: Results from the large database of a multidisciplinary group clinical multicenter study.

Neuroendocrine tumors (NET) include a spectrum of malignancies arising from neuroendocrine cells throughout the body. The objective of this clinical investigation of retrospectively and prospectively collected data was to describe the prevalence, demographic data, clinical symptoms and methods of diagnosis of NET and the treatment and long-term follow-up of patients with NET. Data were provided by the participating centers and assessed for consistency by internal reviewers. All the cases were centrally evaluated (when necessary) by the pathologists in our group. The tissue samples were reviewed by hematoxylin and eosin and immunohistochemical staining techniques to confirm the diagnosis of NET. In total, 532 cases were documented: 461 gastroenteropancreatic-NET (GEP-NET) and 71 bronchial NET (BNET). All the tumors were immunohistochemically defined according to the World Health Organization (WHO) and European Neuroendocrine Tumor Society criteria. The most common initial symptoms in GEP-NET were abdominal pain, diarrhea, bowel obstruction, flushing, gastrointestinal bleeding and weight loss. The most common tumor types were carcinoid (58.0%), non-functional pancreatic tumor (23.0%), metastatic NET of unknown primary (16.0%) and functional pancreatic tumor (3.0%). Of the BNET, 89.0% were typical and 11.0% atypical carcinoids. Of the patients with GEP-NET, 59.2% had distant metastasis at diagnosis. The locations of the primary tumors in GEP-NET were the small bowel (26.9%), pancreas (25.2%), colon-rectum (12.4%), appendix (7.6%), stomach (6.9%), esophagus (2.8%), duodenum (2.0%) and unknown primary (16.3%). The histological subtypes based on the WHO classification were well-differentiated NET (20.1%), well-differentiated neuroendocrine carcinomas (66.5%) and poorly differentiated neuroendocrine carcinomas (10.3%). Overall, 67.3% of the patients underwent surgery, 41.2% with curative intent and 26.1% for palliative purposes. The 5-year survival rates were 65.1% (95% confidence interval, 58.0-71.4%) in GEP-NET and 100.0% in typical carcinoid of the lung. This observational, non-interventional, longitudinal study aimed to accumulate relevant information regarding the epidemiology, clinical presentation and current practices in the treatment of NET patients in Argentina, providing insight into regional differences and patterns of care in this heterogeneous disease.

Timoma y miastenia gravis: algunas reflexiones / Thymoma and myasthenia gravis: some reflections

La miastenia gravis es un desorden autoinmune cuyo espectro de síntomas abarca desde la debilidad ocular hasta la depresión respiratoria. Por tanto, debe tratarse como tal asociando corticoides e inmunosupresores, de ser necesario, a los fines de obtener estabilidad clínica al momento del procedimiento quirúrgico. Ello es independiente de la presencia o no de un timoma. La paciente presentaba síntomas bulbares (afectación de músculos orofaríngeos y fonatorios), perteneciendo al menos a un estadío IIb de la clasificación Clínica de Osserman, lo que implicaba que tal vez las condiciones clínicas en las cuales fue llevada a cirugía no fueron las más adecuadas, y pudieron motivar las complicaciones posteriores

[Surgically treated bronchopulmonary carcinoid tumours. Prognostic value of TNM staging 7a edition]. / Tumores carcinoides pulmonares tratados quirúrgicamente. Valor pronóstico de la 7a estadificación TNM.

We analyzed 43 women (61%) and 28 men (39%) surgically treated for carcinoid tumors from Jan/1975 to Dec/2011. Median age: 38 years (13-67). Typical carcinoid (TC) appeared in 63 (89%) patients, 8 (11%) suffered from atypical carcinoid (AC). Median follow-up: 4 years (1-24). TC stages were: IA = 33 (52%), IB = 10 (16%), IIA = 2 (3%), IIB = 2 (3%), IIIA = 12 (19%) and IIIB = 2 (3%); AC stages were: IA = 1 (12.5%), IIB = 1 (12.5%), IIIA = 2 (25%) and IIIB = 4 (50%). TNM classification did not show significant differences on 5-years survival period by stage (p = 0.689), even according to histological type (TC: p = 0.547; AC: p = 0.592). The disease-free survival rate was significantly lower (TC: 3 years vs. AC: 2 years, p = 0.000) and relapses were more frequent in AC (AC: 50% vs. TC: 2%, p = 0.000). The 7th TNM staging was not influential in estimating survival from carcinoid tumours in our population. The histological subtype was a better prognostic factor.

Tumores carcinoides pulmonares tratados quirúrgicamente. Valor pronóstico de la 7a estadificación TNM. / [Surgically treated bronchopulmonary carcinoid tumours. Prognostic value of TNM staging 7a edition].

We analyzed 43 women (61

) and 28 men (39

) surgically treated for carcinoid tumors from Jan/1975 to Dec/2011. Median age: 38 years (13-67). Typical carcinoid (TC) appeared in 63 (89

) patients, 8 (11

) suffered from atypical carcinoid (AC). Median follow-up: 4 years (1-24). TC stages were: IA = 33 (52

), IB = 10 (16

), IIA = 2 (3

), IIB = 2 (3

), IIIA = 12 (19

) and IIIB = 2 (3

); AC stages were: IA = 1 (12.5

), IIB = 1 (12.5

), IIIA = 2 (25

) and IIIB = 4 (50

). TNM classification did not show significant differences on 5-years survival period by stage (p = 0.689), even according to histological type (TC: p = 0.547; AC: p = 0.592). The disease-free survival rate was significantly lower (TC: 3 years vs. AC: 2 years, p = 0.000) and relapses were more frequent in AC (AC: 50

vs. TC: 2

, p = 0.000). The 7th TNM staging was not influential in estimating survival from carcinoid tumours in our population. The histological subtype was a better prognostic factor.

Tumores primitivos traqueales / Tracheal primary Tumours

Antecedentes: Los tumores primitivos de la tráquea son infrecuentes y el éxito del tratamiento quirúrgico depende de la precisa indicación y selección de pacientes. Objetivos: Evaluar los factores histopatológicos y quirúrgicos que pudieran influir en la supervivencia de una serie de pacientes con tumores primarios de tráquea tratados quirúrgicamente. Material y métodos: Se estudiaron todos los pacientes con diagnóstico de tumor primitivo traqueal desde enero del 1971 hasta junio del 2011. Dieciséis de estos pacientes fueron motivo de una publicación previa. Las variables analizadas fueron: edad, tipo histológico, longitud de la resección y presencia de enfermedad en márgenes de resección. Para el análisis de supervivencia se utilizó el log rank test y las curvas de Kaplan Meier utilizando el paquete estadístico STATA 9.0. Los datos están expresados en medianas, rangos, IC 95% y porcentajes. El número de casos por grupo invalida realizar análisis multivariado. Resultados: Fueron estudiados 54 pacientes: 22 hombres (41%) y 32 mujeres (59%). Mediana de edad: 50 años. El tipo histológico más frecuente fue el carcinoma adenoide quístico (41%), seguido por el carcinoma epidermoide (19%), los tumores carcinoides (7.4%), adenocarcinomas (7.4%), el carcinoma mucoepidermoide de bajo grado (6%) y el fibrosarcoma (6%); el resto (13.2%) correspondió a lesiones benignas. La mediana de seguimiento para todos ellos fue de 2 años (rango 1-26 años). Al analizar separadamente los tumores adenoquísticos (22) y epidermoides (10), encontramos que la edad mayor a 50 años (HR 3.27, IC 95% 1.24-8.67, p = 0.017), el diagnóstico de carcinoma epidermoide (HR 12.29, IC 95% 3.18-47.49, p = 0.00), la presencia de márgenes de resección positivos (HR 5.78, IC 95% 1.42-23.64, p = 0.015) y las resecciones mayores a 6 cm (HR 11.86, IC 95% 3.31-42.44 p = 0.00) fueron factores asociados significativamente a menor tiempo de supervivencia. Conclusiones: En esta serie de tumores traqueales observamos que los pacientes mayores a 50 años, el carcinoma epidermoide, las resecciones extensas y los márgenes insuficientes fueron factores de mal pronóstico. Estos factores deben tenerse en consideración al establecer la estrategia terapéutica en cada paciente.

Background: Primary tracheal tumors are infrequent and their successful treatment depends on the selection of patients and precise surgical indications. The aim of this paper was to evaluate the histopathology and surgical factors that may influence survival in a series of patients with tracheal tumors that underwent surgery, endoscopic resection, prosthesis, and oncologic treatment. Methods: We revised the records of 54 patients with the diagnosis of tracheal tumors from January 1971 through June 2011. A report on sixteen of these patients was published previously. The following features were taken into account: age, histological type of the tumor, extent of resection of the involved trachea and the presence of remaining disease in the margins. The log Rank test and Kaplan Meier curves were used for survival analysis. Data were expressed as median, ranges, CI 95% and percentages. Multivariate analysis was not performed due to the small number of cases per group. Results: The series consisted of 54 patients, 22 men (41%) and 32 women (59%) . The median age was 50 years. The commonest histological type was adenocystic carcinoma (41%) followed by squamous cell carcinoma (19 %,) carcinoid tumors (7.4%) adenocarcinoma (7.4%), mucoepidermoid carcinoma (6%) and fibrosarcoma (6%). The remaining tumors were benign lesions (13.2%). The median follow up was 2 years, (range 1-26 years). Analyzing separately adenocystic carcinomas (22) and squamous cell carcinomas (10), we found that age older than 50 years (HR 3.27, 95% CI 1.24-8.67, p = 0.017), diagnosis of squamous cell carcinoma (HR 12.29, 95 % 3.18-47.49, p = 0.00), the presence of tumor in the margins (HR 5.78, 95% CI 1.42-23.64, p = 0.015), and resections greater than 6 cm (HR 11.86, 95% CI 3.31-42.44 p = 0.00) were significantly associated with shorter survival time. Conclusion: This larger series of cases confirm, and extend the conclusions of our previous report. We found that in both, adenocystic carcinoma (ACC) and squamous cell carcinoma (SCC), the age, the presence of tumor in the resection margins, and the extent of resection (more than 6 cm) were significantly associated with a poorer prognosis and shorter survival time.

Tumores primitivos traqueales / Tracheal primary Tumours

Antecedentes: Los tumores primitivos de la tráquea son infrecuentes y el éxito del tratamiento quirúrgico depende de la precisa indicación y selección de pacientes. Objetivos: Evaluar los factores histopatológicos y quirúrgicos que pudieran influir en la supervivencia de una serie de pacientes con tumores primarios de tráquea tratados quirúrgicamente. Material y métodos: Se estudiaron todos los pacientes con diagnóstico de tumor primitivo traqueal desde enero del 1971 hasta junio del 2011. Dieciséis de estos pacientes fueron motivo de una publicación previa. Las variables analizadas fueron: edad, tipo histológico, longitud de la resección y presencia de enfermedad en márgenes de resección. Para el análisis de supervivencia se utilizó el log rank test y las curvas de Kaplan Meier utilizando el paquete estadístico STATA 9.0. Los datos están expresados en medianas, rangos, IC 95% y porcentajes. El número de casos por grupo invalida realizar análisis multivariado. Resultados: Fueron estudiados 54 pacientes: 22 hombres (41%) y 32 mujeres (59%). Mediana de edad: 50 años. El tipo histológico más frecuente fue el carcinoma adenoide quístico (41%), seguido por el carcinoma epidermoide (19%), los tumores carcinoides (7.4%), adenocarcinomas (7.4%), el carcinoma mucoepidermoide de bajo grado (6%) y el fibrosarcoma (6%); el resto (13.2%) correspondió a lesiones benignas. La mediana de seguimiento para todos ellos fue de 2 años (rango 1-26 años). Al analizar separadamente los tumores adenoquísticos (22) y epidermoides (10), encontramos que la edad mayor a 50 años (HR 3.27, IC 95% 1.24-8.67, p = 0.017), el diagnóstico de carcinoma epidermoide (HR 12.29, IC 95% 3.18-47.49, p = 0.00), la presencia de márgenes de resección positivos (HR 5.78, IC 95% 1.42-23.64, p = 0.015) y las resecciones mayores a 6 cm (HR 11.86, IC 95% 3.31-42.44 p = 0.00) fueron factores asociados significativamente a menor tiempo de supervivencia. Conclusiones: En esta serie de tumores traqueales observamos que los pacientes mayores a 50 años, el carcinoma epidermoide, las resecciones extensas y los márgenes insuficientes fueron factores de mal pronóstico. Estos factores deben tenerse en consideración al establecer la estrategia terapéutica en cada paciente.(AU)

Background: Primary tracheal tumors are infrequent and their successful treatment depends on the selection of patients and precise surgical indications. The aim of this paper was to evaluate the histopathology and surgical factors that may influence survival in a series of patients with tracheal tumors that underwent surgery, endoscopic resection, prosthesis, and oncologic treatment. Methods: We revised the records of 54 patients with the diagnosis of tracheal tumors from January 1971 through June 2011. A report on sixteen of these patients was published previously. The following features were taken into account: age, histological type of the tumor, extent of resection of the involved trachea and the presence of remaining disease in the margins. The log Rank test and Kaplan Meier curves were used for survival analysis. Data were expressed as median, ranges, CI 95% and percentages. Multivariate analysis was not performed due to the small number of cases per group. Results: The series consisted of 54 patients, 22 men (41%) and 32 women (59%) . The median age was 50 years. The commonest histological type was adenocystic carcinoma (41%) followed by squamous cell carcinoma (19 %,) carcinoid tumors (7.4%) adenocarcinoma (7.4%), mucoepidermoid carcinoma (6%) and fibrosarcoma (6%). The remaining tumors were benign lesions (13.2%). The median follow up was 2 years, (range 1-26 years). Analyzing separately adenocystic carcinomas (22) and squamous cell carcinomas (10), we found that age older than 50 years (HR 3.27, 95% CI 1.24-8.67, p = 0.017), diagnosis of squamous cell carcinoma (HR 12.29, 95 % 3.18-47.49, p = 0.00), the presence of tumor in the margins (HR 5.78, 95% CI 1.42-23.64, p = 0.015), and resections greater than 6 cm (HR 11.86, 95% CI 3.31-42.44 p = 0.00) were significantly associated with shorter survival time. Conclusion: This larger series of cases confirm, and extend the conclusions of our previous report. We found that in both, adenocystic carcinoma (ACC) and squamous cell carcinoma (SCC), the age, the presence of tumor in the resection margins, and the extent of resection (more than 6 cm) were significantly associated with a poorer prognosis and shorter survival time.(AU)

Factores de pronóstico y resultados a largo plazo de timomas tratados quirúrgicamente en una cohorte de pacientes argentinos / Prognostic factors and long-term results of surgically treated thymoma in a cohort of patients Argentine

Los timomas representan el tumor más frecuente del mediastino anterior. El objetivo del trabajo es presentar las características clínico patológicas de los timomas tratados quirúrgicamente desde enero de 1971 hasta diciembre del 2008 en el Hospital de Rehabilitación Respiratoria María Ferrer, e investigar los factores que afectan la supervivencia. De los 131 casos analizados, 11 fueron perdidos de seguimiento (6%); de los restantes 120, 26 se hallaban fallecidos al final del estudio (21.7%). Se analizaron las siguientes variables: edad, sexo, síntomas de miastenia gravis al momento del diagnóstico, estadificación de Masaoka(1994) del tumor original, clasificación histológica de la OMS (1999), radioterapia postoperatoria y evolución clínica de la miastenia gravis según la clasificación modificada de Osserman. Fueron analizados 66 hombres (54%) y 56 mujeres (46%), con una mediana de edad de 48 años (rango13-78); 78 presentaban miastenia gravis al momento del diagnóstico (64%), y el 97% de ellos persistían sintomáticos luego del tratamiento quirúrgico. En el análisis univariado, la presencia de miastenia gravis al momento del diagnóstico (HR 0.527, IC 95% 0.243 - 1.141, p = 0.10), la evolución clínica de la enfermedad (HR 18.81, IC 95% 4.070 - 86.886,p = 0.000) y el estadio de Masaoka (HR 2.044, IC 95% 0.934 - 4.474, p = 0.074) se asociaron significativamente con la frecuencia de la muerte en pacientes con timoma. En el análisis multivariado, ese valor resultó ser casi 7 veces mayor en timomas invasores que en los estadios I y II (HR 7.272, IC 95% 2.19 - 24.11, p = 0.001), mientras que la radioterapia adyuvante disminuyó en un 79% este riesgo en nuestra población (HR 0.214 IC 95% 0.0648 - 0.7085, p= 0.12)...

Thymomas are neoplasias originating from epithelial cellsof the thymus. The aim is to present a serie of surgicallytreated thymomas at the Hospital de Rehabilitación Respi -ratoria María Ferrer from January 1971 to December 2008and to determine which factors affected the survival ofthese patients during the follow-up time. All patients withdiagnostic of thymoma surgically treated were included.A total of 131 cases were analized, 11 of which were lostto follow-up (6%); of the remaining 120, 26 were dead atthe end of the study (21.7%). The following variables wereanalyzed: age, gender, symptoms of myasthenia gravis atthe time of diagnosis, staging of Masaoka (1994) of theoriginal tumor, the 1999 WHO classification, postoperativeradiotherapy treatment and clinical course of myastheniagravis defined by the modified Osserman classification.Out of the 120 patients studied, 66 were men (54%) and 56female (46%), with a median age of 48 years old (range 13-78); 78/120 had myasthenia gravis at the time of diagnosis(64%), and 97% of them had persistent symptoms aftersurgical treatment. In univariate analysis, symptoms ofmyasthenia gravis at the time of diagnosis (HR 0.527, 95%CI 0.243 - 1.141, p = 0.10), clinical course of myastheniaaccording to the Osserman classification (HR 18.81, CI95% 4.070 - 86.886, p = 0.000) and staging of Masaoka(HR 2.044, 95% CI 0.934-4.474, p = 0.074) showed a signi -ficant association with the frequency of death in patientswith thymoma. In multivariate analysis, the risk of deathin patients with invasive thymomas proved to be almost7 times higher than in stages I and II (HR 7.272, 95% CI2.19 - 24.11, p = 0.001), whereas the postoperative adjuvanttherapy decreased 79% this risk in our population (HR0.214, 95% CI 0.0648 - 0.7085, p = 0.012)...

Plásticas bronquiales como alternativa terapéutica en lesiones centrales / Bronchoplastic as a therapeutic alternative in central lesions

Introducción: Los procedimientos broncoplásticos son útiles en lesiones de localización central. El objetivo es describir la serie de plásticas bronquiales realizadas por el mismoequipo quirúrgico en dos centros de Argentina. Pacientes y métodos: 54 plásticas bronquiales realizadas desde enero de 1978 hasta diciembre del 2009 fueron analizadas. Las lesiones fueron categorizadas como benignas,de bajo y alto grado de malignidad para el análisis. Resultados: Se practicaron 29 lobectomías asociadas a plástica bronquial (54%), 21 resecciones en manguito (39%) y 4 lobectomías asociadas a plástica bronquial y arterial(7%). El promedio de edad de los pacientes con lesiones de bajo grado de malignidad es significativamente menor (34 años vs 53 p=0.0025), mientras que la prevalencia del sexo masculino (37.5% vs 75%, p=0.051), el antecedente de tabaquismo (31% vs 75%, p=0.002) y el número de plásticas vasculares (2.5% vs 37.5%, p=0.002) fue mayor entre los carcinomas. El riesgo de muerte fue 9 veces mayor entre los carcinomas (HR8.64, IC 95% 1.6-47.7, p=0.013), sin diferencias significativas en la supervivencia a 5 años y 10 años entre los dos grupos. Conclusiones: los procedimientos broncoplásticos permiten una resección oncológicaviable con preservación de parénquima pulmonar sin afectar la supervivencia alejada.

Introduction: bronchoplastic procedures are useful in tumours of central location.The aim of this study is to describe the range of bronchoplastic procedures performed by the same surgical team at two centers in Argentina. Patients and methods: The study included 54 bronchoplastic therapies made fromJanuary 1978 through December 2009. The lesions were classified as benign, low grade of malignancy and high grade of malignancy. Results: 29 sleeve lobectomies (54%), 21 sleeve resections (39%) and 4 lobectomieswith bronchovascular plastic procedures (7%) were performed. The mean age ofpatients with low grade of malignancy was significantly lower (34 years vs. 53 years; p = 0.0025), whereas male prevalence (37.5% vs 75%, p = 0.051), smoking habit history (31% vs 75%, p = 0.002) and number of bronchovascular plastic procedures(2.5% vs 37.5%, p = 0.002) was higher in cases of high grade of malignancy. The risk of death was 9 times higher in these patients (HR 8.64, 95% CI 1.6-47.7, p = 0.013) but no significant differences in survival at 5 and 10 years between the twogroups were observed. Conclusions: bronchoplastic procedures allow oncologic resection with preservationof lung parenchyma without affecting survival.

Sternal metastasis of breast cancer: ex vivo hypothermia and reimplantation.

Breast cancer frequently metastasizes to the bone. When the sternum is involved, it usually presents as a solitary lesion. In such cases, resection is indicated, including with the intention to cure. This case report describes a technique for a complete exeresis of the sternum, ex vivo repair under hypothermia, and reimplantation. Cryosurgery is a well-known technique to resect bone metastases and was the procedure used in our patient. The follow-up after 2 years shows no evidence of tumor recurrence, with excellent results on aesthetic levels.

Cirugía de las lesiones benignas traqueales evolución alejada / Surgery of the tracheal benign injuries remote evolution

Antecedentes: Las estenosis laringotraqueales benignas se originan en su mayoría como consecuencia de la asistencia mecánica (ARM) prolongada. Las medidas terapéuticas a emplear dependerán del grado de obstrucción de la via aérea. La endoscopia intervencionista constituye el primer paso hacia el tratamiento quirúrgico definitivo. Objetivo: Mostrar resultados a largo plazo. Lugar de aplicación: Hospital de Rehabilitación Respiratoria "María Ferrer". Diseño: Retrospectivo. Descriptivo. Pacientes y Métodos: Se analizaron 100 pacientes sometidos a resección y reconstrucción con anastomosis término-terminal por estenosis laringotraqueales benignas, elegidos al azar sobre más de 400 pacientes operados, con seguimiento mínimo posoperatorio de un año. 65 pacientes eran masculinos y 35 femeninos. La media de edad 33,8 años (rango 15-69). Más de 50% de los casos tuvieron algún tratamiento endoscópico previo (dilataciones, láser, endoprótesis). Se evaluaron los resultados del seguimiento alejado. Resultados: Se realizaron 80 plásticas traqueales y 23 subglóticas con los siguientes resultados: buenos en 81,6% de los casos, satisfactorios en 7,8% y fracasos en 5,8%. Las complicaciones posoperatorias más frecuentes fueron granulomas en la anastomosis e infección de herida quirúrgica. La mortalidad alejada ha sido 2%. Conclusiones: 1. Las lesiones laringotraqueales secuelares post asistencia respiratorias mecánica prolongada continúan siendo frecuentes pese a las medidas destinadas a su prevención. 2. El seguimiento alejado ha demostrado que el índice de recidivas y/o complicaciones es extremadamente bajo, teniendo en cuenta el número de pacientes con lesiones más complejas (subglóticas y con cirugías previas) de esta muestra. 3. Si bien las prótesis endoluminales han resuelto lesiones complejas y resultan de gran utilidad, su uso indiscriminado debe ser evitado. 4. Los resultados son más exitosos y las cirugías de resección y reconstrucción debe ser considerada de...

Influence of apoptosis and cell cycle regulator proteins on chemotherapy response and survival in stage IIIA/IIIB NSCLC patients.

BACKGROUND: Prognosis for non-small cell lung cancer (NSCLC) patients is very poor. Prediction of the response to treatment in individual patients may be possible using molecular biological alterations such as clinical biomarkers. We investigated the predictive value of apoptosis and cell cycle regulator proteins for neoadjuvant chemotherapy response in stage IIIA/IIIB NSCLC patients. METHODS: We evaluated p53, bcl-2, p21WAF1/CIP1, p27Kip1, and Ki67 immunohistochemical expression and apoptotic index in mediastinal lymph node metastases from 23 IIIA and 10 IIIB NSCLC patients before treatment with neoadjuvant platinum-based chemotherapy. Univariate analysis was performed to evaluate the relationship between protein expression and survival or time to progression (TTP). RESULTS: Median follow-up was 25 months (range, 4-112), median TTP was 11 months (range, 0-112), and median overall survival was 22 months (range, 4-112). Of 32 assessable patients, 18 (56%) had stable disease, 12 (38%) had a PR, and two (6%) had progressive disease. Of the 22 patients assessable for pN2 following chemotherapy, 16 (77%) were positive. Univariate analysis showed that shorter TTP correlated with progressive disease (p = 0.000), positive pN2 after chemotherapy (p = 0.026), high Ki67 (p = 0.022), and high p21WAF1/CIP1 (p = 0.038). CONCLUSION: Our results suggest that in IIIA/IIIB NSCLC patients, a high level of p21WAF1 expression in mediastinal lymph node metastases before neoadjuvant platinum-based chemotherapy is associated with a poor outcome. Our results suggest that expression of p21WAF1, which plays a role in preventing apoptosis, may be significant when selecting chemotherapy for NSCLC patients.

Risk of recurrence in patients with surgically resected stage I non-small cell lung carcinoma: histopathologic and immunohistochemical analysis.

STUDY OBJECTIVE: To evaluate the prognostic value of histopathologic variables and molecular markers in a group of patients with stage I non-small cell lung cancer (NSCLC). SETTING: "María Ferrer" Hospital of Buenos Aires, Argentina. PATIENTS: Pathologic stage IA and IB patients who underwent radical surgery and nonneoadjuvant therapy for NSCLC between January 1985 and December 1999. MEASUREMENTS AND RESULTS: Fifty-three patients fulfilling the inclusion criteria were identified. The overall survival was 52.8%, and 28% of patients had recurrent disease. We found significant differences between squamous cell carcinoma (SCC) and adenocarcinoma in mitotic counting (p = 0.001) and lymphatic permeation (p = 0.01). SCCs showed higher proliferation (MIB-1 grades 2 and 3) [p = 0.001], Bcl-2 expression (p = 0.038), and CD44 expression (p = 0.019) than adenocarcinomas. The log-rank test showed that mitosis count, necrosis, MIB-1, and Bcl-2 were predictive factors for relapse. All of them were associated with increased relapse and a shorter time to recurrence. Multivariate analysis using the Cox proportional hazards regression model showed that mitosis count, Bcl-2 expression, and grade 3 of MIB-1 emerged as independent prognostic factors of recurrence. CONCLUSIONS: We found that mitosis count and MIB-1 expression had significant value to predict recurrence, reflecting the aggressiveness of high-rate proliferative tumors. We could also show that patients with positive Bcl-2 tumors had a poor outcome, probably related to the uncontrolled cell growth that the expression of Bcl-2 promotes. Our observations are of potential interest for the development of rational postresection treatment strategies based on the estimated risk of recurrence of patients with NSCLC.

Neoadjuvant chemotherapy with gemcitabine and cisplatin in stage IIIA/B non-small cell lung cancer.

PURPOSE: We studied cisplatin plus gemcitabine as induction (neoadjuvant) therapy in patients with stage III non-small cell lung cancer (NSCLC) to assess its objective remission rate, resectability, survival, and toxicity. PATIENTS AND METHODS: Patients with stage III NSCLC received 2 cycles of gemcitabine 1250 mg/m2 on days 1, 8, and 15, plus cisplatin 100 mg/m2 on day 2. Subsequently, patients were assigned to local therapy--surgery or radiotherapy. RESULTS: Twenty-nine eligible patients (male/female: 21/8) with a median age of 59 years (range, 43-71 years) were enrolled between October 1996 and February 1999. A total of 80 cycles were given, with a median of 3 per patient (range, 1-4 cycles). Overall, toxicities were mild; only one patient had febrile neutropenia, and there were no grade 4 non-hematological toxicities. There was one toxic death following afebrile grade 4 neutropenia. Overall clinical response rate (2 complete responses [CRs] + 16 partial responses [PRs]) was 62% (95% CI, 45%-79%); 10 patients had stable disease and none progressed; one patient was not evaluable. Eight of the 18 operated patients had pathological response: 1 CR and 7 downstagings to N(-); 14 patients were resected. Median survival was 17 months (95% CI, 13-21 months), with 1-year and 2-year actuarial survival rates of 61% and 29%, respectively. CONCLUSIONS: Gemcitabine plus cisplatin is a very active and well-tolerated induction regimen in stage III NSCLC. Comparative studies with other standard regimens are warranted.

Tratamiento del cáncer de pulmón, ¿cuánto se ha avanzado? / Advances in the management of lung cancer

Recent advances in the management of lung cancer are detailed in this study. results with the use of neoadjuvant therapy, preoperative chemotherapy and radiotherapy, are also discussed, and comparing these procedures with surgery alone in the different stages of the disease

Tratamiento del cáncer de pulmón, ¿cuánto se ha avanzado? / Advances in the management of lung cancer

Recent advances in the management of lung cancer are detailed in this study. results with the use of neoadjuvant therapy, preoperative chemotherapy and radiotherapy, are also discussed, and comparing these procedures with surgery alone in the different stages of the disease