José María Matilla

Prognostic factors in neuroendocrine lung tumors: a Spanish multicenter study

Background. This study examines the experience of the Spanish Multicenter Study of Neuroendocrine Tumors of the Lung through the clinical data and behavior of patients treated for this pathologic process. Methods. From 1980 to 1997, 361 cases of neuroendocrine carcinomas (NEC) were treated surgically. Patients were enrolled in a protocol using the pathologic and follow-up reports. According to Dreslers’ criteria, the cases were segregated into grade 1 (typical carcinoid), grade 2 (atypical carcinoid), grade 3 large cell type, and grade 3 small cell type. Several variables were reviewed in all patients. Statistical analysis was performed to determine whether clinical characteristics and differentiation were associated with significant differences in the prognosis. Results. A total of 261 cases of NEC were identified with grade 1, 43 with grade 2, and with grade 3: 22 of large and 35 of small cells. Five-year survival for different grades was as follows: grade 1, 96%; 2, 72%; 3 large cell type, 21%; and 3 small cell type, 14%. When a comparative analysis between typical and atypical carcinoids was performed a significant difference for mean age, tumor size, nodal metastases, and recurrence was observed. However, female sex, nodal metastases, and recurrence rate differed between atypical carcinoids and grade 3 NEC of large cells. A difference in recurrence rate was found between patients with both types of grade 3 NEC. Conclusions. The progressive deterioration of tumor organization highlights that neuroendocrine tumors constitute a continuous spectrum. A careful observation of pathologic findings is necessary to individualize their prognostic factors.

Open-Window Thoracostomy and Thoracomyoplasty to Manage Chronic Pleural Empyema

BACKGROUND The purpose of this study is to report our 15-year experience treating chronic empyemas after pulmonary resection and tuberculosis. METHODS Open-window thoracostomy and thoracomyoplasty were used to treat 40 patients with chronic pleural empyema characterized by residual empyematic cavity, bronchopleural fistula, and persistent pleural infections that were secondary to tuberculosis (n = 22) or pulmonary resection (n = 18). Between 2 and 7 months after thoracostomy, thoracomyoplasty was performed to eliminate a persistent pleural cavity. In 2 patients with postpulmonary resection empyema and a large bronchopleural fistula, intrathoracic transposition of the latissimus dorsi flap and open-window thoracostomy were performed simultaneously to close the fistula. RESULTS The pleural space was eliminated per primam intentionem in 21 of 22 patients with tuberculosis and in 14 of 18 with a postpulmonary resection empyema. Another myoplasty was performed in an additional 3 patients to eliminate the pleural space. During open-window thoracostomy, the latissimus dorsi muscle was preserved with minimal injury to the anterior serratus muscle. One patient died postoperatively. CONCLUSIONS Successful treatment of chronic pleural empyema requires adequate timing of surgical procedures. Our two-procedure technique is relatively simple and safe.

Quistes hidatídicos de mediastino: 8 casos

La hidatidosis en el ser humano es una enfermedad parasitaria producida por el crecimiento quistico de la larva de la tenia Echinococcus granulosus . Los organos mas afectados son el higado y el pulmon. La localizacion mediastinica es muy rara y se han descrito aproximadamente 100 casos en la bibliografia. Presentamos 8 casos de quistes hidatidicos de mediastino (QHM) intervenidos en un periodo de 21 anos. La distribucion fue similar en ambos sexos. La edad oscilo entre 10 y 74 anos. En los QHM la sintomatologia depende del tamano, localizacion y afectacion de estructuras proximas. La complicacion mas grave es la rotura del quiste y el paso del material hidatidico a la sangre, lo que puede provocar shock anafilactico e incluso la muerte del paciente. Actualmente, la ecografia, la tomografia computarizada (TAC) y la resonancia magnetica (RM) facilitan el diagnostico. El tratamiento es la exeresis del quiste y de la periquistica. Se debe sospechar QHM en las lesiones quisticas mediastinicas en paises de alta incidencia de hidatidosis. Hydatidosis in humans is a parasitic disease produced by cystic growth of the larvae of the tapeworm Echinococcus granulosus, affecting mainly the liver and lung. Larvae are rarely present in the mediastinum, although approximately 100 cases have been described in the literature. We report eight cases of hydatid cysts of the mediastinum (HCM) treated surgically over a period of 21 years. The incidence was similar in males and females and ages ranged from 10 to 74 years. Symptoms depend on size, location and involvement of neighboring structures in HCM. The most serious complication is cyst rupture with consequent transfer of hydatid material to the blood, possibly causing anaphylactic shock and even death. Currently, sonography, computed tomography and magnetic resonance images facilitate diagnosis. Treatment involves excision of the cyst and pericystic tissue. CHM should be suspected when mediastinal cysts are found in countries where the incidence of hydatidosis is high.

Neuroendocrine tumors of the lung.

Purpose of review The aim of this article is to answering different questions related to the treatment and prognosis of neuroendocrine lung tumors. Recent findings In neuroendocrine lung tumors, regardless of the grade of tumoral malignancy, the general growth during the past years of the nodal involvement percentage detected in lung neuroendocrine tumors might be explained by accepting surgical treatment as the norm and a complete mediastinal nodal dissection. Among non-small-cell carcinomas, large cell neuroendocrine carcinoma is the tumor with the worst prognosis. Nodal invasion clearly decreases the possibility of long-term survival in these patients, confirming the importance of preoperative and perioperative staging. A definitive survival advantage for postoperative adjuvant therapy has yet to be reported; tumoral genetics studies may contribute to specifying its indication. The importance of neuroendocrine differentiation in non-small-cell lung carcinomas for the treatment and prognosis of these tumors is a reason to intensify research. Summary In the surgical treatment of lung neuroendocrine carcinomas, nodal mediastinal dissection should always be performed. In the large neuroendocrine carcinoma, experience confirms the possibility of surgical treatment in early stages; in all cases, adjuvant treatment should always be established. The presence of synaptophysin in squamous carcinoma tumors and adenocarcinoma tumors in stage I seems to be associated with a worse prognosis.

Atypical carcinoid tumours of the lung: prognostic factors and patterns of recurrence.

Background Atypical carcinoids (AC) of the lung are rare intermediate-grade neuroendocrine neoplasms. Prognostic factors for these tumours are undefined. Methods Our cooperative group retrieved data on 127 patients operated between 1980 and 2009 because of an AC. Several clinical and pathological features were studied. Results In a univariable analysis, T-status (p=0.005), N-status (p=0.021), preoperative M-status (previously treated) (p=0.04), and distant recurrence developed during the outcome (p<0.001) presented statistically significant differences related to survival of these patients. In a multivariable analysis, only distant recurrence was demonstrated to be an independent risk factor for survival (p<0.001; HR: 13.1). During the monitoring, 25.2% of the patients presented some kind of recurrence. When we studied recurrence factors in a univariable manner, sublobar resections presented significant relationship with locoregional recurrence (p<0.001). In the case of distant recurrence, T and N status presented significant differences. Patients with preoperative M1 status presented higher frequencies of locoregional and distant recurrence (p=0.004 and p<0.001, respectively). In a multivariable analysis, sublobar resection was an independent prognostic factor to predict locoregional recurrence (p=0.002; HR: 18.1). Conclusions Complete standard surgical resection with radical lymphadenectomy is essential for AC. Sublobar resections are related to locoregional recurrence, so they should be avoided except for carefully selected patients. Nodal status is an important prognostic factor to predict survival and recurrence. Distant recurrence is related to poor outcome.

Tendencias en los factores pronósticos de los tumores pulmonares neuroendocrinos

Objetivo Este estudio tiene como objetivo determinar la tendencia de distintos factores pronosticos en carcinomas neuroendocrinos del pulmon a traves del analisis de 2 grupos de pacientes tratados quirurgicamente. Pacientes y metodos En el grupo A se incluyeron los primeros 361 casos, tratados entre 1980 y 1997—261 carcinoides tipicos (CT), 43 carcinoides atipicos (CA), 22 carcinomas neuroendocrinos de celulas grandes (CNECG) y 35 carcinomas neuroendocrinos de celulas pequenas (CNECP)—, que se estudiaron retrospectivamente. El grupo B estuvo compuesto por 404 casos, recogidos desde 1998 a 2002 —308 CT, 49 CA, 18 CNECG y 29 CNECP—, que se estudiaron prospectivamente. Las variables clinicas consideradas fueron: sexo, edad media, localizacion tumoral, tamano tumoral, afectacion ganglionar, estadio, metastasis y recurrencia local. Se utilizo la clasificacion TNM del carcinoma broncogenico de 1997 y se practico un estudio de supervivencia y de factores que influyen en ella. Se realizo un analisis estadistico uni y multivariante con los datos obtenidos. Resultados Por lo que se refiere al CT y al CA, se observaron diferencias significativas en los 2 grupos de pacientes en cuanto a la edad media, el tamano tumoral, la afectacion ganglionary la recurrencia. Entre CA y CNECG, el sexo, la afectacion anglionar y la recurrencia difirieron en el grupo A; lo mismo ocurrio en el grupo B, con la excepcion de la afectacion ganglionar. Entre CNECG y CNECP, la diferencia en la afectacion ganglionar observada en el grupo A no estuvo presente en los pacientes del grupo B. Respecto a la supervivencia, global y por afectacion ganglionar, se observaron diferencias significativas en ambos grupos al comparar CT frente a CA y CA frente a CNECG; no se encontraron diferencias entre CNECG y CNECP. El tipo histologico y la afectacion ganglionar mostraron la mayor influencia pronostica en analisis multivariante. Conclusiones En los carcinomas neuroendocrinos de pulmon se observa una tendencia definida en sus factores pronosticos. El tipo histologico y la deteccion de afectacion ganglionar se muestran como los factores con mayor influencia en la supervivencia.

Trends in Prognostic Factors for Neuroendocrine Lung Tumors

OBJECTIVE The aim of this study was to analyze trends in a variety of prognostic factors for neuroendocrine lung carcinomas through analysis of 2 groups of surgically treated patients. PATIENTS AND METHODS Group A contained the first 361 patients, treated between 1980 and 1997. That group was analyzed retrospectively and contained 261 patients with typical carcinoid tumors, 43 with atypical carcinoid tumors, 22 with large-cell neuroendocrine carcinoma, and 35 with small-cell neuroendocrine carcinoma. Group B contained 404 patients enrolled prospectively between 1998 and 2002: 308 with typical carcinoid tumors, 49 with atypical carcinoid tumors, 18 with large-cell neuroendocrine carcinoma, and 29 with small-cell neuroendocrine carcinoma. The following clinical variables were considered: sex, mean age, tumor site, tumor size, lymph node involvement, stage, metastasis, and local recurrence. The 1997 TNM classification was used for staging of lung cancer and survival analysis was performed along with assessment of factors influencing survival. Statistical analysis of the data involved univariate and multivariate analysis. RESULTS In both groups, significant differences were observed between patients with typical and atypical carcinoid tumors in terms of mean age, tumor size, node involvement, and recurrence. In group A, female sex, node involvement, and recurrence differed between patients with atypical carcinoid tumors and those with large-cell neuroendocrine carcinoma; the same was true for group B, with the exception of lymph node involvement. Node involvement differed between patients with small-cell versus large-cell neuroendocrine carcinoma in group A but not group B. Both groups displayed significant differences in overall survival and survival of patients with lymph node involvement between patients with typical and atypical carcinoid tumors and between patients with atypical carcinoid tumors and those with large-cell neuroendocrine carcinoma; no differences were observed between patients with large-cell versus small-cell neuroendocrine carcinoma. Histological type and lymph node involvement had the greatest influence on prognosis in the multivariate analysis. CONCLUSIONS A well-defined trend is observed in prognostic factors for neuroendocrine lung tumors. Histological type and lymph node involvement show the greatest influence on survival.

Interleukin-8 Expression in Lung Tissue During Ischemia-Reperfusion

OBJECTIVE Local cytokine production is a pathogenic factor in ischemia-reperfusion injury in early graft dysfunction. This study analyzed interleukin 8 (IL-8) messenger RNA (mRNA) expression in lung tissue and the association between IL-8 mRNA levels and interstitial lung changes in an experimental model of warm lung ischemia-reperfusion. MATERIAL AND METHODS We studied 16 New Zealand rabbits divided into 3 groups: control, ischemia (tissue taken from right lower lobe after 1, 2, or 3 hours of ischemia), and reperfusion (tissue taken from right upper and middle lobes after 1 hour of ischemia and 1, 2, or 3 hours of reperfusion). Expression of IL-8 mRNA was determined by reverse transcription and polymerase chain reaction. Interstitial infiltration by polymorphonuclear neutrophils was determined. The Mann-Whitney U-test was used for statistical comparisons, with P< .05 considered to indicate a significant result. RESULTS During ischemia, IL-8 mRNA levels were elevated at the end of hour 1 (P=.009) with respect to the control group, but not thereafter. Interstitial changes were minimal. IL-8 mRNA levels during reperfusion were similar to those observed during ischemia, with a slight increase at the end of hour 2. There were no significant differences between hours 1, 2, and 3. Polymorphonuclear neutrophil recruitment occurred at the beginning of reperfusion (P=.014), but no significant differences were observed at hours 2 or 3. Progressive thickening of alveolar septa and edema was documented. CONCLUSIONS Changes in IL-8 mRNA expression during ischemia precede interstitial infiltration by polymorphonuclear neutrophils during reperfusion, suggesting that the 2 processes are related. Quantification of IL-8 mRNA expression could facilitate early diagnosis of graft dysfunction.

The Significance of Histology: Typical and Atypical Bronchial Carcinoids

The aim of this study is to assess in bronchial carcinoid tumors, the prognostic factors in relation to the histology that would determine their most appropriate therapy. The histologic aggressiveness is a determining factor in tumor size and nodal involvement in these tumors. The knowledge of the histologic limits of typical and atypical carcinoid contributes to the recognition of a better valuation of the proportional significance that nodal involvement and histologic grade have in a tumors prognosis.

Tratamiento quirúrgico del cáncer de pulmón: evaluación comparativa de los sistemas de estadificación de 1986 y 1997. Resultados en 500 pacientes consecutivos

Objetivo Evaluar la influencia de diferentes variables en la supervivencia con referencia a la estadificacion de 1986 y 1997. Pacientes y metodos Se incluyeron en el estudio 500 pacientes afectados de cancer de pulmon no de celulas pequenas, tratados quirurgicamente de 1980 a 1997; 473 eran varones y 27 mujeres. Resecciones practicadas: 184 lobectomias, 16 bilobectomias, 244 neumonectomias, 2 lobectomias broncoplasticas y 54 segmentectomias. Histologia: 338 carcinomas epidermoides, 86 adenocarcinomas, 40 carcinomas de celulas grandes, 36 tumores mixtos. Diferenciacion: 216 G1, 91 G2, 193 G3. Estadios de 1986: I: 246 (49,2%) (T1: 32; T2: 214); II: 27 (5,4%); IIIa: 197 (39,4%) (N0: 84; N1: 2; N2: 111); IIIb 23 (4,6%) (N0: 12; N2: 11), y IV: 7 (1,4%) (N0: 4; N2: 3). Se utilizo la estadificacion de 1997 para la comparacion de la supervivencia entre los tumores Ia y Ib, y IIb y IIIa. Resultados Transcurridos entre 2 y 17 anos, 141 pacientes (28%) permanecen vivos, 26 (5%) perdidos y 333 han muerto. Mortalidad intraoperatoria: 2 (0,4%); postoperatoria: 36 (7,2%). De los 462 pacientes restantes, 295 fallecieron por diversas causas: metastasis 130 (44%), recidiva 81 (27%), causas funcionales 17 (6%), causas independientes 54 (18%), causas desconocidas 13 (4%). Supervivencia a 5 y 10 anos: global 36 y 26%; histologia: carcinomas epidermoides 36 y 26%; adenocarcinomas 35 y 26%; estadios: I: 51 y 41% (Ia, 81 y 75%; Ib, 44 y 33%); IIIa: 24 y 15 (IIb de 1997: 27 y 17%; IIIa de 1997: 20 y 13%); de acuerdo con factor N: N0: 44 y 34%; N2: 17 y 8% (1986) y 17 y 11% (1997). Conclusiones En este trabajo, la supervivencia hallada es concordante con otros estudios. La utilidad de la estadificacion de 1997 se puede establecer en funcion de las diferencias de supervivencia hallada entre los estadios Ia y Ib y IIb y IIIa. Se aprecia una influencia de factores N y T, la histologia y el estadio de la aparicion de metastasis, asi como el factor T en la de recidivas.