Composite anatomical-clinical-molecular prognostic model in non-small cell lung cancer.

The objective of the present study was to elaborate a survival model that integrates anatomic factors, according to the 2010 seventh edition of the tumour, node and metastasis (TNM) staging system, with clinical and molecular factors. Pathologic TNM descriptors (group A), clinical variables (group B), laboratory parameters (group C) and molecular markers (tissue microarrays; group D) were collected from 512 early-stage nonsmall cell lung cancer (NSCLC) patients with complete resection. A multivariate analysis stepped supervised learning classification algorithm was used. The prognostic performance by groups was: areas under the receiver operating characteristic curve (C-index): 0.67 (group A), 0.65 (Group B), 0.57 (group C) and 0.65 (group D). Considering all variables together selected for each of the four groups (integrated group) the C-index was 0.74 (95% CI 0.70-0.79), with statistically significant differences compared with each isolated group (from p = 0.006 to p < 0.001). Variables with the greatest prognostic discrimination were the presence of another ipsilobar nodule and tumour size > 3 cm, followed by other anatomical and clinical factors, and molecular expressions of phosphorylated mammalian target of rapamycin (phospho-mTOR), Ki67cell proliferation index and phosphorylated acetyl-coenzyme A carboxylase. This study on early-stage NSCLC shows the benefit from integrating pathological TNM, clinical and molecular factors into a composite prognostic model. The model of the integrated group classified patients with significantly higher accuracy compared to the TNM 2010 staging.

Criteria of functional and oncological operability in surgery for lung cancer: a multicenter study. The Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery (GCCB-S).

This study was undertaken to determine how much agreement was prevalent in the criteria of functional operability (a patient's capacity for tolerating surgery) and oncological operability (the preoperative assessment of the potential for excising all tumoral tissue with a prognostically favorable result) used in the hospitals participating in the Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery (GCCB-S). The GCCB-S includes 17 hospitals in which all consecutive cases of lung cancer in which thoracotomy is performed have been registered since 1993. A survey was sent to all participating centers requesting a semiquantitative evaluation of the level of agreement between the functional and oncological operability criteria used in the hospital and the functional and oncological operability criteria established by consensus among the members of the Coordinating Group of the GCCB-S. The consensus criteria were established mainly by evaluating evidence from the literature. Fourteen hospitals completed the survey: in 13 hospitals (93%) the consensus functional operability criteria were used 'just about always' (in more than 90% of cases) and in one hospital 'almost always' (between 80 and 90% of cases). In 14 hospitals the consensus oncological operability criteria were used 'just about always' (more than 90% of cases), although in five centers (36%) other tests, mainly abdominal imaging, were also used systematically. In conclusion, this GCCB-S study detected a broad agreement among the participating hospitals as to the minimal criteria for preoperative evaluation of the operability of patients with lung cancer.

Determination of tissue polypeptide-specific antigen in pleural fluid and serum from patients with pleural effusion.

As a tool for differentiating malignant and benign pleural effusions, we evaluated the diagnostic value of the assay of tissue polypeptide-specific antigen (TPS) in pleural fluid and serum, and of the pleural fluid TPS/serum TPS ratio in patients with pleural effusion. We studied prospectively 147 consecutive patients who had pleural effusions: 43 malignant pleural effusions and 104 benign pleural effusions. TPS levels were measured by RIA. The sensitivity and specificity of these measurements were: TPS in pleural fluid (cutoff 20,000 U/L): 0.21 and 0.98; TPS in serum (cutoff 300 U/L); 0.31 and 0.96; pleural fluid TPS/serum TPS ratio (cutoff 1200): 0.07 and 0.99. All these values enhanced the sensitivity of cytologic analysis of pleural fluid. However, we conclude that TPS assay in pleural fluid and serum, and the pleural fluid TPS/serum TPS ratio have limited diagnostic value in patients with pleural effusion.

[Pancoast's syndrome secondary to non-Hodgkin's lymphoma]. / Síndrome de Pancoast secundario a linfoma no hodgkiniano.

Pancoast's syndrome is usually found coincident with bronchogenic carcinoma. We describe a case of non-Hodgkin's lymphoma presenting with Pancoast's syndrome in a patient with a history of thoracoplasty.

[Recurrent amiodarone lung toxicity after withdrawal of the drug and treatment with corticoids]. / Toxicidad pulmonar recurrente por amiodarona tras retirada del fármaco y tratamiento con corticoides.

We present a case of recidivation in amiodarone-induced pulmonary toxicity 4 months after suspension of the drug, while treatment with corticoids was underway. Possible causes suggested are the persistence of high blood levels of amiodarone and the rapid decrease of corticoid dose.

[Analysis of proliferating cell nuclear antigen (PCNA) expression in 24 cases of primary non-small cell pulmonary carcinomas and correlation with survival]. / Análisis de la expresión del antígeno nuclear de proliferación celular (PCNA) en 24 carcinomas primarios de pulmón de células no pequeñas y correlación con la supervivencia.

Proliferating cell nuclear antigen (PCNA) is a 36 kD nuclear protein involved in DNA replication that is believed to provide an indication of proliferation in some neoplasms. This study analyzes PCNA expression in 24 cases of primary non-small cell lung cancer using monoclonal PC-10 antibodies in paraffin embedded material. We found significant inter- and intra-tumoral variations in PCNA expression, and no statistically significant relation between the amount of PCNA expression and the size and location of tumors, index of mitosis, histological tumor type or patient age. We found a statistically significant relation (r = 0.47; p < 0.05) between survival and amount of PCNA expression in a sample of 19 cases, but no statistically significant differences in survival related to whether PCNA expression was slight (0-25), moderate (25%-50%) or high (> 50%), and no prognostic value for degree of PCNA expression.

[Diseases diagnosed at a pneumology unit integrated with its health area. Comparison with historical controls]. / Patología diagnosticada en una unidad neumológica integrada con su área de salud. Comparación con controles históricos.

An understanding of changes in pulmonology disease patterns observed at a general hospital before and after implantation of a population-based model of health care not only provides useful insight into the diseases treated but also aids adjustment of health care service organization. The aim of this study was to compare data collected after 1992 (when the new system was established) with records kept by the same pulmonology group in earlier years (1974-1986). Data after 1992 described patients attended in Health District 11 by the newly organized pneumologists. For the two periods the most common pneumological diagnoses were chronic air flow obstruction and chronic hypersecretory bronchitis. The most common non pneumological diagnoses were systemic arterial hypertension, obesity, diabetes, liver disease and hiatus hernia/gastroesophageal reflux. The prospective study covered a larger population and was closer to primary care, including as it did patients at clinics unattached to hospitals. In the earlier hospital-based experience the most common diagnoses were acute respiratory infection, chronic air flow obstruction and asthma, apart from those patients referred in whom no respiratory disease was found. With the organizational integration of hospital and health district pulmonology service, contact between patients and specialists has increased. Record systems have been established for a well-defined population to permit better forecasting at less cost and facilitate contact with primary care givers and epidemiological studies.

[High prevalence of long-term domiciliary oxygen therapy with a low percentage of inappropriate prescription in the Madrid health care area. Evaluation of the correct use]. / Alta prevalencia de oxigenoterapia crónica domiciliaria, con bajo porcentaje de indicación incorrecta en un área de salud de Madrid. Valoración del uso correcto.

UNLABELLED: The efficacy of long-term domiciliary oxygen therapy (DOT) has been confirmed in patients who comply with guidelines; however, the prevalence in different populations varies greatly although no satisfactory explanation has been found for this. OBJECTIVES: To assess the prevalence of inappropriate use of DOT in the health care area of the Community of Madrid, where demographic and health care features are well-defined. MATERIAL AND METHODS: Descriptive, transversal population study enrolling all patients with DOT in our health care area over a period of one year (May 1995 to Mayo 1995). Inappropriate use was defined as characterized by at least one of the following conditions: inappropriate prescription, poor compliance or continued smoking. RESULTS: The total number of patients was 860, the prevalence of DOT use being 178.3 per 100,000 inhabitants for the period. Ninety-three refused to participate. Nearly half the patients ha been using oxygen therapy for over two years. Seventy percent were followed by pneumologists. Seventy-four percent were men, with a mean age of 70 +/- 9 yr. Criteria for prescription were not followed in 9.7% of the cases. Chronic obstructive pulmonary disease was the reason for prescribing DOT in 59.7%. Use was appropriate in 719 cases. Use was inappropriate in 337 (46.9%), related to poor compliance in 60.5%, current smoking in 11%, and inappropriate prescription in 5.6% and for more than one criterion in 22.8%. CONCLUSIONS: The prevalence of DOT use in our health care area is very high. The percentage of inappropriate use is high, although similar to that of other populations, and highly related to poor compliance. The percentage of inappropriate prescription is low. Possible reasons for the high prevalence are discussed.

[Prospective study of 1,000 consecutive patients with pleural effusion. Etiology of the effusion and characteristics of the patients]. / Estudio prospectivo de 1.000 pacientes consecutivos con derrame pleural. Etiología del derrame y características de los pacientes.

OBJECTIVE: To describe the characteristics of patients with pleural effusion (PE) and the causes of PE in a prospective, consecutive series of patients. SETTING: A tertiary care hospital associated with the Universidad Complutense de Madrid (Spain). PATIENTS: One thousand consecutive patients with PE for whom clinical signs indicated the need for diagnostic thoracocentesis were studied prospectively in our service from December 1991 to July 2000. RESULTS: The most common cause of PE was neoplasm (n = 364 patients). The most common place of origin of the tumor was the lung (n = 125), followed by the pleura (mesothelioma, n = 48). The most common histologic type was adenocarcinoma (n = 128). Tuberculosis was the second most common cause of PE (n = 155). PE was transudate in 118 patients, mainly secondary to heart failure. Among the 42 patients who were positive for human immunodeficiency virus (HIV), the most common cause of PE was tuberculosis. Tuberculosis was also the most likely cause of PE in patients under 40 years of age. CONCLUSIONS: The most common causes of PE were neoplasm and tuberculosis. Tuberculosis was the most common cause in patients under 40 years of age and in those infected by HIV.

[The Will-Rogers phenomenon. Stage migration in bronchogenic carcinoma after applying certainty criteria]. / El fenómeno Will-Rogers. Migración de estadios en carcinoma broncogénico, tras aplicar criterios de certeza clasificatoria.

OBJECTIVE: To quantify changes in tumor-node-metastasis (TNM) staging (numerical migration) and survival (prognostic migration) that arise when certainty criteria are applied to a patient population with non-small cell lung cancer (NSCLC) treated surgically. METHODS: The population consisted of 1,844 patients with NSCLC who underwent surgery between 1993 and 1996 at hospitals participating in the Bronchogenic Carcinoma Co-operative Group of the Spanish Society of Pneumology and Thoracic Surgery (GCCB-S). For every patient, surgical-pathological TNM staging (p) was based on two classifications: initial staging by each participating GCCB-S center (pTNM-i) and a second classification bearing greater classificatory certainty (pTNM-cc) resulting from the application of stricter criteria. Numerical migration was said to have occurred in cases where the two classifications did not coincide, and the possible prognostic migration under the new staging was then assessed. RESULTS: The results revealed great numerical migration in the pN0 classification (from 1,091 cases to 665). The changes did not result in prognostic migration either for the group as a whole or for pT1-2N0M0 cases. However, for pT3N0M0 cases, median survival increased by 13 months. The difference in three-year survival (S3) for pT3N0M0-i without certainty confirmation [S3 = 0.30 (95%CI 0.18-0.42), n=59] and pT3N0M0-cc [S3=0.54 (95%CI = 0.44-0.64), n = 92] was significant (log-rank, p = 0.035). Such behavior was not observed for pT1-2N0M0. CONCLUSIONS: The numerical migration observed as a result of applying surgical-pathological classificatory certainty criteria is relevant but the prognostic repercussion is scarce, except in cases classified as pT3N0M0, in which a significant positive prognostic migration is observed (the "Will Rogers phenomenon").

[Lymphoid interstitial pneumonia resolved through antiretroviral therapy in an adult infected by human immunodeficiency virus]. / Neumonía intersticial linfoidea en un paciente adulto con infección por el VIH, resuelta con tratamiento antirretroviral.

Lymphoid interstitial pneumonia (LIP) is a rare entity characterized by the infiltration of interstitial tissues and alveolar spaces by lymphocytes, plasma cells, and other lymphoreticular structures. The etiology of LIP is unknown, although associations with autoimmune and infectious factors have been described. The incidence of LIP has risen in recent years, mainly in children with acquired immunodeficiency syndrome (AIDS), while remaining less common in the adult population. No agreement has been reached regarding the diagnostic tests necessary for a firm diagnosis although suspicion is usually based on clinical and radiographic findings, with confirmation provided by examination of histological samples. The most common treatment is corticosteroids, either alone or in combination with other immunosuppressant agents although no evidence from controlled trials is available and cases have been reported in which LIP resolved in AIDS patients with antiretroviral therapy alone. We report the case of a human immunodeficiency virus-infected adult who was diagnosed with LIP by open lung biopsy and who responded to antiretroviral drugs with no need for associated corticosteroid therapy.

[Pleural mesothelioma: experience with 62 cases in 9 years]. / Mesotelioma pleural: experiencia durante 9 años y descripción de 62 casos.

OBJECTIVES: To describe the diagnostic approach, clinical and radiological characteristics, and survival of patients with pleural mesothelioma treated in our hospital over a 9-year period. PATIENTS AND METHOD: All patients with a diagnosis of pleural mesothelioma diagnosed in our hospital from January 1992 through December 2000 were studied. RESULTS: Sixty-two patients (49 men) with a mean age of 65 years (range, 45-85) were diagnosed. Probable or known contact with asbestos was established for 41 patients (66%). Ninety-four percent of the patients had chest pain or dyspnea at the onset of clinical assessment. The tumor was situated in the right hemithorax in 33 patients; 59 patients had pleural effusion, and 3 only had pleural thickening. The pleural fluid was bloody in 19% of patients, glucose levels were less than 60 mg/dL in 44%, and the pH of pleural fluid was less than 7.20 in 19%. The diagnosis was established by pleural biopsy for 52%, and by thoracoscopy or thoracotomy for 44%. The median survival was 11 months (95% confidence interval, 8-15); the probability of survival was 0.22 after 2 years, and 0.09 after 5. For the subgroup of patients with epithelial tumors the probability of survival was 0.31 after 2 years and 0.16 after 5 years. In the univariate analysis the predictors of survival were general clinical status (Karnofsky scale), platelet count, serum albumin level, pleural pH, glucose and lactate dehydrogenase levels, and histological type. CONCLUSIONS: The clinical, radiological, and biochemical characteristics of the pleural fluid from patients with pleural mesothelioma and their survival rate were described.

[Delays in the diagnosis and surgical treatment of bronchogenic carcinoma. Cooperative Group on Bronchogenic Carcinoma of SEPAR (GCCB-S)]. / Demoras en el diagnóstico y en el tratamiento quirúrgico del carcinoma broncogénico. Grupo Cooperativo de Carcinoma Broncogénico de SEPAR (GCCB-S).

The aim of this study was to determine the delay between clinical suspicion and diagnosis of bronchogenic carcinoma, and between diagnosis and performance of therapeutic thoracotomy. The study population included 598 patients undergoing surgery between October 1995 and September 1996 registered in the Bronchogenic Carcinoma Cooperation Group of SEPAR (BCCG-S), and 49 patients from our hospital undergoing surgery during the same period. The mean delay between diagnosis and thoracotomy was 45.15 days (SD 34.7 days) for BCCG-S patients and 53.5 days (SD 22 days) for our hospital patients. In the second group, mean time elapsing between diagnosis suspicion and performance of bronchoscopy was known to be 9.5 days (SD 14.7 days), with the lowest periods recorded for inpatients (3.1 +/- 1.7 days) and for patients who did not require chest x ray guided bronchoscopy (5 +/- 5.8 days). These data are similar to those published for hospitals in other countries. They must be considered long delays and should be shortened.

[Ambulatory diagnosis of patients requiring a pleural biopsy. Study of 100 consecutive cases]. / Diagnóstico ambulatorio de los pacientes que precisan biopsia pleural. Estudio de 100 casos consecutivos.

Our aim was to describe our experience with outpatients requiring pleural biopsy. The first 100 patients with pleural exudate from whom at least one pleural biopsy specimen was taken on an outpatient basis at our hospital since January 1993. Clinical and radiological signs were recorded for all patients. We also analyzed complications, frequency of use of other diagnostic test and time required for diagnosis. The mean age of the 100 patients (64 men) was 56 years. Outpatient study of these patients was not prevented by the advanced age on the sample (with 35 patients older than 79), the size of the pleural effusions (23 of which were large), or the diagnosis of diseases with poor prognoses (with 43 effusions diagnosed as neoplastic). Complications encountered in taking the biopsy specimens were similar to those reported for other series. The mean time until diagnosis was 7.4 days. Biopsies can often be obtained from patients with pleural effusion on an outpatient basis, even when clinical symptoms vary widely, without increasing the number of complications and within a reasonable period of time.

[Mechanical ventilation in a respiratory ward. Evolution from 1994 to 2000]. / Ventilación mecánica en hospitalización neumológica. Evolución en el período 1994-2000.

OBJECTIVE: To investigate the absolute and relative frequency of mechanical ventilation in the management of patients on a respiratory medicine ward between 1994 and 2000. To describe reasons for admission, mean hospital stay and outcomes. SETTING: A tertiary-care university hospital. METHODS: Observational, descriptive study of a case series. RESULTS: During the study period, 257 admissions involved mechanical ventilation of 132 patients. During that time, there was a progressive increase in the total number of ventilated patients as well as in the relative frequency, such that ventilated patients eventually accounted for 6.1% of all admissions for respiratory care in 2000. Nearly 80% of admissions were related to the service's home mechanical ventilation program, either to initiate and adapt ventilation for new patients or to treat exacerbations or diagnose and treat other medical or surgical problems in already-ventilated patients. Patients transferred from the intensive care unit (ICU) because of weaning difficulties (median ventilation, 31 days) had the highest mean stay. Nine of the 132 patients had to be transferred to the ICU and 18 died while hospitalized (7% of admissions and 13.6% of patients). The patients who died were those who were more acutely and severely ill (acute exacerbation in home-ventilated patients, patients with acute respiratory failure treated initially with non-invasive ventilation and patients transferred from the ICU due to weaning difficulties). CONCLUSIONS: Admissions requiring mechanical ventilation have increased and most are related to the home mechanical ventilation program. The mean stay and the mortality rate were related to the reason for admission.

[Mediastinoscopy and thoracotomy in bronchogenic carcinoma (V) (author's transl)]. / Mediastinoscopia y toracotomía en el carcinoma broncogénico (V).

The opinion of the Bronchogenic Carcinoma Cooperative Group is that mediastinoscopy is at present an irreplaceable method for the determination of the resection limits in patients with bronchogenic carcinoma. Mediastinoscopy cannot be replaced by roentgenologic or isotopic studies of the mediastinum, since the invasion of the ganglionar capsule or of the mediastinal fat can only be determined by histopathologic examination. Following a classification based on macro- and microscopic morphological criteria, surgery has achieved a 64 percent of thoracotomies with "presumably curative" resections. Patients with epidermoid carcinomas were the main candidates to surgery. Lastly the role of the so-called bronchogenic carcinoma "markers" or substances that can indirectly indicate the course of the disease is discussed. The value of humoral and cell-mediated immunologic studies for introducing other therapeutic variants after curative surgery is pointed out. The definite conclusions regarding the clinical and surgical therapeutic aspects of the Bronchogenic Carcinoma Cooperative Group are detailed.

[Metastasis and special explorations in the study of the spread of bronchogenic carcinoma (author's transl)]. / Metástasis y exploraciones especiales en el estudio de extensión del carcinoma broncogénico (CB) (IV).

The results of a prospective study on bronchogenic carcinoma are analyzed. The most frequent metastatic localization being the bone (24 percent), followed by the brain (21 percent) and the pleura (20 percent). The type which most frequently metastatized to the brain is the epidermoid carcinoma. The as yet unresolved difficulties in the diagnosis of metastasis to the adrenal glands as well as to the liver are pointed out, conducting a comparative study with data from necropsies in order to corroborate such defficiencies. We systematically practiced radioisotope bone scanning, eliminating the bone radiography and carrying it out only in areas with pathologic isotopic uptake. Biopsy of the iliac crest should be performed in all cases of undifferentiated small-cell type, although this is not necessary with the other histopathologic types. Finally, the criteria for the identification of liver metastasis, in the absence of more proper pilot studies, should be the same as those established in 1974; physical examination and determination of hepatic enzymes; if the results are abnormal, a liver scanning should be indicated, and if it is normal, it will be necessary to perform a liver biopsy by peritoneoscopy.

[Classification of the disease and pathologic type of bronchogenic carcinoma (III) (author's transl)]. / Clasificación de la enfermedad y estirpe en el carcinoma broncogénico (III).

The classification of bronchogenic carcinoma according to its extension and evolutive stages is useful in order to be able to organize epidemiologic and therapeutic studies, as well for exchanging information. At the present time, however, it is very difficult to establish a common classification for all of the groups working on bronchogenic carcinoma. The Bronchogenic Carcinoma Cooperative Group classified the cases following parameters such as operability, resectability, localized or generalized disease, and do not completely agree with the value of the TNM classifications. In the same way in respect to the different pathologic type of bronchogenic carcinoma, the traditional decision not to operate that follows the presentation of the undifferentiated types comes under discussion. This is due to the wide diagnostic variability in the evaluation of the different pathologic types according to the experience of various pneumopathologists published in the literature.

[Epidemiologic data on bronchogenic carcinoma (author's transl)]. / Datos epidemiológicos en el carcinoma broncogenico (II).

The Bronchogenic Carcinoma Co-operative Group analyzed the epidemiologic data of 240 cases of bronchogenic carcinoma in a prospective study. When risk factors (exposure to potencial pathogenic substances) were studied, a relationship was noted between the incidence at an early age and the presence of nondifferentiated small cell carcinoma. The number of years of exposure to tobacco had a direct effect on the curative value of the thoracotomy and the survival rate. Forty years of smoking appeared to be borderline for a poor prognosis. Localization of the tumor by bronchoscopy showed a frequency in the left main bronchus (18 percent) more than twice than in the right (8 percent). In 25 percent of the cases the tumor was more peripheral than the subsegmental situation according to the bronchofiberoptic examination. Evaluation of clinical data only showed a lack of correlation between the different symptoms and the various means of evaluation and the prognosis of the disease. For example, a patient with hemoptysis has a statistically higher probability of having an epidermoid tumor and a greater possibility of a successful curative thoracotomy (23 percent as opposed to 17 percent for the rest). The group of incidental cases (9 percent of the total) was analyzed. The degree of resectability was higher as compared with the rest (62 percent against 34 percent) as well as the absence of nondifferentiated small cell type carcinomas.

[Clinical protocol for study and treatment of bronchogenic carcinoma (author's transl)]. / Protocolo para el estudio y el tratamiento del carcinoma broncogénico (I).

Bronchogenic carcinoma constitutes one of the primary causes of death in our population. The only means of controlling the disease in a significant way is by surgery, which about a third of the patients undergo. This fact, together with the age at which the pathology appears, its frequent association with chronic pulmonary disease, and the rapidity of its metastatic spread, make it necessary to establish a protocol for the study, diagnosis, and treatment of bronchogenic carcinoma. These norms should be applicable in prospective epidemiologic studies and for evaluating methods of diagnosis and treatment. The Interhospital Bronchogenic Carcinoma Co-operative Group has established a protocol, which includes the criteria of operability, resectability, preoperative examinations, indications of mediastinoscopy, etc. The authors mention the histopathologic classification, the TNM criteria, and the characteristics of localized or advanced disease.