[Role of imaging techniques in the TNM classification of non-small cell bronchogenic carcinoma]. / Papel de las técnicas de imagen en la nueva clasificación TNM del carcinoma broncogénico no microcítico.

The Seventh Edition of the TNM Classification for non-small cell bronchogenic carcinomas include a series of changes in the T and M descriptor, in particular a re-classification of malignant pleural and pericardial effusions and of separated tumour nodes, new tumour size cut-off values and sub-divisions of the T1-T2 and M1 categories. We review these corrections that led to the changes in the staging system that affects stages II-III. Furthermore, we describe and illustrate the role of the different imaging techniques in tumour staging (CT, PET, PET-CT and MRI), highlighting their respective indications, advantages and disadvantages, as well their complementary function.

[Comparative survival study between the old and new bronchogenic carcinoma classification]. / Estudio comparativo de supervivencias entre la actual y la antigua clasificación del carcinoma broncogénico.

INTRODUCTION: A new classification of bronchogenic carcinoma has been made by the International Association for the Study of Lung Cancer (IASLC) and published by Frank C. Detterbeck et al in the journal Chest (2009). The Thoracic Surgery Department of the Gerona (Spain) University Hospital has re-staged a series of patients with bronchogenic carcinoma who had attempted curative surgery, with the aim of comparing the survival (survival for T, survival for M, and survival by disease staging) between the old and new classification, and also to determine whether these changes in survival are statistically significant. Another one of the objectives of the study is to see whether there is agreement between the current survival of our surgical series and that published by the IASLC. PATIENTS AND METHODS: Data on 855 patients who had attempted bronchogenic carcinoma curative surgery were entered into a data base. They were radiologically, clinically and histologically staged according to the new and old staging. Survival was calculated according to the T, M, N, and histology stages. A statistical analysis was performed using the SPSS program and the changes in survival between both classifications were analysed. RESULTS: No statistically significant changes were observed in survival (P=.58) with the new classification in stage IIA, but there were statistically significant changes in survival (P=.0001) in stage IIIB. DISCUSSION: The study confirms that the current TNM classification is useful, since it shows changes in survival in 2 histological stages (one of them statistically significant). The survival data of our series now fits better with those provided by the IASLC.

Use of the proposals of the international association for the study of lung cancer in the forthcoming edition of lung cancer staging system to predict long-term prognosis of operated patients.

PURPOSE: To evaluate the utility of the proposals of the International Association for the Study of Lung Cancer (IASLC) in the forthcoming 7th edition of lung cancer staging system to classify patients submitted to radical surgical resection of non-small cell lung cancer and to compare their value in predicting long-term prognosis with the existing 6th edition of the American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) TNM classification. METHODS: Nine hundred twenty-one patients received an anatomic resection and hilar-mediastinal dissection for primary non-small cell lung cancer during the period 1990 to 2005. Histopathologic staging following the actual AJCC/UICC TNM classification were as follows: 207 T1, 562 T2, 148 T3, and 4 T4; 570 N0, 149 N1, 198 N2, and 4 N3; 163 stage IA, 346 IB, 23 IIA, 157 IIB, 224 IIIA, and 8 IIIB. Stages reclassified using the proposals of IASLC for the new staging system were as follows: 101 T1a, 106 T1b, 400 T2a, 103 T2b, 210 T3, and 1 T4; 163 stage IA, 262 IB, 157 IIA, 106 IIB, 230 IIIA, and 4 IIIB. RESULTS: Follow-up was obtained for 836 patients. Mean follow-up was 46.5 +/- 48.9 months. N-status (unchanged between the 2 classifications) was confirmed to be a significant prognostic factor. Significant differences in 10-year disease-related survival were demonstrated between stages IIB and IIIA only (35% vs 14%) of the AJCC/UICC TNM classification and between stages IB and IIA (60% vs 46%) and stages IIB and IIIA (39% vs 15%) of the IASLC proposals for a new classification. DISCUSSION: The proposals of IASLC in the forthcoming 7th edition of the lung cancer staging system are demonstrated to be better able to separate prognostically distinct groups of patients operated for non-small cell lung cancer than the accepted existing 6th AJCC/UICC TNM classification.

The IASLC Lung Cancer Staging Project: proposals for the inclusion of broncho-pulmonary carcinoid tumors in the forthcoming (seventh) edition of the TNM Classification for Lung Cancer.

OBJECTIVE: In the 2003 Supplement for tumor, node, metastasis (TNM) Staging classification it states that TNM staging "applies to all types of carcinoma including small cell carcinoma; however, it does not apply to carcinoids." Despite this caveat, most publications on typical and atypical carcinoids use the TNM staging system for nonsmall cell carcinoma and are able to demonstrate prognostic significance for the different stages. For this reason, as the next TNM Staging proposal is being considered, we sought to investigate the carcinoid cases submitted to the International Association for the Study of Lung Cancer (IASLC) database, as well as the National Cancer Institute Surveillance Epidemiology and End Results (SEER). MATERIALS AND METHODS: In the data collected for the IASLC Staging Project database over the time period 1990 to 2000, there were 513 broncho-pulmonary carcinoids. A total of 1619 broncho-pulmonary carcinoid cases diagnosed over the period 1990-2002 were analyzed from the SEER database, including 1437 surgical cases. Pathologic slides were not available for histologic review. RESULTS: Most of tumors in both the IASLC and SEER databases were Stage I (82% and 78%, respectively), as defined by the IASLC proposals for the 7th edition of TNM staging system. T status was a statistically significant predictor of survival for both the SEER data (p < 0.0001) and the IASLC database (p = 0.0156), though for different reasons. N status showed significant survival correlations in both data sets (p < 0.0001). The effect of M status was significant (p < 0.0001) within the SEER data and not studied in the IASLC cases, which were almost exclusively M0. We found that all three T, N, and M categories as defined for non-small cell lung cancer are generally useful for staging of pulmonary carcinoid tumors. Significant differences in survival for overall stages I versus II versus III/IV were identified in both data sets. Patients with multiple same lobe nodules had a 100% 5-year survival, which may be a reason to reevaluate their status in the IIB category in future analyses. CONCLUSIONS: In summary, the IASLC proposals for the 7th edition of TNM are helpful in predicting prognosis for broncho-pulmonary carcinoid tumors. It is the recommendation of the IASLC Staging project that TNM be applied to broncho-pulmonary carcinoid tumors. A prospective collection of data through an International Registry of Pulmonary Neuroendocrine Tumors planned by the IASLC will allow for further detailed analysis of staging data for broncho-pulmonary carcinoids.

Pulmonary preinvasive neoplasia.

Advances in molecular biology have increased our knowledge of the biology of preneoplastic lesions in the human lung. The recently published WHO lung tumour classification defines three separate lesions that are regarded as preinvasive neoplasia. These are (1) squamous dysplasia and carcinoma in situ (SD/CIS), (2) atypical adenomatous hyperplasia (AAH), and (3) diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIP-NECH). SD/CIS is graded in four stages (mild, moderate, severe, and CIS), based upon the distribution of atypical cells and mitotic figures. Most airways showing SD/CIS demonstrate a range of grades; many epithelia are hard to assess and the reproducibility of this complex system remains to be established. Detailed criteria are, however, welcome and provide an objective framework on which to compare various molecular changes. Alterations in gene expression and chromosome structure known to be associated with malignant transformation can be demonstrated in CIS, less so in dysplasias, but also in morphologically normal epithelium. The changes might be sequential, and their frequency and number increase with atypia. Less is known of the "risk of progression" of SD/CIS to invasive "central" bronchial carcinoma. It may take between one and 10 years for invasion to occur, yet the lesion(s) may be reversible if carcinogen exposure ceases. AAH may be an important precursor lesion for peripheral "parenchymal" adenocarcinoma of the lung: the "adenoma" in an adenoma-carcinoma sequence. There is good morphological evidence that AAH may progress from low to high grade to bronchioloalveolar carcinoma (BAC; a non-invasive lesion by definition). Invasion then develops within BAC and peripheral lung adenocarcinoma evolves. The molecular events associated with this progression are not well understood and studies are hampered by a lack of clear criteria to distinguish high grade AAH from BAC. Nonetheless, as with SD/CIS, the patterns of expression of tumour associated genes are consistent with neoplastic progression. We have little idea of the incidence of AAH in the normal or "smoking" populations. It is found more frequently in cancer bearing lungs, especially in those with adenocarcinoma, and is more common in women. No data are available on the risk of progression of AAH. DIPNECH is an exceptionally rare lesion associated with the development of multiple carcinoid tumours. Almost nothing is known of its biology. Knowledge of these lesions will be crucial in the design and understanding of lung cancer screening programmes, where it is likely that the morphological and, more importantly perhaps, the molecular characteristics of these lesions will provide useful targets for detection and possibly even treatment.

[Value and limits of surgery in stage IIIB non-small-cell bronchial cancers]. / Place et limites de la chirurgie des cancers bronchiques non à petites cellules au stade IIIB.

According to the TNM staging system for lung cancers, stage III is divided into IIIA and IIIB. This division was based upon the principle that patients with IIIA disease could theoretically benefit from complete resection, contrasting with IIIB patients for whom surgery is not feasible. The poor prognosis of stage IIIB is largely due to its classical inoperability. From the surgical point of view, stage IIIB can be subdivided into four subgroups: 1) N3 where resection is possible in selected patients through median sternotomy; 2) T4 where extended surgery can be considered in selected patients; 3) N3 + T4; 4) malignant pleural or pericardial effusion contraindicating any radical surgery. Criteria for resectability could be defined to include some IIIB patients in multimodality protocols in which surgery would become possible after induction therapy: definitive inoperability excludes any possibility of surgery, even in cases in which radiotherapy alone or combined with chemotherapy leads to complete remission; immediate inoperability allows patients to be included in protocols evaluating induction treatments designed to render tumours resectable.

Tumour markers in the diagnosis of bronchial carcinoma: new options using fuzzy logic-based tumour marker profiles.

The diagnosis of lung cancer and early knowledge of its histological type are very important; however, this is still a difficult subject for the physician. The aim of this study was to improve the diagnostic efficiency of tumour markers in the diagnosis of bronchial carcinoma by mathematical evaluation of a tumour marker profile employing fuzzy logic modeling. A panel of five tumour markers, including CYFRA 21-1, CEA, NSE, and five additional parameters was determined in 281 patients with confirmed primary diagnosis of bronchial carcinoma of different histology and stage. A further 131 persons, who had acute and chronic benign lung diseases, served as a control group. A classificator was developed using a fuzzy-logic rule-based system. The diagnostic value of the combined tumour markers was significantly better than that of the individual markers and of a combination of CYFRA 21-1, CEA, and NSE. The discrimination of malignant vs benign diseases was realized with a sensitivity of 87.5% and specificity of 85.5%. The rate of correct classification of small-cell vs non-small-cell lung carcinoma was 90.6% and 91.1%, respectively; for squamous cell carcinoma vs adenocarcinoma it was 76.8% and 78.8%, respectively. Our detailed analysis has shown that the fuzzy logic system improves diagnostic accuracy up to a rate of 20%, especially in early stages and in patients with all marker levels in the grey area. Our concept proved to be more powerful than measurement of single markers or the combination of CEA, CYFRA 21-1, and NSE. Its use may help in distinguishing between malignant and benign disease and make it possible to define different subgroups of patients earlier in the course of their disease.

Clinical utility of tissue polypeptide antigen determination in lung cancer management.

In view of the fact that pulmonary malignancies still represent an important cause of tumor death and that the high rate of unsuccessful treatment may be partly due to the late clinical presentation, efforts should be spent not only to develop new and effective treatments but also to improve early diagnosis and to identify prognostic factors and parameters useful for the monitoring of the treatment. Tumor markers, if used properly, can provide a useful support for the management of patients suffering from various malignancies, including lung cancer patients. The clinical significance of one of the most widely used tumor markers, Tissue Polypeptide Antigen (TPA), has been reviewed and showed this marker to be useful to the clinician for the management of patients with pulmonary malignancy, as a complementary tool for diagnosing and staging the tumor as well as for monitoring treatment response or relapse occurrence.

El cáncer broncogénico en el Hospital General de México: estudio de dos décadas / Broncogenic cancer in the General Hospital of Mexico: a estudy of two decades

De 1 855 tumores torácicos detectados entre 1971 y 1990, 923 (50 por ciento) correspondieron a cáncer broncogénetico (CaBr). La relación entre el sexo masculino y el femenino fue, en promedio, de 1.95:1. Los tipo histológico más frecuentes encontrados en hombres fueron: epidermoide 34.2 por ciento, adenocarcinoma 28.4 por ciento y de células pequeñas 13.2 por ciento; en mujeres: adenocarcinoma 38.9 por ciento, epidermoide 28.9 por ciento y mixto 7.7 por ciento, con una diferencia significativa entre los dos sexos para este tipo de tumores. considerando la relación entre fumadores y no fumadores, en el sexo masculino predominaron los tipos epidermoide, adenocarcinoma, indiferenciados de células pequeñas, indiferenciados de células grandes y tumores mixtos en los fumadores (p < 0.001); en el sexo femenino estas mismas extirpes predominaron en las no fumadoras. La comparación con el grupo sin CaBr mostró que el epidermoide, el adenocarcinoma y el de células pequeñas ocurren con más frecuencias en fumadores. El 92.2 por ciento de los casos se encontró en estadio III (Tumor Node Metastasys) y la oportunidad del tratamiento radical fue nula; la radioterapia y la quimioterapia tuvieron posibilidades muy limitadas; sólo 94 casos fueron quirúrgicos, con resección total en 36. Se requiere de los programas antitabáquicos se intensifiquen por la elevada frecuencia de CaBr en fumadores

Among 1855 thoracic neoplasms seen from 1971 to 1990, there were 923 with bronchogenic carcinoma (CaBr), 50%. The relation male: female was 1.95:1. Sixty three period thirty one percent were male. The histologic type were epidermoid 32.2%, adenocarcinoma 28.4% and small cells 13.2% in men; in women adenocarcinoma 38.9%, epidermoid 28.9% and mixed 7.7% with a significative difference for both sexes for these neoplasms. Other types were less frequent. There is significative difference between smokers and non smokers of both sexes p < 0.001. Epidermoid, adenocarcinoma, small cells, large cells and mixed were the most frequent in male smokers, in women these varieties were more frequent in nonsmokers. Comparison with the reference group with no CaBr suggests that epidermoid, adenocarcinoma and small cells carcinomas have a great possibility to be found in male smokers. Ninety two period two percent of cases were stage III (Tumor Node Metastasys) with no chance for radical treatment. Only 94 were subject to surgery with 36 total resections. CaBr is an important problem in the General Hospital of Mexico. Antismoking programmes must be stressed in relation to the frequency of CaBr in smokers.

[Cytochemical studies for determining the histogenesis of anaplastic and poorly differentiated lung tumors]. / Zytochemische Untersuchungen zur Bestimmung der Histogenese bei anaplastischen bzw. schlecht differenzierten Lungentumoren.

Proper histogenetic classification of pulmonary tumours is most important in choosing the best possible treatment. Since this is very difficult especially in case of anaplastic or poorly differentiated tumours, additional pointers on histogenesis, supplied by complementary histochemical examinations, are very helpful. 105 bronchial carcinomas were examined cytochemically by means of air-dried smear preparations (imprint, brush an puncture smears). Cytochemical examinations were performed in respect of alkaline phosphatase, acid phosphatase, PAS reaction and unspecific esterase. It was found that the dedifferentiated squamous cell carcinomas were alkaline phosphatase-negative and weakly positive to acid phosphatase and unspecific esterase, whereas dedifferentiated adenocarcinomas were strongly positive to acid phosphatase and unspecific esterase. The PAS reaction was always slightly to moderately positive. Small-cell bronchial carcinomas were negative in all cytochemical examinations.