Management of bronchial carcinoids: international practice survey among the European Society of Thoracic Surgeons.

OBJECTIVE: This study aims to assess the international practice of management of bronchial carcinoids. MATERIALS & METHODS: A survey designed by the Neuroendocrine Tumors of the Lung Working Group, was conducted among the members of the European Society of Thoracic Surgeons. RESULTS: A total of 172 centers worldwide replied to the questionnaire. General agreement was observed concerning the use of anatomic resections and parenchyma-sparing surgery, the importance of lymphadenectomy, the adjuvant regimens in N(+) atypical carcinoids and the role of surgery for local recurrences. Controversies emerged in the use of nuclear medicine imaging and measurement of serum markers and on the timing of follow-up. CONCLUSION: This survey provides the largest international overview of the current practice in the management of bronchial carcinoids and identifies discrepancies that could be the focus of future investigations.

Endovascular treatment of posttraumatic pseudoaneurysm of the internal mammary artery.

Pseudoaneurysm of the internal mammary artery is an unusual complication of wounds to the chest. We report a case of a 41-year-old man who sustained a stab chest wound and posttraumatic pseudoaneurysm of the internal mammary artery, resulting in hemomediastinum and hemothorax. The patient was successfully treated using emergency endovascular coil embolization. Because this injury is extremely rare, the literature is reviewed, and several principles are suggested to improve the management.

Prognostic significance of histopathological factors in survival and recurrence of atypical carcinoid tumours.

OBJECTIVES: Atypical carcinoids are neuroendocrine neoplasms of intermediate degree and low frequency. The aim of this study is to analyse their clinical characteristics and the importance of different histopathological factors in their prognosis. METHODS: Multicentre cooperative group EMETNE prospectively reviewed 153 patients operated on between 1998 and 2016 with diagnosis of atypical carcinoids. Clinical variables and histopathological features were assessed. RESULTS: Mean age was 54.36 years, similar for both genders. Concerning pathological study, mean tumour size was 31.7 mm. Rosettes were presented in 17% of the cases and tumoural necrosis in 23.3%. The cell proliferation factor Ki-67 index was 10.7%. The 2- and 5-year overall survival rates were 95.8% and 88.9%, respectively. In the univariate study, statistically significant differences in survival were found for each of the categories of T, N and M factors. Mitotic index and quantification of expression of Ki-67 showed influence in overall survival, although without statistical significance. In the multivariate analysis, factors N, M and mitotic index behaved as independent prognostic factors related to survival. Median disease-free interval in the series was 163.35 months. In cases with loco-regional recurrence, 53% had positive hiliar or mediastinal nodal involvement at the time of the surgery. In the univariate analysis, we observed statistically significant differences in disease-free interval in patients with nodal involvement (P = 0.024) and non-anatomical resections (P = 0.04). Histological characteristics showed no statistically significant differences in disease-free interval. CONCLUSIONS: Lymph node involvement, the development of distant metastasis and mitotic index, more than Ki-67 determination, were shown as independent prognostic factors related to survival of these patients.

Anatomical resections are superior to wedge resections for overall survival in patients with Stage 1 typical carcinoids.

OBJECTIVES: Typical carcinoids (TCs) are rare, slow-growing neoplasms, usually characterized by satisfactory surgical outcomes. Due to the rarity of TCs, international guidelines for the management of particular clinical presentations currently do not exist. In particular, non-anatomical resections (wedges) are sometimes advocated for Stage 1 TCs because of their indolent behaviour. The aim of this paper was to evaluate the most effective type of surgery for Stage 1 TCs, using the European Society of Thoracic Surgeons retrospective database of the Neuroendocrine Tumors of the Lung Working Group. METHODS: We analysed the effect of surgical procedure on the survival of patients with Stage 1 TCs. Overall survival (OS) was calculated from the date of intervention. The cumulative incidence of cause-specific death (tumour- and non-tumour-related) was also estimated. The impact of the surgical procedure (i.e. lobectomy vs segmentectomy vs wedge resection) on survival was investigated using the Cox model with shared frailty (for OS, accounting for the within-centre correlation) and the Fine and Gray model (for cause-specific mortality) using the approach based on the multinomial propensity score. Effects were estimated including in the model the logit-transformed propensity scores of segmentectomy and wedge resection as covariates. RESULTS: A total of 876 patients with Stage 1 TCs (569 women, 65%) were included in this study. The median age was 60 years (interquartile range 47-69). At the last follow-up, 66 patients had died: The 5-year OS rate was 94.3% [95% confidence interval (CI) 92.2-95.9]. The 5-year cumulative incidences of tumour- and non-tumour-related deaths were 2.4% (95% CI 1.4-3.9) and 3.9% (95% CI 2.5-5.6%), respectively. The analysis performed using the multinomial propensity score approach confirmed the significantly worse survival of patients treated with a wedge resection compared to those treated with a lobectomy (hazard ratio 2.01, 95% CI 1.09-3.69; P = 0.024). Similar effects of wedge resection are detectable for cause-specific deaths: tumour-related (hazard ratio 2.28, 95% CI 0.86-6.02; P = 0.096) and non-tumour-related (hazard ratio 1.74, 95% CI 0.89-3.40; P = 0.105). CONCLUSIONS: In a large cohort of patients, we were able to demonstrate the superiority of anatomical surgical resection in Stage 1 TCs in terms of OS. This result should therefore be considered for future clinical guidelines for the management of TCs.

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.

Typical and atypical carcinoid tumours: analysis of the experience of the Spanish Multi-centric Study of Neuroendocrine Tumours of the Lung.

BACKGROUND: This study examines the experience of the Spanish Multi-centric Study of Neuroendocrine Tumours of the Lung with patients treated surgically for typical and atypical carcinoid tumours. METHODS: From 1980 to 2002, 661 patients were treated surgically for 569 typical carcinoid tumours and 92 atypical carcinoid tumours. Three hundred and four cases were studied retrospectively from 1980 to 1997 (261 typical carcinoid and 43 atypical carcinoid tumours); the other 357 new cases (308 typical carcinoid and 49 atypical carcinoid tumours) were collected prospectively from 1998 to 2002. Tumours were classified according the 1999 classification from the WHO and the International Association for the Study of Lung Cancer (IASLC). Several variables were reviewed in all patients. Univariate and multivariate statistical analyses were performed in order to determine whether clinical characteristics were associated with significant differences in survival. RESULTS: In the total of the patients, 5-year survival for different tumours was as follows: typical carcinoid: overall survival 97%; with nodal involvement 100%; atypical carcinoid: overall 78%; with nodal involvement 60%. A significant difference in survival was found between patients in the retrospective and prospective groups with atypical carcinoid and nodal involvement. The comparative analysis of several factors in typical and atypical carcinoid tumours showed a significant difference for mean age, tumour size, nodal involvement and distant metastases. CONCLUSION: Nodal involvement and histological sub-type appear as the most important factors influencing the prognosis. Adequate lung resection and systematic radical mediastinal lymphadenectomy should always be performed. Sleeve resection could be performed in central typical and atypical carcinoid tumours, avoiding pneumonectomy.

[Trends in prognostic factors for neuroendocrine lung tumors]. / Tendencias en los factores pronósticos de los tumores pulmonares neuroendocrinos.

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]. / Estudio de la expresión de interleucina-8 en el tejido pulmonar durante la isquemia-reperfusión.

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.

Surgical treatment of low and intermediate grade lung net.

BACKGROUND: Carcinoids now constitute complex tumours which require a multidisciplinary approach and long-term follow-up. Surgical intervention is nowadays confirmed as the mainstay of treatment. METHODS: From 1980 to 2015, EMETNE-SEPAR collected 1,339 patients treated surgically for bronchial carcinoid (1,154 typical and 185 atypical carcinoids). Standard and conservative procedures were considered with regard to surgical approach. All the patients with carcinoid were pathologically coded following the standards of the 7th edition 2009 TNM lung cancer staging. Statistical analyses were performed in order to determine whether histology, nodal affectation and surgical technique were associated with significant differences in survival, presence of metastases and local recurrence. RESULTS: The influence of the surgical procedure on overall survival, the presence of metastases and local recurrence were demonstrated as no significant in our sample in central tumours (P>0.05). Sublobar resections in peripheral tumours are related to a decrease in survival in typical carcinoids (P=0.008) with nodal involvement and an increased number of recurrences in atypical carcinoids without nodal involvement (P=0.018). CONCLUSIONS: In central typical carcinoid, the use of lung-sparing bronchoplastic techniques could influence local recurrence in some cases. This observation demands the intraoperative pathologic verification of an adequate surgical margin by frozen section. Peripheral typical carcinoids have been surgically treated, occasionally, by sublobar resection. However, in peripheral atypical carcinoid after a limited sublobar resection the observed increase of the probability of local recurrence makes it, in our opinion, not advisable.

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 tumor's prognosis.

[Treatment of lung cancer with chest wall invasion]. / Tratamiento del cáncer de pulmón con invasión de la pared torácica.

The aim of this study was to analyze chest wall invasion, the indication and multidisciplinary nature of treatment, the methods used for parietal reconstruction and the technical problems posed by this procedure in patients with lung cancer and chest wall invasion. Chest wall invasion from adjacent malignancies affects 5% of patients with a bronchogenic carcinoma. Preoperative determination of parietal invasion aids the planning of an appropriate therapeutic approach. Positron emission tomography combined with computed tomography (PET/CT) improves the study of T-factor and metastatic nodal involvement and distant metastases. As a rule, surgical treatment should attempt complete tumoral resection: lobectomy, resection of the parietal pleura and/or of the chest wall--ensuring tumor-free margins--and hilar and mediastinal lymphadenectomy. We also analyzed the distinct prognostic factors for survival, as well as the indication for induction or adjuvant therapy. Chest wall reconstruction involves recreating the most anatomical and physiological conditions possible in the chest cavity and surrounding muscles. The ideal reconstruction would achieve adequate parietal stability and coverage to preserve functionality, with the cosmetic result being an important, but secondary, consideration. Many materials are available for reconstruction and the choice of material should be individualized in each patient. A multidisciplinary team able to plan and perform the resection and subsequent reconstruction, oversee postoperative management and treat complications early is essential.

[Respiratory disease registries in Spain: fundamentals and organization]. / Registros de enfermedades respiratorias en España: fundamentos y organización.

This present paper describes the general characteristics, objectives and organizational aspects of the respiratory disease registries in Spain with the aim to report their activities and increase their diffusion. The document compiles information on the following registries: the Spanish Registry of Patients with Alpha-1 Antitrypsin Deficiency, Spanish Registry of Bronchiectasis, International Registry of Thromboembolic Disease, Spanish Registry of Occupational Diseases, Spanish Registry of Pulmonary Artery Hypertension, Registry of Pleural Mesothelioma, Spanish Registry of Tuberculosis and Spanish Multi-center Study of Neuroendocrine Pulmonary Tumors. Our paper provides information on each of the registries cited. Each registry has compiled specific clinical information providing data in real situations, and completes the results obtained from clinical assays. Said information has been published both in national as well as international publications and has lead to the creation of various guidelines. Therefore, the activities of the professionals involved in the registries have spread the knowledge about the diseases studied, promoting the exchange of information among workgroups.

The number of pulmonary metastases: influence on practice and outcome.

From 1940 to the mid-1960s, pulmonary metastasectomy was performed infrequently and only in selected cases. Although the number of nodules was not considered a contraindication to resection, patients with bilateral disease were believed to have a poor prognosis and, thus, were not considered for operation. Later in 1970, metastasectomy was being undertaken with more liberal indications with respect to numbers being removed. It must be borne in mind that the number of metastases is a reflection of the degree of dissemination of the cancer, although in current practice, the presence of multiple metastases is not a contraindication to metastasectomy in either epithelial cancers or sarcomas.

Thoracic lymphatic involvement in patients having pulmonary metastasectomy: incidence and the effect on prognosis.

Mediastinal and hilar lymph node involvement are rarely reported in the literature concerning pulmonary metastasectomy. The first problem is to determine with accuracy the incidence and location of thoracic lymph node involvement in patients with lung metastases. Determination of the impact on survival of this type of lymphatic spread may contribute to assessing whether metastatic nodal disease identified preoperatively is an absolute contraindication to metastasectomy. Systematic mediastinal lymph node dissection has revealed a statistically significant difference in survival between patients with lymph node involvement and those without lymph node metastases. Videomediastinoscopy to identify involved mediastinal lymph nodes can be safely performed and may have a role in a more accurate staging of the metastatic disease. The authors conclude that attention should be paid to ensuring that we do not operate on patients in whom we will leave behind diseases that we cannot reach. The discovery of mediastinal lymph node involvement may also influence decisions with respect to postresection adjuvant therapy.

Pulmonary metastasectomy in breast cancer.

Metastatic breast cancer has been defined as a systemic disease. Although resection of pulmonary metastases is a common treatment in other primary malignancies, the role of breast cancer metastasectomy is more contentious. Solitary or fewer numbers of pulmonary metastases and longer disease-free interval are, as in other cancers where pulmonary metastasectomy is performed, significant prognostic factors. For proven pulmonary metastases, the level of evidence for a curative approach is low, but some patients might benefit from a metastasectomy followed by an elective and appropriate complementary oncological treatment.

[Detection of lymph node involvement and surgical treatment of pulmonary neoplastic processes. Current state of diagnostic and therapeutic procedures]. / Detección de la afectación ganglionar y tratamiento quirúrgico de los procesos neoplásicos pulmonares. Estado actual de distintos procederes diagnósticos y terapéuticos.

An analysis is made of different publications associated with the surgical staging and treatment of primary and metastasic pulmonary neoplastic processes. A suitable treatment program is essential to determine lymph node involvement in patients with bronchogenic carcinoma. The indication and sequence of the procedure to use (CT-PET, transbronchial puncture, videomediastinoscopic ultrasound guided transbronchial needle aspiration) is evaluated in accordance to the sensitivity, specificity and positive and negative predictive value of the different methods. Another interesting challenge is to define the criteria for indicating a sublobar resection in certain tumours and patients. Different factors, age, lung function, tumour location and type of sublobar resection, are analysed. Levels of evidence and recommendations of the procedure are also considered. Surgical resection is an accepted therapeutic option in the treatment of colorectal cancer lung metastases. Its indication is based on acceptable survival rates and knowledge of the impact of various factors (interval free of disease, number of metastases, presence of liver metastasis, presence of lymph node involvement, or increased pre-operative levels of carcinoembryonic antigen), is analysed in detail.

Quiste broncogénico cervical en adultos. Presentación de un caso y revisión de la literatura / Cervical Bronchogenic Cyst in Adults. Case Report and Literature Review

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Prognostic significance of synaptophysin in stage I of squamous carcinoma and adenocarcinoma of the lung.

BACKGROUND: The prognostic significance of the presence of a neuroendocrine marker (synaptophysin, SY) was analyzed in stage I of squamous carcinoma and adenocarcinoma of the lung. METHODS: A multicentric retrospective study was conducted with immunohistochemical staining in a single center of 318 patients resected for squamous carcinoma or adenocarcinoma in pathologic stage I. RESULTS: In all, 162 cases of squamous carcinoma and 156 cases of adenocarcinoma were identified, which included 105 patients in stage IA (50 patients with squamous carcinoma and 55 patients with adenocarcinoma) and 213 in stage IB (112 with squamous carcinoma and 101 with adenocarcinoma). Eighty-six tumors showed a presence of SY+ (27%). Univariate analysis showed lower survival rates at 5 years for those patients older than 70 years of age compared with those patients younger than 70 years of age (60.35% vs 70.57%; P = .007) and for those patients with SY+ compared with those with SY- (52.48% vs 72.68%; P = .0017). Patients with SY+ tumors showed a higher rate of recurrence than patients with SY- tumors (50% vs 33.6%; P = .008). Multivariate analysis showed that those patients greater that 70 years of age (hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.14-2.65) and the presence of SY (HR, 2.15; 95% CI, 1.40-3.30) were significant independent prognostic factors associated with a poor outcome. CONCLUSIONS: Stage I of squamous carcinoma and adenocarcinoma of the lung with SY+ has a poor prognosis, with a higher frequency of recurrence and lower survival rates.