The current role of surgery and SBRT in early stage of small cell lung cancer

Early stage small cell lung cancer (T1-2N0M0SCLC) represents 7% of all SCLC. The standard treatment in patients with intrathoracic SCLC disease is the use of concurrent chemoradiotherapy (CRT). Nowadays, the recommended management of this highly selected group is surgical resection due to favorable survival outcomes. For medically inoperable patients or those who refuse surgery, there is an increasing interest in evaluating the role of Stereotactic Body Radiotherapy (SBRT) for T1-2N0SCLC, transferring the favorable experience obtained on inoperable NSCLC (Non-Small-cell Lung Cancer). In the era of multimodality treatment, adjuvant systemic therapy plays an important role even in the management of early SCLC, increasing the disease-free survival (DFS) and Overall Survival (OS). The benefit of Prophylactic Cranial Irradiation (PCI), that currently has a Category I recommendation for localized stage SLCL, remains controversial in this selected subgroup of patients due to the lower risk of brain metastasis. This review summarizes the most relevant data on the local management of T1-2N0M0SCLC (surgery and radiotherapy), and evaluates the relevance of adjuvant treatment. Provides a critical evaluation of best current clinical management options for T1-2N0M0 SCLC

Study protocol for an observational cohort evaluating incidence and clinical relevance of perioperative elevation of high-sensitivity troponin I and N-terminal pro-brain natriuretic peptide in patients undergoing lung resection

INTRODUCTION: Myocardial injury after non-cardiac surgery has been defined as myocardial injury due to ischaemia, with or without additional symptoms or ECG changes occurring during or within 30 days after non-cardiac surgery and mainly diagnosed based on elevated postoperative cardiac troponin (cTn) values. In patients undergoing thoracic surgery for lung resection, only postoperative cTn elevations are seemingly not enough as an independent predictor of cardiovascular complications. After lung resection, troponin elevations may be regulated by mechanisms other than myocardial ischaemia. The combination of perioperative natriuretic peptide measurement together with high-sensitivity cTns may help to identify changes in ventricular function during thoracic surgery. Integrating both cardiac biomarkers may improve the predictive value for cardiovascular complications after lung resection. We designed our cohort study to evaluate perioperative elevation of both high-sensitivity troponin I (hs-TnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients undergoing lung resection and to establish a risk score for major cardiovascular postoperative complications. METHODS AND ANALYSIS: We will conduct a prospective, multicentre, observational cohort study, including 345 patients undergoing elective thoracic surgery for lung resection. Cardiac biomarkers such as hs-TnI and NT-proBNP will be measured preoperatively and at postoperatively on days 1 and 2. We will calculate a risk score for major cardiovascular postoperative complications based on both biomarkers' perioperative changes. All patients will be followed up for 30 days after surgery. ETHICS AND DISSEMINATION: All participating centres were approved by the Ethics Research Committee. Written informed consent is required for all patients before inclusion. Results will be disseminated through publication in peer-reviewed journals and presentations at national or international conference meetings. TRIAL REGISTRATION NUMBER: NCT04749212

Riesgo quirúrgico tras resección pulmonar anatómica en cirugía torácica. Modelo predictivo a partir de una base de datos nacional multicéntrica

Introduction: the aim of this study was to develop a surgical risk prediction model in patients undergoing anatomic lung resections from the registry of the Spanish Video-Assisted Thoracic Surgery Group (GEVATS). Methods: data were collected from 3,533 patients undergoing anatomic lung resection for any diagnosis between December 20, 2016 and March 20, 2018. We defined a combined outcome variable: death or Clavien Dindo grade IV complication at 90 days after surgery. Univariate and multivariate analyses were performed by logistic regression. Internal validation of the model was performed using resampling techniques. Results: the incidence of the outcome variable was 4.29% (95% CI 3.6-4.9). The variables remaining in the final logistic model were: age, sex, previous lung cancer resection, dyspnea (mMRC), right pneumonectomy, and ppo DLCO. The performance parameters of the model adjusted by resampling were: C-statistic 0.712 (95% CI 0.648-0.750), Brier score 0.042 and bootstrap shrinkage 0.854. Conclusions: the risk prediction model obtained from the GEVATS database is a simple, valid, and reliable model that is a useful tool for establishing the risk of a patient undergoing anatomic lung resection

Estudio de los factores pronóstico clínico-patológicos de las metástasis pulmonares de sarcoma

Els pacients amb tumor primari d'origen sarcomatós podran presentar fins a un 50% dels casos, metàstasis a distància, essent el pulmó el principal òrgan diana. A causa de les altes taxes de recurrència, la selecció del subconjunt de pacients que obtindran un benefici a la supervivència amb la resecció quirúrgica és important. Hi ha criteris ben establerts per a la cirurgia de metastasectomia pulmonar, però múltiples factors influiràn en l'evolució del pacient i seràn pronòstic per a la supervivència i la recurrència de la malaltia. Actualment no estan ben establerts quins són. La justificació de l'estudi sorgeix de la necessitat de determinar els factors de risc que cal tenir en compte per establir una indicació quirúrgica en les metàstasis pulmonars d'un sarcoma, i quins d'aquests factors ofereixen un millor pronòstic en relació amb la supervivència. La hipòtesi de l'estudi és que hi ha uns factors pronòstic que influeixen en la supervivència dels pacients amb metàstasis pulmonars de sarcoma que encara no estàn clarament definits. L'objectiu principal de l'estudi és identificar quins són aquests factors pronòstic associats a una supervivència més gran. Els objectius secundaris són analitzar si hi ha diferències segons el subtipus histològic de sarcoma, la via d'abordatge, el tipus de resecció realitzada, la sincronicitat de la malaltia, l'afectació ganglionar, el temps lliure de malaltia i valorar el benefici de la realització de remetastasectomies . El disseny de l'estudi és observacional, descriptiu, retrospectiu i prospectiu de pacients amb metàstasis pulmonars de sarcoma i intervinguts quirúrgicament mitjançant una resecció de les metàstasis pulmonars. Tots els pacients tractats al servei de cirurgia toràcica de l'Hospital de la Santa Creu i Sant Pau. No es van recollir mostres biològiques dels pacients. L'estudi no estava inclòs dins de cap registre internacional. No es va fer un càlcul de la mida mostral. Es van incloure tots els pacients intervinguts de resecció de metàstasis pulmonars de sarcoma, que complien els criteris d'inclusió durant el període comprès entre juny de 2014 i desembre de 2016 de manera retrospectiva i de gener de 2017 a gener de 2021 de manera prospectiva. Vam intervenir un total de 57 pacients als quals se'ls va realitzar 80 cirurgies de resecció de metàstasis, 34 homes i 23 dones amb edat mitjana de 52,8 +/- 14 anys. A l'anàlisi multivariant, trobem com a factors pronòstic que milloren la supervivència global: realitzar una cirurgia radical (R0), el temps lliure de malaltia major a un any, el nombre de nòduls pulmonars ressecats menor a 3 i l'absència d'afectació ganglionar. A la SLE va afectar a més d'aquests, tenir una metàstasi metacrònica. La mitjana de supervivència global va ser de 33.2 mesos (IC95% 25.1 ; - ). La Sv 1a va ser del 84%, 43% als 3 anys i Sv 5a de 20%. Com a conclusions podem dir que hem identificat com a factors pronòstic que influeixen en la supervivència global dels pacients afectes de metàstasis pulmonars de sarcoma els següents: realitzar una cirurgia radical, el temps lliure de malaltia, el nombre de nòduls ressecats i l'afectació ganglionar. Per a la supervivència lliure de malaltia són factors pronòstic negatius: la cirurgia no radical, l'ILE < 12 mesos i la malaltia sincrònica. A la nostra sèrie, ni el subtipus histològic de sarcoma, ni la via d'abordatge realitzada, ni el tipus de resecció van influir a la SG ni a la SLE.Los pacientes con tumor primario de origen sarcomatoso podrán presentar hasta en un 50% de los casos, metástasis a distancia, siendo el pulmón el principal órgano diana. Debido a las altas tasas de recurrencia, la selección del subconjunto de pacientes que obtendrán un beneficio en la supervivencia con la resección quirúrgica es importante. Existen criterios bien establecidos para la cirugía de metastasectomía pulmonar pero múltiples factores influirán en la evolución del paciente y serán pronósticos para la supervivencia y la recurrencia de la enfermedad. Actualmente no están bien establecidos cuáles son. La justificación del estudio surge de la necesidad de determinar los factores de riesgo a tener en cuenta para establecer una indicación quirúrgica en las metástasis pulmonares de un sarcoma, y cuáles de estos factores, ofrecen un mejor pronóstico en relación a la supervivencia. La hipótesis del estudio es que existen unos factores pronóstico que influyen en la supervivencia de los pacientes con metástasis pulmonares de sarcoma que aún no están claramente definidos. El objetivo principal del estudio es identificar cuáles son estos factores pronóstico asociados a una mayor supervivencia. Los objetivos secundarios son analizar si existen diferencias según el subtipo histológico de sarcoma, la vía de abordaje, el tipo de resección realizada, la sincronicidad de la enfermedad, la afectación ganglionar, el tiempo libre de enfermedad y valorar el beneficio de la realización de remetastasectomías. El diseño del estudio es observacional, descriptivo, retrospectivo y prospectivo de pacientes afectos de metástasis pulmonares de sarcoma e intervenidos quirúrgicamente mediante una resección de las metástasis pulmonares. Todos los pacientes fueron tratados en el servicio de cirugía torácica del Hospital de la Santa Creu i Sant Pau. No se recogieron muestras biológicas de los pacientes. El estudio no estaba incluído dentro de ningún registro internacional. No se realizó un cálculo del tamaño muestral. Se incluyeron todos los pacientes intervenidos de resección de metástasis pulmonares de sarcoma, que cumplían los criterios de inclusión durante el período comprendido entre junio de 2014 y diciembre de 2016 de forma retrospectiva y de enero de 2017 a enero de 2021 de forma prospectiva. Intervinimos un total de 57 pacientes a los que se les realizó 80 cirugías de resección de metástasis, 34 hombres y 23 mujeres con edad media de 52,8 +/- 14 años. En el análisis multivariante, encontramos como factores pronóstico que mejoran la supervivencia global: realizar una cirugía radical (R0), el tiempo libre de enfermedad mayor a un año, el número de nódulos pulmonares resecados menor a 3 y la ausencia de afectación ganglionar. En la SLE afectó además de estos, el tener una metástasis metacrónica. La mediana de supervivencia global fue de 33.2 meses (IC95% 25.1 ; - ). La Sv 1a fue del 84%, 43% a los 3 años y Sv 5a de 20%. Como conclusiones podemos decir que hemos identificado como factores pronóstico que influyen en la supervivencia global de los pacientes afectos de metástasis pulmonares de sarcoma los siguientes: realizar una cirugía radical, el tiempo libre de enfermedad, el número de nódulos resecados y la afectación ganglionar. Para supervivencia libre de enfermedad son factores pronóstico negativos: la cirugía no radical, el ILE < 12 meses y la enfermedad sincrónica. En nuestra serie, ni el subtipo histológico de sarcoma, ni la vía de abordaje realizada, ni el tipo de resección influyeron en la SG ni en la SLE.Patients with a primary tumor of sarcomatous origin may present distant metastases in up to 50% of cases, with the lung being the main target organ. Due to high recurrence rates, selection of the subset of patients who will derive a survival benefit from surgical resection is important. There are well-established criteria for pulmonary metastasectomy surgery, but multiple factors will influence the patient's outcome and will be prognostic for survival and disease recurrence. Currently it is not well established what they are. Justify the study arises from the needed to determine the risk factors to establish a surgical indication in lung metastases from a sarcoma, and which of these, offer a better prognosis. Hypothesis of the study is that there are some prognostic factors that influence the survival of patients with sarcoma lung metastases that are not yet clearly defined. The main objective of the study is to identify which prognostic factors are associated with better survival. Secondary objectives are to analyze whether there are differences according to the histological subtype of sarcoma, surgery approach, type of pulmonary resection, synchronicity of the disease, lymph node involvement, time free of disease and to assess the benefit of performing redometastasectomy. Design of the study is observational, descriptive, retrospective and prospective of patients affected by lung metastases from sarcoma and who underwent pulmonary metastasectomy. All patients treated in the thoracic surgery service of the Hospital de la Santa Creu i Sant Pau. No biological samples were collected from the patients. The study was not included in any international registry. A sample size calculation was not performed. All patients who underwent pulmonary metastasectomy who met the inclusion criteria during the period between June 2014 and December 2016 retrospectively and from January 2017 to January 2021 prospectively were included. A total of 57 patients who underwent 80 pulmonary metastasectomy, 34 men and 23 women with a mean age of 52.8 +/- 14 years. In the multivariate analysis, we found prognostic factors that improve overall survival: performing radical surgery (R0), disease-free time greater than one year, number of resected pulmonary nodules less than 3, and absence of lymph node involvement. In DFS, in addition to these, it affected having a metachronous metastasis. Median overall survival was 33.2 months (95% CI 25.1 ; - ). OS 1a was 84%, 43% at 3 years and OS 5a 20%. As conclusions, we have identified the following as prognostic factors that influence the overall survival of patients with lung metastases form sarcoma: performing radical surgery, disease-free time, the number of resected nodules and lymph node involvement. For disease-free survival, negative prognostic factors are: non-radical surgery, DFT <12 months, and synchronous disease. In our series, neither the histological subtype of sarcoma, nor the approach performed, nor the type of resection influenced OS or DFS

Video-assisted mediastinoscopic lymphadenectomy combined with transcervical thoracoscopy

Surgical techniques remain the gold standard to diagnose and staging lung and pleural tumours. Non-invasive techniques have become more accurate but actually they are not enough to plan and evaluating prognosis of lung and pleural tumours. In some cases, we need to explore the pleural cavity and the mediastinal lymph node status to confirm or rule out tumour dissemination. The combination of video-assisted mediastinoscopic lymphadenectomy (VAMLA) and thoracoscopy through a single transcervical incision allows the surgeon to widen the range of the exploration and to improve the staging for lung and pleural cancers. VAMLA allows to perform a complete lymphadenectomy of the subcarinal space, the right and pretracheal areas. We consider sampling more safety on the left side to avoid left recurrent nerve injuries. Once this mediastinal tissue is removed, the right mediastinal pleura can be identified and incised. Once mediastinal pleura is opened, a 5 mm 30º thoracoscope is inserted through the video- mediastinoscope into the pleural cavity. It allows to obtain samples of parietal or visceral pleural, pleural fluid or lung nodules if present. In case of left-sided thoracoscopy the access to the left pleural cavity is anterior to the aortic arch as for extended cervical mediastinoscopy. The combination of VAMLA and thoracoscopy is useful to explore the mediastinum and the pleural space from a single incision and in the same surgical setting through the transcervical approach

New TNM staging in lung cancer (8th edition) and future perspectives

Background: Carrying out a correct anatomical classification of lung cancer is crucial to take clinical and therapeutic decisions in each patient. Aim: TNM staging classification provides an accurate anatomical description about the extension of the disease; however, the anatomical burden of the disease is just one aspect that changes the prognosis. Relevance for patients: TNM staging classification is a tool that predicts survival, but we must consider that TNM is just one of the factors that concern the prognosis. The impact of a factor over the prognosis is complex due to: It depends on the specific environment, the treatment strategy, among others, and our level of certainty makes difficult to include all the factors just in a group of stages. In some groups, there are difficulties to get large series due to the low frequency of cases and the small number of events (metastasis, locoregional recurrence). It does not allow to obtain evidence in a short period of time. On the other hand, in the next years, new markers will be incorporated in the coming years, which are going to be included in the new TNM classification. It could help to improve the classification giving more information about prognosis and risk of recurrence. All these aspects are being used by the International Association for the Study of Lung Cancer (IASLC) to develop a new prognosis model. This continues the evolution of TNM system, allows us to overcome the difficulties, and build a flexible framework enough to continue improving the individual prognosis of the patients

Next-generation sequencing reveals a new mutation in the LTBP2 gene associated with microspherophakia in a Spanish family

Abstract Background Microspherophakia is a rare autosomal recessive eye disorder characterized by small spherical lens. It may present as an isolated finding or in association with other ocular and/or systemic disorders. This clinical and genetic heterogeneity requires the study of large genes (ADAMTSL4, FBN1, LTBP2, ADAMTSL-10 and ADAMTSL17). The purpose of the present study is to identify the genetic cause of this pathology in a consanguineous Spanish family. Methods A clinical exome sequencing experiment was executed by the TruSight One® Sequencing Panel (TSO) from Illumina©. Sanger sequencing was used to validate the NGS results. Results Only the insertion of an adenine in exon 36 of the LTBP2 gene (c.5439_5440insA) was associated with pathogenicity. This new mutation was validated by Sanger sequencing and segregation analysis was also performed. Haplotype analyses using the polymorphic markers D14S1025, D14S43 and D14S999 close to the LTBP2 gene indicated identity by descent in this family. Conclusion We describe the first case of a microspherophakia phenotype associated with a novel homozygous mutation in the LTBP2 gene in a consanguineous Caucasian family by means of NGS technology

Clinical characteristics and outcomes of thymoma-associated myasthenia gravis

Background and purpose: Prognosis of myasthenia gravis (MG) in patients with thymoma is not well established. Moreover, it is not clear whether thymoma recurrence or unresectable lesions entail a worse prognosis of MG. Methods: This multicenter study was based on data from a Spanish neurologist-driven MG registry. All patients were aged >18 years at onset and had anti-acetylcholine receptor antibodies. We compared the clinical data of thymomatous and nonthymomatous patients. Prognosis of patients with recurrent or nonresectable thymomas was assessed. Results: We included 964 patients from 15 hospitals; 148 (15.4%) had thymoma-associated MG. Median follow-up time was 4.6 years. At onset, thymoma-associated MG patients were younger (52.0 vs. 60.4 years, p < 0.001), had more generalized symptoms (odds ratio [OR]: 3.02, 95% confidence interval [CI]: 1.95-4.68, p < 0.001) and more severe clinical forms according to the Myasthenia Gravis Foundation of America (MGFA) scale (OR: 1.6, 95% CI: 1.15-2.21, p = 0.005). Disease severity based on MGFA postintervention status (MGFA-PIS) was higher in thymomatous patients at 1 year, 5 years, and the end of follow-up. Treatment refractoriness and mortality were also higher (OR: 2.28, 95% CI: 1.43-3.63, p = 0.001; hazard ratio: 2.46, 95% CI: 1.47-4.14, p = 0.001). Myasthenic symptoms worsened in 13 of 27 patients with recurrences, but differences in long-term severity were not significant. Fifteen thymomatous patients had nonresectable thymomas with worse MGFA-PIS and higher mortality at the end of follow-up. Conclusions: Thymoma-associated MG patients had more severe myasthenic symptoms and worse prognosis. Thymoma recurrence was frequently associated with transient worsening of MG, but long-term prognosis did not differ from nonrecurrent thymoma. Patients with nonresectable thymoma tended to present severe forms of MG.Sin financiación6.288 JCR (2021) Q1, 33/212 Clinical Neurology1.662 SJR (2021) Q1, 20/172 NeurologyNo data IDR 2020UE