Altered splicing machinery in lung carcinoids unveils NOVA1, PRPF8 and SRSF10 as novel candidates to understand tumor biology and expand biomarker discovery.

BACKGROUND: Lung neuroendocrine neoplasms (LungNENs) comprise a heterogeneous group of tumors ranging from indolent lesions with good prognosis to highly aggressive cancers. Carcinoids are the rarest LungNENs, display low to intermediate malignancy and may be surgically managed, but show resistance to radiotherapy/chemotherapy in case of metastasis. Molecular profiling is providing new information to understand lung carcinoids, but its clinical value is still limited. Altered alternative splicing is emerging as a novel cancer hallmark unveiling a highly informative layer. METHODS: We primarily examined the status of the splicing machinery in lung carcinoids, by assessing the expression profile of the core spliceosome components and selected splicing factors in a cohort of 25 carcinoids using a microfluidic array. Results were validated in an external set of 51 samples. Dysregulation of splicing variants was further explored in silico in a separate set of 18 atypical carcinoids. Selected altered factors were tested by immunohistochemistry, their associations with clinical features were assessed and their putative functional roles were evaluated in vitro in two lung carcinoid-derived cell lines. RESULTS: The expression profile of the splicing machinery was profoundly dysregulated. Clustering and classification analyses highlighted five splicing factors: NOVA1, SRSF1, SRSF10, SRSF9 and PRPF8. Anatomopathological analysis showed protein differences in the presence of NOVA1, PRPF8 and SRSF10 in tumor versus non-tumor tissue. Expression levels of each of these factors were differentially related to distinct number and profiles of splicing events, and were associated to both common and disparate functional pathways. Accordingly, modulating the expression of NOVA1, PRPF8 and SRSF10 in vitro predictably influenced cell proliferation and colony formation, supporting their functional relevance and potential as actionable targets. CONCLUSIONS: These results provide primary evidence for dysregulation of the splicing machinery in lung carcinoids and suggest a plausible functional role and therapeutic targetability of NOVA1, PRPF8 and SRSF10.

Lung transplantation in patients with a history of anatomical native lung resection.

OBJECTIVES: History of anatomical lung resection complicates lung transplantation (LTx). Our aim was to identify indications, intraoperative approach and outcome in these challenging cases in a retrospective multicentre cohort analysis. METHODS: Members of the ESTS Lung Transplantation Working Group were invited to submit data on patients undergoing LTx after a previous anatomical native lung resection between January 2005 and July 2020. The primary end point was overall survival (Kaplan-Meier estimation). RESULTS: Out of 2690 patients at 7 European centres, 26 (1%) patients (14 males; median age 33 years) underwent LTx after a previous anatomical lung resection. The median time from previous lung resection to LTx was 12 years. The most common indications for lung resection were infections (n = 17), emphysema (n = 5), lung tumour (n = 2) and others (n = 2). Bronchiectasis (cystic fibrosis or non-cystic fibrosis related) was the main indication for LTx (n = 21), followed by COPD (n = 5). Two patients with a previous pneumonectomy underwent contralateral single LTx and 1 patient with a previous lobectomy had ipsilateral single LTx. The remaining 23 patients underwent bilateral LTx. Clamshell incision was performed in 12 (46%) patients. Moreover, LTx was possible without extracorporeal life support in 13 (50%) patients. 90-Day mortality was 8% (n = 2) and the median survival was 8.7 years. CONCLUSIONS: The history of anatomical lung resection is rare in LTx candidates. The majority of patients are young and diagnosed with bronchiectasis. Although the numbers were limited, survival after LTx in patients with previous anatomical lung resection, including pneumonectomy, is comparable to reported conventional LTx for bronchiectasis.

Spanish Society of Thoracic Surgery (SECT) consensus document. Long-term follow-up for operated patients with lung cancer.

The most effective treatment for lung cancer is complete lung resection, although recurrences reach up to 10% and the appearance of second neoplasms, up to 6%. Therefore, the follow-up of these patients will be essential for the early detection and treatment of these events; however there is no definition of the form, time and cadence of these follow-ups. In this consensus document, we try to define them based on the available scientific evidence. A critical review of the literature is carried out (meta-analysis, systematic reviews, reviews, consensus recommendations of scientific societies, randomized controlled studies, non-randomized controlled studies, observational studies and case series studies) and communications to the main congresses on oncology and thoracic surgery in Spanish, English and French. The evidences found are classified following the GRADE system. It is defined according to the existing evidence that the patient resected for lung cancer should be followed up, as well as that this follow-up should be close during the first years and with CT (not being necessary to follow up with PET-CT, biomarkers or bronchoscopy). Cessation of smoking is also recommended in this follow-up.

Spanish Society of Thoracic Surgery (SECT) consensus document. Long-term follow-up for operated patients with lung cancer. / Documento de consenso de la Sociedad Española de Cirugía Torácica (SECT). Seguimiento a largo plazo de los pacientes operados de cáncer de pulmón.

The most effective treatment for lung cancer is complete lung resection, although recurrences reach up to 10% and the appearance of second neoplasms, up to 6%. Therefore, the follow-up of these patients will be essential for the early detection and treatment of these events; however, there is no definition of the form, time and cadence of these follow-ups. In this consensus document, we try to define them based on the available scientific evidence. A critical review of the literature is carried out (meta-analysis, systematic reviews, reviews, consensus recommendations of scientific societies, randomized controlled studies, non-randomized controlled studies, observational studies and case series studies) and communications to the main congresses on oncology and thoracic surgery in Spanish, English and French. The evidences found are classified following the GRADE system. It is defined according to the existing evidence that the patient resected for lung cancer should be followed up, as well as that this follow-up should be close during the first years and with CT (not being necessary to follow up with PET-CT, biomarkers or bronchoscopy). Cessation of smoking is also recommended in this follow-up.

Ganglioneuroma dependiente del nervio frénico: localización inusual / Ganglioneuroma of the Phrenic Nerve: An Unusual Site

No disponible

Tratamiento quirúrgico de quilotórax postrasplante pulmonar por linfangioleiomiomatosis / Surgical Treatment of Chylothorax After Lung Transplantation for Lymphangioleiomyomatosis

No disponible

Thoracotomy Wound Dehiscence After Lung Transplant Is an Effective Surgical Solution: A Case Report.

Post-thoracotomy wound dehiscence after a lung transplant carries with it morbidity in the postoperative period. While this complication has been widely reported in the literature after a clamshell incision, the thoracotomy dehiscence's surgical solution has not received much emphasis. We present an original technical solution to deal with this complication, performed successfully in a 62-year-old woman diagnosed as having idiopathic pulmonary hemosiderosis after a single lung transplant. This surgical treatment consists of necrotic rib tissue removal, pleural effusion drainage, pulmonary adhesion removal, and chest wall defect reparation with bioabsorbable mesh. This operative technique results safe and effective for thoracotomy dehiscence reparation.

Early Surgical Management of Bronchial Dehiscence After Single-Lung Transplantation: A Case Report.

Anastomotic airway complications after lung transplantation affect up to 20% of patients. Bronchial stenosis is the most frequent complication, while dehiscence of bronchial anastomosis is a rarely seen complication, with report incidences between 1% and 10%. Despite its low incidence, dehiscence of bronchial anastomoses remains a disastrous complication in the posttransplantation period without a well-established management protocol. We present a challenging case of complete bronchial dehiscence after unilateral lung transplantation in a patient with interstitial lung fibrosis (ILF) that occurred on postoperative day 10. The dehiscence was diagnosed early and the patient's status was stable for repeat thoracotomy, therefore, an early surgical approach was preferable to conservative management or bronchoscopy. Aggressive early surgical management in a stable patient allows for complete debridement with removal of the detritus that impedes correct anastomosis healing and permits the removal of microbial vegetations with successful results.

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.

Valoración funcional preoperatoria / No disponible

No disponible

Clinical management of atypical carcinoid and large-cell neuroendocrine carcinoma: a multicentre study on behalf of the European Association of Thoracic Surgeons (ESTS) Neuroendocrine Tumours of the Lung Working Group†.

OBJECTIVES: In 2012, the European Society of Thoracic Surgeons (ESTS) created the Lung Neuroendocrine Tumors Working Group (NETs-WG) with the aim to develop scientific knowledge on clinical management of such rare neoplasms. This paper outlines the outcome and prognostic factors of two aggressive NETs: atypical carcinoids (ACs) and large-cell neuroendocrine carcinomas (LCNCs). METHODS: Using the ESTS NETs-WG database, we retrospectively collected data on 261 patients in seven institutions in Europe, between 1994 and 2011. We used a Cox regression model to evaluate variables affecting patient survival and disease-free survival. Univariate and multivariate analysis were also carried out. RESULTS: Five-year overall survival rates for ACs and LCNCs were 77 vs 28% (P < 0.001), respectively. We found that for ACs, age (P < 0.001), tumour size (P = 0.015) and sub-lobar surgical resection (P = 0.005) were independent negative prognostic factors; for LCNCs, only pTNM stage III tumours (P = 0.016) negatively affected outcome in the multivariate analysis. Local recurrences and distant metastases developed in 93 patients and were statistically more frequent in LCNCs (P = 0.02). CONCLUSIONS: The biological aggressiveness of ACs and LCNCs has been demonstrated with this study. Our aim is to confirm these results with enhanced data collection through the ESTS NETs database.

[Chest trauma]. / Traumatismos torácicos.

Chest trauma is a frequent problem arising from lesions caused by domestic and occupational activities and especially road traffic accidents. These injuries can be analyzed from distinct points of view, ranging from consideration of the most severe injuries, especially in the context of multiple trauma, to the specific characteristics of blunt and open trauma. In the present article, these injuries are discussed according to the involvement of the various thoracic structures. Rib fractures are the most frequent chest injuries and their diagnosis and treatment is straightforward, although these injuries can be severe if more than three ribs are affected and when there is major associated morbidity. Lung contusion is the most common visceral lesion. These injuries are usually found in severe chest trauma and are often associated with other thoracic and intrathoracic lesions. Treatment is based on general support measures. Pleural complications, such as hemothorax and pneumothorax, are also frequent. Their diagnosis is also straightforward and treatment is based on pleural drainage. This article also analyzes other complex situations, notably airway trauma, which is usually very severe in blunt chest trauma and less severe and even suitable for conservative treatment in iatrogenic injury due to tracheal intubation. Rupture of the diaphragm usually causes a diaphragmatic hernia. Treatment is always surgical. Myocardial contusions should be suspected in anterior chest trauma and in sternal fractures. Treatment is conservative. Other chest injuries, such as those of the great thoracic and esophageal vessels, are less frequent but are especially severe.

Traumatismos torácicos / Chest trauma

Los traumatismos torácicos (TT) constituyen un problema frecuente, consecuencia de lesiones originadas poractividades domésticas, laborales y, especialmente, accidentes de tráfico. Se pueden analizar desde diversospuntos de vista, considerando los más graves sobre todo en el contexto de los politraumatismos. Y también laspeculiaridades de los traumatismos cerrados y los abiertos.En este trabajo se estudian según la afectación de las diversas estructuras torácicas. Las fracturas costales sonlos TT más frecuentes, su diagnóstico y tratamiento es sencillo, aunque pueden ser graves en casos de afectaciónde más de 3 arcos costales y cuando el paciente presenta morbilidad asociada importante. La contusiónpulmonar es la lesión visceral más frecuente. Suele presentarse en TT graves y a menudo asociada a otras lesionestorácicas e intratorácicas. Su tratamiento se basa en medidas de soporte general. Son también frecuenteslas complicaciones pleurales como el hemotórax y neumotórax. Su diagnóstico es también sencillo y sutratamiento se basa en el drenaje pleural.Otras situaciones complejas también se analizan en este trabajo, destacando los traumatismos de la vía aérea,muy graves por lo general en los TT cerrados y con menor repercusión e incluso susceptibles de tratamientoconservador en los iatrógenos por intubación traqueal. Las roturas diafragmáticas suelen dar lugar a una herniadiafragmática. Su tratamiento es siempre quirúrgico. Las contusiones miocárdicas deben sospecharse enTT anteriores y fracturas de esternón. Su tratamiento es conservador. Otros TT como los de los grandes vasostorácicos y esofágicos son menos frecuentes, aunque de especial gravedad(AU)

Chest trauma is a frequent problem arising from lesions caused by domestic and occupational activities andespecially road traffic accidents. These injuries can be analyzed from distinct points of view, ranging fromconsideration of the most severe injuries, especially in the context of multiple trauma, to the specificcharacteristics of blunt and open trauma.In the present article, these injuries are discussed according to the involvement of the various thoracicstructures. Rib fractures are the most frequent chest injuries and their diagnosis and treatment isstraightforward, although these injuries can be severe if more than three ribs are affected and when there ismajor associated morbidity. Lung contusion is the most common visceral lesion. These injuries are usuallyfound in severe chest trauma and are often associated with other thoracic and intrathoracic lesions. Treatmentis based on general support measures. Pleural complications, such as hemothorax and pneumothorax, arealso frequent. Their diagnosis is also straightforward and treatment is based on pleural drainage.This article also analyzes other complex situations, notably airway trauma, which is usually very severe inblunt chest trauma and less severe and even suitable for conservative treatment in iatrogenic injury due totracheal intubation. Rupture of the diaphragm usually causes a diaphragmatic hernia. Treatment is alwayssurgical. Myocardial contusions should be suspected in anterior chest trauma and in sternal fractures.Treatment is conservative. Other chest injuries, such as those of the great thoracic and esophageal vessels, areless frequent but are especially severe(AU)

Ganglioneuroma mediastínico, un hallazgo fortuito en metastasectomía pulmonar y hepática de tumor de células germinales / Mediastinal ganglioneuroma, a fortuitous finding in lung metastasectomy and liver germ cell tumour

No disponible