Postoperative morbidity after anatomical lung resections by VATS vs thoracotomy: Treatment and intention-to-treat analysis of the Spanish Video-Assisted Thoracic Surgery Group.

OBJECTIVES: In recent years, video-assisted thoracoscopic lung resections (VATS) have been associated with lower morbidity than open surgery. The aim of our study is to compare postoperative morbidity among patients from the national database of the Spanish Group of Video-Assisted Thoracic Surgery (GE-VATS) after open and video-assisted anatomic lung resections using a propensity score analysis. METHODS: From December 2016 to March 2018, a total of 3533 patients underwent anatomical lung resection at 33 centers. Pneumonectomies and extended resections were excluded. A propensity score analysis was performed to compare the morbidity of the thoracotomy group (TG) vs the VATS group (VATSG). Treatment and intention-to-treat (ITT) analyses were conducted. RESULTS: In total, 2981 patients were finally included in the study: 1092 (37%) in the TG and 1889 (63%) in the VATSG for the treatment analysis; and 816 (27.4%) in the TG and 2165 patients (72.6%) in the VATSG for the ITT analysis. After propensity score matching, in the treatment analysis, the VATSG was significantly associated with fewer overall complications than the TG OR 0.680 [95%CI 0.616, 0.750]), fewer respiratory (OR 0.571 [0.529, 0.616]) cardiovascular (OR 0.529 [0.478, 0.609]) and surgical (OR 0.875 [0.802, 0.955]) complications, lower readmission rate (OR 0.669 [0.578, 0.775]) and a reduction of hospital length of stay (-1.741 ([-2.073, -1.410]). Intention-to-treat analysis showed only statistically significant differences in overall complications (OR 0.76 [0.54-0.99]) in favor of the VATSG. CONCLUSION: In this multicenter population, VATS anatomical lung resections have been associated with lower morbidity than those performed by thoracotomy. However, when an intention-to-treat analysis was performed, the benefits of the VATS approach were less prominent.

Impact of COVID-19 pandemic in thoracic surgery training in Spain.

In the more than 2 years since its emergence, the SARS-CoV-2 pandemic has prompted important changes in healthcare systems and their organization. The aim of this study is to determine the implications in specialized thoracic surgery training as well as the repercussions on thoracic surgery residents. With this objective, the Spanish Society of Thoracic Surgery has conducted a survey among all its trainees and those who had finished their residency during the last 3 years. It consisted of 24 multiple-answer closed questions about the impact of the pandemic on their services, their training, and their personal experience. The response rate was 42% (52 out of a target population of 120). The effect of the pandemic on thoracic surgery services was high or extreme according to 78.8% of the participants. Academic activities were completely cancelled in 42.3% of the cases, and 57.7% of the respondents were required to treat hospitalized COVID patients (25% part-time, and 32.7% full-time). More than 80% of the survey participants believed that changes during the pandemic negatively affected their training, and 36.5% would prefer to extend their training period. In sum, we observe how the pandemic has had deep negative effects on specialized training in thoracic surgery in Spain.

Low-Dose Gamma Radiation Sterilization for Decellularized Tracheal Grafts.

One of the main key aspects in ensuring that a transplant evolves correctly is the sterility of the medium. Decellularized tracheal transplantation involves implanting an organ that was originally in contact with the environment, thus not being sterile from the outset. While the decellularization protocol (through detergent exposition [2% sodium dodecyl sulfate], continuous stirring, and osmotic shocks) is conducted in line with aseptic measures, it does not provide sterilization. Therefore, one of the main challenges is ensuring sterility prior to in vivo implantation. Although there are established gamma radiation sterilization protocols for inorganic materials, there are no such measures for organic materials. Additionally, the protocols in place for inorganic materials cannot be applied to organic materials, as the established radiation dose (25 kGy) would completely destroy the implant. This paper studies the effect of an escalated radiation dose in a decellularized rabbit trachea. We maintained the dose range (kGy) and tested escalated doses until finding the minimal dose at which sterilization is achieved. After determining the dose, we studied effects of it on the organ, both histologically and biomechanically. We determined that while 0.5 kGy did not achieve sterility, doses of both 1 kGy and 2 kGy did, with 1 kGy, therefore, being the minimal dose necessary to achieve sterilization. Microscopic studies showed no relevant changes compared to non-sterilized organs. Axial biomechanical characteristics were not altered at all, and only a slight reduction in the force per unit of length that the organ can radially tolerate was observed. We can therefore conclude that 1 kGy achieves complete sterilization of decellularized rabbit trachea with a minimal, if any, effects on the organ.

[Impact of the COVID-19 pandemic on thoracic surgery training in Spain]. / Impacto de la pandemia por COVID-19 en la formación de los cirujanos torácicos en España.

In the more than 2 years since its emergence, the SARS-CoV-2 pandemic has prompted important changes in healthcare systems and their organization. The aim of this study is to determine the implications in specialized thoracic surgery training as well as the repercussions on thoracic surgery residents. With this objective, the Spanish Society of Thoracic Surgery has conducted a survey among all its trainees and those who had finished their residency during the last 3 years. It consisted of 24 multiple-answer closed questions about the impact of the pandemic on their services, their training, and their personal experience. The response rate was 42% (52 out of a target population of 120). The effect of the pandemic on thoracic surgery services was high or extreme according to 78.8% of the participants. Academic activities were completely cancelled in 42.3% of the cases, and 57.7% of the respondents were required to treat hospitalized COVID patients (25% part-time, and 32.7% full-time). More than 80% of the survey participants believed that changes during the pandemic negatively affected their training, and 36.5% would prefer to extend their training period. In sum, we observe how the pandemic has had deep negative effects on specialized training in thoracic surgery in Spain.

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.

Surgical Risk Following Anatomic Lung Resection in Thoracic Surgery: A Prediction Model Derived from a Spanish Multicenter Database. / 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.

A Standardised Approach to the Biomechanical Evaluation of Tracheal Grafts.

The ideal tracheal substitute must have biomechanical properties comparable to the native trachea, but currently there is no standardised approach to evaluating these properties. Here we propose a novel method for evaluating and comparing the properties of tracheal substitutes, thus systematising both measurement and data curation. This system was tested by comparing native rabbit tracheas to frozen and decellularised specimens and determining the histological characteristics of those specimens. We performed radial compression tests on the anteroposterior tracheal axis and longitudinal axial tensile tests with the specimens anastomosed to the jaw connected to a measuring system. All calculations and results were adjusted according to tracheal size, always using variables relative to the tracheal dimensions, thus permitting comparison of different sized organs. The biomechanical properties of the decellularised specimens were only slightly reduced compared to controls and significant in regard to the maximum stress withstood in the longitudinal axis (-0.246 MPa CI [-0.248, -0.145] MPa) and the energy stored per volume unit (-0.124 mJ·mm-3 CI [-0.195, -0.055] mJ·mm-3). The proposed method is suitable for the systematic characterisation of the biomechanical properties of different tracheal substitutes, regardless of the size or nature of the substitute, thus allowing for direct comparisons.

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.

Effect of COVID-19 on Thoracic Oncology Surgery in Spain: A Spanish Thoracic Surgery Society (SECT) Survey.

After the first wave of COVID-19, the Spanish Society of Thoracic Surgeons (SECT) surveyed its members to assess the impact of the pandemic on thoracic oncology surgery in Spain. In May 2020, all SECT members were invited to complete an online, 40-item, multiple choice questionnaire. The questionnaire was developed by the SECT Scientific Committee and sent via email. The overall response rate was 19.2%. The respondents answered at least 91.5% of the items, with only one exception (a question about residents). Most respondents (89.3%) worked in public hospitals. The reported impact of the pandemic on routine clinical activity was considered extreme or severe by 75.5% of respondents (25.5% and 50%, respectively). Multidisciplinary tumour boards were held either with fewer members attending or through electronic platforms (44.6% and 35.9%, respectively). Surgical activity decreased by 95.7%, with 41.5% of centers performing surgery only on oncological patients and 11.7% only in emergencies. Nearly 60% of respondents reported modifying standard protocols for early-stage cancer and in the preoperative workup. Most centers (≈80%) reported using full personal protective equipment when operating on COVID-19 positive patients. The COVID-19 pandemic severely affected thoracic oncology surgery in Spain. The lack of common protocols led to a variable care delivery to lung cancer patients.

Decellularized tracheal prelamination implant: A proposed bilateral double organ technique.

In tracheal replacement transplantation, prelamination is a critical stage. Nowadays, the most widely used prelamination technique is the prethoracic fascia flap with lateral thoracic artery. We propose a flap based on the internal thoracic artery, which allows a relatively non-aggressive double organ implant, and we have tested its efficacy in decellularized tracheas. Tracheas of albino New Zealand rabbits were decellularized following a protocol that uses detergents and cryogenization, sterilized with 1kGy gamma radiation, and tutorized with a stent. Bilateral pedicled flaps made of pectoral fascia and a muscular component were harvested through a longitudinal 3-cm central thoracic incision, wrapping the tracheas with them in 16 rabbits, remaining them implanted for 2, 4, 8, and 12 weeks. The tracheas were then studied histologically using standard stainings plus immunohistochemistry (CD31). The models were adjusted with Bayesian statistics using ordinal regression; results as odds ratios and credibility intervals. All analysis were performed using R software. Acute inflammatory cell invasion was observed at 2 weeks, which almost disappeared at week 8 after implant. Only macrophages and giant cells increased between Weeks 8 and 12 (OR 10.487, CI [1.603-97.327]). The cartilage maintained its structure, with slight signs of ischemia in a few cases. New CD31-positive vessels were observed from Week 2 and increasing thereafter, reaching a maximum peak at Week 8. We propose a bilateral implant technique that is viable and effective as a prelamination option for two concurrent tracheas, achieving perfect vascularization and integration of the organ with hardly any inflammatory response in the medium or long term.

Optimization of a decellularization protocol of porcine tracheas. Long-term effects of cryopreservation. A histological study.

OBJECTIVE: The aim of this study was to optimize a decellularization protocol in the trachea of Sus scrofa domestica (pig) as well as to study the effects of long-term cryopreservation on the extracellular matrix of decellularized tracheas. METHODS: Porcine tracheas were decellularized using Triton X-100, SDC, and SDS alone or in combination. The effect of these detergents on the extracellular matrix characteristics of decellularized porcine tracheas was evaluated at the histological, biomechanical, and biocompatibility level. Morphometric approaches were used to estimate the effect of detergents on the collagen and elastic fibers content as well as on the removal of chondrocytes from decellularized organs. Moreover, the long-term structural, ultrastructural, and biomechanical effect of cryopreservation of decellularized tracheas were also estimated. RESULTS: Two percent SDS was the most effective detergent tested concerning cell removal and preservation of the histological and biomechanical properties of the tracheal wall. However, long-term cryopreservation had no an appreciable effect on the structure, ultrastructure, and biomechanics of decellularized tracheal rings. CONCLUSION: The results presented here reinforce the use of SDS as a valuable decellularizing agent for porcine tracheas. Furthermore, a cryogenic preservation protocol is described, which has minimal impact on the histological and biomechanical properties of decellularized porcine tracheas.

How do we Classify a Central Tumor? Results of a Multidisciplinary Survey from the SEPAR Thoracic Oncology Area. / ¿Cómo clasificamos un tumor central? Resultados de una encuesta multidisciplinaria propuesta desde el área de Oncología Torácica de SEPAR.

INTRODUCTION: In patients with non-small cell lung cancer (NSCLC) and normal mediastinal imaging tests, centrally located tumors have greater occult mediastinal involvement. Clinical guidelines, therefore, recommend invasive mediastinal staging in this situation. However, definitions of centrality in the different guidelines are inconsistent. The SEPAR Thoracic Oncology area aimed to evaluate the degree of familiarity with various concepts related to tumor site among professionals who see patients with NSCLC in Spain. METHODS: A questionnaire was distributed to members of Spanish medical societies involved in the management of NSCLC, structured according to the 3 aspects to be evaluated: 1) uniformity in the definition of central tumor location; 2) uniformity in the classification of lesions that extend beyond dividing lines; and 3) ability to delineate lesions in the absence of dividing lines. RESULTS: A total of 430 participants responded. The most voted definition of centrality was «lesions in contact with hilar structures¼ (49.7%). The lines most often chosen to delimit the hemitorax were concentric hilar lines (89%). Most participants (92.8%) classified tumors according to the side of the dividing line that contained most of their volume. Overall, 78.6% were able to correctly classify a central lesion in the absence of dividing lines. CONCLUSIONS: In our survey, the most widely accepted definition of centrality is not one of the proposals specified in the clinical guidelines. The results reflect wide variability in the classification of tumor lesions.

Spanish Video-Assisted Thoracic Surgery Group: Method, Auditing, and Initial Results From a National Prospective Cohort of Patients Receiving Anatomical Lung Resections.

INTRODUCTION: Our study sought to know the current implementation of video-assisted thoracoscopic surgery (VATS) for anatomical lung resections in Spain. We present our initial results and describe the auditing systems developed by the Spanish VATS Group (GEVATS). METHODS: We conducted a prospective multicentre cohort study that included patients receiving anatomical lung resections between 12/20/2016 and 03/20/2018. The main quality controls consisted of determining the recruitment rate of each centre and the accuracy of the perioperative data collected based on six key variables. The implications of a low recruitment rate were analysed for "90-day mortality" and "Grade IIIb-V complications". RESULTS: The series was composed of 3533 cases (1917 VATS; 54.3%) across 33 departments. The centres' median recruitment rate was 99% (25-75th:76-100%), with an overall recruitment rate of 83% and a data accuracy of 98%. We were unable to demonstrate a significant association between the recruitment rate and the risk of morbidity/mortality, but a trend was found in the unadjusted analysis for those centres with recruitment rates lower than 80% (centres with 95-100% rates as reference): grade IIIb-V OR=0.61 (p=0.081), 90-day mortality OR=0.46 (p=0.051). CONCLUSIONS: More than half of the anatomical lung resections in Spain are performed via VATS. According to our results, the centre's recruitment rate and its potential implications due to selection bias, should deserve further attention by the main voluntary multicentre studies of our speciality. The high representativeness as well as the reliability of the GEVATS data constitute a fundamental point of departure for this nationwide cohort.

Video-Assisted Thoracic Surgical Repair of the Airway.

We communicate the first reported application of video-assisted thoracic surgery for early repair of a postintubation tracheal laceration. The patient was a 60-year-old man. After an initial unsuccessful approach with conservative measures, surgical repair was indicated. The patient underwent 2-port video-assisted thoracic surgery for direct tracheal repair using a 3-0 resorbable monofilament running suture and two reinforcing X-stitches. Bronchoscopic control after 2 and 4 weeks showed complete restoration of the airway, with no complication.

Clinical Significance of Molecular Micrometastasis in the Sentinel Lymph Node of Early-stage Non-Small Cell Lung Cancer Patients.

OBJECTIVES: Metastatic affectation of lymph node is the main prognostic factor in localized lung cancer. A pathologic study of the obtained samples, even after adequate lymphadenectomy, showed tumor relapses for 20% of stage I patients after oncological curative surgery. We evaluated the prognostic value of molecular micrometastasis in the sentinel lymph node of patients with early-stage lung cancer. PATIENTS AND METHODS: The sentinel node was marked immediately after performing thoracotomy by peritumorally injecting 0.25 mCi of nanocoloid of albumin (Nanocol1) labeled with Tc-99m in 0.3 mL. Guided by a Navigator1 gammagraphic sensor, we proceeded to its resection. The RNA of the tissue was extracted, and the presence of genes CEACAM5, BPIFA1, and CK7 in mRNA was studied. The significant association between the presence of micrometastasis, clinicopathologic characteristics, and patients' outcome was assessed. RESULTS: Eighty-nine stage I-II non-small cell lung cancer patients were included in the study. Of the 89 analyzed sentinel lymph nodes, 44 (49.4%) were positive for CK7, 24 (26.9%) for CEACAM5, and 17 (19.1%) for BPIFA1, whereas 10 (11.2%) were positive for the 3 analyzed genes. A survival analysis showed no significant relation between the presence of molecular micrometastasis in the sentinel node and patients' progression. CONCLUSIONS: The molecular analysis of the sentinel node in patients with early-stage lung cancer shows node affectation in cases staged as stage I/II by hematoxylin-eosin or an immunohistochemical analysis. However, this nodal affectation was not apparently related to patients' outcome.

Association of PD-1, PD-L1, and CTLA-4 Gene Expression and Clinicopathologic Characteristics in Patients With Non-Small-Cell Lung Cancer.

INTRODUCTION: Recent studies show a potential benefit of therapies that target programmed death receptor 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitory checkpoints in a subgroup of patients with non-small-cell lung cancer (NSCLC), without the clinicopathologic characteristics related to positive responses to these treatments being well determined. The aim of this study was to determine PD-1, PD-L1, and CTLA-4 gene expression at the mRNA level in tumoral tissue from patients with NSCLC and analyze their possible relationship with the clinicopathological characteristics and their potential prognostic role. PATIENTS AND METHODS: PD-1, PD-L1, and CTLA-4 expression levels were analyzed using real-time quantitative reverse transcriptase polymerase chain reaction in fresh-frozen tumor and normal adjacent lung tissue samples from 78 patients with NSCLC. Later, a significant association between mRNA levels, clinicopathologic characteristics, and patient's survival was assessed. RESULTS: No significant correlation between gene expression levels and sex, age, histological type, smoking status, pathologic stage, or tumor differentiation was found. However, higher levels of PD-1 were significantly associated with worse prognosis in patients with NSCLC, and PD-L1 overexpression was associated with a worse prognosis in stage I patients and in Grade 1 to 2 tumors. CONCLUSION: Alterations in PD-1/PD-L1 and CTLA-4 expression in lung tumoral tissue seem not to be related to age, sex, smoking status, histological type, pathological stage, or tumor differentiation degree. However, PD-1 and PD-L1 overexpression might predict worse survival in patients with stage I NSCLC and in well differentiated tumors.

[Sentinel lymph node in pulmonary carcinoma. Molecular study after radioisotope detection]. / El ganglio centinela en el carcinoma pulmonar. Estudio molecular tras detección con radioisótopo.

INTRODUCTION: Metastatic lymph node affectation is the main prognostic factor in localized lung cancer. Pathological study of the obtained samples even after an adequate lymphadenectomy, present tumoral relapses of 40% of stage I patients after oncological curative surgery. In this paper we have studied micrometastasis in the sentinel lymph node by molecular methods in patients with stage I lung cancer. MATERIAL AND METHODS: The sentinel node was marked by injecting peritumorally performed just after performing the thoracotomy with 2 mCi of nanocoloid of albumin (Nanocol®) marked with 99mTc in 0.3 ml. Guided with a Navigator® gammagraphic sensor, we proceeded to its resection. RNA of the tissue was extracted and the presence of genes CEACAM5, PLUNC and CK7 in mRNA was studied. RESULTS: Twenty nine 29 patients were included. Of the tested genes, CEACAM5 and PLUNC were the ones that showed a high expression in lung tissue. Of the 29 analyzed sentinel lymph nodes, 7 (24%) were positive in the molecular study. A positive sentinel lymph node was found in 4/7 adenocarcinomas and 3/12 squamous-cell tumors. Affected lymph nodes were: station 5 (1/3), station 7 (0/6), station 9 (0/1); station 10 (5/11); station 11 (1/1). CONCLUSIONS: Detection of sentinel node in patients with stage I lung cancer by marking with radioisotope is a feasible technique. The application of molecular techniques shows the tumoral affectation in cases staged as stage I.

[Diseases of the diaphragm]. / Patología del diafragma.

The diaphragm is the main muscle involved in ventilation and is supplied exclusively by the phrenic nerves. Congenital defects of the diaphragm muscle or phrenic nerve injury cause diaphragmatic paralysis-eventration. Prognosis and treatment depend on whether involvement is unilateral or bilateral and on the patient's previous clinical status. In addition, the diaphragm is an anatomical barrier between the thoracic and abdominal cavities and is traversed by the esophagus and important vascular and nerve structures. Abnormal dilation of the natural orifices of the diaphragm or loss of its continuity can cause abdominal structures to pass into the chest cavity, an occurrence known as diaphragmatic hernias. According to their etiology, hernias are divided into congenital, acquired and traumatic. Clinical manifestations, prognosis and treatment depend mainly on hernia size and age at diagnosis. Like any muscle, the diaphragm can develop benign or malignant primary tumors. However, diaphragm involvement due to tumors arising in adjacent organs is much more common. The prognosis is good in benign primary tumors and poor in both primary and secondary malignant tumors. This article reviews the main anatomical and physiological characteristics of the diaphragm, routes of surgical access and the most frequent diseases affecting this structure.