Pathological complete response in a patient with pleural mesothelioma treated with immunotherapy: a case report.

The role of immunotherapy in the multimodal treatment for pleural mesothelioma (PM) is still under investigation, particularly in the preoperative setting. Pathological complete response (pCR) has been previously described after chemotherapy and immunotherapy; however, there is no prior experience reported with immunotherapy alone before surgery. We report the case of a 58-year-old male with biphasic PM treated with immunotherapy, resulting in a major clinical partial response. Following a multidisciplinary evaluation between thoracic surgeons, medical oncologists, pathologists, radiologists and radiation oncologists, the patient underwent surgery with radical intent through a right extended pleurectomy/decortication (eP/D). Histopathological examination of the specimen confirmed a pathological Complete Response (pCR). This case supports the feasibility and potential efficacy of combining preoperative immunotherapy with surgery in the management of advanced PM.

Endobronchial solitary fibrous tumors: An enigma for diagnosis.

Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms constituting less than 2% of all soft tissue tumors. They typically originate in the thoracic cavity, mainly in the pleura, but can also occur in other various sites such as lung parenchyma, pericardium, and bronchus. In this study, a 49-year-old non-smoking female with a history of allergies presented to our pulmonary clinic with a chronic cough. An explorative bronchoscopy revealed an intrabronchial mass in the left superior bronchi, and a 68 Ga-DOTATOC positron emission computed tomography suggested a carcinoid tumor. Subsequent pulmonary segmentectomy unveiled a well-circumscribed polypoid lesion diagnosed as a low-grade bronchus SFT through histopathological and immunohistochemical assessments. The patient was asymptomatic after surgical excision and showed no other lesion during the 6-month follow-up. The endobronchial location of SFT is uncommon, with only a few reported cases in the literature, underscoring the necessity of considering various differential diagnoses, including carcinoid, mucoepidermoid carcinoma, endobronchial pleomorphic adenoma, hamartoma, leiomyoma, and metastasis, depending on location and imaging features. This report underscores the importance of careful histological and immunohistochemical evaluation in understanding and appropriately stratifying the risk associated with polypoid lesions.

Lung Transplantation in Patients with Previous or Unknown Oncological Disease: Evaluation of Short- and Long-Term Outcomes.

The accurate selection of the recipient is a crucial aspect in the field of lung transplantation (LTX), especially if patients were previously affected by oncological disease. The aim of this bicentric retrospective study was to evaluate short- and long-term outcomes in patients with previous oncological disease or unknown neoplasia found on native lungs submitted to LTX, compared to a control group. A total of 433 patients were included in the analysis, 31 with malignancies (Group 1) and 402 without neoplastic disease (Group 2). The two groups were compared in terms of short- and long-term outcomes. Patients in Group 1 were older (median age 58 years vs. 50 years, p = 0.039) and mostly affected by idiopathic pulmonary fibrosis (55% vs. 40% p = 0.002). Even though in Group 1 a lower rate of late post-operative complications was found (23% vs. 45%, p = 0.018), the median overall survival (OS) was lower compared to the control group (10 months vs. 29 months, p = 0.015). LTX represents a viable therapeutic option for patients with end-stage lung disease and a history of neoplastic disease. However, every case should be carefully debated in a multidisciplinary setting, considering oncological (histology, stage, and proper disease free-interval) and clinical factors (patient's age and comorbidities). A scrupulous post-transplant follow-up is especially mandatory in those cases.

A Multicenter Retrospective Case-Control Study on Simple vs Extended Sleeve Lobectomies.

BACKGROUND: Sleeve resection is currently the gold standard procedure for centrally located non-small cell lung cancer (NSCLC). Extended sleeve lobectomy (ESL) consists of an atypical bronchoplasty with resection of >1 lobe and carries several technical difficulties compared with simple sleeve lobectomy (SSL). Our study compared the outcomes of ESL and SSL for NSCLC. METHODS: This multicenter, retrospective, cohort study included 1314 patients who underwent ESL (155 patients) or SSL (1159 patients) between 2000 and 2018. The primary end points were 30-day and 90-day mortality, overall survival (OS), disease-free survival (DFS), and complications. RESULTS: No differences were found between the 2 groups in general characteristics and surgical and survival outcomes. In particular, there were no differences in early and late complication frequency, 30- and 90-day mortality, R status, recurrence, OS (54.26 ± 33.72 months vs 56.42 ± 32.85 months, P = .444), and DFS (46.05 ± 36.14 months vs 47.20 ± 35.78 months, P = .710). Mean tumor size was larger in the ESL group (4.72 ± 2.30 cm vs 3.81 ± 1.78 cm, P < .001). Stage IIIA was the most prevalent stage in ESL group (34.8%), whereas stage IIB was the most prevalent in SSL group (34.3%; P < .001). The multivariate analyses found nodal status was the only independent predictive factor for OS. CONCLUSIONS: ESL gives comparable short- and long-term outcomes to SSL. Appropriate preoperative staging and exclusion of metastases to mediastinal lymph nodes, as well as complete (R0) resection, are essential for good long-term outcomes.

Perioperative outcomes in redo VATS for pulmonary ipsilateral malignancy: A single center experience.

BACKGROUND: The role of video-assisted thoracoscopic surgery for oncological major pulmonary resections is now well established; however, the literature within pulmonary re-operations is still limited. The purpose of this study is to evaluate the safety and efficacy of redo thoracoscopic resections for ipsilateral pulmonary malignancy. METHODS: Data from patients undergoing video-assisted thoracoscopic surgery at the Unit of Thoracic Surgery of Padua were analyzed, comparing the results between the first and second ipsilateral surgery. The retrospective study included patients who underwent 2 thoracoscopic surgeries for oncological reasons between 2015 and 2022. The variables considered included patients' baseline characteristics, pre, intra, and postoperative data. RESULTS: The study enrolled 51 patients undergoing ipsilateral thoracoscopic re-operation. The statistical analysis showed that surgical time (95min vs 115min; p = 0.009), the presence of intrapleural adhesions at second surgery (30 % vs 76 %; p < 0.001), overall pleural fluid output (200 vs 560 ml; p = 0.003), time with pleural drainage (2 vs 3 days; p = 0.027), air leaks duration time (p = 0.004) and post-operative day of discharge (3 vs 4 days; p = 0.043) were significantly higher in the re-operation group. No statistical differences were observed between the 2 groups respect to R0 resection rate (90.2 % vs 89.1 %; p=>0.9) and complications (5.8 % vs 15.6 %; p = 0.11). The conversion rate to open surgery was 11.8 %. CONCLUSION: Although some differences emerged between the first and second intervention, they had minimal impact on the clinical course of the patients. Therefore, thoracoscopic surgery has been shown to be safe and effective in re-operations with satisfying perioperative outcomes. To achieve such results, these procedures should be reserved for experienced surgeons.

Microscopical Variables and Tumor Inflammatory Microenvironment Do Not Modify Survival or Recurrence in Stage I-IIA Lung Adenocarcinomas.

Microscopical predictors and Tumor Immune Microenvironment (TIME) have been studied less in early-stage NSCLC due to the curative intent of resection and the satisfactory survival rate achievable. Despite this, the emerging literature enforces the role of the immune system and microscopical predictors as prognostic variables in NSCLC and in adenocarcinomas (ADCs) as well. Here, we investigated whether cancer-related microscopical variables and TIME influence survival and recurrence in I-IIA ADCs. We retrospectively collected I-IIA ADCs treated (lobectomy or segmentectomy) at the University Hospital (Padova) between 2016 and 2022. We assigned to pathological variables a cumulative pathological score (PS) resulting as the sum of them. TIME was investigated as tumor-infiltrating lymphocytes (TILs < 11% or ≥11%) and PD-L1 considering its expression (<1% or ≥1%). Then, we compared survival and recurrence according to PS, histology, TILs and PD-L1. A total of 358 I-IIA ADCs met the inclusion criteria. The median PS grew from IA1 to IIA, indicating an increasing microscopical cancer activity. Except for the T-SUVmax, any pathological predictor seemed to be different between PD-L1 < 1% and ≥1%. Histology, PS, TILs and PD-L1 were unable to indicate a survival difference according to the Log-rank test (p = 0.37, p = 0.25, p = 0.41 and p = 0.23). Even the recurrence was non-significant (p = 0.90, p = 0.62, p = 0.97, p = 0.74). According to our findings, resection remains the best upfront treatment in I-IIA ADCs. Microscopical cancer activity grows from IA1 to IIA tumors, but it does not affect outcomes. These outcomes are also unmodified by TIME. Probably, microscopical cancer development and immune reaction against cancer are overwhelmed by an adequate R0-N0 resection.

Radiomics of spinal muscles: toward a radiological biomarker for allograft rejection in lung transplant.

PURPOSE: To assess the role of muscle composition and radiomics in predicting allograft rejection in lung transplant. MATERIAL AND METHODS: The last available HRCT before surgery of lung transplant candidates referring to our tertiary center from January 2010 to February 2020 was retrospectively examined. Only scans with B30 kernel reconstructions and 1 mm slice thickness were included. One radiologist segmented the spinal muscles of each patient at the level of the 11th dorsal vertebra by an open-source software. The same software was used to extract Hu values and 72 radiomic features of first and second order. Factor analysis was applied to select highly correlating features and then their prognostic value for allograft rejection was investigated by logistic regression analysis (level of significance p < 0.05). In case of significant results, the diagnostic value of the model was computed by ROC curves. RESULTS: Overall 200 patients had a HRCT prior to the transplant but only 97 matched the inclusion criteria (29 women; mean age 50.4 ± 13 years old). Twenty-one patients showed allograft rejection. The following features were selected by the factor analysis: cluster prominence, Imc2, gray level non-uniformity normalized, median, kurtosis, gray level non-uniformity, and inverse variance. The radiomic-based model including also Hu demonstrated that only the feature Imc2 acts as a predictor of allograft rejection (p = 0.021). The model showed 76.6% accuracy and the Imc2 value of 0.19 demonstrated 81% sensitivity and 64.5% specificity in predicting lung transplant rejection. CONCLUSION: The radiomic feature Imc2 demonstrated to be a predictor of allograft rejection in lung transplant.

Intrathymic Localization of Melanoma: A Brief Report of Two Cases and a Review of the Literature.

Intrathymic localizations of melanoma represent a very rare entity, with fewer than ten cases of intrathymic melanoma described in the literature. Herein, we describe two cases of patients who underwent surgical removal of a thymic mass at our thoracic surgery department between 2015 and 2022. The final pathological examination revealed a malignant melanoma in both cases; we therefore carried out a literature review to identify such rare and similar cases. In the first case, the intrathymic localization of melanoma was the first manifestation of the disease, posing a dilemma regarding the metastatic and primitive nature of the neoplasm. The second case described a thymic metastasis from a known previous cutaneous melanoma, for which the patient had successfully been treated six years earlier. After carefully reviewing the literature, we identified only six cases of verified primary intrathymic melanomas and one case of intrathymic metastasis resulting from melanoma previously described. Pathologists should be aware of the occurrence of this rare entity and mindful of the differential diagnoses. Several tools, including immunostaining of melanocytic markers and molecular investigations, are mandatory for final pathological diagnosis.

Macrophages-derived Factor XIII links coagulation to inflammation in COPD.

Background: The local, extravascular, activation of the coagulation system in response to injury is a key factor mediating the resulting inflammatory response. Coagulation Factor XIIIA (FXIIIA) found in alveolar macrophages (AM) and dendritic cells (DC), by influencing fibrin stability, might be an inflammatory modifier in COPD. Aims: To study the expression of FXIIIA in AM and Langerin+DC (DC-1) and their relation to the inflammatory response and disease progression in COPD. Methods: In 47 surgical lungs, 36 from smokers (22 COPD and 14 no-COPD) and 11 from non-smokers we quantified by immunohistochemistry FXIIIA expression in AM and DC-1 along with numbers of CD8+Tcells and CXCR3 expression in lung parenchyma and airways. Lung function was measured prior to surgery. Results: The percentage of AM expressing FXIII (%FXIII+AM) was higher in COPD than no-COPD and non-smokers. DC-1 expressed FXIIIA and their numbers were higher in COPD than no-COPD and non-smokers. DC-1 positively correlated with %FXIII+AM (r=0.43; p<0.018). CD8+Tcells, which were higher in COPD than in no-COPD, were correlated with DC-1 (p<0.01) and %FXIII+AM. CXCR3+ cells were increased in COPD and correlated with %FXIII+AM (p<0.05). Both %FXIII+AM (r=-0.6; p=0.001) and DC-1 (r=-0.7; p=0.001) correlated inversely with FEV1. Conclusion: FXIIIA, an important link between the extravascular coagulation cascade and inflammatory response, is significantly expressed in alveolar macrophages and dendritic cells of smokers with COPD, suggesting that it could play an important role in the adaptive inflammatory reaction characteristic of the disease.

Vascular/epithelial changes as late sequelae after recovery from SARS-COV-2 infection: an in-vivo comparative study.

AIMS: While there is partial evidence of lung lesions in patients suffering from long COVID there are substantial concerns about lung remodelling sequelae after COVID-19 pneumonia. The aim of the present retrospective comparative study was to ascertain morphological features in lung samples from patients undergoing tumour resection several months after SARS-CoV-2 infection. METHODS AND RESULTS: The severity of several lesions with a major focus on the vascular bed was analysed in 2 tumour-distant lung fragments of 41 cases: 21 SARS-CoV-2 (+) lung tumour (LT) patients and 20 SARS-CoV-2 (-) LT patients. A systematic evaluation of several lesions was carried out by combining their scores into a grade of I-III. Tissue SARS-CoV-2 genomic/subgenomic transcripts were also investigated. Morphological findings were compared with clinical, laboratory and radiological data. SARS-CoV-2 (+) LT patients with previous pneumonia showed more severe parenchymal and vascular lesions than those found in SARS-CoV-2 (+) LT patients without pneumonia and SARS-CoV-2 (-) LT patients, mainly when combined scores were used. SARS-CoV-2 viral transcripts were not detected in any sample. SARS-CoV-2 (+) LT patients with pneumonia showed a significantly higher radiological global injury score. No other associations were found between morphological lesions and clinical data. CONCLUSIONS: To our knowledge, this is the first study that, after a granular evaluation of tissue parameters, detected several changes in lungs from patients undergoing tumour resection after SARS-CoV-2 infection. These lesions, in particular vascular remodelling, could have an important impact overall on the future management of these frail patients.

Precision Surgery in NSCLC.

Non-small cell lung cancer (NSCLC) is still one of the leading causes of death worldwide. This is mostly because the majority of lung cancers are discovered in advanced stages. In the era of conventional chemotherapy, the prognosis of advanced NSCLC was grim. Important results have been reported in thoracic oncology since the discovery of new molecular alterations and of the role of the immune system. The advent of new therapies has radically changed the approach to lung cancer for a subset of patients with advanced NSCLC, and the concept of incurable disease is still changing. In this setting, surgery seems to have developed a role of rescue therapy for some patients. In precision surgery, the decision to perform surgical procedures is tailored to the individual patient; taking into consideration not only clinical stage, but also clinical and molecular features. Multimodality treatments incorporating surgery, immune checkpoint inhibitors, or targeted agents are feasible in high volume centers with good results in terms of pathologic response and patient morbidity. Thanks to a better understanding of tumor biology, precision thoracic surgery will facilitate optimal and individualized patient selection and treatment, with the goal of improving the outcomes of patients affected by NSCLC.

Molecular Profiling of Tissue Samples with Chronic Rejection from Patients with Chronic Lung Allograft Dysfunction: A Pilot Study in Cystic Fibrosis Patients.

Chronic rejection (CR) is the main culprit for reduced survival and quality of life in patients undergoing lung transplantation (Ltx). High-throughput approaches have been used to unveil the molecular pathways of CR, mainly in the blood and/or in bronchoalveolar lavage. We hypothesized that a distinct molecular signature characterizes the biopsies of recipients with clinically confirmed histological signs of CR. Eighteen cystic fibrosis patients were included in the study and RNA sequencing was performed in 35 scheduled transbronchial biopsies (TBBs): 5 with acute cellular rejection, 9 with CR, and 13 without any sign of post-LTx complication at the time of biopsy; 8 donor lung samples were used as controls. Three networks with 33, 26, and 36 differentially expressed genes (DEGs) were found in TBBs with CR. Among these, seven genes were common to the identified pathways and possibly linked to CR and five of them (LCN2, CCL11, CX3CL1, CXCL12, MUC4) were confirmed by real-time PCR. Immunohistochemistry was significant for LCN2 and MUC4. This study identified a typical gene expression pattern in TBBs with histological signs of CR and the LCN2 gene appeared to play a central role. Thus, it could be crucial in CR pathophysiology.

A multicentric evaluation of pediatric lung transplantation in Italy.

BACKGROUND: Pediatric lung transplantation is performed in highly experienced centers due to the peculiar population characteristics. The literature is limited and not representative of individual countries' differences. The purpose of this study was to analyze the Italian experience. METHODS: A multicentric retrospective analysis was performed on 110 pediatric patients (<18 years old) who underwent lung transplantation from 1992 to 2019 at 9 Italian centers. Heart-lung transplantations and lung retransplantations were excluded. RESULTS: The population was composed of 44 male and 66 female patients, with a median age of 15 years. The most frequent indication was cystic fibrosis (83%). One quarter of patients were transplanted in an emergency setting. Median donors' Oto score and age were 1 and 15 years, respectively, with 43% of adult donors. In 17% of patients a graft reduction was performed. Postoperatively, the median duration of mechanical ventilation, intensive care unit, and in-hospital stay were 48 hours, 11 and 35 days, respectively. Thirty-day mortality was 6%, and 1-, 5-, and 10-year survival was 72%, 52%, and 33%, respectively. Risk factors for mortality were Oto score and recipients' body mass index. CONCLUSIONS: The outcomes of pediatric lung transplantation in Italy are comparable with current literature. Particular attention should be paid to the Oto score and recipient body mass index. Conversely, adult donors and graft reductions can be safely used to expand the donor pool.

Evaluation of Tissue Ischemia/Reperfusion Injury in Lung Recipients Supported by Intraoperative Extracorporeal Membrane Oxygenation: A Single-Center Pilot Study.

Intraoperative veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) as intraoperative hemodynamic support during lung transplantation is becoming a standard practice due to promising clinical results. Nevertheless, studies on tissue/molecular pathways investigating ischemia/reperfusion injury are still lacking. Patients receiving a bilateral lung transplantation between January 2012 and December 2018 at the University Hospital of Padova were included in this retrospective single-center observational study. The present study aimed to investigate ischemia/reperfusion injury in 51 tissue specimens obtained from 13 recipients supported by intraoperative VA-ECMO and 38 who were not. Several tissue analyses, including apoptosis evaluation and inducible nitric oxide synthase expression, were performed on the biopsies at the time of transplantation. Lung samples from the ECMO group (both pre- and post-reperfusion) were comparable, or for some parameters better, than samples from the non-ECMO group. Leukocyte margination was significantly lower in the ECMO group than in the non-ECMO group. Primary graft dysfunction, mainly at 24 and 48 h, was correlated with the tissue injury score of the post-reperfusion biopsy. The interquartile ranges for all morphological parameters showed high grade variability between pre- and post-reperfusion in the non-ECMO group. These preliminary data support the use of intraoperative ECMO based on lower lung tissue ischemia/reperfusion injury. Larger case series are mandatory to confirm our findings.

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.

Sarcopenia as a Predictor of Short- and Long-Term Outcomes in Patients Surgically Treated for Malignant Pleural Mesothelioma.

Surgery for malignant pleural mesothelioma (MPM) should be reserved only for patients who have a good performance status. Sarcopenia, a well-known predictor of poor outcomes after surgery, is still underinvestigated in MPM. The aim of this study is to evaluate the role of sarcopenia as a predictor of short-and long-term outcomes in patients surgically treated for MPM. In our analysis, we included patients treated with a cytoreductive intent in a multimodality setting, with both pre- and post-operative CT scans without contrast available. We excluded those in whom a complete macroscopic resection was not achieved. Overall, 86 patients were enrolled. Sarcopenia was assessed by measuring the mean muscular density of the bilateral paravertebral muscles (T12 level) on pre-and post-operative CTs; a threshold value of 30 Hounsfield Units (HU) was identified. Sarcopenia was found pre-operatively in 57 (66%) patients and post-operatively in 61 (74%). Post-operative sarcopenic patients had a lower 3-year overall survival (OS) than those who were non-sarcopenic (34.9% vs. 57.6% p = 0.03). Pre-operative sarcopenia was significantly associated with a higher frequency of post-operative complications (65% vs. 41%, p = 0.04). The evaluation of sarcopenia, through a non-invasive method, would help to better select patients submitted to surgery for MPM in a multimodality setting.

Multidrug-Resistant and Extended-Spectrum ß-Lactamase Gram-Negative Bacteria in Bilateral Lung Transplant Recipients: Incidence, Risk Factors, and In-Hospital Mortality.

BACKGROUND: In recent decades, the incidence of multidrug-resistant (MDR) and extended-spectrum ß-lactamase (ESBL) gram-negative (GN) bacteria has increased progressively among lung transplantation (LT) recipients. A prompt diagnosis, prevention, and management of these pathogens remain the cornerstone for successful organ transplantation. RESEARCH QUESTION: What are the incidence of MDR and ESBL GN bacteria within the first 30 days after LT and related risk of in-hospital mortality? What are the potential clinical predictors of isolation of MDR and ESBL GN bacteria? STUDY DESIGN AND METHODS: All consecutive LT recipients admitted to the ICU of the University Hospital of Padua (February 2016-December 2021) were screened retrospectively. Only adult patients undergoing the first bilateral LT and not requiring invasive mechanical ventilation, extracorporeal membrane oxygenation, or both before surgery were included. MDR and ESBL GN bacteria were identified using in vitro susceptibility tests and were isolated from the respiratory tract, blood, urine, rectal swab, or surgical wound or drainage according to a routine protocol. RESULTS: One hundred fifty-three LT recipients were screened, and 132 were considered for analysis. Median age was 52 years (interquartile range, 41-60 years) and 46 patients (35%) were women. MDR and ESBL GN bacteria were identified in 45 patients (34%), and 60% of patients demonstrated clinically relevant infection. Pseudomonas aeruginosa (n = 22 [49%]) and Klebsiella pneumoniae (n = 17 [38%]) were frequently isolated after LT from the respiratory tract (n = 21 [47%]) and multiple sites (n = 18 [40%]). Previous recipient-related colonization (hazard ratio [HR], 2.48 [95% CI, 1.04-5.90]; P = .04) and empirical exposure to broad-spectrum antibiotics (HR, 6.94 [95% CI, 2.93-16.46]; P < .01) were independent predictors of isolation of MDR and ESBL GN bacteria. In-hospital mortality of the MDR and ESBL group was 27% (HR, 6.38 [95% CI, 1.98-20.63]; P < .01). INTERPRETATION: The incidence of MDR and ESBL GN bacteria after LT was 34%, and in-hospital mortality was six times greater. Previous recipient-related colonization and empirical exposure to broad-spectrum antibiotics were clinical predictors of isolation of MDR and ESBL GN bacteria.

Tracheal resection and anastomosis for squamous cell carcinoma.

Tracheal malignant tumors are uncommon lesions. The rarity of this condition may generate uncertainties in the diagnosis and treatment. For this reason especially, the surgical treatment should be performed only in centers with a high expertise in tracheal surgery. If the involved tracheal tract is less than 4-5 cm and the tumor is localized, the treatment of choice is based on a segmental tracheal resection with an end-to-end anastomosis. In this video tutorial, we describe how we perform tracheal resection with an end-to-end anastomosis in a patient with a squamous cell carcinoma.

RNA Sequencing of Epithelial Cell/Fibroblastic Foci Sandwich in Idiopathic Pulmonary Fibrosis: New Insights on the Signaling Pathway.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease characterized by irreversible scarring of the distal lung. IPF is best described by its histopathological pattern of usual interstitial pneumonia (UIP), characterized by spatial heterogeneity with alternating interstitial fibrosis and areas of normal lung, and temporal heterogeneity of fibrosis characterized by scattered fibroblastic foci (FF), dense acellular collagen and honeycomb changes. FF, comprising aggregated fibroblasts/myofibroblasts surrounded by metaplastic epithelial cells (EC), are the cardinal pathological lesion and their presence strongly correlates with disease progression and mortality. We hypothesized that the EC/FF sandwich from patients with UIP/IPF has a distinct molecular signature which could offer new insights into the crosstalk of these two crucial actors in the disease. Laser capture microdissection with RNAseq was used to investigate the transcriptome of the EC/FF sandwich from IPF patients versus controls (primary spontaneous pneumothorax). Differentially expressed gene analysis identified 23 up-regulated genes mainly related to epithelial dysfunction. Gene ontology analysis highlighted the activation of different pathways, mainly related to EC, immune response and programmed cell death. This study provides novel insights into the IPF pathogenetic pathways and suggests that targeting some of these up-regulated pathways (particularly those related to secreto-protein/mucin dysfunction) may be beneficial in IPF. Further studies in a larger number of lung samples, ideally from patients with early and advanced disease, are needed to validate these findings.