Giant intrathoracic cystic schwannoma resected by video-assisted thoracoscopic surgery.

Schwannoma is a benign tumour originating from the Schwann cells. Patients can remain asymptomatic, as the onset of symptoms usually depends on the compressive effect on adjacent organs; dimensional and morphological variability increase the time for the diagnosis. We report the case of a successful surgical resection, performed by video-assisted thoracoscopic surgery, on a patient with radiological evidence of a massive cystic intrathoracic neoformation, histologically revealed to be a peculiar Schwannoma.

Concomitant Intubation with Minimal Cuffed Tube and Rigid Bronchoscopy for Severe Tracheo-Carinal Obstruction.

BACKGROUND: Our aim was to report on the use of an innovative technique for airway management utilizing a small diameter, short-cuffed, long orotracheal tube for assisting operative rigid bronchoscopy in critical airway obstruction. METHODS: We retrospectively reviewed the clinical data of 36 patients with life-threatening critical airway stenosis submitted for rigid bronchoscopy between January 2008 and July 2021. The supporting ventilatory tube, part of the Translaryngeal Tracheostomy KIT (Fantoni method), was utilized in tandem with the rigid bronchoscope during endoscopic airway reopening. RESULTS: Indications for collateral intubation were either tumors of the trachea with near-total airway obstruction (13), or tumors of the main carina with total obstruction of one main bronchus and possible contralateral involvement (23). Preliminary dilation was necessary before tube placement in only 2/13 patients with tracheal-obstructing tumors (15.4%). No postoperative complications were reported. There was one case of an intraoperative cuff tear, with no further technical problems. CONCLUSIONS: In our experience, this innovative method proved to be safe, allowing for continuous airway control. It enabled anesthesia inhalation, use of neuromuscular blockage and reliable end-tidal CO2 monitoring, along with protection of the distal airway from blood flooding. The shorter time of the procedure was due to the lack of need for pauses to ventilate the patient.

Massive, life-threatening hemoptysis due to localized granulomatosis with polyangiitis.

Massive hemoptysis may be related to a wide spectrum of diseases whose differential diagnosis can be challenging, also due to the medical emergency condition.We present a case of a 33-year-old woman presented to our department with sudden, life-threatening hemoptysis from unknown etiology, which required a rescue pulmonary lobectomy after resuscitation maneuvers. Histology proved to be a localized Wegener granulomatosis. Our case shows that granulomatosis should always be considered among the possible, although rarer, causes of massive hemoptysis.

A New Medium (HistoCold) for Surgical Specimens Preserving to Improve the Preanalytic Issues in Histopathological Samples Handling: Morphologic and Antigenic Analysis.

Introduction: The onset of precision medicine has led to the integration of traditional morphologic tissues evaluation with biochemical and molecular data for a more appropriate pathological diagnosis. The preanalytic phase and, particularly, timing of cold ischemia are crucial to guarantee high-quality biorepositories of formalin-fixed paraffin-embedded (FFPE) tissues for patients' needs and scientific research. However, delayed fixation using the gold-standard and carcinogenic fixative neutral-buffered formalin (NBF) can be a significant limitation to diagnosis and biopathological characterization. HistoCold (patented; Bio-Optica Milano S.p.A., Milano, Italy) is a nontoxic, stable, and refrigerated preservative solution for tissue handling. This study examined HistoCold's potential role in improving the preanalytic phase of the pathological diagnostic process. Materials and Methods: Breast, lung, or colorectal cancers (20, 25, and 10 cases, respectively) that were to be surgically resected were recruited between 2019 and 2021. Once specimens were surgically removed, three residual samples for each patient were first promptly immersed into HistoCold for 24, 48, and 72 hours and then FFPE. These were compared with routine specimens regarding morphologic features (hematoxylin and eosin) and tissue antigenicity (immunohistochemical stains). Results: Good concordance regarding both the morphologic characteristics of the neoplasms and their proteins expression between the routine and HistoCold handled tissues were found. The tissue handling with the solution never affected the histopathological diagnosis. Conclusions: The use of HistoCold for samples transporting is easy, allows for improving the management of cold ischemia time, and monitoring the fixation times in NBF, resulting in good quality tissue blocks for biobanking. Moreover, it could be a candidate to eliminate formalin from operating theaters. HistoCold looks very promising for the preanalytic phase of human tissues handling in the era of precision medicine, to provide the best service to patients, and to scientific research.

Prognostic Significance of Pulmonary Multifocal Neuroendocrine Proliferation With Typical Carcinoid.

BACKGROUND: The clinical significance of multifocal pulmonary neuroendocrine proliferation (MNEP), including tumorlets and pulmonary neuroendocrine cell hyperplasia, in association with typical carcinoid (TC), is still debated. METHODS: We evaluated a retrospective series of TC with long-term follow-up data prospectively collected from 2 institutions and compared the outcome between TC alone and MNEP plus TC. Several baseline covariates were imbalanced between the MNEP plus TC and TC groups; therefore, we conducted 1:1 propensity score matching and inverse probability of treatment weighting in the full sample. In the matched group, the association of clinical, respiratory, and work-related factors with the group was determined through univariable and multivariable conditional logistic regression analysis. RESULTS: A total of 234 TC patients underwent surgery: 41 MNEP plus TC (17.5%) and 193 TC alone (82.5%). In the MNEP plus TC group, older age (P < .001), peripheral tumors (P = .0032), smaller tumor size (P = .011), and lymph node spread (P = .02) were observed compared with the TC group. Relapses occurred in 8 patients in the MNEP plus TC group (19.5%) and 7 in the TC group (3.6%). After matching, in 36 pairs of patients, a significantly higher 5-year progression-free rate was observed for the TC group (P < .01). Similar results were observed using inverse probability of treatment weighting in the full sample. The odds of being in the MNEP plus TC group was higher for those with work-related exposure to inhalant agents (P = .008), asthma or bronchitis (P = .002), emphysema, fibrosis, and inflammatory status (P = .032), or micronodules on the chest computed tomography scan and respiratory insufficiency (P = .036). CONCLUSIONS: The association with MNEP seems to represent a clinically and prognostic relevant factor in TC. Hence, careful preoperative workup, systematic pathologic evaluation, including nontumorous lung parenchyma, and long-term postoperative follow-up should be recommended in these patients.

Accuracy of 18F-FDG in Detecting Stage I Lung Adenocarcinomas According to IASLC/ATS/ERS Classification.

BACKGROUND: Only a small number of studies have explored the clinicopathological features of pulmonary adenocarcinoma (PA) associated with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) false-negative (FN) results. Herein, we investigated the FDG-PET diagnostic performance by stratifying PAs according to International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification. METHODS: From January 2002 to December 2016, all consecutive patients who underwent pulmonary resection for stage I PA at six thoracic surgery institutions were retrospectively reviewed. The diagnostic performance of FDG-PET was analysed according to IASLC/ATS/ERS classification and two validated subclassifications. Univariable and multivariable logistic analysis were used to identify predictors of FDG-PET FN results. RESULTS: Five hundred and fifty (550) patients with stage I PA were included in the analyses. Most of the patients were male (n=354 [64.4%]) and smokers (n=369 [67.1%]). Ninety-seven (n=97 [17.6%]) FN cases were observed at FDG-PET imaging. On multivariable analysis, a lepidic pattern was found to be independently associated with FDG-PET FN results (odds ratio [OR], 3.20; p<0.001), while a solid pattern more commonly presented with a positive finding (OR, 0.40; p=0.066). According to Nakamura's classification, we observed an independent association between lepidic pattern and FDG-PET FN results (OR, 3.17; p<0.001), while solid/micropapillary patterns were independently related with increased FDG uptake (OR, 0.35; p=0.021). According to Yoshizawa's classification, Intermediate-grade tumours were independently correlated with FN FDG-PET results (OR, 2.78; p=0.005). CONCLUSIONS: In our cohort, histopathological features were significantly associated with FDG uptake. In particular, some adenocarcinoma subtypes (mostly Lepidic pattern) have a tendency towards FN FDG-PET findings. The correlation between computed tomography findings, clinical characteristics, and FDG uptake is mandatory, in order to tailor the precise diagnostic and therapeutic pathway for each patient.

Genome-wide expression of the residual lung reacting to experimental Pneumonectomy.

BACKGROUND: Acute or chronic irreversible respiratory failure may occur in patients undergoing pneumonectomy. Aim of this study was to determine transcriptome expression changes after experimental pneumonectomy in swine model. Experimental left pneumonectomy was performed in five pigs under general anaesthesia. Both the resected and the remaining lung, after 60 post-operative completely uneventful days, underwent genome-wide bulk RNA-Sequencing (RNA-Seq). RESULTS: Histological analysis showed dilation of air spaces and rupture of interalveolar septa. In addition, mild inflammation, no fibrosis, radial stretch of the bronchus, strong enlargement of airspaces and thinning of the blood supply were observed. Bioinformatic analyses of bulk RNA-Seq data identified 553 Differentially Expressed Genes (DEGs) at adjusted P-value below 0.001, between pre- and post-pneumonectomy. The top 10 up-regulated DEGs were Edn1, Areg, Havcr2, Gadd45g, Depp1, Cldn4, Atf3, Myc, Gadd45b, Socs3; the top 10 down-regulated DEGs were Obscn, Cdkn2b, ENSSSCG00000015738, Prrt2, Amer1, Flrt3, Efnb2, Tox3, Znf793, Znf365. Leveraging digital cytometry tools, no difference in cellular abundance was found between the two experimental groups, while the analysis of cell type-specific gene expression patterns highlighted a striking predominance of macrophage-specific genes among the DEGs. DAVID-based gene ontology analysis showed a significant enrichment of "Extrinsic apoptotic signaling pathway" (FDR q = 7.60 × 10- 3) and "Response to insulin" (FDR q = 7.60 × 10- 3) genes, along with an enrichment of genes involved as "Negative regulators of DDX58/IFIH1 signaling" (FDR q = 7.50 × 10- 4) found by querying the REACTOME pathway database. Gene network analyses indicated a general dysregulation of gene inter-connections. CONCLUSION: This translational genomics study highlighted the existence both of individual genes, mostly dysregulated in certain cellular populations (e.g., macrophages), and gene-networks involved in pulmonary reaction after left pneumonectomy. Their involvement in lung homeostasis is largely supported by previous studies, carried out both in humans and in other animal models (under homeostatic or disease-related conditions), that adopted candidate-gene approaches. Overall, the present findings represent a preliminary assessment for future, more focused, studies on compensatory lung adaptation, pulmonary regeneration and functional reload.

Impact of Epithelial-Mesenchymal Immunophenotype on Local Aggressiveness in Papillary Thyroid Carcinoma Invading the Airway.

Primary thyroid tumours show different levels of aggressiveness, from indolent to rapidly growing infiltrating malignancies. The most effective therapeutic option is surgery when radical resection is feasible. Biomarkers of aggressiveness may help in scheduling extended resections such as airway infiltration, avoiding a non-radical approach. The aim of the study is to evaluate the prognostic role of E-cadherin, N-cadherin, Aryl hydrocarbon receptor (AhR), and CD147 in different biological behaviours. Fifty-five samples from three groups of thyroid carcinomas were stained: papillary thyroid carcinomas (PTCs) infiltrating the airway (PTC-A), papillary intra-thyroid carcinomas (PTC-B) and poorly differentiated or anaplastic thyroid carcinomas (PDTC/ATC). High expressions of N-cadherin and AhR were associated with higher locoregional tumour aggressiveness (p = 0.005 and p < 0.001 respectively); PDTC/ATC more frequently showed a high expression of CD147 (p = 0.011), and a trend of lower expression of E-cadherin was registered in more aggressive neoplasms. Moreover, high levels of AhR were found with recurrent/persistent diseases (p = 0.031), particularly when tumours showed a concomitant high N-cadherin expression (p = 0.043). The study suggests that knowing in advance onco-biological factors with a potential role to discriminate between different subsets of patients could help the decision-making process, providing a more solid therapeutic indication and an increased expectation for radical surgery.

Pulmonary Hamartoma Associated With Lung Cancer (PHALC Study): Results of a Multicenter Study.

PURPOSE: Pulmonary hamartoma is the most common benign tumor of the lung. We analyzed a 20-year historical series of patients with pulmonary hamartoma undergoing surgical resection, aiming to evaluate the characteristics, the outcomes, and the association between hamartoma and lung cancer. METHODS: It was a retrospective multicenter study including the data of all consecutive patients with pulmonary hamartoma undergoing surgical resection. The end-points were to evaluate: (i) the characteristics of hamartoma, (ii) outcomes, and (iii) whether hamartoma was a predictive factor for lung cancer development RESULTS: Our study population included 540 patients. Upfront surgical or endoscopic resection was performed in 385 (71%) cases while in the remaining 155 (29%) cases, the lesions were resected 20 ± 3.5 months later due to increase in size. In most cases, lung sparing resection was carried out including enucleation (n = 259; 48%) and wedge resection (n = 230; 43%) while 5 (1%) patients underwent endoscopic resection. Only two patients (0, 2%) had major complications. One patient (0.23%) had recurrence after endoscopic resection, while no cases of malignant degeneration were seen (mean follow-up:103.3 ± 93 months). Seventy-six patients (14%) had associated lung cancer, synchronous in 9 (12%) and metachronous in 67 (88%). Only age > 70-year-old (p = 0.0059) and smokers > 20 cigarettes/day (p < 0.0001) were the significant risk factors for lung cancer. CONCLUSION: PH was a benign tumor, with no evidence of recurrence and/or of malignant degeneration after resection. The association between hamartoma and lung cancer was a spurious phenomenon due to common risk factors.

Kynurenine/Tryptophan Ratio as a Potential Blood-Based Biomarker in Non-Small Cell Lung Cancer.

The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) degrade tryptophan (Trp) into kynurenine (Kyn) at the initial step of an enzymatic pathway affecting T cell proliferation. IDO1 is highly expressed in various cancer types and associated with poor prognosis. Nevertheless, the serum Kyn/Trp concentration ratio has been suggested as a marker of cancer-associated immune suppression. We measured Kyn and Trp in blood samples of a wide cohort of non-small-cell lung cancer (NSCLC) patients, before they underwent surgery, and analyzed possible correlations of the Kyn/Trp ratio with either IDO1 expression or clinical-pathological parameters. Low Kyn/Trp significantly correlated with low IDO1 expression and never-smoker patients; while high Kyn/Trp was significantly associated with older (≥68 years) patients, advanced tumor stage, and squamous cell carcinoma (Sqcc), rather than the adenocarcinoma (Adc) histotype. Moreover, high Kyn/Trp was associated, among the Adc group, with higher tumor stages (II and III), and, among the Sqcc group, with a high density of tumor-infiltrating lymphocytes. A trend correlating the high Kyn/Trp ratio with the probability of recurrences from NSCLC was also found. In conclusion, high serum Kyn/Trp ratio, associated with clinical and histopathological parameters, may serve as a serum biomarker to optimize risk stratification and therapy of NSCLC patients.

Rescue Tracheostomy for Patients With Unresectable Large Growing Neck Masses.

Most patients with undifferentiated thyroid cancer have unresectable disease with a very high rate of airway compromise. Tracheostomy typically entails technical issues in these cases. In fact, it can be very difficult to expose or simply locate the trachea beneath the mass, and the extensive soft tissue involvement can force the surgeon to cut the tumor to place the tracheostomy tube. The combined use of rigid bronchoscopy and percutaneous tracheostomy techniques, applied in an open surgical procedure, can greatly simplify the procedure. Furthermore, by this method, the airways are quickly secured and the risk of intraoperative bleeding is reduced.

High PD-L1/IDO-2 and PD-L2/IDO-1 Co-Expression Levels Are Associated with Worse Overall Survival in Resected Non-Small Cell Lung Cancer Patients.

Programmed death ligand 1 (PD-L1) expression is a predictive biomarker of the success of PD-1/PD-L1 inhibitor therapy for patients with advanced non-small cell lung cancer (NSCLC) but its role as a prognostic marker for early-stage resectable NSCLC remains unclear. We studied gene expression levels of immune-related genes PD-1, PD-L1, PD-L2, IDO-1, IDO-2 and INFγ in tumor tissue of surgically resected NSCLC and correlated the finding with clinicopathological features and patient outcomes. A total of 191 consecutive early-stage NSCLC patients who underwent curative pulmonary resection were studied. The mRNA expression levels of immune-related genes were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) using RT2 Profiler PCR Arrays (Qiagen). PD-1, PD-L2 and IDO-2 gene expression levels were significantly higher in patients with squamous histology (p = 0.001, p = 0.021 and p < 0.001; respectively). PD-1, PD-L1 and IDO-2 gene expression levels were significantly higher in patients with higher stage (p = 0.005, p = 0.048 and p = 0.002, respectively). The univariate analysis for recurrence-free survival (RFS) and overall survival (OS) showed that patients with higher levels of three-genes (PD-L1/PD-L2/INFγ) (hazard ratio (HR)) 1.90 (95% confidence interval (CI), 1.13-3.21), p = 0.015) were associated with a worse RFS, while patients with higher levels of both genes (PD-L1/IDO-2) or (PD-L2/IDO-1) were associated with a worse OS (HR 1.63 95% CI, 1.06-2.51, p = 0.024; HR 1.54 95% CI, 1.02-2.33, p = 0.04; respectively). The multivariate interaction model adjusted for histology and stage confirmed that higher levels of three genes (PD-L1/PD-L2/INFγ) were significantly associated with worse RFS (HR 1.98, p = 0.031) and higher levels of both genes (PD-L1/IDO-2) and (PD-L2/IDO-1) with worse OS (HR 1.98, p = 0.042, HR 1.92, p = 0.022). PD-L1/IDO-2 and PD-L2/IDO-1 co-expression high levels are independent negative prognostic factors for survival in early NSCLC. These features may have important implications for future immune-checkpoint therapeutic approaches.

A risk stratification scheme for synchronous oligometastatic non-small cell lung cancer developed by a multicentre analysis.

BACKGROUNDS: Oligometastatic Non-Small Cell Lung Cancer (NSCLC) patients represent a category without a standard therapeutic approach. However, in selected oligometastatic NSCLC, radical surgery seems to offer a good prognosis. This retrospective study aimed to analyse the long-term outcomes of synchronous oligometastatic patients treated with curative intent and identify the factors associated with better results and the proposal of a risk stratification system for classifying the synchronous oligometastatic NSCLC. METHODS: The medical records of patients from 18 centres with pathologically diagnosed synchronous oligometastatic NSCLC were retrospectively reviewed. The inclusion criteria were synchronous oligometastatic NSCLC, radical surgical treatment of the primary tumour with or without neoadjuvant/adjuvant therapy and radical treatment of all metastatic sites. The Kaplan - Meier method estimated survivals. A stratified backward stepwise Cox regression model was assessed for multivariable survival analyses. RESULTS: 281 patients were included. The most common site of metastasis was the brain, in 50.89 % patients. Median overall survival was 40 months (95 % CI: 29-53). Age ≤65 years (HR = 1.02, 95 % CI: 1.00-1.05; p = 0.019), single metastasis (HR = 0.71, 95 % CI: 0.45-1.13; p = 0.15) and presence of contralateral lung metastases (HR = 0.30, 95 % CI: 0.15 - 0.62; p = 0.001) were associated with a good prognosis. The presence of pathological N2 metastases negatively affected survival (HR = 2.00, 95 % CI: 1.21-3.32; p = 0.0065). These prognostic factors were used to build a simple risk classification scheme. CONCLUSIONS: Treatment of selected synchronous oligometastatic NSCLC with curative purpose could be conducted safely and at acceptable 5-year survival levels, especially in younger patients with pN0 disease.

Type A thymoma invading the trachea: a case report.

Thymomas generally grow applying pressure to the adjacent organs but they may infiltrate the capsule and extend directly to them. Invasion of the airway is extremely rare and generally related to high-grade thymomas. Few cases of thymoma with endobronchial polypoid growth and only one patient with tracheal invasion have been reported. We present a typical type A thymoma with endoluminal growth almost completely obstructing the trachea. A 93-year-old man was referred to our hospital with severe dyspnea and wheezing. He already presented a diagnosis of type A thymoma, discovered occasionally 8-year before and followed up with a yearly computed tomography (CT) scan. The CT scan of the thorax at admission, revealed a bulky anterior mediastinal tumor with an endotracheal growth, almost obstructing the airway. The fiberoptic bronchoscopy confirmed severe tracheal stenosis caused by a vegetating endoluminal tumor. Due to the severity of symptoms, we performed an emergency rigid bronchoscopy aimed to relieve the upper airway. The endotracheal tumor had a relatively small base of implant and was totally removed with mechanical resection. Pathological examination revealed a proliferation of oval or spindle neoplastic cells with bland nuclei and inconspicuous nucleoli and very few immature lymphocytes. Tracheal invasion by type A thymoma was finally diagnosed. No clinical evidence of endotracheal recurrence was recorded after a 15-month follow-up.

Indications and Results of Sternal Allograft Transplantation: Learning From a Worldwide Experience.

BACKGROUND: Reconstruction of the anterior chest wall defect after sternectomy is a challenge for cardiothoracic surgeons. In 2010, the Padua group published the first case of cadaveric sternum transplantation after sternectomy. This multicenter study reports the clinical indications and early and long-term results of sternal chondral allograft transplantation. METHODS: This is a retrospective multicenter study from 7 academic centers. We collected demographic data, surgical indications, technical details, and early postoperative results. The complications, long-term stability, and tolerance of the allografts were also analyzed. RESULTS: Between January 2008 and December 2019, 58 patients underwent sternectomy followed by reconstruction using cadaveric-cryopreserved sternochondral allografts. Thirty-two patients were male, median age 63.5 years (interquartile range, 50-72 years). Indications for sternectomy were secondary sternal tumors (n = 13), primary sternal tumors (n = 15), and nonneoplastic disease (n = 30). Thirty patients underwent total sternectomy, 16 lower-body sternectomy, and 12 upper-body manubrium resection. The 30-day mortality was 5%; overall morbidity was 31%. Six early reoperations were necessary because of bleeding (n = 1), titanium plate dislocation (n = 1), and resuture of the skin in the lower part of the incision (n = 4). Overall, 5-year survival was 74%. In all the survived patients, the reconstructions were stable and free from mechanical or infective complications. CONCLUSIONS: The main indications for sternal allograft implantation were complex poststernotomy dehiscence followed by primary or secondary tumor involvement of the sternum. The collected results demonstrate that sternochondral allograft transplantation is a safe and effective method in reconstructing the anterior chest wall after sternectomy. Further studies to demonstrate the integration of the bone grafts into the patients' sternal wall will be made.

Dynamic titanium prosthesis based on 3D-printed replica for chest wall resection and reconstruction.

3D-printing technologies can assist the surgical planning and prosthesis engineering for the management of extended chest wall resection. Different types of prosthesis have been utilized over time, but some concerns remain about their impact on the respiratory function. Here we present a new kind of 3D-printed titanium prosthesis designed to be either strong and flexible. The prosthesis was created on a 1:1 3D-printed anatomic replica of the chest, used to delineate surgical margins and to define the reconstructive requirements.

Classification Model to Estimate MIB-1 (Ki 67) Proliferation Index in NSCLC Patients Evaluated With 18F-FDG-PET/CT.

BACKGROUND/AIM: Proliferation biomarkers such as MIB-1 are strong predictors of clinical outcome and response to therapy in patients with non-small-cell lung cancer, but they require histological examination. In this work, we present a classification model to predict MIB-1 expression based on clinical parameters from positron emission tomography. PATIENTS AND METHODS: We retrospectively evaluated 78 patients with histology-proven non-small-cell lung cancer (NSCLC) who underwent 18F-FDG-PET/CT for clinical examination. We stratified the population into a low and high proliferation group using MIB-1=25% as cut-off value. We built a predictive model based on binary classification trees to estimate the group label from the maximum standardized uptake value (SUVmax) and lesion diameter. RESULTS: The proposed model showed ability to predict the correct proliferation group with overall accuracy >82% (78% and 86% for the low- and high-proliferation group, respectively). CONCLUSION: Our results indicate that radiotracer activity evaluated via SUVmax and lesion diameter are correlated with tumour proliferation index MIB-1.

Indoleamine 2,3-Dioxygenase 2 Immunohistochemical Expression in Resected Human Non-small Cell Lung Cancer: A Potential New Prognostic Tool.

Indoleamine 2,3-dioxygenase 2 (IDO2) is an analog of the tryptophan degrading and immunomodulating enzyme indoleamine 2,3-dioxygenase 1 (IDO1). Although the role of IDO1 is largely understood, the function of IDO2 is not yet well-elucidated. IDO2 overexpression was documented in some human tumors, but the linkage between IDO2 expression and cancer progression is still unclear, in particular in non-small cell lung cancer (NSCLC). Immunohistochemical expression and cellular localization of IDO2 was evaluated on 191 formalin-fixed and paraffin-embedded resected NSCLC. Correlations between IDO2 expression, clinical-pathological data, tumor-infiltrating lymphocytes (TILs), immunosuppressive tumor molecules (IDO1 and programmed cell death ligand-1 - PD-L1 -) and patients' prognosis were evaluated. IDO2 high expression is strictly related to high PD-L1 level among squamous cell carcinomas group (p = 0.012), to either intratumoral or mixed localization of TILs (p < 0.001) and to adenocarcinoma histotype (p < 0.001). Furthermore, a significant correlation between IDO2 high expression and poor non-small cell lung cancer prognosis was detected (p = 0.011). The current study reaches interesting knowledge about IDO2 in non-small cell lung cancer. The close relationship between IDO2 expression, PD-L1 increased levels, TILs localization and NSCLC poor prognosis, assumed IDO2 as a potential prognostic biomarker to be exploited for optimizing innovative combined therapies with immune checkpoint inhibitors.

Prognostic factors of lung cancer in lymphoma survivors (the LuCiLyS study).

BACKGROUND: Second cancer is the leading cause of death in lymphoma survivors, with lung cancer representing the most common solid tumor. Limited information exists about the treatment and prognosis of second lung cancer following lymphoma. Herein, we evaluated the outcome and prognostic factors of Lung Cancer in Lymphoma Survivors (the LuCiLyS study) to improve the patient selection for lung cancer treatment. METHODS: This is a retrospective multicentre study including consecutive patients treated for lymphoma disease that subsequently developed non-small cell lung cancer (NSCLC). Data regarding lymphoma including age, symptoms, histology, disease stage, treatment received and lymphoma status at the time of lung cancer diagnosis, and data on lung carcinoma as age, smoking history, latency from lymphoma, symptoms, histology, disease stage, treatment received, and survival were evaluated to identify the significant prognostic factors for overall survival. RESULTS: Our study population included 164 patients, 145 of which underwent lung cancer resection. The median overall survival was 63 (range, 58-85) months, and the 5-year survival rate 54%. At univariable analysis no-active lymphoma (HR: 2.19; P=0.0152); early lymphoma stage (HR: 1.95; P=0.01); adenocarcinoma histology (HR: 0.59; P=0.0421); early lung cancer stage (HR: 3.18; P<0.0001); incidental diagnosis of lung cancer (HR: 1.71; P<0.0001); and lung cancer resection (HR: 2.79; P<0.0001) were favorable prognostic factors. At multivariable analysis, no-active lymphoma (HR: 2.68; P=0.004); early lung cancer stage (HR: 2.37; P<0.0001); incidental diagnosis of lung cancer (HR: 2.00; P<0.0001); and lung cancer resection (HR: 2.07; P<0.0001) remained favorable prognostic factors. Patients with non-active lymphoma (n=146) versus those with active lymphoma (n=18) at lung cancer diagnosis presented better median survival (64 vs. 37 months; HR: 2.4; P=0.02), but median lung cancer specific survival showed no significant difference (27 vs. 19 months; HR: 0.3; P=0.17). CONCLUSIONS: The presence and/or a history of lymphoma should not be a contraindication to resection of lung cancer. Inclusion of lymphoma survivors in a lung cancer-screening program may lead to early detection of lung cancer, and improve the survival.

Microalbuminuria assessment after thoracic surgery: Early identification of complication risks.

INTRODUCTION: Microalbuminuria (MA) is considered a reflection of systemic capillary leak and an early marker of acute stress reaction to the surgical insult, proportional to the severity of the initiating condition and predictive of the individual response to surgical stress. OBJECTIVES: We conducted a prospective study to assess for the variation of MA within 4 days after thoracic surgery. We correlated observed MA levels with both their respective PaO2 /FiO2 respiratory ratio and the onset of postoperative complications. METHODS: This single-centre study enrolled 255 consecutive patients having an American Society of Anaesthesiologists (ASA) score ≤ 3. The mean age was 62 years with 67% male. All patients were scheduled for elective pulmonary resection. MA was measured in urine samples as the albumin-to-creatinine ratio (A/C), prior to, at and after extubation up to 96 hours. PaO2 /FiO2 was measured at extubation and on the first postoperative day. RESULTS: Overall, preoperative A/C levels resulted normal, with a significant average increase at extubation which peaked 6 hours later (P < 0.001). Larger postoperative A/C increases were observed in patients who developed postoperative complications, compared to those without these complications (P < 0.019). Moreover, patients undergoing major open pulmonary resections had larger postoperative A/C increases, compared to those undergoing minor video-assisted thoracic surgery resections (P < 0.006). At the time of extubation, A/C was inversely related to the PaO2 /FiO2 ratio (r = -0.25; P = 0.038). Peak A/C > 61 mg/g (P = 0.0003) was associated with postoperative cardio-pulmonary complications (OR 3.85; P = 0.003). CONCLUSION: Within 6 hours after extubation, MA assessment may be a rapid and relatively inexpensive method for better predicting perioperative risk in an ASA score ≤ 3 population.