Immune checkpoint analysis of T-cell responses to pp65 and IE-1 antigens in end-stage lung diseases.

Lung transplant (LTX) patients are at high risk of cytomegalovirus (CMV) infection, which is often associated with high mortality and morbidity. Reactivation of CMV causes cell injury due to the cytopathic effect of viral replication and triggering of T cell immunity. The aim of this study was to compare expression of immune checkpoints (ICs) (PD-1, CTLA-4, LAG-3 and TIGIT) in CD4, CD8 and CD56 and activation markers CD137, CD154 and CD69 of end-stage patients awaiting lung transplant. Eighteen pre-LTX positive for anti-CMV IgG titres and 18 healthy subjects were enrolled. IC and activation markers have been evaluated through flow cytometric analysis in HC and pre-LTX patients. Reactive (QF+) and unreactive (QF-) patients were stratified according to QuantiFERON-CMV assays. ICs' and activation markers' expression were determined before and after in vitro stimulation with pp-65 and IE-1 antigens. Lower expression of PD-1 was observed in CD4 and CD8 cells of pre-LTX patients than controls, whereas CTLA4 appeared upregulated in CD56 and CD8 cells. TIGIT is increased on the surface of CD4, CD8 and NK cells after peptide stimulation in QF-negative patients and PD-1 is only downregulated after stimulation in the QF-positive patients. This study provides new evidence of immune dysregulation in patients with end-stage lung disorders, particularly in relation to immune checkpoint cell biology. The change in QF+ mostly happens on cytotoxic cells NK and CD8, while the changes in QF- were observed in adaptive immune cells, including CD4 and CD8.

Survival After Lung Transplantation for Chronic Hypersensitivity Pneumonitis: Results From a Large International Cohort Study.

Repeated exposure to antigens via inhalation is the primary cause of hypersensitivity pneumonitis, a form of interstitial pneumonia. The chronic form of hypersensitivity pneumonitis leads to progressive loss of respiratory function; lung transplantation is the only therapeutic option for chronically ill patients. The ESTS Lung Transplantation Working Group conducted a retrospective multicentred cohort study to increase the body of knowledge available on this rare indication for lung transplantation. Data were collected for every patient who underwent lung transplant for hypersensitivity pneumonitis in participating centres between December 1996 and October 2019. Primary outcome was overall survival; secondary outcome was freedom from chronic lung allograft dysfunction. A total of 114 patients were enrolled from 9 centres. Almost 90% of patients were diagnosed with hypersensitivity pneumonitis before transplantation, yet the antigen responsible for the infection was identified in only 25% of cases. Eighty per cent of the recipients received induction therapy. Survival at 1, 3, and 5 years was 85%, 75%, and 70%, respectively. 85% of the patients who survived 90 days after transplantation were free from chronic lung allograft dysfunction after 3 years. The given study presents a large cohort of HP patients who underwent lung transplants. Overall survival rate is higher in transplanted hypersensitivity pneumonitis patients than in those suffering from any other interstitial lung diseases. Hypersensitivity pneumonitis patients are good candidates for lung transplantation.

Cytomegalovirus Infection Is Associated with Development of Chronic Lung Allograft Dysfunction.

BACKGROUND: Cytomegalovirus (CMV) is the major and most common opportunistic infection complicating lung transplant (LTX). The aim of this study was to analyse the epidemiological aspects of CMV infection in lung transplant patients subject to a pre-emptive anti-CMV approach and to study the impact of this infection on lung transplant outcome, in terms of onset of chronic lung allograft dysfunction (CLAD). METHODS: This single-centre retrospective study enrolled 87 LTX patients (median age 55.81 years; 41 females, 23 single LTX, 64 bilateral LTX). All patients were managed with a pre-emptive anti-CMV approach. The incidences of the first episode of CMV infection, 1, 3, 6 and 12 months after LTX, were 12.64%, 44.26%, 50.77% and 56.14%. A median interval of 41 days elapsed between LTX and the first episode of CMV infection. The median blood load of CMV-DNA at diagnosis was 20,385 cp/ml; in 67.64% of cases, it was also the peak value. Patients who had at least one episode had shorter CLAD-free survival. Patients who had three or more episodes of CMV infection had the worst outcome. RESULTS: CMV infection was confirmed to be a common event in lung transplant patients, particularly in the first three months after transplant. It had a negative impact on transplant outcome, being a major risk factor for CLAD. The hypothesis that lower viral replication thresholds may increase the risk of CLAD is interesting and deserves further investigation.

Drug-repositioning screening identified fludarabine and risedronic acid as potential therapeutic compounds for malignant pleural mesothelioma.

Objectives Malignant pleural mesothelioma (MPM) is an occupational disease mainly due to asbestos exposure. Effective therapies for MPM are lacking, making this tumour type a fatal disease. Materials and Methods In order to meet this need and in view of a future "drug repositioning" approach, here we screened five MPM (Mero-14, Mero-25, IST-Mes2, NCI-H28 and MSTO-211H) and one SV40-immortalized mesothelial cell line (MeT-5A) as a non-malignant model, with a library of 1170 FDA-approved drugs. Results Among several potential compounds, we found that fludarabine (F-araA) and, to a lesser extent, risedronic acid (RIS) were cytotoxic in MPM cells, in comparison to the non-malignant Met-5A cells. In particular, F-araA reduced the proliferation and the colony formation ability of the MPM malignant cells, in comparison to the non-malignant control cells, as demonstrated by proliferation and colony formation assays, in addition to measurement of the phospho-ERK/total-ERK ratio. We have shown that the response to F-araA was not dependent upon the expression of DCK and NT5E enzymes, nor upon their functional polymorphisms (rs11544786 and rs2295890, respectively). Conclusion This drug repositioning screening approach has identified that F-araA could be therapeutically active against MPM cells, in addition to other tumour types, by inhibiting STAT1 expression and nucleic acids synthesis. Further experiments are required to fully investigate this.

Impact of SARS-CoV-2 outbreak on heart and lung transplant: A patient-perspective survey.

BACKGROUND: The risk of COVID-19 is expected to be higher among solid organ transplant. The aim of the present study was to evaluate the incidence of COVID-19 and the impact of the SARS-CoV-2 outbreak on the personal hygiene and expectations in heart and lung transplant recipients. METHODS: A telephone survey of heart (n = 69) and lung (n = 41) transplant patients and a group of controls (n = 41) was conducted concerning personal hygiene before and after the outbreak; the impact on subjective expectations regarding graft outcome; symptoms possibly associated with SARS-CoV-2 infection; and diagnosis of COVID-19. RESULTS: Seventy nine percent of the patients declared they increased the use of face masks and handwash. Behavior at home regarding self-isolation did not change. About half the patients said they were afraid of the virus. A higher percentage of Lung transplant (LTX) were convinced that SARS-CoV-2 could have a negative impact on the outcome of their graft. 28% declared that they were afraid to come to the hospital for routine examinations and asked to postpone. Nine LTX and five Heart transplant (HTX) patients experienced symptoms that could have been associated with SARS-CoV-2 infection, but none of them underwent a nasopharyngeal swab. Only one LTX was diagnosed with the infection. CONCLUSIONS: In our study, we observed a low incidence of COVID-19 in heart and lung transplant patients (0.9%), similar to that of the general population of our Region. Isolation measures were already observed before the pandemic and were further strengthened in most cases. Particular attention should also be paid to new psychological and physical complications indirectly linked to the COVID-19 pandemic.

The Role of Galectins in Chronic Lung Allograft Dysfunction.

BACKGROUND: Galectins are proteins that bind ß-galactosides such as N-acetyllactosamine present in N-linked and O-linked glycoproteins and that seem to be implicated in inflammatory and immune responses as well as fibrotic mechanisms. This preliminary study investigated serum galectins as clinical biomarkers in lung transplant patients with chronic lung allograft dysfunction (CLAD), phenotype bronchiolitis obliterans syndrome (BOS). MATERIALS AND METHODS: Nineteen lung transplant patients [median age (IQR), 55 (45-62) years; 53% males] were enrolled in the study. Peripheral blood concentrations of galectins-1, 3 and 9 were determined with commercial ELISA kits. RESULTS: Galectin-1 concentrations were higher in BOS than in stable LTX patients (p = 0.0394). In logistic regression analysis, testing BOS group as dependent variable with Gal-1 and 3 as independent variables, area under the receiver operating characteristics (AUROC) curve was 98.9% (NPV 90% and PPV 88.9%, p = 0.0003). With the stable LTX group as dependent variable and Gal-1, 3 and 9 as independent variables, AUROC was 92.6% (NPV 100% and PPV 90%, p = 0.0023). In stable patients were observed an inverse correlation of Gal-3 with DLCO% and KCO%, and between Gal-9 and KCO%. CONCLUSION: Galectins-1, 3 and 9 are possible clinical biomarkers in lung transplant patients with diagnostic and prognostic meaning. These molecules may be directly implicated in the pathological mechanisms of BOS. The hypothesis that they could be new therapeutic targets in BOS patients is intriguing and also worth exploring.

PRMT5 silencing selectively affects MTAP-deleted mesothelioma: In vitro evidence of a novel promising approach.

Malignant mesothelioma (MM) is an aggressive asbestos-related cancer of the serous membranes. Despite intensive treatment regimens, MM is still a fatal disease, mainly due to the intrinsic resistance to current therapies and the lack of predictive markers and new valuable molecular targets. Protein arginine methyltransferase 5 (PRMT5) inhibition has recently emerged as a potential therapy against methylthioadenosine phosphorylase (MTAP)-deficient cancers, in which the accumulation of the substrate 5'-methylthioadenosine (MTA) inhibits PRMT5 activity, thus sensitizing the cells to further PRMT5 inhibition. Considering that the MTAP gene is frequently codeleted with the adjacent cyclin-dependent kinase inhibitor 2A (CDKN2A) locus in MM, we assessed whether PRMT5 could represent a therapeutic target also for this cancer type. We evaluated PRMT5 expression, the MTAP status and MTA content in normal mesothelial and MM cell lines. We found that both administration of exogenous MTA and stable PRMT5 knock-down, by short hairpin RNAs (shRNAs), selectively reduced the growth of MTAP-deleted MM cells. We also observed that PRMT5 knock-down in MTAP-deficient MM cells reduced the expression of E2F1 target genes involved in cell cycle progression and of factors implicated in epithelial-to-mesenchymal transition. Therefore, PRMT5 targeting could represent a promising new therapeutic strategy against MTAP-deleted MMs.

EIF4G1 and RAN as Possible Drivers for Malignant Pleural Mesothelioma.

For malignant pleural mesothelioma (MPM) novel therapeutic strategies are urgently needed. In a previous study, we identified 51 putative cancer genes over-expressed in MPM tissues and cell lines. Here, we deepened the study on nine of them (ASS1, EIF4G1, GALNT7, GLUT1, IGF2BP3 (IMP3), ITGA4, RAN, SOD1, and THBS2) to ascertain whether they are truly mesothelial cancer driver genes (CDGs) or genes overexpressed in an adaptive response to the tumoral progression ("passenger genes"). Through a fast siRNA-based screening, we evaluated the consequences of gene depletion on migration, proliferation, colony formation capabilities, and caspase activities of four MPM (Mero-14, Mero-25, IST-Mes2, and NCI-H28) and one SV40-immortalized mesothelial cell line (MeT-5A) as a non-malignant model. The depletion of EIF4G1 and RAN significantly reduced cell proliferation and colony formation and increased caspase activity. In particular, the findings for RAN resemble those observed for other types of cancer. Thus, we evaluated the in vitro effects of importazole (IPZ), a small molecule inhibitor of the interaction between RAN and importin-ß. We showed that IPZ could have effects similar to those observed following RAN gene silencing. We also found that primary cell lines from one out of three MPM patients were sensitive to IPZ. As EIF4G1 and RAN deserve further investigation with additional in vitro and in vivo studies, they emerged as promising CDGs, suggesting that their upregulation could play a role in mesothelial tumorigenesis and aggressiveness. Furthermore, present data propose the molecular pathways dependent on RAN as a putative pharmacological target for MPM patients in the view of a future personalized medicine.

Helicobacter pylori Infection Does Not Impact on Lung Transplant Outcome.

BACKGROUND: Helicobacter pylori (HP) is a spiral, gram-negative, microaerophilic bacterium that colonises the human gastric mucosa and is associated with gastrointestinal and extragastrointestinal disorders. Since no data are yet available on HP infection in lung transplant patients, we evaluated the prevalence and impact of HP infection in a population of such patients. METHODS: Sixty-seven lung transplant patients were enrolled in the study (35 females and 32 males, age 48.4 ± 13.3 years), 54 underwent bilateral and 13 single lung transplant. Serum antibodies against HP and CagA were assayed in all subjects. RESULTS: The prevalence of HP infection in lung transplant patients was similar to that in the general population (49.25% vs. 51.4%), whereas HP-positive patients showed lower CagA positivity (9% vs. 50.2%, p < 0.0001). There was a higher prevalence of HP infection in patients who underwent lung transplant because of pulmonary fibrosis (p = 0.049), and a lower prevalence in COPD patients (p = 0.011). No correlation was found between HP infection in lung transplant patients and graft outcome. No differences in primary graft dysfunction, acute rejection or bronchiolitis obliterans syndrome-free survival were found. However, more patients who required three or more post-transplant re-hospitalisations were observed among HP-positive patients. CONCLUSIONS: The prevalence of HP infection in lung transplant patients was comparable to that of the general population and to that reported in heart and kidney transplant recipients. It did not seem to impact short-, mid- or long-term lung allograft outcome. H. pylori infection did not prove to be clinically relevant in lung transplant patients.

Airway-Centered Pleuroparenchymal Fibroelastosis Associated with Non-Necrotizing Granulomas: A Rare New Entity.

Pleuroparenchymal fibroelastosis is a rare form of upper-lobe-dominant progressive pulmonary fibrosis characterized histologically by visceral pleural thickening with collagenous fibrosis, subpleural elastosis, and intra-alveolar collagenous fibrosis. It was first described 25 years ago by Amitani et al. This report firstly describes a new variant or rare phenotype of PPFE with airway involvement, minimal pleuroparenchymal connections, and non-necrotizing granulomas.

Long-Term Results and Prognostic Factors of Pulmonary Metastasectomy in Patients with Metastatic Transitional Cell Carcinoma.

Objective We wanted to assess the prognostic factors and the efficacy of the treatment in patients who underwent lung resections for transitional cell carcinoma metastases. Materials and Methods This is a retrospective, multicenter study. Between January 1995 and May 2014, 69 patients underwent lung metastasectomy with curative intent. We evaluated primary site of the tumor, the role of adjuvant chemotherapy after urological operation, disease-free interval (DFI; lower or higher than 24 months), type of lung resection, number of lung metastases, presence of metastatic lymph nodes, and diameter of the metastasis (less or more than 3 cm). Results Among 69 patients, 55 (79%) had bladder as primary site of disease and 12 of them received a transurethral bladder resection. Fourteen (21%) patients developed primary tumor in the renal pelvis or ureter; 53 (76%) patients presented with a single metastasis, 16 (24%) with multiple metastasis. The median DFI was 37 months and the median follow-up was 50 months. Sampling lymphadenectomy was done in 42 patients and nodal metastases were found in 7 patients. The overall 5-year survival was 52%, median 62 months. At univariate analysis, the DFI had a significant impact on survival (5-year survival of 58% for patients with DFI ≥ 24 months vs. 46%; p = 0.048) and diameter of metastasis (5-year survival of 59% for diameter less than 3 cm group vs. 33%; p = 0.001). The multivariate analysis confirmed metastasis' diameter as an independent prognostic factor (p = 0.001). Conclusion Our study found that, in addition to DFI that remains a common prognostic factor in patients with metastatic lung disease, in lung metastases by transitional cell carcinoma, the diameter of the lesion is another significant prognostic factor.

Mortality on the Waiting List for Lung Transplantation in Patients with Idiopathic Pulmonary Fibrosis: A Single-Centre Experience.

PURPOSE: Lung transplantation (LTX) is nowadays accepted as a treatment option for selected patients with end-stage pulmonary disease. Idiopathic pulmonary fibrosis (IPF) is characterized by the radiological and histologic appearance of usual interstitial pneumonia. It is associated with a poor prognosis, and LTX is considered an effective treatment to significantly modify the natural history of this disease. The aim of the present study was to analyse mortality during the waiting list in IPF patients at a single institution. METHODS: A retrospective analysis on IPF patients (n = 90) referred to our Lung Transplant Program in the period 2001-2014 was performed focusing on patients' characteristics and associated risk factors. RESULTS: Diagnosis of IPF was associated with high mortality on the waiting list with respect to other diagnosis (p < 0.05). No differences in demographic, clinical, radiological data and time spent on the waiting list were observed between IPF patients who underwent to LTX or lost on the waiting list. Patients who died showed significant higher levels of pCO2 and needed higher flows of O2-therapy on effort (p < 0.05). Pulmonary function tests failed to predict mortality and no other medical conditions were associated with survival. CONCLUSIONS: Patients newly diagnosed with IPF, especially in small to medium lung transplant volume centres and in Countries where a long waiting list is expected, should be immediately referred to transplantation, delay results in increased mortality. Early identification of IPF patients with a rapid progressive phenotype is strongly needed.

Prevalence of concomitant aortic disease and lung cancer: an exploratory study.

Background: Lung cancer and aortic disease share multiple risk factors. The co-presence of both diseases defines a peculiar type of patient who needs a specific protocol of treatment and follow-up. The aim of our study was to evaluate the prevalence of aortic disease in a population of patients with a diagnosis of primary lung cancer. Methods: A retrospective, single center analysis of all patients admitted to the Thoracic Surgery Unit from January 2015 to January 2021. Demographic and baseline characteristics were retrieved from hospital electronic charts. All patients were screened for aortic disease, reviewing thoraco-abdominal Computed Tomography with contrast medium administration performed for oncological reasons. A cancer-free control group was obtained for comparison. Multilinear regression analysis was performed to identify the risk factors for the presence of aortic disease. Results: A total of 264 patients were preliminarily identified. After reviewing for exclusion criteria, a total of 148 patients were included in the analysis. Most of the patients were male (62.2%) with a mean age of 71±8.7 years. Cardiovascular risk factors were extensively prevalent in the population study. The incidence of aortic pathologies in the group of patients suffering from primary lung cancer was 27% (40 patients). The majority presented thoracic aortic aneurysms (11.5%). Comparison between the lung cancer group and the control group highlighted a substantial difference in terms of aortic disease prevalence (27% vs. 2.9%; P<0.0001). The regression analysis revealed that coronary artery disease [odds ratio (OR) 4.6988, P=0.001], peripheral artery disease (OR 7.7093, P=0.002), hypertension (OR 4.0152, P=0.03) and history of previous non-aortic vascular surgery procedures (OR 6.4509, P=0.003) were risk factors for aortic disease in patients with primary lung cancer. Conclusions: Patients with lung cancer have a high prevalence of aortic disease, defining a peculiar subset of patients who deserve a specific protocol of treatment and follow-up. Further studies are needed to define a dedicated standardized multidisciplinary approach.

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.

Lung Resection for Non-Small Cell Lung Cancer following Bronchoscopic Lung Volume Reduction for Heterogenous Emphysema.

Bronchoscopic lung volume reduction (BLVR) is a minimally invasive treatment for emphysema. Lung cancer may be associated with emphysema due to common risk factors. Thus, a growing number of patients undergoing BLVR may develop lung cancer. Herein, we evaluated the effects of lung resection for non-small cell lung cancer in patients undergoing BLVR. The clinical data of patients undergoing BLVR followed by lung resection for NSCLC were retrospectively reviewed. For each patient, surgical and oncological outcomes were recorded to define the effects of this strategy. Eight patients were included in our series. In all cases but one, emphysema was localized within upper lobes; the tumor was detected during routine follow-up following BLVR and it did not involve the treated lobe. The comparison of pre- and post-BLVR data showed a significant improvement in FEV1 (29.7 ± 4.9 vs. 33.7 ± 6.7, p = 0.01); in FVC (28.5 ± 6.6 vs. 32.4 ± 6.1, p = 0.01); in DLCO (31.5 ± 4.9 vs. 38.7 ± 5.7, p = 0.02); in 6MWT (237 ± 14 m vs. 271 ± 15 m, p = 0.01); and a reduction in RV (198 ± 11 vs. 143 ± 9.8, p = 0.01). Surgical resection of lung cancer included wedge resection (n = 6); lobectomy (n = 1); and segmentectomy (n = 1). No major complications were observed and the comparison of pre- and post-operative data showed no significant reduction in FEV1% (33.7 ± 6.7 vs. 31.5 ± 5.3; p = 0.15) and in DLCO (38.7 ± 5.7 vs. 36.1 ± 5.4; p = 0.15). Median survival was 35 months and no cancer relapses were observed. The improved lung function obtained with BLVR allowed nonsurgical candidates to undergo lung resection for lung cancer.

Robotic thymectomy in thymic tumours: a multicentre, nation-wide study.

OBJECTIVES: Robotic thymectomy has been suggested and considered technically feasible for thymic tumours. However, because of small-sample series and the lack of data on long-term results, controversies still exist on surgical and oncological results with this approach. We performed a large national multicentre study sought to evaluate the early and long-term outcomes after robot-assisted thoracoscopic thymectomy in thymic epithelial tumours. METHODS: All patients with thymic epithelial tumours operated through a robotic thoracoscopic approach between 2002 and 2022 from 15 Italian centres were enrolled. Demographic characteristics, clinical, intraoperative, postoperative, pathological and follow-up data were retrospectively collected and reviewed. RESULTS: There were 669 patients (307 men and 362 women), 312 (46.6%) of whom had associated myasthenia gravis. Complete thymectomy was performed in 657 (98%) cases and in 57 (8.5%) patients resection of other structures was necessary, with a R0 resection in all but 9 patients (98.6%). Twenty-three patients (3.4%) needed open conversion, but no perioperative mortality occurred. Fifty-one patients (7.7%) had postoperative complications. The median diameter of tumour resected was 4 cm (interquartile range 3-5.5 cm), and Masaoka stage was stage I in 39.8% of patients, stage II in 56.1%, stage III in 3.5% and stage IV in 0.6%. Thymoma was observed in 90.2% of patients while thymic carcinoma occurred in 2.8% of cases. At the end of the follow-up, only 2 patients died for tumour-related causes. Five- and ten-year recurrence rates were 7.4% and 8.3%, respectively. CONCLUSIONS: Through the largest collection of robotic thymectomy for thymic epithelial tumours we demonstrated that robot-enhanced thoracoscopic thymectomy is a technically sound and safe procedure with a low complication rate and optimal oncological outcomes.

Washout-Computed Tomography Discriminates Pulmonary "Fat-poor" Hamartomas From Neuroendocrine Neoplasms: A Simple Method in the Radiomics Era.

PURPOSE: Pulmonary hamartomas (HAs) and neuroendocrine neoplasms (NENs) are often impossible to discriminate using high-resolution computed tomography (CT) as they share morphologic features. This challenge makes differential diagnosis crucial as HAs are invariably benign, whereas NENs must be considered malignant, thus requiring them to be evaluated for surgical excision.Our aim was, therefore, to develop a simple method to discriminate between pulmonary "fat-poor" HAs and NENs using contrast-enhanced CT (CECT). MATERIALS AND METHODS: Between September 2015 and December 2021, 95 patients with a histologically proven diagnosis of lung NENs (74) and HAs (21) and who underwent a preoperative CECT scan were initially identified through a review of our pathologic and radiologic databases. Among these, 55 cases (18 HAs and 37 NENs), which have been studied with biphasic CECT, were ultimately selected and reviewed by 3 radiologists with different levels of experience, analyzing their morphologic and enhancement features.The enhancement analysis was performed by placing a region of interest within the lesion in noncontrast (NCp), postcontrast (PCp, 55 to 65 s after intravenous contrast injection), and delayed phases (Dp, 180 to 300 s). A subgroup of 35 patients who underwent 18FDG-PET/CT was evaluated in a secondary analysis. RESULTS: HU values were significantly different between NENs and HAs in the PCp ( P <0.001). NCp and Dp attenuation values did not show significant differences in the 2 groups. Differences in values of HUs in PCp and Dp allowed to discriminate between NENs and HAs. CONCLUSION: Wash-out analysis, ΔHU (PCp-Dp), can perfectly discriminate pulmonary "fat-poor" HAs from NENs.

Coming Back to the Basics. Comment on Cangir et al. A CT-Based Radiomic Signature for the Differentiation of Pulmonary Hamartomas from Carcinoid Tumors. Diagnostics 2022, 12, 416.

We read with great interest the article by Cangir et al., "A CT-Based Radiomic Signature for the Differentiation of Pulmonary Hamartomas from Carcinoid Tumors", published on 5 February 2022 [...].

Malignant Pleural Mesothelioma: Preliminary Toxicity Results of Adjuvant Radiotherapy Hypofractionation in a Prospective Trial (MESO-RT).

Malignant Pleural Mesothelioma (MPM) is a rare malignancy with an overall poor prognosis. The standard therapeutic strategy in early-stage disease is trimodality therapy. In this publication, we report the preliminary toxicity results of the first 20 patients treated with accelerated hypofractionated radiotherapy. Between July 2017 to June 2019, 20 MPM patients were enrolled and treated with accelerated hypofractionated radiotherapy using helical tomotherapy and intensity-modulated arc therapy. The prescription dose was 30 Gy in five daily fractions, while an inhomogeneous dose escalation to 40 Gy was prescribed based solely upon the presence of gross residual tumor. Only one case of G3 toxicity was reported, which was a bilateral pneumonitis that occurred two years after treatment probably due to superinfection. Median Time to Progression reached 18.2 months while one- and three-year Overall Survival rates were 85% (95% CI:60.4-94.9) and 49.5% (95% CI:26.5-68.9), respectively. Treatment of the intact lung with pleural intensity-modulated arc irradiation is a novel treatment strategy that appears to be safe, feasible, and without a high grade of lung toxicity. Survival rates and Time to Progression are encouraging.