Clinical and biological effects of different energetic surgical devices currently used for mini-invasive anatomical lung resections for the treatment of NSCLC: a prospective interventional study.

BACKGROUND: This study aims to compare three commonly used energy devices for dissection during Video-Assisted Thoracoscopic Surgery (VATS) lobectomy: monopolar hook, advanced bipolar, and ultrasonic device, in terms of duration of the surgical procedure and clinical intra- and post-operative outcomes. MATERIALS AND METHODS: In this prospective single-center study, 75 patients undergoing VATS lobectomy for non-small cell lung cancer between January 2022 and May 2023 were enrolled and divided into 3 groups based on the device used during the surgical procedure (Group 1: Ultrasonic Device, Group 2: Advanced Bipolar, Group 3: Monopolar Hook). The duration of the surgical procedure, daily pleural fluid production, post-operative pain, length of hospital stay, and occurrence of post-operative complications were compared for each group. In a subgroup of 20 patients (10 from Group 1 and 10 from Group 3), concentrations of inflammatory cytokines in pleural fluid at 3 h and 48 h post-surgery were analyzed. RESULTS: Pleural fluid production on the first and second post-operative days was significantly lower in patients treated with the Ultrasonic device compared to the other two groups (p < 0.001). The duration of the surgical procedure was significantly shorter when using the Ultrasonic device (p < 0.001). There were no significant differences in length of hospital stay (p = 0.975), pain on the first and second post-operative days (p = 0.147 and p = 0.755, respectively), and blood hemoglobin levels on the first post-operative day (p = 0.709) and at discharge (p = 0.795). No differences were observed in terms of post-operative complications, although the incidence of post-operative cardiac arrhythmias was borderline significant (p = 0.096), with no cases of arrhythmias recorded in Group 1. IL-10 levels in pleural fluid of patients in Group 3 peaked at 3 h post-surgery, with a significant reduction at 48 h (p = 0.459). DISCUSSION: The use of the ultrasonic device during VATS lobectomy may reduce pleural fluid production and shorten the duration of the surgical procedure compared to using a monopolar hook or advanced bipolar device. The choice of energy device may influence the local inflammatory response, although further studies are needed to confirm these results.

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.

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.

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.

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 [...].

Clinical score for colorectal cancer patients with lung-limited metastases undergoing surgical resection: Meta-Lung Score.

BACKGROUND: Radical resection of isolated lung metastases (LM) from colorectal cancer (CRC) is debated. Like Fong's criteria in liver metastases, our study was meant to assign a clinical prognostic score in patients with LM from CRC, aiming for better surgery selection. METHODS: We retrospectively analyzed data from 260 CRC patients who underwent curative LM resection from December 2002 to January 2022, verifying the impact of different clinicopathological features on the overall survival (OS). RESULTS: At the univariate analysis: higher baseline CEA levels (p = 0.0001), disease-free survival less than or equal to 12 months (m) (p = 0.0043), LM size larger than 2 cm (p = 0.0187), multiple resectable nodules (p = 0.0083), and positive nodal status of the primary tumor (p = 0.0011) were associated with worse prognosis. In a Cox regression model, these characteristics retained their independent role for OS (p < 0.0001) and were chosen as criteria to be assigned one point each for clinical risk score. The 5-year survival rate in patients with 0 points was 88%, while no patients with a 5-point score survived at 2 years. Based on the 0-1 vs. 2-5 score range, we obtained a significant difference in median OS: not reached vs. 40.8 months (95 %CI 36 to 87.5), respectively (p < 0.0001) stratifying patients into good and poor prognosis. The prognostic role of the score was also confirmed in terms of median RFS: not reached in 0-1 scored patients vs. 30.5 months (95 %CI 19.4 to 42) in patients with 2-5 scores (p = 0.0006). CONCLUSIONS: When LM from CRC is resectable, the Meta-Lung Score provides valuable prognostic information. Indeed, while upfront surgery should be considered in patients with scores of 0 to 1, it should be cautiously suggested in patients with scores of 2 to 5, for whom a prognosis comparison between preventive surgery and other treatments should be investigated in prospective randomized clinical trials.

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.

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.

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.

Analysis of Primary Cilium Expression and Hedgehog Pathway Activation in Mesothelioma Throws Back Its Complex Biology.

The primary cilium (PC) is a sensory organelle present on the cell surface, modulating the activity of many pathways. Dysfunctions in the PC lead to different pathologic conditions including cancer. Hedgehog signaling (Hh) is regulated by PC and the loss of its control has been observed in many cancers, including mesothelioma. Malignant pleural mesothelioma (MPM) is a fatal cancer of the pleural membranes with poor therapeutic options. Recently, overexpression of the Hh transcriptional activator GL1 has been demonstrated to be associated with poor overall survival (OS) in MPM. However, unlike other cancers, the response to G-protein-coupled receptor smoothened (SMO)/Hh inhibitors is poor, mainly attributable to the lack of markers for patient stratification. For all these reasons, and in particular for the role of PC in the regulation of Hh, we investigated for the first time the status of PC in MPM tissues, demonstrating intra- and inter-heterogeneity in its expression. We also correlated the presence of PC with the activation of the Hh pathway, providing uncovered evidence of a PC-independent regulation of the Hh signaling in MPM. Our study contributes to the understanding MPM heterogeneity, thus helping to identify patients who might benefit from Hh inhibitors.

A Drug Screening Revealed Novel Potential Agents against Malignant Pleural Mesothelioma.

The lack of effective therapies remains one of the main challenges for malignant pleural mesothelioma (MPM). In this perspective, drug repositioning could accelerate the identification of novel treatments. We screened 1170 FDA-approved drugs on a SV40-immortalized mesothelial (MeT-5A) and five MPM (Mero-14, Mero-25, IST-Mes2, NCI-H28 and MSTO-211H) cell lines. Biological assays were carried out for 41 drugs, showing the highest cytotoxicity and for whom there were a complete lack of published literature in MPM. Cytotoxicity and caspase activation were evaluated with commercially available kits and cell proliferation was assayed using MTT assay and by clonogenic activity with standard protocols. Moreover, the five most effective drugs were further evaluated on patient-derived primary MPM cell lines. The most active molecules were cephalomannine, ouabain, alexidine, thonzonium bromide, and emetine. Except for alexidine, these drugs inhibited the clonogenic ability and caspase activation in all cancer lines tested. The proliferation was inhibited also on an extended panel of cell lines, including primary MPM cells. Thus, we suggest that cephalomannine, ouabain, thonzonium bromide, and emetine could represent novel candidates to be repurposed for improving the arsenal of therapeutic weapons in the fight against MPM.

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.

Lung Cancer Imaging: Screening Result and Nodule Management.

Background: Lung cancer (LC) represents the main cause of cancer-related deaths worldwide, especially because the majority of patients present with an advanced stage of the disease at the time of diagnosis. This systematic review describes the evidence behind screening results and the current guidelines available to manage lung nodules. Methods: This review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The following electronic databases were searched: PubMed, EMBASE, and the Web of Science. Results: Five studies were included in the systematic review. The study cohort included 46,364 patients, and, in this case series, LC was detected in 9028 patients. Among the patients with detected LC, 1261 died of lung cancer, 3153 died of other types of cancers and 4614 died of other causes. Conclusions: This systematic review validates the use of CT in LC screening follow-ups, and bids for future integration and implementation of nodule management protocols to improve LC screening, avoid missed cancers and to reduce the number of unnecessary investigations.

Perioperative Outcome of Robotic Approach Versus Manual Videothoracoscopic Major Resection in Patients Affected by Early Lung Cancer: Results of a Randomized Multicentric Study (ROMAN Study).

INTRODUCTION: We report the results of the first prospective international randomized control trial to compare the perioperative outcome and surgical radicality of the robotic approach with those of traditional video-assisted surgery in the treatment of early-stage lung cancer. METHODS: Patients with clinical stage T1-T2, N0-N1 non-small cell lung cancer (NSCLC) were randomly assigned to robotic-assisted thoracoscopic surgery (RATS) or video-assisted thoracic surgery (VATS) resection arms. The primary objective was the incidence of adverse events including complications and conversion to thoracotomy. The secondary objectives included extent of lymph node (LN) dissection and other indicators. RESULTS: This trial was closed at 83 cases as the probability of concluding in favor of the robot arm for the primary outcome was null according to the observed trend. In this study, we report the results of the analysis conducted on the patients enrolled until trial suspension. Thirty-nine cases were randomized in the VATS arm and 38 in the robotic arm. Six patients were excluded from analysis. Despite finding no difference between the two arms in perioperative complications, conversions, duration of surgery, or duration of postoperative stay, a significantly greater degree of LN assessment by the robotic technique was observed in regards to the median number of sampled LN stations [6, interquartile range (IQR) 4-6 vs. 4, IQR 3-5; p = 0.0002], hilar LNs (7, IQR 5-10 vs. 4, IQR 2-7; p = 0.0003), and mediastinal LNs (7, IQR 5-10 vs. 5, IQR 3-7; p = 0.0001). CONCLUSIONS: The results of this trial demonstrated that RATS was not superior to VATS considering the perioperative outcome for early-stage NSCLC, but the robotic approach allowed an improvement of LN dissection. Further studies are suggested to validate the results of this trial. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, identifier NCT02804893.

Advancement in Diagnostic Imaging of Thymic Tumors.

Thymic tumors are rare neoplasms even if they are the most common primary neoplasm of the anterior mediastinum. In the era of advanced imaging modalities, such as functional MRI, dual-energy CT, perfusion CT and radiomics, it is possible to improve characterization of thymic epithelial tumors and other mediastinal tumors, assessment of tumor invasion into adjacent structures and detection of secondary lymph nodes and metastases. This review aims to illustrate the actual state of the art in diagnostic imaging of thymic lesions, describing imaging findings of thymoma and differential diagnosis.

Robotic surgery vs. open surgery for thymectomy, a retrospective case-match study.

The robotic approach in the treatment of thymus diseases has been described in many papers, but few studies have compared the early outcome of patients after robotic and open transsternal procedure. Our study aims to confirm the non-inferiority of the robotic technique in terms of feasibility, safety and postoperative patient recovery compared to the open standard. This is a retrospective cohort study in which we compare 114 patients who underwent thymectomy for a thymus disease at our thoracic surgery unit. Our robotic surgery programme started in February 2012 with the treatment of mediastinal diseases. Since then, we have performed 57 robotic thymectomies (Group A). This series was compared with 57 patients who underwent open thymectomies (Group B) performed before 2012, and all were properly matched through a propensity score. Hospital and ICU stay, postoperative pain, use of painkillers, operative time and complications rate were analysed. Postoperative pain, evaluated through the Visual Analogue Scale (VAS), was significantly lower in the robotic surgery group (p < 0.001), which was associated with a trend to lower use of painkillers in Group A, although it was not significant (p = 0.06). No statistical differences were observed between the two groups in terms of ICU stay (p = 0.080), although the total hospital stay was significantly longer in Group B (p = 0.003). No statistical differences were observed in operative time (p = 0.492) and complications rate (p = 0.950). The robotic-assisted technique showed the same operative time and complications rate compared with open surgery, thereby confirming its safety and feasibility in myasthenic patients as well as in Masaoka I-II thymomas. The lower postoperative pain and the shorter hospital stay associated with prompt mobilisation and faster chest drainage removal showed the great advantage of the minimally invasive robotic approach in these patients.

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.