Pneumonectomy for Unilateral Proximal Interruption of Pulmonary Artery: A Case Series from the Literature.

BACKGROUND: Unilateral proximal interruption of the pulmonary artery (UPIPA) is a rare congenital disease, and its optimal management remains undefined in the existing literature. The occasional necessity for pneumonectomy is still supported by limited evidence. METHODS: A systematic review of the literature was conducted using the PubMed search engine, focusing on UPIPA cases that received pneumonectomy. Thirty-one pertinent articles were selected and included in the analysis. A case reported from our institution was included in the analysis. RESULTS: We found 25 adults and seven children affected by UPIPA who received an indication for pneumonectomy, plus an additional case that was reported by our institution. Among adult patients, the predominant indication was hemoptysis (57%), followed by suspected or confirmed lung cancer (23%). Approximately 46% of surgical procedures were classified as urgent or emergent. Postoperative complications were observed in 36% of cases, with no recorded mortality. In pediatric cases, pneumonectomy was primarily a life-saving intervention, performed urgently or emergently in 75% of instances. A possible late complication in pediatric patients involves a mediastinal shift leading to respiratory distress, which may be mitigated using an inflatable prosthesis. CONCLUSIONS: Pneumonectomy achieves complete resolution of UPIPA symptoms. In the adult population, its primary indication is hemoptysis, with procedures conducted in both elective and urgent/emergent settings. Despite a mortality rate of zero, a notable proportion of patients may experience postoperative complications. In pediatric cases, the clinical presentation varies more extensively, and pneumonectomy is typically reserved for life-threatening situations, emphasizing the need for careful patient selection.

Pulmonary Lobectomy for Early-Stage Lung Cancer with Uniportal versus Three-Portal Video-Assisted Thoracic Surgery: Results from a Single-Centre Randomized Clinical Trial.

Video-assisted thoracic surgery (VATS) is a consolidated approach; however, there is no consensus on the number of ports leading to less postoperative pain. We compared early postoperative pain after uniportal and three-portal VATS lobectomy for early-stage NSCLC. In this randomized clinical trial, patients undergoing VATS lobectomy were randomly assigned to receive uniportal (U-VATS Group) or three-portal (T-VATS Group) VATS. The inclusion criteria were age ≤ 80 years and ASA < 4. The exclusion criteria were clinical T3, previous thoracic surgery, induction therapy, chest radiotherapy, connective tissue or vascular diseases, major organ failure, and analgesics or corticosteroids use. The postoperative analgesia protocol was based on NRS. Pain was measured as analgesic consumption; the secondary endpoints were intra- and postoperative complications, conversion rate, surgical time, dissected lymph nodes, hospital stay, and respiratory function. Out of 302 eligible patients, 120 were included; demographics were distributed homogeneously. The mean cumulative morphine consumption (CMC) in the U-VATS Group after 7 days was lower than in the T-VATS Group (77.4 mg vs. 90.1 mg, p = 0.003). Intraoperative variables and postoperative complications were comparable. The 30-day intercostal neuralgia rate was lower in the U-VATS Group, without reaching statistical significance. Patients undergoing U-VATS showed a lower analgesic consumption compared with the T-VATS Group; analgesic consumption was moderate in both groups.

Telemonitoring: An opportunity in cystic fibrosis lung transplant recipients.

Introduction: Telemedicine has been successfully employed in a wide range of conditions, such as such as chronic lung disease and COVID-19. This study evaluate the role of telemonitoring for the early diagnosis of acute lung allograft dysfunction in cystic fibrosis adults who underwent lung transplant (LuTx). Quality of life and functional level achieved during a 12 months follow up were assessed. Methods: Patients were randomized into two groups; control group received traditional hospital-based follow-up, whereas patients in the intervention group received, on top of standard care, a telemonitoring device, with a pulse oximeter and a spirometer integrated. Telemonitoring data were digitally transmitted to our centre. Results: Sixteen patients were enrolled in each group. No statistically significant difference was found between the two groups in terms of incidence of allograft dysfunction, time from onset of symptoms to diagnosis and time of occurrence from LuTx. Moreover, both groups achieved similar quality of life and functional level. With reference to the telemonitoring group: 1) hospital reported data were consistent with those being remotely registered; 2) adherence to telemonitoring decreased during the follow up; 3) the majority of patients reported a high degree of satisfaction. Conclusion: The COVID19 pandemic highlighted the necessity to investigate alternative practices to treat chronically ill individuals. Telemonitoring is a valuable tool to improve quality care to LuTx recipients.

A real-world experience of transition to robotic-assisted thoracic surgery (RATS) for lung resections.

Objective: We report our experience of transition to robotic-assisted thoracic surgery (RATS) for lung resections with the da Vinci Xi surgical system, exposing short-term results. Materials and methods: This is a single-center, retrospective analysis of RATS lung resections performed between April 2021 and September 2022 during our new robotic program. The surgical approach evolved over time, starting from a four-arm approach with four incisions. Alternative RATS approaches were subsequently evaluated, such as uniportal and biportal. Results: During a 17-month period, 29 lung resections were performed. Of them, 16 were lobectomies, 7 were segmentectomies, and 6 were wedge resections. The most common indication for anatomical lung resection was non-small cell lung cancer. A uniportal approach was used for two simple segmentectomies and a biportal RATS was performed in five lobectomies and two segmentectomies. A mean number of 8.1 lymph nodes and a mean of 2.6 N2 and 1.9 N1 stations were resected during surgery, and no nodal upstaging was observed. Negative resection margins were 100%. There were two (7%) conversions, one to open surgery and one to video-assisted thoracic surgery (VATS). Eight (28%) patients experienced complications with no 30-day mortality. Discussion: High-ergonomic and high-quality views were immediately observed. After some procedures, we abandoned uniportal RATS because of the possibility of arm collisions and the necessity of a VATS-skilled surgeon at the operating table. Conclusion: RATS for lung resections was safe and effective, and from the surgeon's standpoint, several practical advantages over VATS were observed. Further analysis on outcomes will help better understand the value of this technology.

Advances in Lung Transplantation.

Nowadays, lung transplantation is a clinical reality for the treatment of benign end-stage respiratory diseases [...].

Lung Transplantation From Controlled and Uncontrolled Donation After Circulatory Death (DCD) Donors With Long Ischemic Times Managed by Simple Normothermic Ventilation and Ex-Vivo Lung Perfusion Assessment.

Donation after cardiac death (DCD) donors are still subject of studies. In this prospective cohort trial, we compared outcomes after lung transplantation (LT) of subjects receiving lungs from DCD donors with those of subjects receiving lungs from donation after brain death (DBD) donors (ClinicalTrial.gov: NCT02061462). Lungs from DCD donors were preserved in-vivo through normothermic ventilation, as per our protocol. We enrolled candidates for bilateral LT ≥14 years. Candidates for multi-organ or re-LT, donors aged ≥65 years, DCD category I or IV donors were excluded. We recorded clinical data on donors and recipients. Primary endpoint was 30-day mortality. Secondary endpoints were: duration of mechanical ventilation (MV), intensive care unit (ICU) length of stay, severe primary graft dysfunction (PGD3) and chronic lung allograft dysfunction (CLAD). 121 patients (110 DBD Group, 11 DCD Group) were enrolled. 30-day mortality and CLAD prevalence were nil in the DCD Group. DCD Group patients required longer MV (DCD Group: 2 days, DBD Group: 1 day, p = 0.011). ICU length of stay and PGD3 rate were higher in DCD Group but did not significantly differ. LT with DCD grafts procured with our protocols appears safe, despite prolonged ischemia times.

Microvascular and Macrovascular Endothelial Cell Isolation and Purification from Lung-Derived Samples.

The availability of cells isolated from healthy and diseased tissues and organs represents a key element for personalized medicine approaches. Although biobanks can provide a wide collection of primary and immortalized cells for biomedical research, these do not cover all experimental needs, particularly those related to specific diseases or genotypes. Vascular endothelial cells (ECs) are key components of the immune inflammatory reaction and, thus, play a central role in the pathogenesis of a variety of disorders. Notably, ECs from different sites display different biochemical and functional properties, making the availability of specific EC types (i.e., macrovascular, microvascular, arterial, and venous) essential for designing reliable experiments. Here, simple procedures to obtain high-yield, virtually pure human macrovascular and microvascular endothelial cells from the pulmonary artery and lung parenchyma are illustrated in detail. This methodology can be easily reproduced at a relatively low cost by any laboratory to achieve independence from commercial sources and obtain EC phenotypes/genotypes that are not yet available.

Approaches and outcomes of Robotic-Assisted Thoracic Surgery (RATS) for lung cancer: a narrative review.

Robotic-Assisted Thoracic Surgery (RATS) is considered one of the main issues of present thoracic surgery. RATS is a minimally invasive surgical technique allowing enhanced view, accurate and complex movements, and high ergonomics for the surgeon. Despite these advantages, its application in lung procedures has been limited, mainly by its costs. Since now many different approaches have been proposed and the experience in RATS for lungs ranges from wedge resection to pneumonectomy and is mainly related to lung cancer. The present narrative review explores main approaches and outcomes of RATS lobectomy for lung cancer. A non-systematic review of literature was conducted using the PubMed search engine. An overview of lung robotic surgery is given, and main approaches of robotic lobectomy for lung cancer are exposed. Initial experiences of biportal and uniportal RATS are also described. So far, retrospective analysis reported satisfactory robotic operative outcomes, and comparison with VATS might suggest a more accurate lymphadenectomy. Some Authors might even suggest better perioperative outcomes too. From an oncological standpoint, no definitive prospective study has yet been published but several retrospective analyses report oncological outcomes comparable to those of VATS and open surgery. Literature suggests that RATS for lung procedures is safe and effective and should be considered as a valid additional surgical option.

Identification of a new potential plasmatic biomarker panel for the diagnosis of malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare highly aggressive tumor strongly associated with asbestos exposure and characterized by poor prognosis. Currently, diagnosis is based on invasive techniques, thus there is a need of identifying non-invasive biomarkers for early detection of the disease among asbestos-exposed subjects. In the present study, we measured the plasmatic concentrations of Mesothelin, Fibulin-3, and HMGB1 protein biomarkers, and of hsa-miR-30e-3p and hsa-miR-103a-3p Extracellular-Vesicles- embedded micro RNAs (EV-miRNAs). We tested the ability of these biomarkers to discriminate between MPM and PAE subjects alone and in combination. METHODS: the study was conducted on a population of 26 patients with MPM and 54 healthy subjects with previous asbestos exposure (PAE). Mesothelin, Fibulin-3, and HMGB1 protein biomarkers were measured by the enzyme-linked immunosorbent assay (ELISA) technique; the levels of hsa-miR-30e-3p and hsa-miR-103a-3p EV-miRNAs was assessed by quantitative real-time PCR (qPCR). RESULTS: the most discriminating single biomarker resulted to be Fibulin-3 (AUC 0.94 CI 95% 0.88-1.0; Sensitivity 88%; Specificity 87%). After investigating the different possible combinations, the best performance was obtained by the three protein biomarkers Mesothelin, Fibulin-3, and HMGB1 (AUC 0.99 CI 95% 0.97-1.0; Sensitivity 96%; Specificity 93%). CONCLUSIONS: the results obtained contribute to identifying new potential non-invasive biomarkers for the early diagnosis of MPM in high-risk asbestos-exposed subjects. Further studies are needed to validate the evidence obtained, in order to assess the reliability of the proposed biomarker panel.

Lung Transplant for ARDS after COVID-19: Long-Term Outcomes and Considerations about Detrimental Issues.

During the first outbreak of COVID-19 in Italy, based on the only few cases reported from a Chinese centre at the time, we performed lung transplantation in two patients with irreversible acute respiratory distress syndrome (ARDS) after COVID-19 at our centre. After two years, we report the outcomes of these cases and some considerations. The first patient, an 18-year-old male, is in excellent conditions twenty-four months after surgery. The second patient was a 48-year-old man; his airways were colonized by carbapenemase-producing klebsiella pneumoniae at the time of lung transplantation, and he had previously suffered from delirium and hallucinations in the intensive care unit. His postoperative clinical course was complicated by dysexecutive behaviour and then septic shock; he died 62 days after surgery. The recently reported experience of different transplantation centres has led to the inclusion of irreversible acute respiratory distress syndrome (ARDS) after COVID-19 among the indications for lung transplantation in carefully selected patients. Our results confirm the feasibility and the good long-term outcomes of lung transplantation for COVID-19-associated ARDS. Nonetheless, our experience corroborates the need for careful recipient selection: special attention must be paid to the single-organ dysfunction principle, the evaluation of any neuro-psychiatric disorder, and MDR germs colonization, before listing.

Lung Biomolecular Profile and Function of Grafts from Donors after Cardiocirculatory Death with Prolonged Donor Warm Ischemia Time.

The acceptable duration of donor warm ischemia time (DWIT) after cardiocirculatory death (DCD) is still debated. We analyzed the biomolecular profile and function during ex vivo lung perfusion (EVLP) of DCD lungs and their correlation with lung transplantation (LuTx) outcomes. Donor data, procurement times, recipient outcomes, and graft function up to 1 year after LuTx were collected. During EVLP, the parameters of graft function and metabolism, perfusate samples to quantify inflammation, glycocalyx breakdown products, coagulation, and endothelial activation markers were obtained. Data were compared to a cohort of extended-criteria donors after brain death (EC-DBD). Eight DBD and seven DCD grafts transplanted after EVLP were analyzed. DCD's DWIT was 201 [188;247] minutes. Donors differed only regarding the duration of mechanical ventilation that was longer in the EC-DBD group. No difference was observed in lung graft function during EVLP. At reperfusion, "wash-out" of inflammatory cells and microthrombi was predominant in DCD grafts. Perfusate biomolecular profile demonstrated marked endothelial activation, characterized by the presence of inflammatory mediators and glycocalyx breakdown products both in DCD and EC-DBD grafts. Early graft function after LuTx was similar between DCD and EC-DBD. DCD lungs exposed to prolonged DWIT represent a potential resource for donation if properly preserved and evaluated.

Outcomes of extended surgical resections for locally advanced thymic malignancies: a narrative review.

Background and Objective: Thymic malignancies represent the most common anterior mediastinal neoplasms, as well as rare and challenging tumors. Surgery is the cornerstone in the treatment of thymic malignancies, although a multidisciplinary approach is mandatory, for both, locally advanced or metastatic disease. In our narrative review, we explored the recent literature to investigate clinical and radiological assessment, multimodality approach and outcomes of locally advanced thymic tumors. More than one-third of patients affected by an anterior mediastinal mass are asymptomatic at diagnosis. In case of locally advanced thymoma, symptoms are related to compression or invasion of adjacent structures, such as the superior vena cava (SVC), innominate veins and pericardium. Paraneoplastic syndromes, such as myasthenia gravis (MG), are related to release of antibodies, hormones and cytokines. Methods: Diagnostic methods must be chosen accurately to avoid unnecessary surgical resections, to define the best strategy of care, and to plan the surgical strategy. Therefore, each case must be evaluated in a multidisciplinary context, where surgery plays an essential role. Key Content and Findings: In this narrative review, we describe indications and surgical techniques for the treatment of locally advanced thymoma; focusing on oncological outcomes after different approaches. Conclusions: In conclusion, aggressive surgery is always indicated, when possible, and when a complete resection can be planned, yet, the multidisciplinary approach is mandatory, in case of both locally or metastatic advanced disease.

Functional analysis of the airways after pulmonary lobectomy through computational fluid dynamics.

Pulmonary lobectomy, which consists of the partial or complete resection of a lung lobe, is the gold standard intervention for lung cancer removal. The removal of functional tissue during the surgery and the re-adaptation of the remaining thoracic structures decrease the patient's post-operative pulmonary function. Residual functionality is evaluated through pulmonary function tests, which account for the number of resected segments without considering local structural alterations and provide an average at-the-mouth estimation. Computational Fluid Dynamics (CFD) has been demonstrated to provide patient-specific, quantitative, and local information about airways airflow dynamics. A CFD investigation was performed on image-based airway trees reconstructed before and after the surgery for twelve patients who underwent lobectomy at different lobes. The geometrical alterations and the variations in fluid dynamics parameters and in lobar ventilation between the pre and post-operative conditions were evaluated. The post-operative function was estimated and compared with current clinical algorithms and with actual clinical data. The post-operative configuration revealed a high intersubject variability: regardless of the lobectomy site, an increment of global velocity, wall pressure, and wall shear stress was observed. Local flow disturbances also emerged at, and downstream of, the resection site. The analysis of lobar ventilation showed severe variations in the volume flow rate distribution, highlighting the compensatory effects in the contralateral lung with an increment of inflow. The estimation of post-operative function through CFD was comparable with the current clinical algorithm and the actual spirometric measurements. The results confirmed that CFD could provide additional information to support the current clinical approaches both in the operability assessment and in the prescription of personalized respiratory rehabilitation.

Management of intrathoracic phosphaturic mesenchymal tumor by nonintubated uniportal video-assisted thoracic surgery in a fragile patient.

BACKGROUND: Phosphaturic mesenchymal tumors are rare neoplasms, frequently presenting with osteomalacia. These neoplasms usually grow at a slow rate and are associated with unspecific symptoms. CASE: In this study, we present the case of a 70-year-old woman who had been suffering from musculoskeletal pain, hypophosphatemia, and spontaneous fractures. Positron emission tomography with Gallium showed increase uptake in a subpleural lesion. CONCLUSION: The patient underwent surgical excision of the subpleural lesion with a non-intubated uniportal video-assisted thoracoscopic surgery approach.

Interobserver variability in the evaluation of primary graft dysfunction after lung transplantation: impact of radiological training and analysis of discordant cases.

PURPOSE: Radiologic criteria for the diagnosis of primary graft dysfunction (PGD) after lung transplantation are nonspecific and can lead to misinterpretation. The primary aim of our study was to assess the interobserver agreement in the evaluation of chest X-rays (CXRs) for PGD diagnosis and to establish whether a specific training could have an impact on concordance rates. Secondary aim was to analyze causes of interobserver discordances. MATERIAL AND METHODS: We retrospectively enrolled 164 patients who received bilateral lung transplantation at our institution, between February 2013 and December 2019. Three radiologists independently reviewed postoperative CXRs and classified them as suggestive or not for PGD. Two of the Raters performed a specific training before the beginning of the study. A senior thoracic radiologist subsequently analyzed all discordant cases among the Raters with the best agreement. Statistical analysis to calculate interobserver variability was percent agreement, Cohen's kappa and intraclass correlation coefficient. RESULTS: A total of 473 CXRs were evaluated. A very high concordance among the two trained Raters, 1 and 2, was found (K = 0.90, ICC = 0.90), while a poorer agreement was found in the other two pairings (Raters 1 and 3: K = 0.34, ICC = 0.40; Raters 2 and 3: K = 0.35, ICC = 0.40). The main cause of disagreement (52.4% of discordant cases) between Raters 1 and 2 was the overestimation of peribronchial thickening in the absence of unequivocal bilateral lung opacities or the incorrect assessment of unilateral alterations. CONCLUSION: To properly identify PGD, it is recommended for radiologists to receive an adequate specific training.

Physiotherapy approach after lung transplantation in a critically ill COVID-19 patient: a case report.

This study describes the case of an 18-years-old male affected by severe COVID-19, who was receiving bilateral lung transplantation (LT), after 71 days of mechanical ventilation and 55 days of veno-venous extracorporeal membrane oxygenation. From post-operative day 2, early mobilization and physiotherapy treatments were performed. Weaning from mechanical ventilation, the use of non-invasive ventilation and tracheostomy management were included in the treatment. Forty-five days after LT the patient was discharged at home, showing improvements in terms of functional and respiratory parameters, quality of life and mood. While evidences about physiotherapy treatments in lung transplantation post severe COVID-19 remain limited, early approach and a multidisciplinary team may be considered key elements for functional recovery of these subjects.

Management of Pleural Effusion Secondary to Malignant Mesothelioma.

Malignant pleural mesothelioma (MPM) is a highly aggressive pleural tumour which has been epidemiologically linked to occupational exposure to asbestos. MPM is often associated with pleural effusion, which is a common cause of morbidity and whose management remains a clinical challenge. In this review, we analysed the literature regarding the diagnosis and therapeutic options of pleural effusion secondary to mesothelioma. Our aim was to provide a comprehensive view on this subject, and a new algorithm was proposed as a practical aid to clinicians dealing with patients suffering from pleural effusion.

An EBC/Plasma miRNA Signature Discriminates Lung Adenocarcinomas From Pleural Mesothelioma and Healthy Controls.

BACKGROUND: Despite significant improvement in screening programs for cancers of the respiratory district, especially in at-risk subjects, early disease detection is still a major issue. In this scenario, new molecular and non-invasive biomarkers are needed to improve early disease diagnosis. METHODS: We profiled the miRNome in exhaled breath condensate (EBC) and plasma samples from fourteen patients affected by lung AdCa, nine healthy subjects. miRNA signatures were then analyzed in another neoplasia of the respiratory district, i.e. pleural mesothelioma (n = 23) and subjects previously exposed to asbestos were used as controls for this cohort (n = 19). Selected miRNAs were analyzed in purified pulmonary neoplastic or normal epithelial and stromal cell subpopulation from AdCa patients. Finally, the plasmatic miRNA signature was analyzed in a publicly available cohort of NSCLC patients for data validation and in silico analysis was performed with predicted miRNA targets using the multiMiR tool and STRING database. RESULTS: miR-597-5p and miR-1260a are significantly over-expressed in EBC from lung AdCa and are associated with AdCa. Similarly, miR-1260a is also up-regulated in the plasma of AdCa patients together with miR-518f-3p and correlates with presence of lung cancer, whereas let-7f-5p is under-expressed. Analysis of these circulating miRNAs in pleural mesothelioma cases confirmed that up-regulation of miR-518f-3p, -597-5p and -1260a, is specific for lung AdCa. Lastly, quantification of the miRNAs in laser-assisted microdissected lung tissues revealed that miR-518f-3p, 597-5p and miR-1260a are predominantly expressed in tumor epithelial cells. Validation analysis confirmed miR-518f-3p as a possible circulating biomarker of NSCLC. In silico analysis of the potentially modulated biological processes by these three miRNAs, shows that tumor bioenergetics are the most affected pathways. CONCLUSIONS: Overall, our data suggest a 3-miRNAs signature as a non-invasive and accurate biomarker of lung AdCa. This approach could supplement the current screening approaches for early lung cancer diagnosis.