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Patients with interstitial lung disease (ILD) are about five times more likely to develop lung cancer than those without ILD. The presence of ILD in lung cancer patients complicates diagnosis and management, resulting in lower survival rates. Diagnostic and treatment procedures needed for cancer can increase the risk of acute exacerbation (AE), one of the most severe complications for these patients. Bronchoscopic techniques are generally considered safe, but they can trigger AE-ILD, particularly after cryoprobe biopsies. Surgical procedures for lung cancer, including lung biopsies and resections, carry an elevated risk of AE-ILD. Postoperative complications and mortality rates highlight the importance of meticulous surgical planning and postoperative care. Furthermore, cancer treatments, such as chemotherapy, are all burdened by a risk of AE-ILD occurrence. Radiotherapy is important for managing both early-stage and advanced lung cancer, but it also poses risks. Stereotactic body radiation and particle beam therapies have varying degrees of safety, with the latter potentially offering a lower risk of AE. Percutaneous ablation techniques can help patients who are not eligible for surgery. However, these procedures may complicate ILD, and their associated risks still need to be fully understood, necessitating further research for improved safety. Overall, while advancements in lung cancer treatment have improved outcomes for many patients, the complexity of managing patients with concomitant ILD needs careful consideration and multidisciplinary assessment. This review provides a detailed evaluation of these risks, emphasizing the need for personalized treatment approaches and monitoring to improve patient outcomes in this challenging population. [ABSTRACT FROM AUTHOR]

Simple Summary: The therapeutic strategies of NSCLC focus on systemic strategies, mainly chemotherapy and immunotherapy. Unfortunately, cancer has some aces up it's sleeve, in particular the tumoral microenvironment. An intratumoral strategy can be useful to overcome cancer's shelters. Some intratumoral strategies have been analyzed and proved during the last decades, including a treatment based on "classical" antiblastic agents, immunotherapy, and immunomodulating agents, which can be administered by direct injection, inhalation, and intrapleuraly. Other treatments take advantage of ablation techniques, including photodynamic and thermal. Moreover, it is possible to evaluate the use of electric fields, a promising technique, and brachytherapy, a consolidated one. Finally, nanoparticles are interesting and useful both for their direct activity and for their carrier role. Each intratumoral strategy should be chosen based on setting, metastasis status, cancer type, and patient features, etc. Furthermore, the evaluation of a combined approach is fundamental, because intratumoral and systemic strategies together can overcome the other's limitations and mutually enhance one another in order to become more efficient tools in the anticancer war. According to a modern view, cancer no longer follows a purely mechanistic model. Rather, a tumor is conceived as a more complex structure, composed of cancer cells, the activities of which may interact and reshape the so-called tumor microenvironment (TME), leading to preservation of specific tumoral niches and promoting the survival of tumoral stem cells. Background/Objective: Therapeutic strategies must deal with this unique cancer architecture in the near future by widening their range of activities outside the cancer cells and rewiring a TME to ensure it is hostile to cancer growth. Therefore, an intratumoral therapeutic strategy may open the door to a new type of anticancer activity, one that directly injures the tumoral structure while also eliciting an influence on the TME through local and systemic immunomodulation. This review would like to assess the current situation of intratumoral strategies and their clinical implications. Methods We analyzed data from phase I, II, and III trials, comprehensive reviews and relevant clinical and preclinical research, from robust databases, like PUBMED, EMBASE, Cochrane Library, and clinicaltrials.gov. Results: Intratumoral strategies can be quite variable. It is possible the injection and inhalation of traditional antiblastic agents or immunomodulant agents, or intrapleural administration. Ablation strategy is available, both thermal and photodynamic method. Moreover, TTfields and NPs are analyzed and also brachytherapy is mentioned. Intratumoral therapy can find space in "adjuvant"/perioperative or metastatic settings. Finally, intratumoral strategies allow to synergize their activities with systemic therapies, guaranteeing better local and systemic disease control. Conclusions: Intratumoral strategies are overall promising. Antiblastic/immunomodulant injection and NPs use are especially interesting and intriguing. But, there is generally a lack of phase II and III trials, in particular NPs use need additional experimentation and clinical studies. [ABSTRACT FROM AUTHOR]

Background Lung cancer is the leading cause of cancer-related deaths, and surgery is still the first treatment of choice in early and locally advanced cases. One of the iatrogenic complications is the serratus anterior palsy, which could lead to a winged scapula (WS). Unfortunately, the incidence of this deficit in thoracic surgery is unclear. Our primary aim was to determine the incidence of WS in lung cancer patients in a single-center experience. Methods We conducted a retrospective analysis of prospectively collected data with patients eligible for oncological thoracic surgery from March 2013 until January 2014. A physical evaluation of the WS was performed pre- and postoperatively, at the discharge and after 1 year of follow-up. Results A total of 485 patients were evaluated; 135 (27.8%) showed WS. Longer operative time (p < 0.0001), type of surgery (p < 0.0001), lymphadenectomy (p < 0.0001), and neoadjuvant treatment prior surgery (p = 0.0005) were significantly related to the WS injury. Multivariable analysis showed that type of surgery was significantly associated with WS (p < 0.0001). After 1 year, 41.6% still had WS. Conclusion The incidence of WS was similar to the literature. As WS incidence is underdiagnosed, assessment and correct education about possible deficits or impairments should be improved. Moreover, when a minimally invasive approach is not planned, it is a good clinical practice to discuss surgical strategies with surgeons to reduce this deficit. [ABSTRACT FROM AUTHOR]

Lung cancer represents the second most frequent neoplasm and the leading cause of neoplastic death among both women and men, causing almost 25% of all cancer deaths. Patients undergoing lung resection—both for primary and secondary tumors—require careful preoperative cardiopulmonary functional evaluation to confirm the safety of the planned resection, to assess the maximum tolerable volume of resection or to exclude surgery, thus shifting the therapeutic approach toward less invasive options. Cardiopulmonary reserve, pulmonary lung function and mechanical respiratory function represent the cornerstones of preoperative assessment of patients undergoing major lung resection. Spirometry with carbon monoxide diffusing capacity, split function tests, exercise tests and cardiologic evaluation are the gold standard instruments to safely assess the entire cardiorespiratory function before pulmonary resection. Although pulmonary mechanical and parenchymal function, together with cardiorespiratory compliance represent the mainstay of preoperative evaluation in thoracic surgery, the variables that are responsible for fitness in patients who have undergone lung resection have expanded and are being continually investigated. Nevertheless, because of the shift to older patients who undergo lung resection, a global approach is required, taking into consideration variables like frailty status and likelihood of postoperative functional deterioration. Finally, the decision to go ahead with surgery in fragile patients being consideredfor lung resection should be evaluated in a multispecialty preoperative discussion to provide a personalized risk stratification. The aim of this review is to focus on preoperative evaluation of cardiopulmonary reserve and surgical risk stratification of patients candidate for lung cancer resection. It does so by a literature search of clinical guidelines, expert consensus statements, meta-analyses, clinical recommendations, book chapters and randomized trials (1980–2022). [ABSTRACT FROM AUTHOR]

Background: Sleeve lobectomy with bronchoplasty is a safe surgical technique for the management of lung cancer and endobronchial localization of extrapulmonary cancers. However, anastomotic complications can occur, and treatment strategies are not standardized. Methods: Data from 280 patients subjected to bronchoplasty were retrospectively analyzed, focusing on surgical techniques, anastomotic complications, and their management. Multivariate analysis was performed, and Kaplan–Meier curves were used to determine survival. Results: Ninety percent of 280 surgeries were for lung cancer. Anastomotic complications occurred in 6.42% of patients: late stenosis in 3.92% and broncho-pleural fistula in 1.78%. The median survival was 65.90 months (95% CI = 41.76–90.97), with no difference (p = 0.375) for patients with (51.28 months) or without (71.03 months) anastomotic complications. Mortality at 30 days was higher with anastomotic complications (16.7% vs. 3%, p = 0.014). Multivariable analysis confirmed pathological stage (N+) as a risk factor for anastomotic complications (p = 0.016). Our mortality (3.93%) and morbidity rate (41.78%) corresponded to recent series results. Conclusions: In our experience, surgery is preferred to avoid life-threatening complications in bronchopleural fistulas. Bronchoscopic balloon dilatation is preferred for benign strictures. The nodal stage is related to complications (p = 0.0014), reflecting the aggressiveness of surgery, which requires extended radical lymphadenectomy. [ABSTRACT FROM AUTHOR]

Background: In the treatment of Non-Small Cell Lung Cancer (NSCLC) the combination of Immuno- Oncotherapy (IO) and chemotherapy (CT) has been found to be superior to IO or CT alone for patients' survival. Patients and clinicians are confronted with a preference sensitive choice between a more aggressive treatment with a greater negative effect on quality of life versus alternatives that are less effective but have fewer side effects. Objectives: The aims of this study were to: (a) quantify patients' preferences for relevant attributes related to Immuno-Oncotherapy treatment alternatives, and (b) evaluate the maximum acceptable risk (MAR)/Minimum acceptable benefit (MAB) that patients would accept for treatment alternatives. Methods: An online preference survey using discrete-choice experiment (DCE) was completed by NSCLC patients from two hospitals in Italy and Belgium. The survey asked patients' preferences for five patient- relevant treatment attributes. The DCE was developed using a Bayesian D-efficient design. DCE analyses were performed using mixed logit models. Information regarding patient demographics, health literacy, locus of control, and quality of life was also collected. Results: 307 patients (158 Italian, 149 Belgian), stage I to IV, completed the survey. Patients preferred treatments with a higher 5-year survival chance as the most important attribute over all the other attributes. Preference heterogeneity for the attribute weights depended on health literacy, patients' age and locus of control. Patients were willing to accept a substantially increased risks of developing side effects in exchange for the slightest increase (1%) in the chance of surviving at least 5 years from the diagnosis of cancer. Similarly, patients were willing to accept a switch in the mode of administration or complete loss of hair to obtain an increase in survival. Conclusion: In this study, the proportion of respondents who systematically preferred survival over all other treatment attributes was particularly high. Age, objective health literacy and locus of control accounted for heterogeneity in patients' preferences. Evidence on how NSCLC patients trade between survival and other NSCLC attributes can support regulators and other stakeholders on assessing clinical trial evidence and protocols, based on patients' conditions and socio-demographic parameters. [ABSTRACT FROM AUTHOR]

Simple Summary: Surgical resections remain the gold standard for early stages non-small-cell carcinoma (NSCLC) and may be considered for locally advanced tumors. Medical treatment has changed drastically in recent years, especially for advanced stages, for which the development of immunotherapy and molecular targeted therapy significantly increased survival and quality of life. The addition of radical surgical resection following immunotherapy or immuno-chemotherapy is feasible and safe with low surgical-related mortality and morbidity in selected patients with initially unresectable NSCLC. Many new treatment modalities for non-small-cell carcinoma (NSCLC) have been described in the last two decades. Surgical resections remain the gold standard for early stages and may be considered for locally advanced tumors. Medical treatment has changed drastically in recent years, especially for advanced stages, for which the development of immunotherapy and molecular targeted therapy significantly increased survival and quality of life. The addition of radical surgical resection following immunotherapy or immuno-chemotherapy is feasible and safe with low surgical-related mortality and morbidity in selected patients with initially unresectable NSCLC. However, data from multiple ongoing trials with overall survival as the primary endpoint should be awaited before this strategy is introduced into the standard of care. [ABSTRACT FROM AUTHOR]

Lung cancer is the second-most commonly diagnosed cancer and the leading cause of cancer death worldwide. The most common histological type is non-small-cell lung cancer, accounting for 85% of all lung cancer cases. About one out of three new cases of non-small-cell lung cancer are diagnosed at a locally advanced stage—mainly stage III—consisting of a widely heterogeneous group of patients presenting significant differences in terms of tumor volume, local diffusion, and lymph nodal involvement. Stage III NSCLC therapy is based on the pivotal role of multimodal treatment, including surgery, radiotherapy, and a wide-ranging option of systemic treatments. Radical surgery is indicated in the case of hilar lymphnodal involvement or single station mediastinal ipsilateral involvement, possibly after neoadjuvant chemotherapy; the best appropriate treatment for multistation mediastinal lymph node involvement still represents a matter of debate. Although the main scope of treatments in this setting is potentially curative, the overall survival rates are still poor, ranging from 36% to 26% and 13% in stages IIIA, IIIB, and IIIC, respectively. The aim of this article is to provide an up-to-date, comprehensive overview of the state-of-the-art treatments for stage III non-small-cell lung cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: A surgeon's feelings and his/her autonomic nervous system (ANS) response during interventions represent direct indicators of comfort, comfortability, dexterity, and stress during a surgical procedure. We evaluated the autonomic nervous system (ANS) and psychological responses to stress of surgeons during their surgical activity, comparing their robotic activity and their classical surgical activity via an open approach. For different reasons, the robotic approach led to less stimulation of the autonomic nervous system, producing less stress for the surgeons and ensuring greater comfort. (1) Objective: the purpose of this study was to evaluate and quantify the stress to which a surgeon is subjected during his/her surgical activity; we compared the individual clinical and psychological responses to stress of two surgeons during their surgical activities via robotic and open approaches. (2) Materials and methods: This was a prospective observational study in which we progressively collected data concerning the surgical performances of two different thoracic surgeons (October 2021–June 2022). We evaluated 20 lung resections performed via robot-assisted surgery and 20 lung resections performed via an open approach by each surgeon; in particular, we evaluated a panel of pre-, peri-, and postoperative data concerning the interventions, the patients, and other outcomes concerning the autonomic nervous system (ANS) and psychological responses to stress of the surgeons during their surgical activities. (3) Results: When analyzing data concerning the ANS activity of two surgeons, during robotic activity we found lower maximum, minimum, and mean heart rates; lower mean respiratory frequencies; lower body temperatures; and lower mean desaturations compared to the open approach activity for both surgeons. The psychological monitoring showed that the open approach created more physical fatigue and frustration but higher levels of satisfaction and performance evaluation. The robot-assisted surgeries showed higher levels of anxiety. (4) Conclusions: for different reasons, the robotic approach stimulated the ANS to a lesser degree, causing less stress for surgeons and ensuring greater comfort. [ABSTRACT FROM AUTHOR]

Objective: Our purpose is to define the learning curve for robot-assisted thoracoscopic surgery lobectomy by reporting the experience of a single surgeon. Material and methods: We progressively collected the data concerning the surgical performance of a single male thoracic surgeon, from the beginning of his robotic activity as first operator from January 2021 to June 2022. We evaluated several pre-, intra- and postoperative parameters concerning patients and intraoperative cardiovascular and respiratory outcomes of the surgeon, recorded during surgical interventions, in order to evaluate his cardiovascular stress. We used cumulative sum control charts (CUSUM) to analyze the learning curve. Results: A total of 72 lung lobectomies were performed by a single surgeon in this period. Analyzing the CUSUM of several parameters, the inflection point identifying the transition beyond the surgeon learning phase was reached at cases 28, 22, 27 and 33 when considering operating time, mean heart rate, max heart rate and mean respiratory rate, respectively. Conclusions: The learning curve for robotic lobectomy seems to be safe and feasible with a correct robotic training program. The analysis of a single surgeon from the beginning of his robotic activity demonstrates that confidence, competence, dexterity and security are achieved after about 20–30 procedures, without compromising efficiency and oncological radicality. [ABSTRACT FROM AUTHOR]

Objectives: Superior sulcus tumour, which affects the lung's apex, is an uncommon subtype of non-small cell lung cancer (NSCLC). The current study examined the clinical characteristics and management of superior sulcus NSCLC patients in a high-volume referral oncological centre over 22 years. Methods: Retrospective review of 100 surgeries with curative intent for superior sulcus NSCLC over 22 years (July 1998 -- December 2020). The surgical approach was defined according to the lesion site and the anatomy of the thoracic inlet. Survival curves, including non-cancer-related deaths, were drawn using the Kaplan-Meier methods, and the log-rank test was used to evaluate differences in survival across groups of patients. Cox proportional hazards regression was used to assess the association between selected clinical and pathologic characteristics on OS. Results: 54 patients received induction treatments. The surgical approach was anterior thoracotomy in 53 patients, Paulson incision in 30, and a combined in 8. The median postoperative length of stay was 11 days (range: 5 - 27 days). Overall 90-day mortality was 6.93%. The median OS was 24.3 months. After a median follow-up of 3 years, 5-year and 10-year OS rates were 33.9% and 26.4%, respectively. A significantly lower 5-year OS was observed in patients with the nodal disease (46.6% in pN0 vs 13.2% in pN+; p = 0.024), without preoperative treatments (41.0% in patients without preoperative treatments versus 17.4%; p = 0.09) and anteriorly located tumour (anterior vs posterior: 17.4% vs 49.1%; p = 0.032). Cox proportional hazards regression showed better survival in the pT1 stage (HR = 4.6; 95% CI: 1.9 - 11.2; p = 0.00076) and in R0 (HR = 4.2; 95% CI: 1.4 - 12.5; p = 0.010). Conclusions: Superior sulcus tumours still represent a life-threatening condition that, while curable in a significant proportion of cases, requires complex procedures with high surgical risks and a multimodality treatment setting. An optimal surgical approach should be planned to maximise resection completeness and survival. Other factors affecting survival are related to tumour staging, emphasising the importance of a meticulous preoperative workup and candidate selection to identify those expected to benefit from a survival benefit. [ABSTRACT FROM AUTHOR]

Simple Summary: In the modern era, characterized by parenchymal-sparing procedures, in some cases pneumonectomy remains the only therapeutic approach to achieving oncological radicality. One of the most feared complications is undoubtedly respiratory failure and ARDS. Its cause after pneumonectomy is still unclear, and the study of risk factors is a subject of debate. In this paper, we evaluate the main risk factors for ARDS of a large cohort of patients and we classify them in four classes of growing risk in order to quantify their postoperative risk of ARDS and facilitate their global management. (1) Background: The cause of ARDS after pneumonectomy is still unclear, and the study of risk factors is a subject of debate. (2) Methods: We reviewed a large panel of pre-, peri- and postoperative data of 211 patients who underwent pneumonectomy during the period 2014–2021. Univariable and multivariable logistic regression was used to quantify the association between preoperative parameters and the risk of developing ARDS, in addition to odds ratios and their respective 95% confidence intervals. A backward stepwise selection approach was used to limit the number of variables in the final multivariable model to significant independent predictors of ARDS. A nomogram was constructed based on the results of the final multivariable model, making it possible to estimate the probability of developing ARDS. Statistical significance was defined by a two-tailed p-value < 0.05. (3) Results: Out of 211 patients (13.3%), 28 developed ARDS. In the univariate analysis, increasing age, Charlson Comorbidity Index and ASA scores, DLCO < 75% predicted, preoperative C-reactive protein (CRP), lung perfusion and duration of surgery were associated with ARDS; a significant increase in ARDS was also observed with decreasing VO2max level. Multivariable analysis confirmed the role of ASA score, DLCO < 75% predicted, preoperative C-reactive protein and lung perfusion. Using the nomogram, we classified patients into four classes with rates of ARDS ranking from 2.0% to 34.0%. (4) Conclusions: Classification in four classes of growing risk allows a correct preoperative stratification of these patients in order to quantify the postoperative risk of ARDS and facilitate their global management. [ABSTRACT FROM AUTHOR]

Simple Summary: The diagnosis of active neoplastic disease was traditionally judged an absolute contraindication for extracorporeal membrane oxygenator (ECMO) because of long-term results uncertainty and co-existing acquired coagulation disorders often diagnosed in this group of patients. There is a growing body of evidence that circulating tumor cells (CTCs) can be detected in the blood of patients before the primary tumor is diagnosed and in the case of carcinoma recurrence; moreover, on some occasions, they persist in the blood of patients after radical resection of the primary tumor. The aim of this prospective, two-arm study is to compare the number of CTCs before and after surgery in patients undergoing lung cancer resection with and without intraoperative ECMO support. Intraoperative ECMO for lung cancer resections did not impact CTC variation after the procedure and did not impact postoperative complications, ICU stay, hospital total length of stay, and post operative C-reactive protein increase. Background: The diagnosis of active neoplastic disease was traditionally judged an absolute contraindication for extracorporeal membrane oxygenator (ECMO) because of the fear of tumor cells being scattered or seeded. The aim of this study is to compare the number of circulating tumor cells (CTCs) before and after surgery in patients receiving lung cancer resection with and without intraoperative ECMO support. Methods: This is a prospective, non-randomized, two-arms observational study comparing the number of CTCs before and after surgery in patients receiving lung cancer resection with and without intraoperative ECMO support. The ECMO arm includes patients suffering from lung cancer undergoing pulmonary resection with planned intraoperative ECMO support. The non-ECMO arm includes patients suffering from non-early-stage lung cancer undergoing pulmonary resection without planned intraoperative ECMO support. Results: Twenty patients entered the study, eight in the ECMO arm and twelve in the non-ECMO arm. We did not observe any significant difference between the ECMO and non-ECMO groups in terms of postoperative complications (p = 1.00), ICU stay (p = 0.30), hospital stay (p = 0.23), circulating tumor cells' increase or decrease after surgery (p = 0.24), and postoperative C-reactive protein and C-reactive protein increase (p = 0.80). The procedures in the non-ECMO arm were significantly longer than those in the ECMO arm (p = 0.043). Conclusions: Intraoperative ECMO for lung cancer resections did not impact CTC increase or decrease after the procedure. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess if CT-derived body composition values and clinical characteristics are associated with the risk of postsurgical complications in men and women who underwent pneumonectomy for lung cancer. Materials and Methods: Patients who underwent pneumonectomy between 2004 and 2008 were selected. The ethics committee approved this retrospective study with waiver of informed content. Main clinical data collected were sex, age, weight and height to calculate body mass index (BMI), albumin, C-reactive protein, smoking status, side, sarcopenia, presurgical treatments, reoperation, and complications within 30 days after pneumonectomy, classified as: lung complications, cardiac complications, other complications, and any complication. From an axial CT image at the level of L3, automatic segmentations were performed to calculate skeletal muscle area (SMA), skeletal muscle density, subcutaneous adipose tissue, and visceral adipose tissue. Skeletal muscle index was calculated as SMA/square height. Univariate and multivariate logistic regression analyses were performed to estimate the risk of any complication, both on the total population and in a by sex subgroup analysis. All tests were two tailed and considered significant at 5% level. Results: A total of 107 patients (84 men and 23 women) were included. Despite no significant differences in BMI, there were significant differences of body composition values in muscle and adipose tissue parameters between men and women, with women being significantly more sarcopenic than men (p = 0.002). Separate analyses for men and women showed that age and SMA were significantly associated with postoperative complications in men (p = 0.03 and 0.02, respectively). Conclusions: Body composition measurements extracted from routine CT may help in predicting complications after pneumonectomy, with men and women being different in quantity and distribution of muscle and fat, and men significantly more prone to postpneumonectomy complications with the increase of age and the decrease of skeletal muscle area. [ABSTRACT FROM AUTHOR]

Objective Tracheal sleeve pneumonectomy is a challenge in lung cancer management and in achieving long-term oncological results. In November 2018, we started a prospective study on the role of extracorporeal membrane oxygenation (ECMO) in tracheal sleeve pneumonectomy. We aim to present our preliminary results. Methods From November 2018 to November 2019, six patients (three men and three women; median age: 61 years) were eligible for tracheal sleeve pneumonectomy for lung cancer employing the veno-venous ECMO during tracheobronchial anastomosis. Results Only in one patient, an intrapericardial pneumonectomy without ECMO support was performed, but cannulas were maintained during surgery. The median length of surgery was 201 minutes (range: 162–292 minutes), and the average duration of the apneic phase was 38 minutes (range: 31–45 minutes). No complications correlated to the positioning of the cannulas were recorded. There was only one major postoperative complication (hemothorax). At the time of follow-up, all patients were alive; one patient alive with bone metastasis was being treated with radiotherapy. Conclusion ECMO-assisted oncological surgery was rarely described, and its advantages include hemodynamic stability with low bleeding complications and a clean operating field. As suggested by our preliminary data, ECMO-assisted could be a useful alternative strategy in select lung cancer patients. [ABSTRACT FROM AUTHOR]

Background Bilateral lung neoplasms are becoming more common, but distinguishing two primary lung cancers from metastatic disease can be difficult and only long-term follow-up after treatment can disclose the real behavior of the disease. The present study aimed to identify the appropriate candidates for bilateral surgical resections from the perspective of short-term postoperative complications and long-term outcomes. Methods Two hundred and fifteen consecutive patients undergoing bilateral pulmonary resection for lung cancers over a 20-year period were analyzed. Preoperative patient characteristics were noted, including demographic information, operative details, pathologic information including histology and tumor stage according to the eighth edition of the tumor nodes metastases staging system, and the use of neoadjuvant or adjuvant treatments. Results Patients receiving the second pulmonary resection more than 24 months from the first procedure as well as patients receiving bilateral lobectomies had higher overall 3-, 5-, and 10-year survival rates compared with the others. Conclusion Patients receiving the second resection more than 24 months from the first procedure have the best long-term results irrespective of the type of resection. [ABSTRACT FROM AUTHOR]

OBJECTIVES A few studies have already demonstrated survival benefits for local treatment in solitary metastatic non-small-cell lung cancer (NSCLC). The aim of this study is to retrospectively investigate the role of surgery in patients with oligometastatic (OM) NSCLC. METHODS Between January 1998 and December 2018, 57 patients with OM stage IV NSCLC (1 or 2) underwent a multidisciplinary approach including lung cancer surgery, local treatment of the distant metastasis (DM) and systemic medical treatments. RESULTS All patients had DM synchronous to lung cancer. Fifty-one (90%) patients had a single DM whereas 6 (11%) patients had 2 DMs. Forty-eight (84%) patients underwent induction chemotherapy. We performed 47 (82%) lobectomies, 4 (7%) segmentectomies and 6 (11%) pneumonectomies. Pathological lymph node involvement was evident in 28 (49%) patients. Adjuvant chemotherapy was administered in 20 (35%) patients. Forty-six (81%) patients had local treatment of the DM before lung resection, and 11 (19%) patients had after lung resection; 6 (11%) patients had both treatments. The median overall survival (OS) was 30 months, with the 2-, 3- and 5-year OS of 57%, 50% and 30%, respectively. OS was significantly related to lymph node involvement (P  = 0.04), size of the primary tumour (P  < 0.001), neoadjuvant chemotherapy (P  = 0.02) and the time period between metastasis diagnosis and primary tumour removal (P  = 0.04). CONCLUSIONS Multidisciplinary approach is the gold standard in OM patients. Patients with no lymph node involvement are the best candidates, with an acceptable OS. Thus, patients with OM-NSCLC should not be excluded from surgery as a matter of principle. [ABSTRACT FROM AUTHOR]

We evaluated principal risk factors and different therapeutic approaches for post-pneumonectomy bronchopleural fistula (BPF), focusing on open-window thoracostomy (OWT). We retrospectively reviewed all patients treated by pneumonectomy for lung cancer from 1999 to 2014; we evaluated preoperative, operative, and postoperative data; time between operation; and fistula formation, size, treatment, and predicting factors of BPF. Cumulative incidence curves for the development of BPF were drawn according to the Kaplan-Meier method. Differences between groups were assessed with the log rank test. Multivariable Cox proportional hazards regression analysis was used to assess the independent risk factors for BPF. P values <0.05 were considered significant. BPF occurred in 60 of 733 patients (8.2%). Bronchial suture with Stapler (EndoGia) (P = 0.02), right side (P = 0.003), and low preoperative albumin levels (< 3.5 g/dL) (P = 0.02) were independent predicting factors of fistula. Early BPF was treated by thoracotomic (12) or thoracoscopic (2) debridement of necrotic tissue and BPF surgical repair. Late BPF was treated by bronchoscopic application of fibrin glue (3) or endobronchial stent (1), chest tube and cavity irrigation by povidone-iodine (15). OWT was performed in 27 patients, followed by muscle flap interposition in 7 of these 27. The survival time of patients after the treatment of BPF was 29.0 months. The overall survival of patients treated by OWT was 50% at 2 years and 27 (8%) at 4 years. Correct management of BPF depends on several factors. In case of failure of different initial therapeutic approaches, we could consider OWT, followed by myoplasty. [ABSTRACT FROM AUTHOR]

Objectives: To assess the association between CT features and EGFR, ALK, KRAS mutations in non-small cell lung cancer.Methods: Patients undergoing chest CT and testing for the above gene mutations were included. Qualitative evaluation of CTs included: lobe; lesion diameter; shape; margins; ground-glass opacity; density; cavitation; air bronchogram; pleural thickening; intratumoral necrosis; nodules in tumour lobe; nodules in non-tumour lobes; pleural retraction; location; calcifications; emphysema; fibrosis; pleural contact; pleural effusion. Statistical analysis was performed to assess association of features with each gene mutation. ROC curves for gene mutations were drawn; the corresponding area under the curve was calculated. P-values <0.05 were considered significant.Results: Of 285 patients, 60/280 (21.43 %) were positive for EGFR mutation; 31/270 (11.48 %) for ALK rearrangement; 64/240 (26.67 %) for KRAS mutation. EGFR mutation was associated with air bronchogram, pleural retraction, females, non-smokers, small lesion size, and absence of fibrosis. ALK rearrangements were associated with age and pleural effusion. KRAS mutation was associated with round shape, nodules in non-tumour lobes, and smoking.Conclusions: This study disclosed associations between CT features and alterations of EGFR (air bronchogram, pleural retraction, small lesion size, absence of fibrosis), ALK (pleural effusion) and KRAS (round lesion shape, nodules in non-tumour lobes).Key Points: Air bronchogram, pleural retraction, small size relate to EGFR mutation in NSCLC. Pleural effusion and younger age relate to ALK mutation. Round lesion shape, nodules in non-tumour lobes relate to KRAS mutation. [ABSTRACT FROM AUTHOR]

Background: Bilobectomy for lung cancer is considered a high-risk procedure for the increased postoperative complication rate and the negative impact on survival. We analyzed the safety and the oncologic results of this procedure. Methods: We retrospectively reviewed patients who underwent bilobectomy for lung cancer between October 1998 and August 2009. Age, gender, bilobectomy type and indication, complications, pathology, stage, and survival were analyzed. Results: Bilobectomy was performed on 146 patients (101 men; mean age, 62 years). There were 77 upper-middle and 69 middle-lower bilobectomies. Indications were tumor extending across the fissure in 27 (18.5%) patients, endobronchial tumor in 39 (26.7%), extrinsic tumor or nodal invasion of bronchus intermedius in 66 (45.2%), and vascular invasion in 14 (9.6%). An extended resection was performed in 24 patients (16.4%). Induction therapy was performed in 43 patients (29.4%). Thirty-day mortality was 1.4% (n = 2). Overall morbidity was 47.2%. Mean chest tube persistence was 7 days (range, 6 to 46 days). Overall 5-year survival was 58%. Significance differences in survival were observed among different stages (stage I, 70%; stage II, 55%; stage III, 40%; p = 0.0003) and the N status (N0, 69%; N1, 56%; N2, 40%; p = 0.0005). Extended procedure (p = 0.0003) and superior bilobectomy (p = 0.0008) adversely influenced survival. Multivariate analysis demonstrated that an extended resection (p = 0.01), an advanced N disease (p = 0.02), and an upper-mild lobectomy (p = 0.02) adversely affected prognosis. Conclusions: Bilobectomy is associated with a low mortality and an increased morbidity. Survival relates to disease stage and N factor. Optimal prognosis is obtained in patients with lower-middle lobectomy without extension of the resection. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Although it may seem intuitive that obesity is an additional risk factor for surgical patients, few studies have correlated this condition with lung cancer resection. The only data currently available suggest that obesity does not increase the rate of complications after anatomic resection for non-small-cell lung cancer (NSCLC). Methods: We enrolled 154 consecutive patients undergoing standard pneumonectomy for NSCLC at the Department of Thoracic Surgery of the European Institute of Oncology from January 2004 to April 2008. To determine the influence of preoperative body mass index (BMI) on postoperative complications, patients were classified into two groups: (1) BMI≥25kgm−2; n =93 (60.4%); and (2) BMI<25kgm−2; n =61 (39.6%). Data on sex, age, cigarette smoking, preoperative albumin, total proteins and creatinine values, forced expiratory volume in 1s percentage (FEV1%), diffusion lung capacity for carbon monoxide/alveolar volume percentage (DLCO/AV%) and histology and pathological stage were collected. Information on total postoperative complications, 30-day mortality rate, specific pulmonary and cardiac complications, intensive care unit (ICU) admission and hospital stay was collected and analysed for the BMI group. Results: Among the 154 operated patients, 30 (19.5%) were women with a mean age of 63.4 years (range: 36–82). As many as 136 (88.3%) patients were smokers or former smokers; 80 patients (51.9%) received presurgical treatment. A total of 64 (41.6%) right pneumonectomy procedures were performed. Mean±SD for preoperative variables were FEV1%: 83.5±19.2, DLCO/AV: 85.4%±20.3, albumin: 4.07±0.44gdl−1, total proteins: 7.23±0.59gdl−1, creatinine: 0.81±0.23mgdl−1. Ten patients died within the first 30 days (30-day mortality: 6.5%). The male sex was significantly more prevalent in the high BMI group (p =0.039). The preoperative mean creatinine value was significantly higher in the high BMI group (0.86mgdl−1 vs 0.75mgdl−1, p =0.002) and preoperative DLCO/AV values were better in the high BMI group than in the BMI group<25kgm−2 (79.9 vs 88.8, p =0.009). The high BMI group had a higher incidence of respiratory complications (21.5% vs 4.9% p =0.005, odds ratio (OR)=5.3, 95% confidence interval (CI): 1.5, 18.7). No significant differences were observed between the two groups regarding ICU admission, hospital stay, 30-day mortality and total and specific cardiac complications. Conclusions: The risk of respiratory complications in patients with BMI higher than 25kgm−2 undergoing pneumonectomy for lung cancer is 5.3 times higher than that of patients with BMI<25kgm−2. Thoracic surgeons and anaesthesiologists should be aware of this information before planning elective pneumonectomy in overweight and especially in obese patients. [Copyright &y& Elsevier]

Abstract: Background: Pulmonary metastasectomy is an accepted procedure in selected patients, very often requiring multiple non-anatomical resections. Although it is intuitive that functional loss is proportional to the number and extent of pulmonary resections, this link has never been proved and is the hypothesis behind this study. Methods: We retrospectively reviewed pulmonary function changes after lung metastasectomy. Baseline and postoperative spirometric values were evaluated and their changes were correlated to (a) number of resections, (b) extent of resections and (c) intervals between surgery. Results: Sixty-six patients were enrolled (31 men, mean age 56 years, range: 23–75); mean interval between surgery: 54.5 days; mean extent of resection: 11.45cm; mean number of resections: 3. Preoperative mean spirometric values were: FEV1 2.73l (97.75%); FVC 3.11l (95.50%); DLCO/AV 1.21l (99.80%). Mean changes in FEV1, FCV and DLCO/AV were −13.4%, −12.4% and +1.2% respectively. Patients receiving three or more non-anatomical resections had functional loss similar to those undergoing lobectomy. The extent of total resection (>11cm, p <0.05) and the interval between surgery (>90 days, p <0.0001) influenced FEV1 and FVC modifications. At three months none of these functional modifications remained. Sex, age, side of the operation and histology of primary tumor did not affect spirometric changes. Conclusions: Spirometric changes after pulmonary metastasectomy are affected by total volume lung parenchyma resected within the first 90 days. Functional loss after three or more non-anatomical resections is comparable to that recorded after lobectomy. [Copyright &y& Elsevier]

Objective: Pneumonectomy is not always sufficient for the radical resection of cancer. In the present study, pneumonectomy may be associated with an extended resection of mediastinal or parietal structures. The postoperative risk and the oncologic benefits of such an extended procedure have not been sufficiently demonstrated. Methods: We have defined “extended” pneumonectomy (EP) as the removal of the entire lung, associated with one or more of the following structures: superior vena cava, tracheal carina, left atrium, aorta, chest wall, or diaphragm. Our clinical database was retrospectively reviewed to identify patients who underwent EP to assess their postoperative morbidity, mortality, and long-term survival. Results: Between 1998 and 2005, 47 EPs were performed. The “extended” procedure included left atrium resection in 15 patients, combined SVC and carinal resection in 9 patients, aortic resection in 8 patients (in 3 patients with prosthetic replacement), chest wall or diaphragmatic resection in 6 patients, SVC resection in 4 patients, and carinal resection in 4 patients. A partial esophageal muscular resection was performed in 1 patient. Overall 60-day mortality was 8.5%. Major postoperative complications occurred in 8 patients (17%). The 2- and 5-year survival rates for the overall population were 42% and 22.8%, respectively. Interestingly, long-term survivors were recorded only in the group of patients who received induction treatment. Conclusions: Extended pneumonectomy is a feasible procedure with an acceptable risk factor. To improve the selection of patients, all candidates should undergo preoperative mediastinoscopy and induction chemotherapy. In patients with positive response to chemotherapy or stable disease, extended pneumonectomy may afford a radical resection in more than 80% of cases and may result in a permanent cure in some instances. [Copyright &y& Elsevier]

Despite there already being many studies on robotic surgery as a minimally invasive approach for non-small-cell lung cancer (NSCLC) patients, the use of this technique for stage III disease is still poorly described. These are the preliminary results of our prospective study on the safety and effectiveness of robotic approaches in patients with locally advanced NSCLC in terms of postoperative complications and oncological outcomes. Since 2016, we prospectively investigated 19 consecutive patients with NSCLC stage IIIA-pN2 (diagnosed by EBUS-TBNA) who underwent lobectomy and radical lymph node dissection with robotic approaches after induction treatment. Furthermore, we matched a case-control study with 46 patients treated with open surgery during the same period of time, with similar age, comorbidities, clinical stage and tumor size. The individual matched population was composed of 16 robot-assisted thoracic surgeries and 16 patients who underwent open surgery. The median time range of resection was inferior in the open group compared to robotic lobectomy (243 vs. 161 min; p < 0.001). Lymph node resection and positivity were not significantly different (p = 0.96 and p = 0.57, respectively). Moreover, no difference was observed for PFS (p = 0.16) or OS (p = 0.41). In conclusion, we demonstrated that the early outcomes and oncological results of N2-patients after robotic lobectomy were similar to those who had open surgery. Considering the advantages of minimally invasive surgery, robot-assisted lobectomy appears to be a safe approach to patients with locally advanced diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Low hemoglobin (Hb) values—indicating a condition of anemia—are related to impaired nutrition and immune system status, suggesting reduced tolerance to therapies in oncologic patients. In fact, it has been shown that pre-treatment anemia predicts poor outcomes in many neoplastic diseases. Similarly, red cell distribution width—which is a measure of the size of variation of circulating erythrocytes—has been shown to be closely related to poor prognosis both in cardiovascular and in oncologic diseases. The use of the Hb-to-red cell distribution width (RDW) ratio (HRR)—which merges data coming from the two blood parameters—is a prognostic marker in esophageal squamous cell carcinoma, small cell lung cancer, and several other types of solid tumors, emerging as an independent prognostic factor for overall survival and disease-free survival. The aim of the present study was to investigate the prognostic role of pre-operative HRR in resected-pulmonary adenocarcinoma patients undergoing a multidisciplinary treatment. Background: The ratio of hemoglobin to red cell distribution width (HRR) has been described as an effective prognostic factor in several types of cancer. The aim of this study was to investigate the prognostic role of preoperative HRR in resected-lung-adenocarcinoma patients. Methods: We enrolled 342 consecutive patients. Age, sex, surgical resection, adjuvant treatments, pathological stage, preoperative hemoglobin, red cell distribution width, and their ratio were recorded for each patient. Results: Mean age was 66 years (SD: 9.0). There were 163 females (47.1%); 169 patients (49.4%) had tumors at stage I, 71 (20.8%) at stage II, and 102 (29.8%) at stage III. In total, 318 patients (93.0%) underwent lobectomy, and 24 (7.0%) pneumonectomy. Disease-free survival multivariable analysis disclosed an increased hazard ratio (HR) of relapse for preoperative HRR lower than 1.01 (HR = 2.20, 95%CI: (1.30–3.72), p = 0.004), as well as for N1 single-node (HR = 2.55, 95%CI: (1.33–4.90), p = 0.005) and multiple-level lymph node involvement compared to N0 for both N1 (HR = 9.16, 95%CI:(3.65–23.0), p < 0.001) and N2 (HR = 10.5, 95%CI:(3.44–32.2, p < 0.001). Conclusion: Pre-operative HRR is an effective prognostic factor of disease-free survival in resected-lung-adenocarcinoma patients, together with the level of pathologic node involvement. [ABSTRACT FROM AUTHOR]

Simple Summary: Red blood cell distribution width is a measure of the variation of erythrocyte volume. Impaired erythropoiesis can lead to a wide variation in erythrocyte dimension—defined as anisocytosis—indicating that pathological modifications are taking place. Recently, red blood cell distribution width has been advocated as an effective prognostic factor in cardiovascular diseases, acute kidney injury, autoimmune disease, and oncologic settings. In many advanced and several early-stage oncologic conditions, it has shown excellent prognostic efficacy; we therefore investigated what prognostic role red blood cell distribution width may have in resected lung cancer, focusing on pN1 adenocarcinoma patients in whom adjuvant treatments—although well-established—are still proposed case by case. Our findings suggest that red blood cell distribution width is strictly related to disease-free survival; it could therefore be considered as a further tool for planning postoperative adjuvant treatments and setting up an adequate follow-up program. Background: Red blood cell distribution width is a measure of the variation of erythrocyte volume and has recently been advocated as a prognostic tool in neoplastic and non-neoplastic diseases. We studied the prognostic role of preoperative red blood cell distribution width (RDW) in resected pN1 lung adenocarcinoma patients. Methods: Sixty-seven consecutive pN1 lung adenocarcinoma patients operated in the last two years were retrospectively evaluated in the present study. Age, sex, smoking status, type of surgical resection, neoadjuvant and adjuvant treatments, pathological stage, T and N status, tumor size, preoperative hemoglobin (Hb) and RDW, preoperative neutrophils, lymphocytes, and their ratio were collected for each patient. Outpatient follow-up was performed and date of relapse was recorded. Results: There were 24 females (35.8%). Twenty-eight patients (41.8%) belonged to stage 3A and thirty-nine patients (58.2%) to stage 2B. Mean preoperative RDW % was 14.1 (IQR: 12.9–14.8). Univariate analysis disclosed preoperative RDW as strictly related to disease-free survival (p = 0.02), which was confirmed in the exploratory multivariable analysis (p = 0.003). Conclusions: Pre-operative RDW is an effective prognostic factor of disease-free survival in resected pN1 lung adenocarcinoma; it could therefore be considered as a further tool for planning postoperative adjuvant treatments and setting up an adequate follow-up program. [ABSTRACT FROM AUTHOR]

Background: To evaluate whether a model based on radiomic and clinical features may be associated with lymph node (LN) status and overall survival (OS) in lung cancer (LC) patients; to evaluate whether CT reconstruction algorithms may influence the model performance. Methods: patients operated on for LC with a pathological stage up to T3N1 were retrospectively selected and divided into training and validation sets. For the prediction of positive LNs and OS, the Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression model was used; univariable and multivariable logistic regression analysis assessed the association of clinical-radiomic variables and endpoints. All tests were repeated after dividing the groups according to the CT reconstruction algorithm. p-values < 0.05 were considered significant. Results: 270 patients were included and divided into training (n = 180) and validation sets (n = 90). Transfissural extension was significantly associated with positive LNs. For OS prediction, high- and low-risk groups were different according to the radiomics score, also after dividing the two groups according to reconstruction algorithms. Conclusions: a combined clinical–radiomics model was not superior to a single clinical or single radiomics model to predict positive LNs. A radiomics model was able to separate high-risk and low-risk patients for OS; CTs reconstructed with Iterative Reconstructions (IR) algorithm showed the best model performance. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Randomized controlled trial of resection versus radiotherapy after induction of chemotherapy in stage IIIA-N2 non-small-cell lung cancer."

Primary extracranial and extraspinal meningiomas are very rare tumours, and primary pulmonary ones are even more uncommon. They present as a solitary pulmonary nodule, and most of them are benign, except for three cases. We describe a primitive atypical pulmonary meningioma first suspected of being a metastasis in a patient during follow-up ten years after therapy for breast cancer. [ABSTRACT FROM AUTHOR]

Objective: To validate previously identified associations between radiological features and clinical features with Epidermal Growth Factor Receptor (EGFR)/ Kirsten RAt Sarcoma (KRAS) alterations in an independent group of patients with Non-Small Cell Lung Cancer (NSCLC).Material and Methods: A total of 122 patients with NSCLC tested for EGFR/KRAS alterations were included. Clinical and radiological features were recorded. Univariate analysis were performed to look at the associations of the studied features with EGFR/KRAS alterations. Previously calculated composite model parameters for each gene alteration prediction were applied to this validation cohort. ROC (Receiver Operating Characteristic) curves were drawn using the previously validated composite models, and also for each significant individual characteristic of the previous training cohort model. The Area Under the ROC Curve (AUC) with 95% Confidence Intervals (CI) was calculated and compared between the full models.Results: At univariate analysis, EGFR+ confirmed an association with an internal air bronchogram, pleural retraction, emphysema and lack of smoking; KRAS+ with round shape, emphysema and smoking. The AUC (95%CI) in the new cohort was confirmed to be high for EGFR+ prediction, with a value of: 0.82 (0.69-0.95) vs. 0.82 in the previous cohort, whereas it was smaller for KRAS+ prediction, with a value of 0.60 (0.48-0.72) vs. 0.67 in the previous cohort. Looking at single features in the new cohort, we found that the AUC for the models including only smoking was similar to that of the full model (including radiological and clinical features) for both gene alterations.Conclusions: Although this study validated the significant association of clinical and radiological features with EGFR/KRAS alterations, models based on these composite features are not superior to smoking history alone to predict the mutations. [ABSTRACT FROM AUTHOR]

Abstract: Objective: A higher mortality has been reported after pneumonectomy over the age of 70. The aim of the study was to quantify the additional risk due to age after standard pneumonectomy for lung cancer by a case–control study. Methods: Our clinical database was reviewed to search for patients aged 70 years or more who underwent standard pneumonectomy for lung cancer between 1998 and 2005. A control group of patients younger than 70 (one case/two controls) was matched for sex, cardiovascular disease, American Association of Anaesthetists score, respiratory function, side of pneumonectomy, induction chemotherapy and stage. Overall mortality and morbidity were compared. Long-term survival data were also analysed. Results: During the considered period, 35 patients aged 70 years or more underwent pneumonectomy (30 males, median age 73 years, 15 right-sided procedures). The control group was composed of 70 patients. The two groups were homogeneous in the variables used for matching. Overall mortality and morbidity were 11.4 and 54.2% in the elderly group as compared to 4.3 and 41.6% in controls (p-value not significant). Elderly patients experienced a higher rate of respiratory complications (25.7%) as compared to controls (8.3%, p =0.01). At univariate analysis, the only risk factor for death was the occurrence of respiratory complications (OR 6.5, CI 1.8–18.2). At multivariate analysis, age ≥70 years (OR 5.36, CI 1.48–19.3) and preoperative chemotherapy (OR 7.65, CI 2.04–28.6) were confirmed as predictors of respiratory complications. Five-year survival was 17.5% in the elderly group and 53.6% in the control group (p =0.003). Elderly patients with a better respiratory function (FEV1>70%) had a 5-year survival of 45.4%. Conclusions: In the elderly patients, the risk of respiratory complications after pneumonectomy is increased as compared to younger patients with equivalent respiratory function. Age and preoperative chemotherapy are independent risk factors for respiratory complications. A lower mortality and a better long-term survival are obtained in elderly patients with a better respiratory function (FEV1≥70%). [Copyright &y& Elsevier]