Risk factors influencing postoperative pleural empyema in patients with pleural mesothelioma: a retrospective single-Centre analysis.

OBJECTIVES: Postoperative empyema is a severe, potentially lethal complication also present, but poorly studied in patients undergoing surgery for pleural mesothelioma. We aimed to analyse which perioperative characteristics might be associated with an increased risk for postoperative empyema. METHODS: From September 1999 to February 2023 a retrospective analysis of consecutive patients undergoing surgery for pleural mesothelioma at the University Hospital of Zurich was performed. Uni- and multivariable logistic regression was used to identify associated risk factors of postoperative empyema after surgery. RESULTS: 400 PM patients were included in the analysis, of which n = 50 patients developed empyema after surgery (12.5%). Baseline demographics were comparable between patients with (Eyes) and without empyema (Eno). 39% (n = 156) patients underwent extrapleural pneumonectomy, of which 22% (n = 35) developed postoperative pleural empyema; 6% (n = 15) of remaining 244 patients undergoing pleurectomy and decortication (n = 46), extended pleurectomy and decortication (n = 114), partial pleurectomy (n = 54) or explorative thoracotomy (n = 30) resulted in postoperative empyema. In multivariable logistic regression analysis, extrapleural pneumonectomy (odds ratio 2.8, 95% confidence interval 1.5-5.4, p = 0.002) emerged as the only risk factor associated with postoperative empyema when controlled for smoking status. Median overall survival was significantly worse for Eyes (16 months, interquartile range 5-27 months) than for Eno (18 months, interquartile range 8-35 months). CONCLUSIONS: Patients undergoing extrapleural pneumonectomy had a significantly higher risk of developing postoperative pleural empyema compared to patients undergoing other surgery types. Survival of patients with empyema was significantly shorter. A concern emerged of a possible connection between adjuvant radiotherapy and postoperative empyema.

Outcome Analysis of Treatment Modalities for Thoracic Sarcomas.

BACKGROUND: Primary chest wall sarcomas are a rare and heterogeneous group of chest wall tumors that require multimodal oncologic and surgical therapy. The aim of this study was to review our experience regarding the surgical treatment of chest wall sarcomas, evaluating the short- and long-term results. METHODS: In this retrospective single-center study, patients who underwent surgery for soft tissue and bone sarcoma of the chest wall between 1999 and 2018 were included. We analyzed the oncologic and surgical outcomes of chest wall resections and reconstructions, assessing overall and recurrence-free survival and the associated clinical factors. RESULTS: In total, 44 patients underwent chest wall resection for primary chest wall sarcoma, of which 18 (41%) received surgery only, 10 (23%) received additional chemoradiotherapy, 7% (3) received surgery with chemotherapy, and 30% (13) received radiotherapy in addition to surgery. No perioperative mortality occurred. Five-year overall survival was 51.5% (CI 95%: 36.1-73.4%), and median overall survival was 1973 days (CI 95% 1461; -). As determined in the univariate analysis, the presence of metastasis upon admission and tumor grade were significantly associated with shorter survival (p = 0.037 and p < 0.01, respectively). Five-year recurrence-free survival was 71.5% (95% CI 57.6%; 88.7%). Tumor resection margins and metastatic disease upon diagnosis were significantly associated with recurrence-free survival (p < 0.01 and p < 0.01, respectively). CONCLUSION: Surgical therapy is the cornerstone of the treatment of chest wall sarcomas and can be performed safely. Metastasis and high tumor grade have a negative influence on overall survival, while tumor margins and metastasis have a negative influence on local recurrence.

Validated Prognostic Scores to Predict Outcomes in ECLS-Bridged Patients to Lung Transplantation.

Selection of patients who may benefit from extracorporeal life support (ECLS) as a bridge to lung transplant (LTx) is crucial. The aim was to assess if validated prognostic scores could help in selecting patients who may benefit from ECLS-bridging predicting their outcomes. Clinical data of patients successfully ECLS-bridged to LTx from 2009 to 2021 were collected from two European centers. For each patient, we calculated Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score III (SAPS III), Acute Physiology and Chronic Health Evaluation II (APACHE II), before placing ECLS support, and then correlated with outcome. Median values of SOFA, SAPS III, and APACHE II were 5 (IQR 3-9), 57 (IQR 47.5-65), and 21 (IQR 15-26). In-hospital, 30 and 90 days mortality were 21%, 14%, and 22%. SOFA, SAPS III, and APACHE II were analyzed as predictors of in-hospital, 30 and 90 days mortality (SOFA C-Index: 0.67, 0.78, 0.72; SAPS III C-index: 0.48, 0.45, 0.51; APACHE II C-Index: 0.49, 0.45, 0.52). For SOFA, the score with the best performance, a value ≥9 was identified to be the optimal cut-off for the prediction of the outcomes of interest. SOFA may be considered an adequate predictor in these patients, helping clinical decision-making. More specific and simplified scores for this population are necessary.

[Surgical or bronchoscopic lung volume reduction for emphysema therapy]. / Chirurgische oder bronchoskopische Lungenvolumenreduktion zur Emphysemtherapie.

More than 20 years ago, surgical lung volume reduction (LVRS) was already established in patients with advanced emphysema as a palliative therapy option that reduces respiratory distress and improves lung function and quality of life. In addition, bronchoscopic procedures (BLVR) aimed at volume reduction have existed for just over 10 years. The advantages and disadvantages of LVRS and BLVR are discussed in this article.

Relevance of pleural adhesions for short- and long-term outcomes after lung volume reduction surgery.

Objective: Pleural adhesions (PLAs) have been shown to be a possible risk factor for air leak after lung volume reduction surgery (LVRS), but the relevance of PLA for lung function outcome remains unclear. We analyzed our LVRS cohort for the influence of PLA on short-term (ie, prolonged air leak) and long-term outcomes. Methods: Retrospective observational cohort study with 187 consecutive patients who underwent LVRS from January 2016 to December 2019. PLA were defined as relevant if they were distributed extensively at the dorsal pleura; were present in at least at 2 areas, including the dorsal pleura; or present extensively at the mediastinal pleura. In patients with bilateral emphysema, bilateral LVRS was performed preferentially. The objectives were to quantify the association of PLA and rate of prolonged air leak (chest tube >7 days), and the association of PLA with postoperative exacerbations and with forced expiratory volume in 1 second 3 months postoperatively. The associations were quantified with odds ratios for binary outcomes, and with between-group differences for continuous outcomes. To account for missing observations, 100-fold multiple imputation was used. Results: PLAs were found in 46 of 187 patients (24.6%). There was a 32.6% rate of prolonged air leak (n = 61), mean chest tube time was 7.84 days. A total of 94 (50.3%) LVRSs were unilateral and 93 were bilateral. There was evidence for an association between PLA and the rate of prolonged air leak (odds ratio, 2.83; 95% CI, 1.36 to 5.89; P = .006). There was no evidence for an association between PLA and postoperative exacerbations (odds ratio, 1.11; 95% CI, 0.5 to 2.45; P = .79). There was no evidence for an association between PLA and forced expiratory volume in 1 second (estimate -1.52; 95% CI -5.67 to 2.63; P = .47). Both unilateral and bilateral LVRS showed significant postoperative improvements in forced expiratory volume in 1 second by 27% (8.43 units; 95% CI, 3.66-13.12; P = .0006) and by 28% (7.87 units; 95% CI, 4.68-11.06; P < .0001) and a reduction in residual volume of 15% (-33.9 units; 95% CI, -56.37 to -11.42; P = .003) and 15% (-34.9 units; 95% CI, -52.57 to -17.22; P = .0001), respectively. Conclusions: Patients should be aware of potential prolongation of hospitalization due to PLA. However, there might be no relevant influence of PLA on lung function outcomes.

[Lung Cancer Surgery for Severe COPD with Emphysema: Tumor Resection with Improvement of Lung Function]. / Lungenkrebschirurgie bei schwerer COPD mit Emphysem: Tumorresektion mit Verbesserung der Lungenfunktion.

Lung Cancer Surgery for Severe COPD with Emphysema: Tumor Resection with Improvement of Lung Function Abstract. The golden standard for the therapy of early stage non-small cell lung cancer consists of surgical resection, usually performed as lobectomy or segmentectomy. These procedures demand a certain operability, including certain lung functional reserves. Patients with COPD and emphysema usually have lung function values far below that. Nevertheless, these patients can be offered treatmentif at the same time they qualify for concomitant lung volume reduction surgery (LVRS). LVRS with simultaneous tumor resection can consolidate the diagnosis, provide definite histology, correct staging, and thorough tumor resection might even improve the postoperative lung function. As with all patients with a (possible) diagnosis of cancer, the indication must be discussed in an interdiscplinary tumor board.

The Swiss Approach - feasibility of a national low-dose CT lung cancer screening program.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths in Switzerland. Despite this, there is no lung cancer screening program in the country. In the United States, low-dose computed tomography (LDCT) lung cancer screening is partially established and endorsed by guidelines. Moreover, evidence is growing that screening reduces lung cancer-related mortality and this was recently shown in a large European randomized controlled trial. Implementation of a lung cancer screening program, however, is challenging and depends on many country-specific factors. The goal of this article is to outline a potential Swiss lung cancer screening program. FRAMEWORK: An exhaustive literature review on international screening models as well as interviews and site visits with international experts were initiated. Furthermore, workshops and interviews with national experts and stakeholders were conducted to share experiences and to establish the basis for a national Swiss lung cancer screening program. SCREENING APPROACH: General practitioners, pulmonologists and the media should be part of the recruitment process. Decentralisation of the screening might lead to a higher adherence rate. To reduce stigmatisation, the screening should be integrated in a "lung health check". Standardisation and a common quality level are mandatory. The PLCOm2012 risk calculation model with a threshold of 1.5% risk for developing cancer in the next six years should be used in addition to established inclusion criteria. Biennial screening is preferred. LUNG RADS and NELSON+ are applied as classification models for lung nodules. CONCLUSION: Based on data from recent studies, literature research, a health technology assessment, the information gained from this project and a pilot study the Swiss Interest Group for lung cancer screening (CH-LSIG) recommends the timely introduction of a systematic lung cancer screening program in Switzerland. The final decision is for the Swiss Cancer Screening Committee to make.

Surgical management of lung cancer during the COVID-19 pandemic - a narrative review and single-centre report.

The coronavirus disease 2019 (COVID-19) pandemic has had a severe impact on oncological and thoracic surgical practice worldwide. In many hospitals, the care of COVID-19 patients required a reduction of elective surgery, to avoid viral transmission within the hospital, and to save and preserve personnel and material resources. Cancer patients are more susceptible to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and are at an increased risk of a severe course of disease. In many patients with lung cancer, this risk is further increased owing to comorbidities, older age and a pre-existing lung disease. Surgical resection is an important part of the treatment in patients with early stage or locally advanced non-small cell lung cancer, but the treatment of these patients during the COVID-19 pandemic becomes a challenging balance between the risk of patient exposure to SARS-CoV-2 and the need to provide timely and adequate cancer treatment despite limited hospital capacities. This manuscript aims to provide an overview of the surgical treatment of lung cancer patients during the COVID-19 pandemic including the triage and prioritisation as well as the surgical approach, and our own experience with cancer surgery during the first pandemic wave. We furthermore aim to highlight the risk and potential consequences of delayed lung cancer treatment due to the deferral of surgery, screening appointments and follow-up visits. With much attention being diverted to COVID-19, it is important to retain awareness of cancer patients, maintain oncological surgery and avoid treatment delay during the pandemic.

Computed tomography radiomics for the prediction of thymic epithelial tumor histology, TNM stage and myasthenia gravis.

OBJECTIVES: To evaluate CT-derived radiomics for machine learning-based classification of thymic epithelial tumor (TET) stage (TNM classification), histology (WHO classification) and the presence of myasthenia gravis (MG). METHODS: Patients with histologically confirmed TET in the years 2000-2018 were retrospectively included, excluding patients with incompatible imaging or other tumors. CT scans were reformatted uniformly, gray values were normalized and discretized. Tumors were segmented manually; 15 scans were re-segmented after 2 weeks by two readers. 1316 radiomic features were calculated (pyRadiomics). Features with low intra-/inter-reader agreement (ICC<0.75) were excluded. Repeated nested cross-validation was used for feature selection (Boruta algorithm), model training, and evaluation (out-of-fold predictions). Shapley additive explanation (SHAP) values were calculated to assess feature importance. RESULTS: 105 patients undergoing surgery for TET were identified. After applying exclusion criteria, 62 patients (28 female; mean age, 57±14 years; range, 22-82 years) with 34 low-risk TET (LRT; WHO types A/AB/B1), 28 high-risk TET (HRT; WHO B2/B3/C) in early stage (49, TNM stage I-II) or advanced stage (13, TNM III-IV) were included. 14(23%) of the patients had MG. 334(25%) features were excluded after intra-/inter-reader analysis. Discriminatory performance of the random forest classifiers was good for histology(AUC, 87.6%; 95% confidence interval, 76.3-94.3) and TNM stage(AUC, 83.8%; 95%CI, 66.9-93.4) but poor for the prediction of MG (AUC, 63.9%; 95%CI, 44.8-79.5). CONCLUSIONS: CT-derived radiomic features may be a useful imaging biomarker for TET histology and TNM stage.

Lung Volume Reduction Surgery in Patients with Homogeneous Emphysema.

Randomized controlled trials have demonstrated that lung volume reduction surgery (LVRS) improves exercise capacity, lung function, and quality of life in patients with heterogenous emphysema on computed tomographic and perfusion scan. However, most patients have a nonheterogenous type of destruction. These patients, summarized under "homogeneous emphysema," may also benefit from LVRS as long they are severely hyperinflated, and adequate function is remaining with a diffusing capacity of the lungs for carbon monoxide greater than 20% and no pulmonary hypertension. Surgical mortality is low when patients are well selected.

Single-cell profiling of myasthenia gravis identifies a pathogenic T cell signature.

Myasthenia gravis (MG) is an autoimmune disease characterized by impaired neuromuscular signaling due to autoantibodies targeting the acetylcholine receptor. Although its auto-antigens and effector mechanisms are well defined, the cellular and molecular drivers underpinning MG remain elusive. Here, we employed high-dimensional single-cell mass and spectral cytometry of blood and thymus samples from MG patients in combination with supervised and unsupervised machine-learning tools to gain insight into the immune dysregulation underlying MG. By creating a comprehensive immune map, we identified two dysregulated subsets of inflammatory circulating memory T helper (Th) cells. These signature ThCD103 and ThGM cells populated the diseased thymus, were reduced in the blood of MG patients, and were inversely correlated with disease severity. Both signature Th subsets rebounded in the blood of MG patients after surgical thymus removal, indicative of their role as cellular markers of disease activity. Together, this in-depth analysis of the immune landscape of MG provides valuable insight into disease pathogenesis, suggests novel biomarkers and identifies new potential therapeutic targets for treatment.

Lymphovascular invasion is an independent prognostic factor for survival in pathologically proven N2 non-small cell lung cancer.

BACKGROUND: We aimed to analyse the nodal spread of our non-small cell lung cancer pN2 cohort according to tumour location, the possible implications of an unusual spreading pattern, and other factors influencing postoperative survival after anatomical lung resection. METHODS: In this retrospective observational study, clinical data was collected for 124 consecutive non-small cell lung cancer (NSCLC) patients with a pathological N2 (stage IIIA or B) undergoing anatomical lung resection at our institution between 2001 and 2010. Cox regression was used to analyse independent predictors of 5-year overall survival and recurrence-free survival. RESULTS: A total of 105 patients were included in the final analysis. Tumour location in the right upper lobe and middle lobe  was significantly more often associated with involvement of lymph node stations 2 and 4 than NSCLC in the right lower lobe (station 2: right upper vs right lower lobe, p = 0.001 and middle vs right lower lobe, p = 0.038; station 4: right upper vs right lower lobe, p<0.001 and middle vs right lower lobe, p = 0.056), while tumours in the right upper lobe showed significantly less involvement of stations 7 and 8 compared with right lower lobe tumours (station 7 p <0.001, station 8 p = 0.004). Left sided tumours in the upper lobe had significantly more involvement of station 5 compared to lower lobe tumours (p = 0.009). However, atypical lymphatic nodal zone involvement did not emerge as a significant predictor of survival. Lymphovascular invasion was the only independent prognostic factor for 5-year overall survival (hazard ratio [HR] 2.10, p = 0.015) and recurrence-free survival (HR 1.68, p = 0.049) when controlled for adjuvant therapy. CONCLUSION: Lymphovascular invasion was identified as the only independent prognostic factor for 5-year overall survival and recurrence-free survival in our pathologically proven N2 NSCLC cohort when controlled for adjuvant therapy. This study extends the current evidence of an adverse prognostic effect of lymphovascular invasion on a stage III population, confirms the adverse prognostic effect of lymphovascular invasion detected by immunohistochemistry, and thereby reveals another subgroup within the pN2 population with worse prognosis regarding 5-year overall survival and recurrence-free survival.  .

Long-Term Outcomes of Cadaveric Lobar Lung Transplantation: An Important Surgical Option.

BACKGROUND: Cadaveric lobar lung transplantation (L-LTx) is developed to overcome donor-recipient size mismatch. Controversial short- and long-term outcomes following L-LTx have been reported compared to full-sized lung transplantation (F-LTx). This study reports long-term outcomes after L-LTx. METHODS: We reviewed patients undergoing lung transplantation (LTx) between 2000 and 2016. The decision to perform L-LTx was made based mainly on donor-recipient height discrepancy and visual assessment of donor lungs. Predicted donor-recipient total lung capacity (TLC) ratio was calculated more recently. Primary outcome was overall survival. RESULTS: In all, 370 bilateral LTx were performed during the study period, among those 250 (67%) underwent F-LTx and 120 (32%) underwent L-LTx, respectively. One- and 5-year survival rates were 85% vs. 90% and 53% vs. 63% for L-LTx and F-LTx, respectively (p = 0.16). Chronic lung allograft dysfunction (CLAD)-free survival at 5 years was 48% in L-LTx vs. 51% in F-LTx recipients (p = 0.89), respectively. Age, intraoperative extracorporeal membrane oxygenation (ECMO) use, intensive care unit (ICU) stay, and postoperative renal replacement therapy (RRT) were significant prognostic factors for survival using multivariate analysis. CONCLUSIONS: Overall survival and CLAD-free survival following L-LTx were comparable to F-LTx. Given the ongoing donor organ shortage, cadaveric L-LTx remains as an important resource in LTx.

Surgical Outcomes and Risk Analysis of Primary Pulmonary Sarcoma.

BACKGROUND: Primary pulmonary sarcoma (PPS) is a rare malignant lung neoplasm, and there is very little medical evidence about treatment of PPS. The aim of this study is to clarify the clinical characteristics and therapeutic outcome of patients who underwent surgical resection for PPS. METHODS: We retrospectively reviewed the records of patients who underwent surgical resection for PPS in our institution between 1995 and 2014. Cases who only underwent biopsy were excluded. RESULTS: A total of 24 patients (18 males, 6 females), with a median age of 60 (interquartile range: 44-67) years, were analyzed. The surgical procedures performed in these patients were pneumonectomy (n = 10), lobectomy (n = 11), and wedge resection (n = 3). Complete resection was achieved in 16 patients. The pathological stages (tumor, node, metastases lung cancer classification, 8th edition) of the patients were I (n = 4), II (n = 12), III (n = 2), and IV (n = 5), and there were four cases of lymph node metastasis. The 5-year overall survival rate of the patients was 50% (95% confidence interval [CI]: 29-72). Adverse prognostic factors for overall survival were incomplete resection (hazard ratio [HR]: 4.4, 95% CI: 2.1-42), advanced pathological stage (HR 14, 95% CI: 2.8-66), higher pathological grade (HR 4.5, 95% CI: 1.2-17), and tumor size ≥ 7 cm (HR 4.7, 95% CI: 1.1-21). CONCLUSIONS: Our series of PPS revealed that incomplete resection, advanced pathological stage, higher pathological grade, and tumor size were unfavorable factors for long-term survival.

Is There a Prognostic Difference Between Stage IIIA Subgroups in Lung Cancer?

BACKGROUND: Treatment of stage IIIA lung cancer remains controversial because it includes a very heterogeneous group of patients. The purpose of our study was to compare survival between stage IIIA subsets and to externally validate our results with another center's database. METHODS: Patients with completely resected stage IIIA/B lung cancer were retrospectively analyzed. There were 424 patients with stage IIIA and 82 patients with stage IIIB (T3/4 N2) (study cohort). Stage IIIA was divided into 2 subsets according to the tumor localization and tumor size (T3 N1-T4 N0/1, IIIA-T group; n = 308) and the extension of nodal disease (T1/2 N2, IIIA-N2 group; n = 116). The study cohort results were used to create a model for stage IIIA patients, which was validated with another center's database (validation cohort). RESULTS: The multivariate analyses showed age, stage IIIB, and pN2 were independent negative prognostic factors (P < .0001). Survival at 5 years was 51.3% (median, 64 months) for patients in the IIIA-T group and was 25.7% (median, 31 months) in the IIIA-N2 patients (hazard ratio, 1.834; P < .0001). There was no statistical difference in survival between the IIIA-N2 and stage IIIB groups (25.7% vs 25.3%, P = .442). The created model was performed on patients in the validation cohort as a model IIIA-T (T3 N1-T4 N0/1, n = 139) and model IIIA-N2 (T1/2 N2, n = 104). Model IIIA-T patients had a statistically better survival rate than model IIIA-N2 patients (median, 62 months vs 37 months; hazard ratio, 1.707, P < 0.001). CONCLUSIONS: There is a prognostic difference between stage IIIA subgroups in lung cancer patients who undergo surgical treatment.

Lung volume reduction surgery as salvage procedure after previous use of endobronchial valves.

OBJECTIVES: Lung volume reduction (LVR) is an efficient and approved treatment for selected emphysema patients. There is some evidence that repeated LVR surgery (LVRS) might be beneficial, but there are no current data on LVRS after unsuccessful bronchoscopic LVR (BLVR) with endobronchial valves (EBVs). We hypothesize good outcome of LVRS after BLVR with valves. METHODS: In this study, we retrospectively investigated all patients who underwent LVRS between 2015 and 2019 at 2 centres after previous unsuccessful EBV treatment. They were further divided into subgroups with patients who never achieved the intended improvement after BLVR (primary failure) and patients whose benefit was fading over time due to the natural development of emphysema (secondary failure). Patients with severe air leak after BLVR and immediate concomitant LVRS and fistula closure thereafter were analysed separately. RESULTS: A total of 38 patients were included. Of these, 19 patients had primary failure, 15 secondary failure and 4 were treated as an emergency due to severe air leak. At 3 months after LVRS, forced expiratory volume in 1 s had improved significantly by 12.5% (P = 0.011) and there was no 90-day mortality. Considering subgroups, patients with primary failure after BLVR seem to profit more than those with secondary failure. Patients with severe air leak after BLVR did not profit from fistula closure with concomitant LVRS. CONCLUSIONS: LVRS after previous BLVR with EBVs can provide significant clinical improvement with low morbidity, although results might not be as good as after primary LVRS.

Identification of target zones for lung volume reduction surgery using three-dimensional computed tomography rendering.

BACKGROUND: The key issues for performing lung volume reduction surgery (LVRS) is the identification of the target zones. Recently introduced three-dimensional computed tomography rendering methods are used to identify the morphological distribution and its severity of lung emphysema by densitometry. We demonstrate a new software for emphysema imaging and show the pre- and post-operative results in patients undergoing LVRS planned based on this new technology. METHODS: A real-time three-dimensional image analysis software system was used pre- and 3 months post-operatively in five patients with heterogeneous emphysema and a single patient with homogeneous morphology scheduled for LVRS. Focus was on low attenuation areas with <950 HU, distribution on both lungs and the value of the three-dimensional images for planning surgery. Functional outcome was assessed by pulmonary function tests after 3 months. RESULTS: Five patients underwent bilateral LVRS and one patient had unilateral LVRS. All patients showed a median increase in forced expiratory volume in 1 s of 70% (range 30-120%), compared with baseline values. Hyperinflation (expressed as residual volume/total lung capacity ratio) was reduced by 30% (range 5-32%). In the patients with heterogeneous emphysema, the pre- and post-operative computed tomography scans and the densitometries showed a decrease in low attenuation areas by 23% (right side) and by 17% (left side), respectively. CONCLUSION: We demonstrate three-dimensional computed tomography-rendered images for planning personalised remodelling of hyperinflated lungs using LVRS. This user-friendly software has the potential to assist surgeons and interventional pulmonologists to select patients and to visualise target areas in LVRS procedures.