Presence of pleomorphic features but not growth patterns improves prognostic stratification of epithelioid malignant pleural mesothelioma by 2-tier nuclear grade.

AIMS: Nuclear grade has been recently validated as a powerful prognostic tool in epithelioid malignant pleural mesothelioma (E-MPM). In other studies histological parameters including pleomorphic features and growth patterns were also shown to exert prognostic impact. The primary aims of our study are (i) externally validate the prognostic role of pleomorphic features in E-MPM and (ii) investigate if evaluating growth pattern in addition to 2-tier nuclear grade improves prognostication. METHODS AND RESULTS: 614 consecutive cases of E-MPM from our institution over a period of 15 years were retrospectively reviewed, of which 51 showed pleomorphic features. E-MPM with pleomorphic features showed significantly worse overall survival compared to those without (5.4 versus 14.7 months). Tumours with predominantly micropapillary pattern showed the worst survival (6.2 months) followed by solid (10.5 months), microcystic (15.3 months), discohesive (16.1 months), trabecular (17.6 months) and tubulo-papillary (18.6 months). Sub-classification of growth patterns into high grade (solid, micropapillary) and low grade (all others) led to good separation of overall survival (10.5 versus 18.0 months) but did not predict survival independent of 2-tier nuclear grade. A composite score comprised of growth pattern and 2-tier nuclear grade did not improve prognostication compared with nuclear grade alone. Intra-tumoural heterogeneity in growth patterns is ubiquitous. CONCLUSIONS: Our findings support the incorporation of E-MPM with pleomorphic features in the epithelioid subtype as a highly aggressive variant distinct from 2-tier nuclear grade. E-MPM demonstrates extensive heterogeneity in growth pattern but its evaluation does not offer additional prognostic utility to 2-tier nuclear grade.

Synchronous thymoma and lung adenocarcinoma treated with a single mini-invasive approach.

A 75 year-old man with a lesion in the middle lobe of the lung was discovered to also have, during the follow-up period, a mass in the mediastinum, diagnosed as a multi-thymic cyst. Both pathologies were successfully treated with a single surgical approach by video-assisted thoracoscopy. We performed a middle VATS lobectomy with complete lymphadenectomy followed by radical thymectomy without additional incision. The postoperative course was uneventful.

Accuracy of transthoracic ultrasound for the prediction of chest wall infiltration by lung cancer and of lung infiltration by chest wall tumours.

BACKGROUND: We wanted to determine the accuracy of transthoracic ultrasound in the prediction of chest wall infiltration by lung cancer or lung infiltration by chest wall tumours. METHODS: Patients having preoperative CT-scan suspect for lung/chest wall infiltration were prospectively enrolled. Inclusion criteria for lung cancer were: obliteration of extrapleural fat, obtuse angle between tumour and chest wall, associated pleural thickening. The criteria for chest wall tumours were: rib destruction and intercostal muscles infiltration with extrapleural fat obliteration and intrathoracic extension. Lung cancer patients with evident chest wall infiltration were excluded. Transthoracic ultrasound was preoperatively performed. Predictions were checked during surgical intervention. RESULTS: Twenty-three patients were preoperatively examined. Sensitivity, specificity, positive and negative predictive values of transthoracic ultrasound were 88.89%, 100%, 100% and 93.3%, respectively. Youden index was used to determine the best cut-off for tumour size in predicting lung/chest wall infiltration: 4.5cm. At univariate logistic regression, tumour size (<4.5 vs ≥ 4.5cm) (p=0.0072) was significantly associated with infiltration. CONCLUSIONS: Transthoracic ultrasound is a useful instrument for predicting neoplastic lung or chest wall infiltration in cases of suspect CT-scans and could be used as part of the preoperative workup to assess tumour staging and to plan the best surgical approach.

Digital Transformation in Thoracic Surgery: a survey among the European Society of Thoracic Surgeons.

OBJECTIVES: Digital transformation has drastically changed the surgical sector, but few is known about its impact on thoracic surgical practice. The aim of this paper is to report the European Society of Thoracic Surgeons (ESTS) survey results, assessing the impact of and the need for Digital Transformation in Thoracic Surgery. METHODS: A 23-item survey was designed by the ESTS Digital Transformation Working Group to assess the impact of and the need for Digital Transformation in Thoracic Surgery. All ESTS members (1668) were invited to complete the survey between 13 March and 21 May 2022 anonymously. Data analysis was descriptive calculating frequencies and percentages. Group comparison was done using chi-square test. RESULTS: The response rate was 6.3%. Surgeons from 26 European countries participated of which more than 80% were based in academic hospitals. The impact of digital transformation was rated very important (43.8%) and fundamental (22.7%) in more than two-thirds of the cases, regardless of surgeons' age. None of the participants felt that digital transformation was of no importance and more than 85% had implemented digital platforms in their direct patient care. Almost 90% of the surgeons, currently not using digital platforms for training and education, would consider introducing them. About 70% were at least 'somewhat satisfied' with their current engagement in Digital Transformation in Thoracic Surgery. CONCLUSIONS: Digital transformation seems to play a major role across European Thoracic Surgery departments in direct patient care, professional networking and surgical training. However, overall satisfaction with the current status of Digital Transformation in Thoracic Surgery was rather reserved, implying the need to increase the implementation of digital solutions in the latter.

Determining the optimal time to report mortality after lobectomy for lung cancer: An analysis of the time-varying risk of death.

Objective: Surgical mortality has traditionally been assessed at arbitrary intervals out to 1 year, without an agreed optimum time point. The aim of our study was to investigate the time-varying risk of death after lobectomy to determine the optimum period to evaluate surgical mortality rate after lobectomy for lung cancer. Methods: We performed a retrospective study of patients undergoing lobectomy for lung cancer at our institution from 2015 to 2022. Parametric survival models were assessed and compared with a nonparametric kernel estimate. The hazard function was plotted over time according to the best-fit statistical distribution. The time points at which instantaneous hazard rate peaked and stabilized in the 1-year period after surgery were then determined. Results: During the study period, 2284 patients underwent lobectomy for lung cancer. Cumulative mortality at 30, 90, and 180 days was 1.3%, 2.9%, and 4.9%, respectively. Log-logistic distribution showed the best fit compared with other statistical distribution, indicated by the lowest Akaike information criteria value. The instantaneous hazard rate was greatest during the immediate postoperative period (0.129; 95% confidence interval, 0.087-0.183) and diminishes rapidly within the first 30 days after surgery. Instantaneous hazard rate continued to decrease past 90 days and stabilized only at approximately 180 days. Conclusions: In-hospital mortality is the optimal follow-up period that captures the early-phase hazard during the immediate postoperative period after lobectomy. Thirty-day mortality is not synonymous to "early mortality," as instantaneous hazard rate remains elevated well past the 90-day time point and only stabilizes at approximately 180 days after lobectomy.

Primary and secondary cardiac tumors: clinical presentation, diagnosis, surgical treatment, and results.

Cardiac tumours are some of the rarest primary tumours, while cardiac metastasis are more common yet still relatively rare. Seventy five percent of primary cardiac tumours are benign tumours. Cardiac tumours present with a range of obstructive, embolic, arrhythmic or systemic symptoms, and in many cases may present asymptomatically. The clinical presentation depends largely on the size and location of the mass. With advances in cardiac imagining and the introduction of cardiopulmonary bypass, the diagnosis and surgical treatment of these rare tumours has improved the prognosis and outlook for benign and malignant tumours. Management depends on tumour histology, size and location as well as the clinical presentation. Conservative management is reserved for small, benign tumours that can undergo regular echocardiographic follow-up. Symptomatic benign tumours are treated with surgical resection and the results are excellent. Malignant primary cardiac tumours have a poor prognosis with high rates of relapse and a median survival of 10-24 months.

Treatment of Pulmonary Carcinoid Tumors With Bronchoscopic Cryotherapy: A 28-Year Single-center Experience.

BACKGROUND: Pulmonary carcinoids are rare tumors originating from neuroendocrine cells in the lungs. Because of their potentially infiltrative nature, surgical resection remains the treatment of choice. However, not all patients with technically resectable disease will be able to undergo surgery, primarily because of poor lung function or medical co-morbidities. Centrally located, intraluminal tumors have been reported to be amenable to bronchoscopic treatment. We specifically examined the role of cryotherapy in the treatment of bronchial carcinoid tumors. METHODS: Sixty-three patients (52.38% female) who underwent a combined total of 243 cryotherapy procedures for treatment of bronchial carcinoid between 1992 and 2020 in our institution were included in the study. Following discussion in multidisciplinary meetings, patients were considered for first-line cryotherapy when lung resection was deemed not possible or when they had rejected surgery. RESULTS: Cryotherapy resulted in complete remission in 21 (33.33%) patients with maximum tumor diameter less than 20 mm (mean: 11.08 mm, 95% confidence interval: 8.76-13.40), and allowed 22 (34.92%) patients with larger lesions (mean: 24.04 mm, 95% confidence interval: 18.78-29.30) to proceed with parenchymal sparing resections. Marked symptomatic relief (P<0.001) was reported by 58 (92.06%) patients. The median follow-up was 33 months (range: 0 to 243 mo). One (1.59%) patient was diagnosed with recurrence in a contralateral lobe 3 years after surgery and was treated with radiofrequency ablation. CONCLUSIONS: In the absence of a definitive randomized controlled trial comparing bronchoscopic treatment with surgical resection, we provide evidence on the safety and efficacy of cryotherapy and encourage wider adoption of this inexpensive and minimally invasive technique for treatment of bronchial carcinoids.

Circulating tumour cells and circulating cell-free DNA in patients with lung cancer: a comparison between thoracotomy and video-assisted thoracoscopic surgery.

INTRODUCTION: The type of lung cancer surgery impacts on tumour manipulation during surgery and may drive dissemination of cancer cells into the vasculature, thus facilitating metastatic spread. The aim of this study was to investigate the impact of surgically induced trauma using peripheral blood from preoperative and postoperative patients with non-small cell lung cancer (NSCLC) undergoing thoracotomy or video-assisted thoracoscopic surgery (VATS) resection. METHODS: Imaging flow cytometry was used to measure circulating cancer-associated cells (CCs). Circulating cell-free DNA (ccfDNA) isolation was performed using Promega dsDNA HS Assay Kit. DNA integrity measurements were calculated by the ALU247 to ALU115 ratio and cytokine levels measured using the Luminex screening assay. RESULTS: CCs were increased in postoperative blood samples in 54 patients with NSCLC. Patients who underwent thoracotomy instead of VATS had higher numbers of EpCAM (p=0.004) and PanCK-labelled (p=0.03) CCs postoperatively. ccfDNA and DNA integrity index were also significantly increased in postoperative samples (p=0.0009 and p=0.04), with concomitant increase in interleukin 6 and interleukin 10 levels in the same cohorts (p=0.0004 and p=0.034, respectively). CONCLUSIONS: In this study we have shown the potential clinical utility of several biomarkers from liquid biopsies to guide perioperative management, as well as provide a snapshot of the type of surgical resection in terms of circulating tumour cell release. Obtaining reliable readouts from blood can provide crucial information for disease progression, as well as being of prognostic value monitoring patients' response to treatment.

Cryotherapy Ablation in Immunoglobulin G4-Related Disease of the Trachea.

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition comprising a group of disorders with shared clinicopathologic features. Manifestations of IgG4-RD are increasingly recognized in multiple organs, but tracheal involvement remains rare. Patients may present with a mass in the affected organ and most will respond to glucocorticoids, particularly in early stages of disease; however, between 15% and 60% of patients will experience relapse. We consider cryotherapy effective and safe for tumor debulking and symptomatic relief in IgG4-RD. We report on a case of a patient with upper tracheal stenosis exhibiting marked reduction in tumor size and symptom burden, after cryotherapy ablation.

Utility of Nuclear Grading System in Epithelioid Malignant Pleural Mesothelioma in Biopsy-heavy Setting: An External Validation Study of 563 Cases.

Nuclear grading systems for epithelioid malignant pleural mesothelioma (MPM) have been proposed but it remains uncertain if they could be applied in a biopsy-heavy setting. Using the proposed system, we conducted an independent, external validation study using 563 consecutive cases of epithelioid MPM diagnosed at our institution between 2003 and 2017, of which 87% of patients underwent biopsies only. The median number of sites sampled was 1, with a median maximum tissue dimension of 17 mm (biopsy) and 150 mm (resection). The median overall survival (OS) was 14.7 months. The frequencies of grade I, II, and III tumors were 31% (132/563), 52% (292/563), and 17% (94/563). Grade I tumors were associated with the most favorable median OS (24.7 mo) followed by grades II (12.7 mo) and III (7.2 mo). The 2-tier nuclear grade separated tumors into low grade (19.3 mo) and high grade (8.9 mo). In multivariate analysis, 3-tier nuclear grade, 2-tier nuclear grade, and mitosis-necrosis score predicted OS independent of age, procedural type, solid-predominant growth pattern, necrosis, and atypical mitosis (all P<0.001 except 2-tier nuclear grade, P=0.001). In the scenario of a single- site biopsy with tissue dimension ≤10 mm, none but age (P=0.002) were independently predictive. Our data also suggested sampling 3 sites or a maximum tissue dimension of at least 20 mm from a single site is optimal for nuclear grade assessment. In conclusion our study confirmed the utility of nuclear grade in epithelioid MPM using a biopsy-heavy cohort provided the tissue sample met minimum dimensional criteria.

Video-assisted thoracoscopic PlasmaJet ablation for malignant pleural mesothelioma.

The role of surgery in malignant pleural mesothelioma (MPM) remains debatable; nonetheless the relative advantages of different surgical approaches are frequently reassessed and reconsidered. While extensive operations and longer recovery periods can be justified for a group of carefully selected patients, many will present at an advanced stage of their disease or with associated co-morbidities which will exclude them from selection criteria for radical treatment. For these patients, minimally invasive video-assisted procedures may be considered, for purposes of cytoreduction and/or symptomatic relief. Even though there is currently not enough clinical evidence to suggest an improvement in overall survival with limited debulking procedures, it has been suggested that they can improve quality of life over drainage and pleurodesis alone. We consider video-assisted PlasmaJet ablation to potentially have a role in mesothelioma surgery, as it may be used for effective cytoreduction while minimising the risk for complications often associated with extensive pleurectomy procedures, and we report on the use of the PlasmaJet Surgical System in our centre for surgical management of a patient with MPM. After demonstrating safety and absence of major adverse events with this approach, we feel justified in offering the procedure to more of our patients as we aim to collect additional data.

Prognostic value of the DNA integrity index in patients with malignant lung tumors.

INTRODUCTION: Lung cancer survival remains poor in the western world due to late presentation in most cases, leading to difficulty of treatment in these advanced and metastatic patients. Therefore, the development of a robust biomarker for prognosis and to monitor treatment response and relapse would be of great benefit. The use of Alu repeats and DNA Integrity Index has been shown to hold both diagnostic and prognostic value, and as it is obtained from the plasma of patients, it can serve as a non-invasive tool for routine monitoring. This study evaluates the efficiency of this technique in malignant lung cancer patients. METHODS: Plasma samples were collected from 48 patients, consisting of 29 lung cancer patients and 19 non-cancer controls. Alu repeat ratio and confounders were measured. RESULTS: Observations showed a higher Alu repeat ratio amongst the cancer group compared to controls (p=0.035), mean Alu ratio 0.38 (range 0.01-0.93) and 0.22 (0.007-0.44) respectively, ROC curve analysis AUC 0.61 (p=0.22). Analysis by staging was more promising, whereby a higher DNA Integrity Index was seen in advanced cases compared to both early stage and controls, p<0.0001; AUC: 0.92 (P=0.0002) and p=0.0006, AUC - 0.88 (p=0.0007) respectively, however no significant difference was observed in the early stage compared to controls. Short term survival data also showed a DNA Integrity Index of >0.5 to be associated with poorer overall survival p=0.03. CONCLUSION: The results of this study show a potential use of Alu repeats ratios for prognostic purposes in the advanced setting for lung cancer patients.

Selection for adjuvant chemotherapy in completely resected stage I non-small cell lung cancer: external validation of a Chinese prognostic risk model.

BACKGROUND: The ability to sub-stratify survival within stage I is an important consideration as it is assumed that survival is heterogeneous within this sub-group. Liang et al. recently published a nomogram to predict post-operative survival in patients undergoing lung cancer surgery. The aim of our study is external validation of their published nomogram in a British cohort focusing on stages IA and IB to determine applicability in selection of adjuvant chemotherapy within stage I. METHODS: Patient variables were extracted and the score individually calculated. Receiver operative characteristics curve (ROC) was calculated and compared with the original derivation cohort and the discriminatory ability was further quantified using survival plots by splitting our (external) validation cohort into three tertiles and Kaplan Meier plots were constructed and individual curves tested using Cox regression analysis on Stata 13 and R 3.1.2 respectively. RESULTS: A total of 1,238 patients were included for analysis. For all patients from stage IA to IIB the mean (SD) score was 9.95 (4.2). The ROC score comparing patients who died versus those that remained alive was 0.62 (95% CI: 0.58 to 0.67). When divided into prognostic score tertiles, survival discrimination remained evident for the entire cohort, as well as those for stage IA and IB alone. The P value comparing survival between the middle and highest score with baseline (low score) was P=0.031 and P=0.034 respectively. CONCLUSIONS: Our results of external validation suggested lower survival discrimination than reported by the original group; however discrimination between survival remained evident for stage I.

Video-assisted thoracoscopic lobectomy for non-small cell lung cancer: a morbidity limiting approach in a patient on chronic hemodialysis and double agent antiplatelet therapy.

Patients with end-stage renal disease on hemodialysis undergoing surgery for lung cancer represent a high-risk group because of electrolyte imbalance, anemia, hemodynamic instability, bleeding tendency, and immunocompromised state. We describe a patient on hemodialysis with three lung adenocarcinoma of the right lower lobe as an incidental finding during the clinical course of a myocardial infarction treated with drug-eluting stent implantation and double-agent antiplatelet therapy. Considering patient comorbidities, we decided to perform a right lower lobectomy and complete lymph node dissection by a minimally invasive technique. In our experience, the thoracoscopic approach allowed us to perform lobectomy with complete lymph nodes dissection without morbidity. The use of ultrasound scalpel permits a complete lymph node dissection minimizing bleeding even in a double antiplatelet therapy patient.

Thoracoscopic resection of a giant mediastinal parathyroid cyst.

Parathyroid cysts are a rare situation, unusually in the mediastinum. The preoperative diagnosis could be more difficult in some atypical topographies and imaging characteristics in particular in case of huge mediastinal cyst. In the following years traditionally, in case of intrathoracic parathyroid cysts, sternotomy or thoracotomy have been the preferred approaches. We report a case of an older patient with a huge mediastinal parathyroid cyst removed successfully using videothoracoscopy.

Recurrent primary cardiac osteosarcoma: a case report and literature review.

Primary malignant cardiac tumors are very rare. Among malignant tumors, sarcomas occupy first place. In particular, primary cardiac osteosarcoma is extremely rare. To the best of our knowledge, only 42 cases have been reported worldwide. Cardiac malignant tumors usually require complex operations due to the difficulty in completely removing the tumor with acceptable free surgical margins and because of the proximity to vital structures. The current multimodality treatment strategies for cardiac sarcoma are still suboptimal, and surgery in particular frequently has unsatisfactory results. We report a case of recurrent primary cardiac osteosarcoma in a young male who underwent trans-sternal right pneumonectomy and a wide resection of the left and right atrium followed by reconstruction with heterologous pericardium under extracorporeal circulation. The patient died 6 months after the operation due to local and systemic disease recurrence.

Three-dimensional surgical simulation-guided navigation in thoracic surgery: a new approach to improve results in chest wall resection and reconstruction for malignant diseases.

OBJECTIVES: Oncological surgery of the chest wall should be performed to achieve free margins of at least 2 cm for metastasis or 4 cm for primary tumours. When the lesion is not visible or palpable, difficulty in identification may lead to a larger incision and a resection wider than is necessary. METHODS: We report three cases of non-palpable metastatic chest wall lesions in which the preoperative surgical planning and the intraoperative identification of the tumour, and thus the subsequent chest wall reconstruction, was supported using computer-based surgery. RESULTS: The application of high-resolution three-dimensional imaging technology and navigational systems is used in preoperative surgical planning to provide virtual simulations of a patient's skeletal changes and new soft tissue profile. Intraoperatively, a mobile navigation probe was used to identify the lesion, matching surgical landmarks and the preoperative computed tomography imaging, achieving the radical resection of the tumour with correct but not excessive surgical margins. Two patients underwent partial sternectomy followed by sternal allograft reconstruction. The third patient underwent chest wall resection followed by reconstruction using titanium bars and vicryl mesh. In all cases, the postoperative period was uneventful. After a follow-up period of 13.9 and 8 months, respectively, all patients are disease free, without complications. CONCLUSIONS: Application of navigation technology in thoracic surgery should be encouraged because it is easy to use and requires a limited learning curve.

Paraneoplastic dermatomyositis as presentation of thymic carcinoma.

Thymic carcinomas are very rare and heterogeneous groups of anterior mediastinum neoformations with an extremely aggressive behavior. Often, the diagnosis is made in the advanced stages. Paraneoplastic syndromes associated with thymic carcinoma are extremely rare. We report a case of a 64-year-old man presenting with early stage thymic carcinoma which was discovered because of associated paraneoplastic dermatomyositis. The dermatomyositis disappeared completely after radical resection of the tumor. After 20-month follow-up, the patient is in good clinical condition without recidivism of disease.

Successful treatment of parapneumonic empyema after H1N1 infection in a heart transplant recipient.

Pandemic influenza A H1N1 virus is likely to cause severe disease in patients who have received solid organs transplants. In these patients pneumonia is the most frequent clinical feature. Parapneumonic empyema (PPE) may represent the evolution of secondary bacterial respiratory infections. To our knowledge this is the first reported case of PPE during H1N1 influenza A in an adult heart transplanted patient. The patient was treated successfully with surgical empyemectomy and lung decortication, broad-spectrum antibiotics and oseltamivir. Eradication of influenza was obtained in the fifth postoperative day.