Prognostic Factors for Leiomyosarcoma with Isolated Metastases to the Lungs: Impact of Metastasectomy.

BACKGROUND: Leiomyosarcoma (LMS) most frequently metastasizes to the lung. Metastatic LMS is considered incurable. Selected patients may benefit from pulmonary metastasectomy (PM) within multimodal therapy. This study analyzed the prognostic relevance of clinicopathologic factors in these patients. METHODS: Patients with metastatic LMS to the lung treated in our center from 2004 to 2020 were included in this single-center retrospective study. Overall survival (OS), progression-free survival (PFS), and prognostic factors were analyzed. RESULTS: The study had 64 patients (33 males, 52%) with metastatic LMS to the lung. The 5-year OS was 55% after the diagnosis of pulmonary metastases. Age older than 60 years at the primary tumor diagnosis, primary tumor larger than 70 mm, and five or more lung metastases were associated with poorer OS. Of the 64 patients, 44 underwent PM. The postoperative mortality rate was 0%. The patients selected for PM were younger and had smaller primary tumors, fewer metastases, and metastases that more often were metachronous. Metastasis grade (G1 vs. G2/3) and size (20-mm cutoff) were significant prognostic factors for OS (p = 0.05) and PFS (p = 0.028) after PM, respectively. The 44 patients who underwent PM had a survival benefit compared with the patients who were selected but did not undergo PM (n = 6) and the patients who were not selected for PM (n = 14). Three patients (7%) were alive and free of disease at the last follow-up visit respectively 5.5, 9, and 12 years after PM. CONCLUSIONS: For patients with leiomyosarcoma, PM is safe. Despite aggressive multimodal treatment, most patients will experience recurrence and eventually die of their disease. However, a small subgroup of patients could potentially be cured after PM.

Number of metastases and their response to chemotherapy impact survival of patients with isolated lung metastases from bone-derived sarcoma.

BACKGROUND: Pulmonary metastasectomy (PM) is an established treatment for selected patients with metastatic sarcomas. The aim of this study was to examine our institutional experience and evaluate factors predicting outcome. METHODS: We retrospectively reviewed all patients undergoing PM for bone sarcoma in our center from 2001 to 2019. Survival was calculated from the date of PM. Impact on survival of clinical parameters was assessed. RESULTS: Thirty-eight patients (27 males, 71%) were included. Histology was osteosarcoma (n = 20, 53%), Ewing sarcoma (n = 13, 34%) and chondrosarcoma (n = 5, 13%). Twelve patients (31.5%) had synchronous metastases, all received chemotherapy before PM. Median number of metastases was 3 (1 to 29). Twenty (53%) patients had mediastinal lymph node sampling. One patient had positive lymph nodes. Ninety-day mortality was 0%. Three and 5-year PFS were 24.5 and 21%, respectively. Three and 5-year OS were 64.5 and 38.5%, respectively. More than three metastases and progression under chemotherapy were significant independent predictors for OS. CONCLUSION: PM is a safe procedure and encouraging long-term outcome can be achieved. Patients with progression of pulmonary metastases under chemotherapy as well as patients with more than three metastases had significantly worse OS.

Surgical Treatment for Primary Chest Wall Sarcoma: A Single-Institution Study.

BACKGROUND: Primary sarcomas of the chest wall are rare aggressive tumors. Surgery is part of the multimodal treatment. We describe our institutional patient cohort and evaluate prognostic factors. METHODS: All patients who had curative intent surgery for primary chest wall sarcoma from 2004 to 2019 were retrospectively reviewed. Impact on survival-calculated from the date of surgery until last follow-up- was assessed for the following variables: age, gender, type of resection, size, grading, stage, completeness of resection, and neoadjuvant and adjuvant therapy. RESULTS: Twenty-three patients (15 males, 65%) with a median age of 54 y (4 to 82) were included. Most common histology was chondrosarcoma (n = 5, 22%). Seven patients (30%) received neoadjuvant and 13 patients (57%) received adjuvant treatment. R0 resection was achieved in 83%. Extended chest wall resection was performed in 14 patients (61%), including lung (n = 13, 57%), diaphragm (n = 2, 9%) and pericardium (n = 1, 4%). Morbidity and 90-day mortality were 23% and 0%, respectively. Three- and 5-year overall survival was 53% and 35%, respectively. R0 resection was predictor of overall survival (P = 0.029). Tumor grade and extended resections were predictors for recurrence (P = 0.034 and P = 0.018, respectively). CONCLUSIONS: Surgical resection of primary chest wall sarcoma is a safe procedure even when extended resection is required.

Multimodality treatment including surgery for primary pulmonary sarcoma: Size does matter.

BACKGROUND AND OBJECTIVES: Primary pulmonary sarcoma (PPS) accounts for less than 1.1% of all pulmonary tumors. Few outcome data are reported. We evaluated outcome and prognostic factors in our series. METHODS: We retrospectively reviewed all patients who underwent resection for PPS in our center from 2002 to 2018. Survival was calculated from the date of surgery until last follow-up. Impact on survival of gender, type of lung resection, completeness of resection, grade, size, and TNM staging for lung cancer and soft tissue sarcoma (STS) was assessed. RESULTS: Thirteen patients were included. Eight (61.5%) patients received neoadjuvant treatment. Median tumor size at diagnosis was 11.5 cm (1-30 cm). Type of lung resection was wedge (n = 2, 15%), lobectomy (n = 4, 31%), intrapericardial (n = 3, 23%), and extrapleural pneumonectomies (n = 4, 31%). In-hospital mortality was 8%. Overall 5-year survival was 60%. Median disease-free survival was 17 months. Tumor size was a predictor for survival (P = .02) and recurrence (P = .05). Gender (P = .04) and type of lung resection (P = .04) were predictors of survival. T stage for STS of trunk and extremity, and TNM stage for lung cancer were predictors for recurrence (P = .03 and P = .04, respectively). CONCLUSION: Surgical resection within a multimodality therapy concept in highly selected patients can offer good long-term outcome.

Should surgery be part of the multimodality treatment for stage IIIB non-small cell lung cancer?

BACKGROUND: Traditionally, treatment for stage IIIB (T4N2M0 and T1-4N3M0) NSCLC consists in definitive chemoradiation. Surgery is used only anecdotally. Here, we studied outcome for patients treated with multimodality including surgery. METHODS: Patients who underwent surgery for stage IIIB between 2000 and 2015 were retrospectively reviewed and data analyzed. Patients were selected for surgery if they would tolerate multimodality treatment, the tumor was deemed upfront resectable, and N2-N3 involvement was limited to a non-bulky single site. Survival was calculated from the date of surgery until last follow-up. Univariate and multivariate analysis were performed to identify prognostic factors. RESULTS: During the study period, 5416 patients underwent resection for NSCLC in our center. Sixty patients (1%) had clinical stage IIIB. Thirty-two patients had T4N2 NSCLC involving the carina and/or superior vena cava (n = 25, 78%), left atrium (n = 5, 16%), or other (n = 2, 6%). Half of the 28 patients with N3-disease had supraclavicular node involvement. Pneumonectomy was performed in 27 patients (45%). Twenty-nine patients (48%) had induction therapy, with chemotherapy alone. Adjuvant therapy was administered to 52 patients (87%), mostly chemoradiation. Complete resection rate was 92%. Post-operative mortality was 3%. Three- and 5-year overall survivals were 51% and 39%, respectively. Multivariate analysis identified incomplete resection (P = 0.008) and absence of adjuvant treatment (P = 0.032) as poor survival prognostic factors. CONCLUSIONS: Surgery can be considered as a component of multimodality therapy in highly selected patients with stage IIIB NSCLC based on encouraging 5-year survival of 39%.

En Bloc Resection of Pulmonary Sulcus Non-small Cell Lung Cancer Invading the Spine: A Systematic Literature Review and Pooled Data Analysis.

OBJECTIVE: To conduct a systematic literature review and pooled data analysis focusing on outcome after en bloc resection of pulmonary sulcus non-small cell lung cancer (NSCLC) invading the spine. BACKGROUND: This rare type of NSCLC has historically been considered unresectable and fatal. Nowadays, carefully selected patients can be cured when treated surgically within a multimodality concept. METHODS: The MEDLINE database was searched using the PubMed engine to retrieve relevant articles. Corresponding authors were contacted, and shared data were pooled and analyzed. RESULTS: Search strategy yielded 134 articles. Six were relevant and nonduplicative. Four authors shared updated data on 135 patients. All tumors were resected en bloc with the lung, chest wall, and spine. Induction was administered in 85 patients (63%) and consisted of chemotherapy (n = 32), radiation (n = 1), or concurrent chemoradiation (n = 52). Spine resections included total (n = 23), hemi- (n = 94), and partial (n = 18) vertebrectomies. R0 resection was achieved in 120 patients (89%). Adjuvant treatment was administered to 70 patients (52%) and included chemotherapy (n = 16), radiotherapy (n = 22), or chemoradiation (n = 32). Overall, 3-, 5-, and 10-year survival rates were 57%, 43%, and 27%, respectively. Univariate analysis identified the type of resection (R0 vs R1/R2, P < 0.001) as significant prognostic factor among the variables tested (age, histology, pT/pN, type of induction/adjuvant treatment, type of lung/spine resection). CONCLUSIONS: Multimodality therapy including en bloc resection for pulmonary sulcus NSCLC invading the spine provides excellent long-term survival in selected patients. This result establishes a benchmark against which the effects of new treatments can be compared in the future.

Lung neuroendocrine tumors: correlation of ubiquitinylation and sumoylation with nucleo-cytosolic partitioning of PTEN.

BACKGROUND: The tumor suppressor phosphatase and tensin homolog (PTEN) is a pleiotropic enzyme, inhibiting phosphatidyl-inositol-3 kinase (PI3K) signaling in the cytosol and stabilizing the genome in the nucleus. Nucleo-cytosolic partitioning is dependent on the post-translational modifications ubiquitinylation and sumoylation. This cellular compartmentalization of PTEN was investigated in lung neuroendocrine tumors (lung NET). METHODS: Tumor tissues from 192 lung NET patients (surgical specimens = 183, autopsies = 9) were investigated on tissue microarrays. PTEN was H-scored by two investigators in nucleus and cytosol using the monoclonal antibody 6H2.1. Results were correlated with immunoreactivity for USP7 (herpes virus-associated ubiquitin-specific protease 7) and SUMO2/3 (small ubiquitin-related modifier protein 2/3) as well as PTEN and p53 FISH gene status. Clinico-pathologic data including overall survival, proliferation rate and diagnostic markers (synaptophysin, chromogranin A, Mib-1, TTF-1) were recorded. RESULTS: The multicentre cohort included 58 typical carcinoids (TC), 42 atypical carcinoids (AC), 32 large cell neuroendocrine carcinomas (LCNEC) and 60 small cell lung carcinomas (SCLC). Carcinoids were smaller in size and had higher synaptophysin and chromogranin A, but lower TTF-1 expressions. Patients with carcinoids were predominantly female and 10 years younger than patients with LCNEC/SCLC. In comparison to the carcinoids, LCNEC/SCLC tumors presented a stronger loss of nuclear and cytosolic PTEN associated with a loss of PTEN and p53. Concomitantly, a loss of nuclear USP7 but increase of nuclear and cytosolic SUMO2/3 was found. Loss of nuclear and cytosolic PTEN, loss of nuclear USP7 and increase of cytosolic SUMO2/3 thus correlated with poor survival. Among carcinoids, loss of cytosolic PTEN was predominantly found in TTF1-negative larger tumors of male patients. Among SCLC, loss of both cytosolic and nuclear PTEN but not proliferation rate or tumor size delineated a subgroup with poorer survival (all p-values <0.05). CONCLUSIONS: Cellular ubiquitinylation and sumoylation likely influence the functional PTEN loss in high grade lung NET. Both nuclear and cytosolic PTEN immunoreactivity should be considered for correlation with clinico-pathologic parameters.

The ESTS-AIR database-initial results of a multi-institutional database on airway surgery.

OBJECTIVES: Compared to lung resections, airway procedures are relatively rare in thoracic surgery. Despite this, a growing number of dedicated airway centres have formed throughout Europe. These centres are characterized by a close interdisciplinary collaboration and they often act as supra-regional referring centres. To date, most evidence of airway surgery comes from retrospective, single-centre analysis as there is a lack of large-scale, multi-institutional databases. METHODS: In 2018, an initiative was formed, which aimed to create an airway database within the framework of the ESTS database (ESTS-AIR). Five dedicated airway centres were asked to test the database in a pilot phase. A 1st descriptive analysis of ESTS-AIR was performed. RESULTS: A total of 415 cases were included in the analysis. For adults, the most common indication for airway surgery was post-tracheostomy stenosis and idiopathic subglottic stenosis; in children, most resections/reconstructions had to be performed for post-intubation stenosis. Malignant indications required significantly longer resections [36.0 (21.4-50.6) mm] when compared to benign indications [26.6 (9.4-43.8) mm]. Length of hospital stay was 11.0 (4.1-17.3) days (adults) and 13.4 (7.6-19.6) days (children). Overall, the rates of complications were low with wound infections being reported as the most common morbidity. CONCLUSIONS: This evaluation of the 1st cases in the ESTS-AIR database allowed a large-scale analysis of the practice of airway surgery in dedicated European airway centres. It provides proof for the functionality of ESTS-AIR and sets the basis for rolling out the AIR subsection to all centres participating in the ESTS database.

Factors Influencing the Outcome of Patients with Primary Ewing Sarcoma of the Sacrum.

Background: Ewing sarcoma (EwS) is a rare and highly malignant bone tumor primarily affecting children, adolescents, and young adults. The pelvis, trunk, and lower extremities are the most common sites, while EwS of the sacrum as a primary site is very rare, and only few studies focusing on this location are published. Due to the anatomical condition, local treatment is challenging in sacral malignancies. We analyzed factors that might influence the outcome of patients suffering from sacral EwS. Methods: We retrospectively analyzed data of the GPOH EURO-E.W.I.N.G 99 trial and the EWING 2008 trial, with a cohort of 124 patients with localized or metastatic sacral EwS. The study endpoints were overall survival (OS) and event-free survival (EFS). OS and EFS were calculated using the Kaplan-Meier method, and univariate comparisons were estimated using the log-rank test. Hazard ratios (HRs) with respective 95% confidence intervals (CIs) were estimated in a multivariable Cox regression model. Results: The presence of metastases (3y-EFS: 0.33 vs. 0.68; P < 0.001; HR = 3.4, 95% CI 1.7 to 6.6; 3y-OS: 0.48 vs. 0.85; P < 0.001; HR = 4.23, 95% CI 1.8 to 9.7), large tumor volume (≥200 ml) (3y-EFS: 0.36 vs. 0.69; P=0.02; HR = 2.1, 95% CI 1.1 to 4.0; 3y-OS: 0.42 vs. 0.73; P=0.04; HR = 2.1, 95% CI 1.03 to 4.5), and age ≥18 years (3y-EFS: 0.41 vs. 0.60; P=0.02; HR = 2.6, 95% CI 1.3 to 5.2; 3y-OS: 0.294 vs. 0.59; P=0.01; HR = 2.92, 95% CI 1.29 to 6.6) were revealed as adverse prognostic factors. Conclusion: Young age seems to positively influence patients` survival, especially in patients with primary metastatic disease. In this context, our results support other studies, stating that older age has a negative impact on survival. Tumor volume, metastases, and the type of local therapy modality have an impact on the outcome of sacral EwS. Level of evidence: Level 2. This trial is registered with NCT00020566 and NCT00987636.

Current use of extracorporeal life support in airway surgery: a narrative review.

Background and Objective: Extracorporeal life support (ECLS) is widely used in patients with severe respiratory or cardiocirculatory failure. The most commonly used extracorporeal membrane oxygenation (ECMO) modes are veno-venous (V-V) and veno-arterial (V-A) ECMO, which can both be achieved by various types of vascular cannulation. Within the scope of tracheobronchial surgery, intraoperative ECLS may occasionally be necessary to provide sufficient oxygenation to a patient throughout a procedure, especially when conventional ventilation strategies are limited. Additionally, V-A ECMO can provide cardiopulmonary support in emergencies and in cases where hemodynamic instability can occur. Methods: This narrative literature review was carried out to identify the use and the specifics of ECLS in airway surgery over the last years. Data from 168 cases were summarized according to the indication for surgery and the mode of ECLS (V-V, V-A). Key Content and Findings: The most common tracheobronchial pathologies in which support was needed were: primary malignant disease of the airways, malignant infiltration, tracheal stenosis, injury of the airway, and congenital airway disease. With increasing experience in ECLS, the number of reported cases performed with intraoperative ECLS increased steadily over the last decade. Conclusions: A trend favoring the use of V-V ECMO over V-A ECMO was identified. These approaches should now be considered indispensable tools for managing challenging surgical cases.

DOTATOC PET/CT imaging of a typical carcinoid tumor in a human ex-vivo perfused lung lobe.

The use of Isolated lung perfusion (ILP), combined with medical imaging modalities such as positron emission tomography-computed tomography (PET/CT), provides real-time visualization of tumors in ventilated and perfused vital lung tissue. This experiment intends to show the feasibility and benefits of using ILP combined with PET/CT imaging. Following lung surgery on a 49-year-old male, his left lower lobectomy specimen, which held a typical carcinoid tumor, was preserved on normothermic ILP. Gallium-68-Edotreotide ([68Ga]-DOTATOC) was administered into the ILP circuit, and dynamic emission data from PET/CT was acquired. ILP was carried out for 120 minutes. Near physiologic gas exchange and glucose metabolism were preserved throughout the experiment. The time activity curves (TAC) of 5 different volumes of interest (VOI) showed notable differences in tracer uptake over time. The peripheral area of the carcinoid exhibited delayed but high somatostatin receptor agonist uptake compared to the surrounding parenchyma and the intrapulmonary artery. However, the central area of the carcinoid showed very low [68Ga]-DOTATOC uptake. This experiment demonstrates the potential of ILP combined with PET/CT for kinetic modeling in experimental nuclear medicine imaging. By providing visualization of tracer uptake in perfused lung tissue, this model could potentially improve our understanding of tumor physiology and molecular imaging.

Giant middle mediastinal lesions: when tumor size correlates with mesenchymal origin-a retrospective single-center analysis.

Background: The International Thymic Malignancy Interest Group (ITMIG) proposed an internationally accepted division of the mediastinum into three compartments based on computed tomography (CT): anterior (prevascular), middle (visceral) and posterior (paravertebral) compartment. There is no generally accepted definition for the term "giant" when applied to middle mediastinal lesions. We defined the term "giant" and described our surgical experience in treating patients with giant lesions of the middle mediastinum. Methods: CT imaging of patients operated in our center from January 2016 to August 2021 for mediastinal lesions was reviewed. Lesions were categorized to one of the ITMIG-defined compartments. Lesion size at diagnosis was measured at its largest diameter on axial CT imaging. Giant middle mediastinal lesions were defined as lesions having a size ≥90th percentile of our middle mediastinal lesion cohort. Patients with giant middle mediastinal lesions were further analyzed. Results: Thirty-six patients (23%) had lesions located in the middle mediastinal compartment. Most common diagnoses were mediastinal cysts (n=10, 28%), metastatic lesions (n=6, 17%), lymphomas (n=5, 14%), and sarcomas (n=3, 8%). Ninetieth percentile lesion size was 73 mm. As per definition, four patients had giant middle mediastinal lesions. All these four lesions were of mesenchymal origin including oesophageal leiomyoma, synovial sarcoma, leiomyosarcoma and undifferentiated round cell sarcoma. Resection was performed through posterolateral thoracotomy or sternotomy, with or without cardiopulmonary bypass. Conclusions: The term "giant" could be defined as a mass larger or equal to 73 mm. This definition selected specifically lesions with mesenchymal origin and may therefore guide diagnostic algorithm and patient management.

Effect of Radiotherapy Dose on Outcome in Nonmetastatic Ewing Sarcoma.

Purpose: Radiation therapy (RT) is an integral part of Ewing sarcoma (EwS) therapy. The Ewing 2008 protocol recommended RT doses ranging from 45 to 54 Gy. However, some patients received other doses of RT. We analyzed the effect of different RT doses on event-free survival (EFS) and overall survival (OS) in patients with EwS. Methods and Materials: The Ewing 2008 database included 528 RT-admitted patients with nonmetastatic EwS. Recommended multimodal therapy consisted of multiagent chemotherapy and local treatment consisting of surgery (S&RT group) and/or RT (RT group). EFS and OS were analyzed with uni- and multivariable Cox regression models including known prognostic factors such as age, sex, tumor volume, surgical margins, and histologic response. Results: S&RT was performed in 332 patients (62.9%), and 145 patients (27.5%) received definitive RT. Standard dose ≤ 53 Gy (d1) was admitted in 57.8%, high dose of 54 to 58 Gy (d2) in 35.5%, and very high dose ≥ 59 Gy (d3) in 6.6% of patients. In the RT group, RT dose was d1 in 11.7%, d2 in 44.1%, and d3 in 44.1% of patients. Three-year EFS in the S&RT group was 76.6% for d1, 73.7% for d2, and 68.2% for d3 (P = .42) and in the RT group 52.9%, 62.5%, and 70.3% (P = .63), respectively. Multivariable Cox regression revealed age ≥ 15 years (hazard ratio [HR], 2.68; 95% confidence interval [CI], 1.63-4.38) and nonradical margins (HR, 1.76; 95% CI, 1.05-2.93) for the S&RT group (sex, P = .96; histologic response, P = .07; tumor volume, P = .50; dose, P = .10) and large tumor volume (HR, 2.20; 95% CI, 1.21-4.0) for the RT group as independent factors (dose, P = .15; age, P = .08; sex, P = .40). Conclusions: In the combined local therapy modality group, treatment with higher RT dose had an effect on EFS, whereas higher dose of radiation when treated with definitive RT was associated with an increased OS. Indications for selection biases for dosage were found. Upcoming trials will assess the value of different RT doses in a randomized manner to control for potential selection bias.

Association between local treatment modalities and event-free survival, overall survival, and local recurrence in patients with localised Ewing Sarcoma. Report from the Ewing 2008 trial.

BACKGROUND: Local treatment is a crucial element in the standard of care for Ewing sarcoma (EWS). While systemic treatment is improved in randomised clinical trials, local treatment modalities are discussed controversially. We analysed the association between local therapy and event-free survival (EFS), overall survival (OS), and local recurrence (LR) in prospectively collected data of patients with localised EWS. PATIENTS AND METHODS: We analysed data from the international Ewing 2008 study registered between 2009 and 2019 in 117 centres. After induction chemotherapy, patients received surgery, radiotherapy, or a combination thereof. We performed Cox regression, conducted propensity score-weighted sensitivity analysis, and performed subgroup analyses. Hazard ratios (HRs) and 95% confidence intervals are reported. RESULTS: We included 863 patients with localised EWS (surgery alone: 331, combination therapy: 358, definitive radiotherapy: 174). In patients treated with combination therapy compared to surgery alone, EFS HR was 0.84 (0.57-1.24; p = 0.38), OS HR was 0.84 (0.57-1.23; p = 0.41), and LR HR was 0.58 (0.26-1.31; p = 0.19). Hazards of any event were increased in patients treated with definitive radiotherapy compared to surgery only, HR 1.53 (1.02-2.31; p = 0.04). Patients with poor responses to chemotherapy benefitted from combination therapy over definitive surgery with an EFS HR 0.49 (0.27-0.89; p = 0.02). Patients with pelvic tumours benefitted from combination therapy over surgery only regarding LR, HR 0.12 (0.02-0.72; p = 0.02). CONCLUSION: Patients with poor responses to chemotherapy benefitted from radiotherapy added to surgery. In the whole group, radiotherapy alone as opposed to surgery alone increased the hazards of any event.

Mucinous cystadenoma arising in a completely isolated infected ileal duplication cyst.

Gastrointestinal duplications are uncommon congenital lesions that can occur anywhere along the alimentary tract, and the symptoms of which generally develop during infancy or childhood. Completely isolated duplication cysts are an extremely rare variant of duplication, where no communication between the cyst and the adjacent bowel segment is present. We report the unique case of an adult who presented with right lower abdominal pain and systemic signs of inflammation caused by infection of a completely isolated ileal duplication cyst. Histological examination of the cyst additionally revealed a low-grade mucinous cystadenoma. We discuss the clinical presentations, diagnosis and treatment of this rare entity.

A case report of a giant middle mediastinal leiomyosarcoma.

Primary mediastinal leiomyosarcomas are extremely rare soft tissue tumors, accounting for less than 15% of all primary mediastinal sarcomas. Middle mediastinal tumors are very rare, with a prevalence of 0.1% in healthy individuals. Usually, mediastinal leiomyosarcoma originates and involves mediastinal structures such as oesophagus, heart or great vessels. Here we report the rare case of a giant middle mediastinal leiomyosarcoma without involvement of any surrounding structures in a 70 years old female. Main related symptoms were cough and increasing dyspnea. Imaging work-up showed an 11-cm giant middle mediastinal tumor located in the subcarinal space and compressing the oesophagus. Cytopathologic examination of endobronchial ultrasound-guided transbronchial needle aspiration diagnosed leiomyosarcoma. The tumor was completely removed through a right posterolateral thoracotomy in the fifth intercostal space. None of the surrounding structures were involved by the tumor intraoperatively. The patient underwent adjuvant chemoradiation as advised by the sarcoma tumor board (5 cycles of dacarbazine and doxorubicin followed by 60 Gy). At last follow-up, no evidence of recurrence was seen on imaging ten months after surgery. This rare case confirms that giant middle mediastinal leiomyosarcoma may not involve surrounding mediastinal structure and that resection can be completely and safely done without the need for resection of neighboring structures. The relevant literature on the subject is reviewed here.

Reversible occlusion of the pulmonary vasculature by transarterial embolisation with degradable starch microspheres: preclinical assessment in a human isolated lung perfusion model.

BACKGROUND: Transpulmonary embolisation (TPE) using degradable starch microspheres (DSM) is a potential approach to treat pulmonary metastases. However, there is a paucity of detailed information on perfusion dynamics. The aim of this study was to establish a human ex vivo isolated lung perfusion (ILP) model to observe and evaluate the effects of DSM-TPE in a near-physiologic setting. METHODS: ILP was carried out on six surgically resected lung lobes. At baseline, computed tomography (CT), including CT perfusion imaging (CTPI), and histopathological sampling were performed (t30). DSM-TPE was initiated and increased stepwise (t45, t60, t75, and t90) to be followed by CT imaging, histopathological sampling, and pulmonary arterial pressure (PAP). After the last assessment (t90), alpha-amylase was injected into the pulmonary artery to allow for DSM hydrolysation and two additional assessments (t105; t120). Histopathological specimens were evaluated using a semiquantitative ordinal score. CTPI was used for time to peak (TTP) analysis. RESULTS: After DSM administration, PAP and TTP increased significantly: PAP slope 95% confidence interval (CI) 0.104-0.483, p = 0.004; TTP t30 versus t45, p = 0.046. After the addition of alpha-amylase, functional parameters reverted to values comparable to baseline. In histopathological samples, embolisation grades increased significantly until t90 (slope 95% CI 0.027-0.066, p < 0.001) and decreased after addition of alpha-amylase (slope 95% CI -0.060-0.012, p = 0.165), CONCLUSIONS: The ILP model demonstrated successfully both the physiologic effect of DSM-TPE on human lungs and its reversibility with alpha-amylase. Thus, it can be used as a near-physiologic preclinical tool to simulate and assess later clinical approaches.

High-Dose Treosulfan and Melphalan as Consolidation Therapy Versus Standard Therapy for High-Risk (Metastatic) Ewing Sarcoma.

PURPOSE: Ewing 2008R3 was conducted in 12 countries and evaluated the effect of treosulfan and melphalan high-dose chemotherapy (TreoMel-HDT) followed by reinfusion of autologous hematopoietic stem cells on event-free survival (EFS) and overall survival in high-risk Ewing sarcoma (EWS). METHODS: Phase III, open-label, prospective, multicenter, randomized controlled clinical trial. Eligible patients had disseminated EWS with metastases to bone and/or other sites, excluding patients with only pulmonary metastases. Patients received six cycles of vincristine, ifosfamide, doxorubicin, and etoposide induction and eight cycles of vincristine, actinomycin D, and cyclophosphamide consolidation therapy. Patients were randomly assigned to receive additional TreoMel-HDT or no further treatment (control). The random assignment was stratified by number of bone metastases (1, 2-5, and > 5). The one-sided adaptive-inverse-normal-4-stage-design was changed after the first interim analysis via Müller-Schäfer method. RESULTS: Between 2009 and 2018, 109 patients were randomly assigned, and 55 received TreoMel-HDT. With a median follow-up of 3.3 years, there was no significant difference in EFS between TreoMel-HDT and control in the adaptive design (hazard ratio [HR] 0.85; 95% CI, 0.55 to 1.32, intention-to-treat). Three-year EFS was 20.9% (95% CI, 11.5 to 37.9) in TreoMel-HDT and 19.2% (95% CI, 10.8 to 34.4) in control patients. The results were similar in the per-protocol collective. Males treated with TreoMel-HDT had better EFS compared with controls: median 1.0 years (95% CI, 0.8 to 2.2) versus 0.6 years (95% CI, 0.5 to 0.9); P = .035; HR 0.52 (0.28 to 0.97). Patients age < 14 years benefited from TreoMel-HDT with a 3-years EFS of 39.3% (95% CI, 20.4 to 75.8%) versus 9% (95% CI, 2.4 to 34); P = .016; HR 0.40 (0.19 to 0.87). These effects were similar in the per-protocol collective. This observation is supported by comparable results from the nonrandomized trial EE99R3. CONCLUSION: In patients with very high-risk EWS, additional TreoMel-HDT was of no benefit for the entire cohort of patients. TreoMel-HDT may be of benefit for children age < 14 years.

Torque Teno Virus load in lung cancer patients correlates with age but not with tumor stage.

BACKGROUND: Torque teno virus (TTV) is a ubiquitous non-pathogenic virus, which is suppressed in immunological healthy individuals but replicates in immune compromised patients. Thus, TTV load is a suitable biomarker for monitoring the immunosuppression also in lung transplant recipients. Since little is known about the changes of TTV load in lung cancer patients, we analyzed TTV plasma DNA levels in lung cancer patients and its perioperative changes after lung cancer surgery. MATERIAL AND METHODS: Patients with lung cancer and non-malignant nodules as control group were included prospectively. TTV DNA levels were measured by quantiative PCR using DNA isolated from patients plasma and correlated with routine circulating biomarkers and clinicopathological variables. RESULTS: 47 patients (early stage lung cancer n = 30, stage IV lung cancer n = 10, non-malignant nodules n = 7) were included. TTV DNA levels were not detected in seven patients (15%). There was no significant difference between the stage IV cases and the preoperative TTV plasma DNA levels in patients with early stage lung cancer or non-malignant nodules (p = 0.627). While gender, tumor stage and tumor histology showed no correlation with TTV load patients below 65 years of age had a significantly lower TTV load then older patients (p = 0.022). Regarding routine blood based biomarkers, LDH activity was significantly higher in patients with stage IV lung cancer (p = 0.043), however, TTV load showed no correlation with LDH activity, albumin, hemoglobin, CRP or WBC. Comparing the preoperative, postoperative and discharge day TTV load, no unequivocal pattern in the kinetics were. CONCLUSION: Our study suggest that lung cancer has no stage dependent impact on TTV plasma DNA levels and confirms that elderly patients have a significantly higher TTV load. Furthermore, we found no uniform perioperative changes during early stage lung cancer resection on plasma TTV DNA levels.

Lymph Node Dissection in Thymoma: Is it worth it?

OBJECTIVES: Lymph node dissection (LND) and nodal metastases in thymomas remain controversial and understudied. The aim of our study was to evaluate the incidence of nodal metastasis and the short term outcomes of systematic LND in thymomas. MATERIAL AND METHODS: From December 2017 to September 2020, we performed 54 LND conducted according to the International Thymic Malignancy Interest Group (ITMIG) lymph node map. This group was compared to a historical control group of 55 patients who underwent surgery in our center from January 2015 to November 2017. RESULTS: LND was performed in 72 % and in 5 % of the cases in the study cohort group and historical control group, respectively. The number of lymph nodes retrieved was significantly higher in the study cohort group (3.89 per patient vs. 1.62, p = 0.0021). In the whole population studied, nodal metastases were found in 3 patients (2.8 % of all patients) with 5.6 % in the cohort study group vs. 0 % in the control group (p = 0.12). Patients with nodal metastasis had larger tumors (> 7 cm), and a higher histology grade (B2 and B3). There was a trend towards higher risk of laryngeal nerve palsy in the cohort study group (9.3 % vs. 1.8 %, p = 0.11). CONCLUSION: Systematic LND increases the number of lymph node harvested and detects more lymph node metastases, which remains infrequent in thymomas. The impact of LND and the true prognostic significance of lymph node metastases remains controversial. Given the potential complications, LND or sampling should not be perfomed in small, encapsulated and low grade thymomas.