The Prognostic Role of the Number of Involved Structures in Thymic Epithelial Tumors: Results from the ESTS Database.

BACKGROUND: The role of the number of involved structures (NIS) in thymic epithelial tumors (TETs) has been investigated for inclusion in future staging systems, but large cohort results still are missing. This study aimed to analyze the prognostic role of NIS for patients included in the European Society of Thoracic Surgeons (ESTS) thymic database who underwent surgical resection. METHODS: Clinical and pathologic data of patients from the ESTS thymic database who underwent surgery for TET from January 2000 to July 2019 with infiltration of surrounding structures were reviewed and analyzed. Patients' clinical data, tumor characteristics, and NIS were collected and correlated with CSS using Kaplan-Meier curves. The log-rank test was used to assess differences between subgroups. A multivariable model was built using logistic regression analysis. RESULTS: The final analysis was performed on 303 patients. Histology showed thymoma for 216 patients (71.3%) and NET/thymic carcinoma [TC]) for 87 patients (28.7%). The most frequently infiltrated structures were the pleura (198 cases, 65.3%) and the pericardium in (185 cases, 61.1%), whereas lung was involved in 96 cases (31.7%), great vessels in 74 cases (24.4%), and the phrenic nerve in 31 cases (10.2%). Multiple structures (range, 2-7) were involved in 183 cases (60.4%). Recurrence resulted in the death of 46 patients. The CSS mortality rate was 89% at 5 years and 82% at 10 years. In the univariable analysis, the favorable prognostic factors were neoadjuvant therapy, Masaoka stage 3, absence of metastases, absence of myasthenia gravis, complete resection, thymoma histology, and no more than two NIS. Patients with more than two NIS presented with a significantly worse CSS than patients with no more than two NIS (CSS 5- and 10-year rates: 9.5% and 83.5% vs 93.2% and 91.2%, respectively; p = 0.04). The negative independent prognostic factors confirmed by the multivariable analysis were incomplete resection (hazard ratio [HR] 2.543; 95% confidence interval [CI] 1.010-6.407; p = 0.048) and more than two NIS (HR 1.395; 95% CI 1.021-1.905; p = 0.036). CONCLUSIONS: The study showed that more than two involved structures are a negative independent prognostic factor in infiltrative thymic epithelial tumors that could be used for prognostic stratification.

Seven preoperative factors have strong predictive value for postoperative pneumonia in patients undergoing thoracoscopic lung cancer surgery.

Background: Postoperative pneumonia (POP) is a hospital acquired pneumonia that occurs >48 hours after tracheal intubation. The diagnosis of POP should be based on clinical and radiological findings within 30 days after surgery. It is a common complication after thoracoscopic surgery for lung cancer patients. However, the specific impact of preoperative comorbidities on the incidence of POP remains unclear. This study aimed to analyze the preoperative data of patients with lung cancer to help surgeons predict the risk of incidence of POP after thoracoscopic lung resection. Methods: This study is a prospective study that included patients with lung cancer who were scheduled for thoracoscopic surgery in 1 year. All cases came from two medical centers. Preoperative demographic information, tumor information, preoperative comorbidities, quality of life scores, and incidence of POP were collected. Variables were screened by univariate analysis and multivariate regression. Finally, a prediction model was constructed. A total of 53 preoperative factors were included as candidate predictors. The binary outcome variable was defined as the presence or absence of POP. The incidence of POP was the primary outcome variable. The predictive performance of the model was verified internally through 1,000 iterations of bootstrap resampling. Results: A total of 1,229 patients with lung cancer who underwent thoracoscopic surgery were enrolled. In addition, 196 cases (15.95%) had POP; 1,025 (83.40%) patients had comorbid conditions. The total number of comorbidity diagnosed in all samples was 2,929. The prediction model suggested that patients with advanced age, high body mass index (BMI), smoking, poor physical condition, respiratory diseases, diabetes, and neurological diseases were more likely to develop POP. The area under the curve (AUC) and Brier scores were 0.851 and 0.091, respectively. The expected and observed results were in strong agreement, according to the likelihood of POP calibration curve. Conclusions: The constructed model is capable of evaluating the probability of POP occurrence in patients with lung cancer. Seven preoperative factors in patients with lung cancer were found to be associated with increased probability of having pneumonia after thoracoscopic lung resection. This model can help predict the incidence of POP after surgery.

An Overview of the Use of Anti-Angiogenic Agents in the Treatment of Thymic Epithelial Tumors.

Angiogenesis significantly influences the carcinogenesis of thymic epithelial tumors (TET). Both thymomas and thymic carcinoma (TC) overexpress VEGF-A and VEGFR-1 and -2. This review aims to provide an appraisal of the use of anti-angiogenics in the treatment of TET. The literature research identified 16 studies that were deemed eligible for further analysis. Seven studies assessed the clinical efficacy of sunitinib and five studies the use of apatinib and/or anlotinib. The multicenter Japanese phase II REMORA trial investigated the efficacy of lenvatinib, which is a multi-targeted inhibitor of VEGFR, FGFR, RET, c-Kit, and other kinases. The objective response rate was 38% (25.6-52%), which is the highest documented in TET that progressed after first-line chemotherapy. Anti-angiogenic agents may be useful in the treatment of TET, which are not amenable to curative treatment. Their toxicity profile seems to be acceptable. However, angiogenesis inhibitors do not appear to have a major influence on either thymomas or TC, although multikinase inhibitors may have some effect on TC. The current evidence suggests that the most active agent is lenvatinib, whereas sunitinib could be proposed as an acceptable second-line therapy for TC. Further research concerning the combination of immune checkpoint inhibitors with anti-angiogenic drugs is warranted.

Immunotherapy and Targeted Therapies Efficacy in Thymic Epithelial Tumors: A Systematic Review.

BACKGROUND: Thymic epithelial tumors (TET) are rare neoplasms of the anterior mediastinum. Surgery is the mainstay treatment for resectable TET, whereas systemic treatments are reserved for unresectable and metastatic tumors. The development of new treatments, such as immune checkpoint inhibitors (ICI) and targeted therapies, with promising results in other types of solid tumors, has led to the investigation of their potential efficacy in TET. The study of tumor microenvironments (TME) is another field of investigation that has gained the interest of researchers. Taking into account the complex structure of the thymus and its function in the development of immunity, researchers have focused on TME elements that could predict ICI efficacy. MATERIALS AND METHODS: The primary objective of this systematic review was to investigate the efficacy of ICI in TET. Secondary objectives included the toxicity of ICI, the efficacy of targeted therapies in TET, and the evaluation of the elements of TME that may be predictive factors of ICI efficacy. A literature search was conducted in February 2023 using the Ovid Medline and SciVerse Scopus databases. RESULTS: 2944 abstracts were retrieved, of which 31 were retained for the systematic review. Five phase II and one retrospective study assessed ICI efficacy. The overall response rate (ORR) varied from 0% to 34%. Median progression-free survival (PFS) ranged from 3.8 to 8.6 months, being lower in thymic carcinoma (TC) (3.8-4.2 months). Median overall survival (OS) ranged from 14.1 to 35.4 months. Treatment-related adverse events occurred in 6.6% to 27.3% of patients. Sixteen studies assessed targeted therapies. The most active molecule was lenvatinib, with 38% ORR in patients with TC while no activity was detected for imatinib, erlotinib plus bevacizumab, and saracatinib. Ten studies assessed TME elements that could predict ICI efficacy. Four studies focused on the tumor-infiltrating immune cells suggesting improved outcomes in patients with TC and high tumor-infiltrating lymphocyte densities. Another study showed that CD8+, CD20+, and CD204+ tumor-infiltrating immune cells in cancer stroma might be prognostic biomarkers in TC. Another study identified the immune-related long non-coding RNAs as a predictor of response to ICI. Tumor mutational burden was identified as a predictive factor of ICI efficacy in one study. CONCLUSIONS: Despite study heterogeneity, this review shows that ICI could be a therapeutic option for selected patients with TET that are not amenable to curative radical treatment after first-line chemotherapy.

Online Survey Evaluation of Three Years of European Society of Thoracic Surgeons Educational Webinars as Part of The E-learning Platform.

BACKGROUND: E-learning has become an important tool in surgical education in the last decade. The European Society of Thoracic Surgeons launched its e-learning platform in 2013 and started its educational webinars series in 2018. The aim of this paper is to discuss the introduction, evolution and impact of the educational webinars within this e-learning platform. METHODS: Twenty-four English spoken webinars discussing different subdomains in general thoracic surgery (21 expert talks, 2 pro-con debates and 1 multidisciplinary case discussion) were analyzed. An online questionnaire on timing, quality and technical aspects of the webinars was sent to 3012 registrants. RESULTS: The webinars reached 3128 unique registrants from 76 countries worldwide. The mean number of registrants was 355 with 171 live attendees (48%) and 155 replay watchers (36%). Hundred and twenty-six attendees (13.1% of people who registered for at least 4 webinars) completed the questionnaire. Timing and duration of the webinars were rated "very good" to "excellent" in 78%, and the quality of the webinar content and the expertise of the webinar presenters were rated "very good" to "excellent" in 88% and 90%, respectively. The impact on knowledge and clinical practice was scored with a weighted average of 7.27 out of 10 and 6.79 out of 10, respectively. CONCLUSIONS: The ESTS educational webinars were effective in delivering up-to-date knowledge to almost half of the countries around the globe. The impact of these events on knowledge and clinical practice were rated high. New e-learning tools should be added to the surgical educational curriculum.

Tumor Microenvironment in Thymic Epithelial Tumors: A Narrative Review.

The tumor microenvironment (TME) is a complex and constantly changing entity. The TME consists of stromal cells, fibroblasts, endothelial cells, and innate and adaptive immune cells. Cancer development and progression occurs through this interplay between the tumor and the adjacent stroma. Cancer cells are capable of modifying their microenvironment by secreting various message-carrying molecules, such as cytokines, chemokines, and other factors. This action causes a reprogramming of the neighboring cells, which are enabled to play a crucial role in tumor survival and progression. The study of TME has many clinical implications in terms of cancer therapeutics because many new drugs, such as antibodies, kinase inhibitors, and liposome formulations that can encapsulate anti-cancer drugs, can be developed. Although chemotherapy is considered the standard of treatment for advanced disease, recent research has brought to light immunotherapy as a possible systemic alternative. However, the complex structure and function of the thymus hinders its routine use in clinical practice. The aim of this review paper is to discuss the recent advances in the investigation of the unique characteristics of the TME of thymic epithelial tumors that could possibly lead to the development of novel promising therapies.

Prognostic factors and genetic markers in thymic epithelial tumors: A narrative review.

Thymic epithelial tumors (TET) are a group of rare neoplasms of the anterior mediastinum comprising thymomas and thymic carcinomas. The carcinogenesis of TET is mostly unknown. Many studies, mostly retrospective case series, have tried to establish prognostic factors in TET. TET is a very heterogeneous group of tumors with many subtypes for which diagnosis and treatment remains a very challenging task. Despite the disparities among retrospective studies, there are some prognostic factors that are more pertinent such as the completeness of resection, TNM stage and the Masaoka-Koga classification. On the other hand, the identification of different genetic pathways that result in the pathogenesis of TET represents a fascinating field of study that could possibly lead to the development of new targeted therapies. The aim of this review is to discuss the different prognostic factors and genetic markers of TET. The meticulous use of national and international databases could provide sufficient number of patients in order to draw more valid conclusions.

Surgical chest complications after liver transplantation.

Liver transplantation is a major abdominal operation and the intimate anatomic relation of the liver with the right hemidiaphragm predisposes the patient to various manifestations in the chest cavity. Furthermore, chronic liver disease affects pulmonary function before and after liver transplantation resulting in a considerable percentage of patients presenting with morbidity related to chest complications. This review aims to identify the potential chest complications of surgical interest during or after liver transplantation. Complications of surgical interest are defined as those conditions that necessitate an invasive procedure (such as thoracocentesis or a chest tube placement) in the chest or a surgical intervention performed by a thoracic surgeon. These complications will be classified as perioperative and postoperative; the latter will be categorized as early and late. Although thoracocentesis or a chest tube placement is usually sufficient when invasive measures are deemed necessary, in some patients, thoracic surgical interventions are warranted. A high index of suspicion is needed to recognize and treat these conditions promptly. A close collaboration between abdominal surgeons, intensive care unit physicians and thoracic surgeons is of paramount importance.

Can the Ratio SUVmax of the Lesion/SUVmax of Mediastinal Tissues Guide the Choice of Surgical Access for the Resection of Thymic Epithelial Tumors?

Background: There are studies showing the utility of the 18-fluorodeoxyglucose positron emission tomography (18FDG PET) scan in the management of patients with thymic epithelial tumors. It seems to be a correlation between the standard uptake value (SUVmax) of thymic epithelial tumors and the histological type and the stage. This study aims to use the ratio of the SUVmax of the lesion to the SUVmax of the adjacent mediastinal tissues in order to guide the choice of the surgical access. Methods: All patients who presented an anterior mediastinal lesion with a high suspicion of being of thymic origin were included in a prospective database. A ratio inferior to 1 could predict a benign nature and less aggressive behavior, and a minimally invasive approach was performed. A ratio superior to 1 suggested a malignant and aggressive behavior, and a median sternotomy (or a thoracotomy) was performed. Results: There were 15 male (mean age 44.6 ± 16.26 years, range 25-73) and 15 female patients (mean age 50.1 ± 16.94 years, range 25-76). When the ratio is inferior to 1, it predicts benign disease in 80% of cases. When it is superior to 1, it predicts in half of cases advanced histological types (high risk thymomas and thymic carcinomas). On the contrary, it can quite accurately predict advanced Masaoka-Koga stages. Conclusions: The protocol of this study is in accordance with the current literature showing the utility of 18FDG PET scan in the treatment of thymic epithelial tumors. This study goes one step further since the choice of surgical access is based on the SUVmax values. The ratio SUVmax of the lesion/SUVmax of the mediastinal tissues could be a new marker, more pertinent than absolute SUVmax values.

Case Report: Diffuse Large B-Cell Lymphoma in the Wall of a Thymic Cyst.

Thymic cysts are rare lesions (1-5% of all mediastinal masses) and, most of the times, are incidental findings. The coexistence of a lymphoma and a thymic cyst is rare. In the case reported herein, microscopic foci of a diffuse large B-cell lymphoma were identified in the wall of a resected thymic cyst. This case report adds to the current knowledge of this rare entity and highlights the necessity of early surgical resection of mediastinal cysts over watchful waiting.

Is surgical rib fixation in patients aged more than 65 years old associated with worse outcomes compared to younger patients? A retrospective single-center study.

BACKGROUND: There is no robust data regarding rib fixation in elderly patients. The aim of this study is to compare the postoperative outcomes of patients aged less and more than 65 years old. METHODS: Patients operated from January 2012 to December 2018 were retrospectively analyzed. The following data were collected: age, sex, comorbidities, smoking habit, Injury Severity Score (ISS), number of fractured ribs, indication for surgery, associated injuries, time from trauma to surgery, number of fixed ribs, intrathoracic injuries, duration of intubation, ICU stay, postoperative cardiopulmonary complications, blood transfusion, overall and 30-day mortality, length of stay. RESULTS: There was no difference regarding the ISS (p = 0.09), the number of rib fractures (p = 0.291), the indication for surgery, the number of fixed ribs (p = 0.819), the ICU stay (p = 0.096), the postoperative intubation duration (p = 0.059), the cardiopulmonary complications (p = 0.273) and perioperative blood transfusions (p = 0.34). Elderly patients presented more postoperative cognitive complications (p < 0.001). There was no difference in terms of overall mortality (p = 0.06) and 30-day mortality (p = 0.69). Elderly patients stayed longer in the hospital (p < 0.001). CONCLUSIONS: The outcomes of rib fixation in the elderly patients are comparable to younger patients. However, elderly patients experience more frequently postoperative cognitive complications and their hospitalizations are longer.

VATS approach for pulmonary sclerosing pneumocytoma: a case report.

INTRODUCTION: Pulmonary Sclerosing Pneumocytoma (PSP) is a rare type of benign lung tumor usually encountered in middle-aged Asian women. The lesion is mostly found on routine chest x-rays. Though surgery is recognized as the recommended treatment, there is no consensus on the standard operative procedure for this tumor. CASE PRESENTATION: We report a case of a 48 year-old Caucasian woman who presented with a right para-hilar mass mimicking a hydatid cyst. After an unsuccessful initial treatment with oral Albendazole, and a steady growth over 10 years, the patient was programmed for surgical resection by video-thoracoscopic (VATS) approach. We were able to completely resect the tumor by VATS. Histopathological analysis suggested the diagnosis of Pulmonary Sclerosing Pneumocytoma. No further treatment was required and the patient was rapidly discharged. CONCLUSIONS: Pulmonary sclerosing pneumocytoma is a rare form of benign tumor that should be part of the differential diagnosis of lung lesions of unknown origin. Because of its well-defined encapsulated structure allowing total enucleation, VATS can be proposed as a less invasive alternative to classic thoracotomy.

Double right coronary artery: a plea for a standardized nomenclature.

BACKGROUND: Double coronary artery is a rare anomaly with just a few cases reported in the literature. This anomaly started being reported recently with the wide use of coronary angiography. Before the advent of advanced imaging and catheterization facilities most of the available data came from the work of anatomists. Two patients were recently operated in our department. In the first patient the preoperative coronary angiography showed two right coronary arteries. In the second patient a double ostium of the right coronary artery was encountered intraoperatively. We wanted to know the incidence of this anomaly and the available data in the literature. METHODS: A PubMed research was conducted by using the term 'double right coronary artery'. More than 50 case reports and small case series were identified. RESULTS: The review of the literature revealed a lot of controversy and debate. When using the term 'double right coronary artery' authors do not always refer to the same entity. Different definitions and classifications have proposed without, however, gaining wide acceptance. In fact, there is a lot of confusion in the literature and cases that are rather common are presented as being 'extremely rare'. CONCLUSIONS: Even though the real incidence could be over or underestimated due to variability in coronary angiography interpretation, clinicians must be aware of this entity in order to avoid troubleshooting during percutaneous coronary interventions and cardiac surgery. There is need for a close collaboration between interventional cardiologists, anatomists and cardiac surgeons in order to standardize the nomenclature.

Pneumothorax in otherwise healthy non-intubated patients suffering from COVID-19 pneumonia: a systematic review.

BACKGROUND: Cases of spontaneous pneumothorax have been described in patients suffering from coronavirus disease 2019 (COVID-19) pneumonia. The aim of this study is to systematically review all the cases of spontaneous pneumothorax that occurred in healthy patients with no underlying lung disease and who did not receive invasive mechanical ventilation. METHODS: A PubMed research was conducted. The following data were collected: age, sex, side of the pneumothorax, smoking habit, time form onset of symptoms to the diagnosis of pneumothorax, the development of new bullous lesions on computed tomography and the type of treatment. In order to analyze the most homogeneous population possible, intubated patients were deliberately excluded. In total, 44 cases of spontaneous pneumothorax in otherwise healthy patients were taken into account. Since the available data were extracted from small observational studies, no particular bias risk assessment was performed. Descriptive statistics were used to synthesize results. RESULTS: There were 37 male (84.1%) and 6 female (13.6%) patients. The majority of patients (66%) were treated only by chest tube thoracostomy, which most of the times resulted in a complete resolution of the pneumothorax. Simple surveillance was applied in 10 cases. Three patients underwent minimally invasive surgery. In 14 cases (31.8%) air-filled lesions were detected on imaging. Eleven patients received corticosteroids during their hospital stay. In the majority of cases (86.3%) the pneumothorax was resolved. DISCUSSION: Even if the level of evidence, derived from case reports and small case series is low, the existence of a true secondary spontaneous pneumothorax due to SARS-CoV-2 should be recognized. Imaging techniques should be repeated throughout the clinical course of the patients in order to detect newly developed pulmonary complications. Surgical treatment is feasible and patients whose general condition permits, should be offered surgery according to the existing guidelines regarding spontaneous pneumothorax. National registries and databases are necessary in order to better understand the pathogenesis and complications of this novel entity.

Lipiodol lymphangiography as a treatment for refractory postoperative chylothorax: a case report.

Postoperative chylothorax is the most frequent cause of traumatic thoracic chyle leakage. Conservative treatment is primarily used to treat low flow rate chylothoraces and should be initiated as soon as the diagnosis has been made. In case of high flow rate chylothorax or failure of initial treatment, surgery and radiological treatment are indicated. Despite this fact, there is a lack of consensus regarding the best therapeutic option to choose. In the case reported herein, a postoperative chylothorax with a low flow chyle leakage which didn't respond to conservative treatment is demonstrated. We used lipiodol lymphangiography to determine the site of chyle leakage and to successfully treat our patient. Risk factors for non-response to conservative treatment are also discussed.

Pleural empyema caused by Actinomyces turicensis.

Actinomyces turicensis was first identified in 1995. To the best of our knowledge, pleural empyema caused by A. turicensis has never been reported. In the case reported herein, a patient with pleural empyema was treated surgically, and in the bacterial samples, A. turicensis was isolated.

Pneumothorax and Pregnancy: A Systematic Review of the Current Literature and Proposal of Treatment Recommendations.

INTRODUCTION: Spontaneous pneumothorax occurs rarely during pregnancy with less than 100 cases reported in the English literature. There is no strong evidence concerning the treatment of spontaneous pneumothorax during pregnancy and labor. The aim of this study is to systematically review all the reported cases and to suggest recommendations for its diagnosis and treatment. METHODS: A PubMed research was conducted. The following data were collected: maternal age, gestation age (weeks), presence of underlying lung pathology, initial management, definitive management, obstetric outcome, and the complications for the mother and the fetus. RESULTS: Eighty-seven cases were identified. The mean maternal age was 27 years (standard deviation [SD] ± 6). The mean gestational age was 25 weeks (SD ± 11.4). In 37.9% of cases, there was no underlying lung disease. In the majority of cases (67.4%), the initial treatment was the placement of a chest tube. In 48% of cases, the pneumothorax was resolved with conservative treatment. Surgical therapy was performed either antepartum or postpartum. In 58.6% of cases, there was a vaginal delivery, spontaneous or instrumental. In three cases (3.4%), there were fetal complications. CONCLUSION: The analysis of the current literature provides low evidence, since there are only case reports and small case series. It is likely that the frequency of this condition is underestimated. However, this analysis permits to draw some conclusions concerning the timing of pneumothorax treatment, the operative strategy, and the mode of delivery to decrease the risk for the mother and the fetus.

A Single-Center Experience of Osteosynthesis Material Infection after Rib Fixation for Blunt Trauma.

INTRODUCTION: There is no data regarding the incidence and treatment of deep infection affecting the surgical implants after rib fixation. The aim of this study is to share our experience in the management of infected material after surgical rib fixation. METHODS: The medical records of operated patients from January 2012 to December 2018 were retrospectively analyzed. RESULTS: Three patients out of 87 (3.44%) developed an infection. One patient was treated conservatively and two patients were operated for hardware removal. CONCLUSIONS: The lack of evidence prompts for the design of surgical databases to share experience and enhance available data.