Prediction of survival after a lung transplant at 1 year (SALTO cohort) using information available at different key time points.

OBJECTIVES: A lung transplant is the final treatment option for end-stage lung disease. We evaluated the individual risk of 1-year mortality at each stage of the lung transplant process. METHODS: This study was a retrospective analysis of patients undergoing bilateral lung transplants between January 2014 and December 2019 in 3 French academic centres. Patients were randomly divided into development and validation cohorts. Three multivariable logistic regression models of 1-year mortality were applied (i) at recipient registration, (ii) the graft allocation and (iii) after the operation. The 1-year mortality was predicted for individual patients assigned to 3 risk groups at time points A to C. RESULTS: The study population consisted of 478 patients with a mean (standard deviation) age of 49.0 (14.3) years. The 1-year mortality rate was 23.0%. There were no significant differences in patient characteristics between the development (n = 319) and validation (n = 159) cohorts. The models analysed recipient, donor and intraoperative variables. The discriminatory power (area under the receiver operating characteristic curve) was 0.67 (0.62-0.73), 0.70 (0.63-0.77) and 0.82 (0.77-0.88), respectively, in the development cohort and 0.74 (0.64-0.85), 0.76 (0.66-0.86) and 0.87 (0.79 - 0.95), respectively, in the validation cohort. Survival rates were significantly different among the low- (< 15%), intermediate- (15%-45%) and high-risk (> 45%) groups in both cohorts. CONCLUSIONS: Risk prediction models allow estimation of the 1-year mortality risk of individual patients during the lung transplant process. These models may help caregivers identify high-risk patients at times A to C and reduce the risk at subsequent time points.

When to proceed to surgical rib fixation?-A single-institution clinical experience.

Background: Surgical rib fixation for multiple rib fractures and flail chest has become more common in the 2000s with interesting results in selected patients. However, surgical rib fixation lacks a consensus on the delay to surgery and the benefits on postoperative clinical outcomes. Our goal was to determine if delay to surgery can affect postoperative outcomes. Methods: We analyzed a retrospective database including all consecutive patients referred for surgical rib fixation. All outcomes were explored according to trauma mechanism, associated lesions, initial ventilatory status, delay to surgery, surgical technique and a specific focus was made towards post-operative care and pulmonary complications. Logistic regressions were performed to evaluate the association between delay to surgery [before 48 hours (early group), 48 hours to 7 days (mid group), more than 7 days (late group)] and pneumonia and failure of extubating. Results: From 2010 to 2020, 159 patients underwent surgical rib fixation. The median hospital length of stay was 18 days (interquartile range, 13-30 days). Pulmonary infections were encountered in 67 patients (42.2%) with about two third of early pneumonia (<5 days). The one-month mortality rate was 1.9%. Delay to surgery was not associated with either pneumonia (P>0.05) or failure of extubating (P>0.05). Conclusions: Surgical rib fixation can be delayed without increasing the risk of pulmonary complications. Stabilizing other clinical situations can be safely prioritized if needed. A global evaluation including characteristics of trauma and lung evaluation must be considered before surgical stabilization of rib fracture.

A new preoperative localization of pulmonary nodules guided by mixed reality: a pilot study of an animal model.

Background: With the popularity of high-resolution computed tomography (HRCT), more and more pulmonary nodules are being discovered. Video-assisted thoracoscopic surgery (VATS) has become the first choice for surgical treatment of pulmonary nodules. The use of accurate preoperative localization is crucial for successful resection in VATS. At present, there are many kinds of preoperative localization methods, but there are certain disadvantages. This study aimed to evaluate the feasibility and safety of mixed reality (MR)-guided pulmonary nodules localization, which is a new method that can benefit patients to a greater extent. Methods: By constructing an animal model of pulmonary nodules localization, 28 cases of pulmonary nodules were located by MR-guided localization. We recorded the localization accuracy, localization time, insertion attempts, and incidence of complications related to localization under MR-guidance. Results: All 28 nodules were successfully located: the deviation of MR-guided localization was 5.71±2.59 mm, localization time was 8.07±1.44 min, and insertion attempts was 1. A pneumothorax and localizer dislodgement occurred in 1 case, respectively. Conclusions: Since preoperative localization is critical for VATS resection of pulmonary nodules, we investigated a new localization method. As indicated by our study, MR-guided localization of pulmonary nodules is feasible and safe, which is worthy of further research and promotion. We have also registered corresponding clinical trials to further investigate and help to improve our understanding of this technique.

Subtotal Pleurectomy with Intrathoracic Chemo Hyperthermia (HITHOC) for IVa Thymomas: De Novo Versus Recurrent Pleural Disease.

INTRODUCTION: Stage IVa thymoma is a rare disease without a standard of care. Subtotal pleurectomy and HITHOC introduced in highly selected patients may provide interesting oncologic results. The purpose of this study was to distinguish de novo stage IVa tumors (DNT) from distant relapse (DR) with respect to post-operative and long-term outcomes to provide the procedure efficacy. METHODS: From July 1997-December 2021, 40 patients with IVa pleural involvement were retrospectively analyzed. The surgical procedure was subtotal pleurectomy and HITHOC (cisplatin 50 mg/m2, mitomycin 25 mg/m2, 42 °C, 90 min). The post-operative outcome, disease-free interval (DFI) and overall survival (OS) were analyzed. RESULTS: Mean age was 52 ± 12 years. B2 and B3 thymomas were preponderant (27; 67.5%). The median number of pleural nodes were nine (4-81) vs. five (1-36); p = 0.004 * in DNT and DR, respectively. Hospital mortality rate was 2.5%. There were four specific HITHOC complications (10%). DFI were 49 and 85 months (p = 0.02 *), OS were 94 and 118 months (NS), in DNT and DR, respectively. CONCLUSIONS: Subtotal pleurectomy with HITHOC in IVa offers satisfying results in highly selected patients, for both DNT and DR. Due to the disease rarity, multicentric studies are needed to define HITHOC as a standard of care.

Futile lobectomies following video-thoracoscopic exploration for indeterminate pulmonary nodules: a retrospective study.

Background: Lung cancer screening is correlated with an increase in detection of small indeterminate pulmonary nodules and these nodules often require operative resection to obtain the diagnosis. In suspected early-stage lung cancer, video-assisted thoracoscopic surgery (VATS) has become the preferred option. In this context of minimally invasive surgery, diagnostic wedge resection is sometimes difficult to perform for small deep impalpable nodules. So, our purpose was to determine whether performing VATS for indeterminate pulmonary nodule increases the risk of lobectomy for benign lesions. Methods: A retrospective analysis was carried out in our center from January 2013 to January 2019 on patients who underwent resection for a solitary pulmonary nodule suspicious for cancer. Resection method, frozen section analysis, post-operative outcomes, operative and pathology reports were reviewed. Results: Six hundred fifty-one patients underwent surgical exploration for a solitary pulmonary nodule. Thirty hundred and forty-five patients underwent VATS and 306 patients underwent thoracotomy. Patients in the VATS group underwent significantly more wedge resections (P=0.012) and diagnosis of lung cancer was significantly more frequent in the thoracotomy group (P<0.001). One hundred and thirty-two patients (38.3%) in the VATS group and 60 patients (19.6%) in the thoracotomy group underwent lobectomy without frozen section analysis of the pulmonary nodule. There was no significant difference in terms of lobectomy performed for a benign lesion between the two groups. Conclusions: VATS was associated with a higher rate of benign lesion resection but was not associated with a higher rate of lobectomies for benign lesion in our study.

Evolution of the Surgical Management of Lung Cancer Invading the Spine: A Single Center Experience.

For patients with locally advanced non-small cell lung cancer invading the spine, induction chemoradiotherapy combined with radical en bloc resection is the key to obtaining long-term survival. With time, our operative technique evolved to a two-step surgery as we experienced numerous perioperative complications during one step surgery. The aim of our study was to assess postoperative morbimortality and long-term survival of both techniques. We retrospectively reviewed all patients who underwent en bloc resection for lung cancer invading the spine between October 2012 and June 2020. Every patient underwent induction therapy. Sixteen patients were included: nine patients were operated on with one step surgery, seven patients were operated on with two step interventions. Twenty-five percent of patients had major perioperative complications and 56.2% of patients had major post-operative complications. Patients in the "one step" group tended to have more perioperative complications whereas patients in the "two step" group tended to have more post-operative complications. Overall 3-year survival was 40% in the one-step and 86% in the two-step surgery group. Although our practice has been improved by two-step interventions, post-operative morbidity remains significant. As long term survivals are encouraging, this type of treatment should still be proposed for highly selected patients, in specialized centers.

Hamartochondroma Pleural Lesion Mimicking Liposarcoma: A Case Report.

Heterogeneous masses developing in the pleural cavity are most often malignant and can pose diagnostic challenges. Fibrous tumors of the pleura, liposarcoma, thymoma or lipoma most frequently affect this anatomic area. Surgical exploration and resection are often mandatory to make the definitive diagnosis. We report the case of a 54-year-old women who presented with an epigastric and right sub costal pain. A complete preoperative workup revealed a large tissular and fatty mass in the right costo-diaphragmatic angle suggestive of liposarcoma. Surgical resection resulted in the surprising diagnosis of hamartochondroma.

Intestinal Air in the Mediastinum.

CASE PRESENTATION: A 74-year-old man, in excellent physical condition and doing regular intense cycling, was evaluated for transient episodes of thoracic discomfort over a period of several months. His medical history only included a right inguinal hernia, surgically treated, and an abdominal aortic aneurysm measured at 46 mm and treated medically. Physical examination did not reveal much information. The patient did not report gastroesophageal reflux, dysphagia, or history of digestive occlusion. The patient had normal weight and had no trauma history. He had no nicotine or alcohol-dependent behaviors. Vital signs were within normal values. Laboratory test results were normal. Functional status was normal, without anomalies of pulmonary function tests or arterial blood gases. The ECG did not reveal any anomaly.

Epicardial carvernous hemangioma: The diagnostic challenge of a middle mediastinal mass.

Primary tumors in the middle mediastinum are rare and pose diagnostic challenges. Lymphomas, mediastinal cysts and thymomas most frequently affect this anatomic area. Primary cardiac tumors are rare and constitute a differential diagnosis for the inferior middle mediastinum. Surgical exploration and resection is often mandatory in order to make a definitive diagnosis. Here, we report the case of a 69 year-old women who presented with persistent dyspnea. A complete preoperative workup revealed a large tissular mass adjacent to the right atrium. A diagnosis of a typical epicardial cavernous hemangioma was made following surgical resection.

Pleural metastasis of atypical meningioma: a novel therapeutic approach.

Meningiomas are the most common intracranial tumours in adults and they are infrequently associated with a metastasis clinical course. Pleural metastases are extremely rare and no guidelines on a specific treatment have been established. When localized, surgical resection is the mainstay of treatment, but there is a high risk of pleural recurrence. We aimed to describe a novel surgical approach in pleural metastasis of meningiomas. We report the case of a 41-year-old man with the medical history of surgically resected intracranial atypical meningioma. Nine years after diagnosis of atypical meningioma, a CT scan of the chest disclosed 10 pleural implants gathered in the fissure, in the paramediastinal pleura and at the base of the left hemithorax. Surgical resection was decided. Parietal and mediastinal pleura resection with visceral pleural lesions removal were performed. Cytoreductive surgery was associated with intrathoracic hyperthermic chemotherapy. Postoperative course was uneventful and no adjuvant therapy was undertaken. The patient is free of pleural recurrence 12 months post operatively. The present case report suggests that cytoreductive surgery with intrathoracic hyperthermic chemotherapy is feasible and safe in pleural metastasis from meningioma. Prolonged follow-up and prospective studies are mandatory to assess its oncological benefit.

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.

Effect of patient head position on the aspirated volume of regurgitated clear fluid. A fresh human cadaver study.

INTRODUCTION: The relationship between regurgitated and aspirated volume of clear fluids remains undetermined and may depend on anatomical factors and patient position. We aimed to assess whether head position (sniffing vs. extension position) affected this relationship in fresh human cadavers. We also determined the critical volume of water regurgitated that led to pulmonary aspiration of volume ≥ 0.8 mL kg-1 and ≥ 1.5 mL kg-1 for each head position. MATERIAL AND METHODS: Six volumes of water (40, 80, 100, 120, 150, and 200 mL) were injected each twice, in a randomised order, at a flow rate of 20 mL per second, into the oesophagus of seven fresh human cadavers lying in the supine position on a non-tilted table, with the head in the sniffing position and in the extension position. Aspirated volume was measured in the trachea, blindly to the volume injected. RESULTS: Overall, more than 85% of the regurgitated volume was aspirated into the trachea. The volume of aspirated water was significantly greater in the sniffing position than in the extension position. The cut-off volumes of water injected into the oesophagus leading to aspirated volume ≥ 0.8 mL kg-1 and ≥ 1.5 mL kg-1 were, respectively, 0.8 mL kg-1 and 1.5 mL kg-1 in the sniffing position, and 1.2 mL kg-1 and 1.8 mL kg-1 in the extension position. CONCLUSIONS: These results confirm that most of the regurgitated clear fluid enters the trachea in humans lying in the supine position on a non-tilted table, especially when the head is in the sniffing position.

Impact of Lung Biopsy on Lung Function in Idiopathic Pulmonary Fibrosis.

BACKGROUND: Video-assisted surgical lung biopsy (SLB) is performed in 10-30% of cases to establish the diagnosis of idiopathic pulmonary fibrosis (IPF). OBJECTIVES: The aim of the study was to analyze the impact of SLB on lung function in patients eventually diagnosed with IPF. METHODS: This is an observational, retrospective, monocentric study of all consecutive patients eventually diagnosed with IPF in multidisciplinary discussion who underwent SLB over 10 years in a specialized center. The primary end point was the variation in forced vital capacity (FVC) before and after the SLB. The secondary end points were the variations in forced expiratory volume in one second (FEV1), total lung capacity (TLC), carbon monoxide diffusion capacity (DLCO), and morbidity and mortality associated with the SLB. RESULTS: In 118 patients who underwent SLB and were diagnosed with IPF, a relative decrease in FVC of 4.8% (p < 0.001) was found between measurements performed before and after the procedure. The mean FVC decrease was 156 ± 386 mL in an average period of 185 days, representing an annualized decline of 363 ± 764 mL/year. A significant decrease was also observed after SLB in FEV1, TLC, and DLCO. Complications within 30 days of SLB occurred in 14.4% of patients. Two patients (1.7%) died within 30 days, where one of them had poor lung function. Survival at 1 year was significantly poorer in patients with FVC <50% at baseline. CONCLUSION: In this uncontrolled study in patients ultimately diagnosed with IPF, SLB was followed by a significant decline in FVC, which appears to be numerically greater than the average decline in the absence of treatment in the literature. Summary at a Glance: This study evaluated the change in lung function in 118 consecutive patients diagnosed with idiopathic pulmonary fibrosis by surgical lung biopsy. Forced vital capacity decreased by 156 ± 386 mL in a mean of 185 days between the last measurement before and first measurement after biopsy, representing an annualized decline of 363 ± 764 mL/year.

Technique of pressurized intrathoracic aerosol chemotherapy (PITAC) for malignant pleural effusion.

OBJECTIVES: Malignant pleural effusion (MPE) is a devastating evolution of several malignancies. Pressurized intrathoracic aerosol chemotherapy (PITAC) might be a novel therapy option in MPE. METHODS: PITAC is considered for patients with MPE with a performance status <2 and without other metastatic sites. General anesthesia is administered and a double-lumen bronchial tube is inserted. The patient is placed in a lateral decubitus position, and the operation is performed after ipsilateral lung exclusion. Two 12-mm balloon trocars are inserted-one in the seventh intercostal space in the mid-axillary line and one in the fifth intercostal space in the anterior axillary line. Extent of pleural disease and volume of MPE are documented. MPE is removed and parietal pleural biopsy are performed. An intrathoracic pressure of 12 mmHg CO2 is established, and a combination of Cisplatin (10.5 mg/m2 in a total volume of 150 cc NaCl 0.9%) and Doxorubicin (2.1 mg/m2 in a total volume of 50 cc NaCl 0.9%) are aerosolized via nebulizer in the pleural cavity. Vital signs and nebulization are remote-controlled. After 30 min, the remaining toxic aerosol is exhausted using a closed surgical smoke evacuation system. A 24Fr chest tube is inserted in postero-apical position with continuous negative pressure of 20 cm H2O. When needed, PITAC may be repeated every six weeks in alternate with systemic chemotherapy. RESULTS: In our hands, the technique above has shown to be feasible and safe. CONCLUSIONS: Further studies are needed to assess the potential symptomatic and oncological benefits of PITAC in MPE.

Lung cancer surgical treatment after solid organ transplantation: A single center 30-year experience.

OBJECTIVES: Solid organ transplantation is an accepted treatment for end-stage organ failure. Long-lasting immunosuppressive therapy may increase the risk ofde novo malignancies in transplant recipients. Increased risk of bronchogenic carcinoma in this population is controversial but prolonged transplant recipients' survival (obtained in modern transplantation era) may increase the need for lung cancer surgical resection in immunosuppressed patients. Our aim was to assess morbidity, mortality and long-term survival after lung cancer surgical treatment in this population. MATERIALS AND METHODS: In an observational study, the medical charts of all consecutive patients who had undergone surgical treatment for lung cancer after solid organ transplantation were reviewed. These medical records were extracted from the University of Lyon (France) Transplantation database and Thoracic Surgery database. From 1986-2016, 61 patients underwent a surgical treatment for lung cancer after solid organ transplantation. RESULTS: The surgical procedures consisted of 52 lobectomies, 7 pneumonectomies and 2 wedge-resections. 90-day post-operative complications, most of which were pneumonias, affected 31 patients (50.8 %). 90-day postoperative mortality was 9.8 %. Overall survival was 40.6 % at 5 years and 18 % at 10 years. CONCLUSION: Despite a higher rate of infectious complications and 90-day postoperative mortality, surgical treatment for lung cancer must be offered to these patients as it offers a chance to cure earlier- stage disease. Long-term survival rate is satisfactory and similar to that of the general population. In transplant recipients with former smoking history, close follow-up is mandatory to increase early lung cancer diagnosis.

Impact of donor, recipient and matching on survival after high emergency lung transplantation in France.

INTRODUCTION: Since July 2007, the French high emergency lung transplantation (HELT) allocation procedure prioritises available lung grafts to waiting patients with imminent risk of death. The relative impacts of donor, recipient and matching on the outcome following HELT remain unknown. We aimed at deciphering the relative impacts of donor, recipient and matching on the outcome following HELT in an exhaustive administrative database. METHODS: All lung transplantations performed in France were prospectively registered in an administrative database. We retrospectively reviewed the procedures performed between July 2007 and December 2015, and analysed the impact of donor, recipient and matching on overall survival after the HELT procedure by fitting marginal Cox models. RESULTS: During the study period, 2335 patients underwent lung transplantation in 11 French centres. After exclusion of patients with chronic obstructive pulmonary disease/emphysema, 1544 patients were included: 503 HELT and 1041 standard lung transplantation allocations. HELT was associated with a hazard ratio for death of 1.41 (95% CI 1.22-1.64; p<0.0001) in univariate analysis, decreasing to 1.32 (95% CI 1.10-1.60) after inclusion of recipient characteristics in a multivariate model. A donor score computed to predict long-term survival was significantly different between the HELT and standard lung transplantation groups (p=0.014). However, the addition of donor characteristics to recipient characteristics in the multivariate model did not change the hazard ratio associated with HELT. CONCLUSIONS: This exhaustive French national study suggests that HELT is associated with an adverse outcome compared with regular allocation. This adverse outcome is mainly related to the severity status of the recipients rather than donor or matching characteristics.

Optimal management of thymic malignancies: current perspectives.

Thymic epithelial tumors (TETs) belong to orphan oncology. The incidence of TETs is about 1.3-3.2 cases per million worldwide. Following pathology, evolution and prognosis are variable. The World Health Organization classification distinguishes thymomas and thymic carcinomas. TETs are composed of thymic epithelial tumoral cells and normal lymphocytes. The mean age at diagnosis is 50-60 years-old. There are no identified risk factors. TETs are frequently associated with paraneoplastic syndromes as myasthenia gravis. The complete R0 surgical resection is the most significant prognosis factor on survival. In 2010, the French National Institute of Cancer labeled the RYTHMIC network as a specific tumor board including thoracic surgeons, oncologist, and radiation therapist to define standard of care for the management of TETs. The aim of the review was to update knowledge to optimize the standard of care.

Activation of the mTOR/ Akt pathway in thymic epithelial cells derived from thymomas.

The pathogenesis of thymic epithelial tumors remains poorly elucidated. The PIK3/Akt/mTOR pathway plays a key role in various cancers; interestingly, several phase I/II studies have reported a positive effect of mTOR inhibitors in disease control in thymoma patients. A major limit for deciphering cellular and molecular events leading to the transformation of thymic epithelial cells or for testing drug candidates is the lack of reliable in vitro cell system. We analyzed protein expression and activation of key players of the Akt/ mTOR pathway namely Akt, mTOR, and P70S6K in eleven A, B and AB thymomas as well as in normal thymuses. While only Akt and phospho-Akt were expressed in normal thymuses, both Akt and mTOR were activated in thymomas. Phospho-P70S6K was expressed in all thymic tumors whatever their subtypes, and absent in normal thymus. Interestingly, we report the activation of Akt, mTOR and P70S6 proteins in primary thymic epithelial cells maintained for short period of time after their derivation from seven AB and B thymomas. Finally, we showed that rapamycin (100 nM) significantly reduced proliferation of thymoma- derived epithelial cells without inducing cell death. Our results suggest that the activation of the Akt/ mTOR pathway might participate to the cell proliferation associated with tumor growth. Ultimately, our data enhance the potential role of thymic epithelial cells derived from tissue specimens for in vitro exploration of molecular abnormalities in rare thymic tumors.