Carotid webs management in symptomatic patients.

BACKGROUND: Atypical fibromuscular dysplasia (AFMD), also known as carotid web, is a rare underdiagnosed shelf-like fibrous tissue arising from the posterior carotid artery bulb that is a cause of cryptogenic stroke of the anterior cerebral vascularization. Despite the recurrence and severity of strokes caused by embolization associated with AFMD, there are no recommendations on the best strategy to manage single and bilateral lesions, which have unsatisfactory outcomes when treated with medical treatment exclusively. METHODS: From January 2016 to April 2019, 365 patients were operated on for a carotid stenosis in our institution. This cohort included 11 patients (3%), with a median age of 41 years (range, 39-51 years), referred by a stroke unit, treated for a symptomatic (10 strokes and 1 recurrent transient ischemic attack) AFMD lesion. Preoperative workup revealed a contralateral similar lesion in 45% of patients (5/11), which all also underwent surgery during a subsequent hospitalization. The diagnosis was confirmed by histologic examination when open surgery was performed. The 30-day and 1-year outcomes were retrospectively reviewed. RESULTS: Of the 16 AFMD lesions operated, 13 were treated by open surgery (2 by classic endarterectomy and 11 by internal carotid resection-anastomosis) and 3 by carotid artery stenting, respectively, with a mean delay of 85.5 days and 20.5 days after the latest stroke. There was one complication after stenting (external iliac rupture) that was treated by a covered stent, and no perioperative complications after open surgery. The follow-ups at 30 days and 1 year were uneventful for all patients, without any deaths or stroke recurrences. CONCLUSIONS: Symptomatic AFMD is a rare cause of cryptogenic stroke. Bilateral lesions are frequent. Early intervention is associated with favorable perioperative and 1-year outcomes. Open surgery is the first-line therapeutic option in this young patient population.

Surgical Resection of Tumors Invading the Inferior Vena Cava at the Hepatic Vein and Thoracic Levels.

BACKGROUND: Our aim was to describe the results of our program of surgical resection of tumors invading the inferior vena cava (IVC) at the hepatic and thoracic levels. We hypothesized that similar surgical outcomes may be obtained compared to tumor resection below the hepatic vein level if the liver function was preserved. METHODS: We performed a single-center retrospective study of 72 consecutive patients who underwent surgical resection from 1996 to 2019 for tumors invading the IVC. We compared two groups based on tumor location below (group I/II) or above (group III/IV) the inferior limit of hepatic veins. RESULTS: Tumor histology was similarly distributed between groups. In group III/IV (n = 35), sterno-laparotomy was used in 83% of patients, cardiopulmonary bypass in 77%, and deep hypothermic circulatory arrest in 17%; 23% underwent liver resection. Corresponding proportions in group I/II were 3%, 0%, 0%, and 8%. In group III/IV, 4 patients required emergency resection. Mortality on day 30 was 17% (n = 6) in group III/IV and 0% in group I/II (P = 0.01). There was no liver failure among the 66 postoperative survivors and 5 out of 6 patients who died postoperatively presented a preoperative or postoperative liver failure (P < 0.001). Overall survival was not significantly different between groups with a median follow-up of 15.1 months. R0 resection was achieved in 66% of group I/II and 49% of group III/IV patients (P = 0.03). CONCLUSION: Surgical resection of tumors invading the inferior vena cava at hepatic vein and thoracic levels should be reserved to carefully selected patients without preoperative liver failure to minimize postoperative mortality.

Non-small cell lung carcinomas with CTNNB1 (beta-catenin) mutations: A clinicopathological study of 26 cases.

Beta-catenin, encoded by the CTNNB1 gene, plays an important role in cell proliferation. Mutations of CTNNB1 are oncogenic in several tumor types and are often associated with a nuclear abnormal expression. However, such mutations have only rarely been reported in non-small cell lung carcinomas and their clinical signification is not well described. Our study was conducted on 26 CTNNB1-mutated non-small cell lung carcinomas. Tumors were routinely tested by next generation sequencing for mutations in exon 3 of CTNNB1 gene. Twenty three cases were from a series of 925 tumors (2.48%). The hospital files and pathological data, from surgical samples (n = 16), small biopsies (n = 5) and trans-bronchial fine needle aspirations (n = 5), were reviewed. Immunohistochemistry was performed with an anti-beta-catenin antibody. There were 10 female and 16 male patients aged 52 to 83. Eleven of 25 patients were no-smoking or light smokers. Three cases were diagnosed while under treatment with EGFR tyrosine kinase inhibitor. There were 25 adenocarcinomas and 1 squamous cell carcinoma. Most adenocarcinomas had a papillary component and were TTF1-positive. One case was a well-differentiated fetal adenocarcinoma. Eleven cases (42%) with CTNNB1 mutations showed associated EGFR mutations. The frequency of CTNNB1 mutations was higher among EGFR mutated carcinomas. Immunohistochemistry showed heterogeneous nuclear or cytoplasmic abnormal expression. Our study shows that CTNNB1 mutations mostly occur in TTF1-positive adenocarcinomas with a papillary pattern. These mutations are often associated with EGFR mutations and possibly interfer in the mechanism of resistance to tyrosine kinase inhibitors. Our experience suggests that immuno-histochemistry cannot be used for screening.

Smooth Muscle Phenotype in Idiopathic Pulmonary Hypertension: Hyper-Proliferative but not Cancerous.

Idiopathic pulmonary arterial hypertension (IPAH) is a complex disease associated with vascular remodeling and a proliferative disorder in pulmonary artery smooth muscle cells (PASMCs) that has been variably described as having neoplastic features. To decode the phenotype of PASMCs in IPAH, PASMCs from explanted lungs of patients with IPAH (IPAH-PASMCs) and from controls (C-PASMCs) were cultured. The IPAH-PASMCs grew faster than the controls; however, both growth curves plateaued, suggesting contact inhibition in IPAH cells. No proliferation was seen without stimulation with exogenous growth factors, suggesting that IPAH cells are incapable of self-sufficient growth. IPAH-PASMCs were more resistant to apoptosis than C-PASMCs, consistent with the increase in the Bcl2/Bax ratio. As cell replication is governed by telomere length, these parameters were assessed jointly. Compared to C-PASMCs, IPAH-PASMCs had longer telomeres, but a limited replicative capacity. Additionally, it was noted that IPAH-PASMCs had a shift in energy production from mitochondrial oxidative phosphorylation to aerobic glycolysis. As DNA damage and genomic instability are strongly implicated in IPAH development a comparative genomic hybridization was performed on genomic DNA from PASMCs which showed multiple break-points unaffected by IPAH severity. Activation of DNA damage/repair factors (γH2AX, p53, and GADD45) in response to cisplatin was measured. All proteins showed lower phosphorylation in IPAH samples than in controls, suggesting that the cells were resistant to DNA damage. Despite the cancer-like processes that are associated with end-stage IPAH-PASMCs, we identified no evidence of self-sufficient proliferation in these cells-the defining feature of neoplasia.

Early Development of Right Ventricular Ischemic Lesions in a Novel Large Animal Model of Acute Right Heart Failure in Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Our aim was to develop a model of acute right heart failure (ARHF) in the setting of pulmonary hypertension and to characterize acute right ventricular lesions that develop early after hemodynamic restoration. METHODS AND RESULTS: We used a described piglet model of chronic pulmonary hypertension (cPH) induced by pulmonary artery occlusions. We induced ARHF in animals with cPH (ARHF-cPH group, n = 9) by volume loading and iterative acute pulmonary embolism until hemodynamic compromise followed by dobutamine infusion for hemodynamic restoration before sacrifice for right ventricular tissue evaluation. The median duration of ARHF before sacrifice was 162 (135-189) minutes. Although ventriculoarterial coupling (measured with multibeat pressure-volume loops) and stroke volume decreased after iterative pulmonary embolism and improved with dobutamine, relative pulmonary to systemic pressure increased by 2-fold and remained similarly increased with dobutamine. Circulating high-sensitivity troponin I increased after hemodynamic restoration. We found an increase in right ventricular subendocardial and subepicardial focal ischemic lesions and in expression of autophagy-related protein LC3-II (Western blot) in the ARHF-cPH group compared with the cPH (n = 5) and control (n = 5) groups. CONCLUSIONS: We developed and phenotyped a novel large animal model of ARHF on cPH in which right ventricular ischemic lesions were observed early after hemodynamic restoration.

Right ventricular reserve in a piglet model of chronic pulmonary hypertension.

Right ventricular (RV) response to exercise or pharmacological stress is not well documented in pulmonary hypertension (PH). We investigated the relationship between RV reserve and ventricular-arterial coupling. Surgical ligation of the left pulmonary artery was performed in 13 Large White piglets (PH group), thereafter weekly embolisations of the right lower lobe were performed for 5 weeks. A control group of six piglets underwent sham procedures. Right heart catheterisation and echocardiography were performed at week 6. Pressure-volume loops were recorded before and after dobutamine infusion. Induction of experimental PH resulted in a higher mean ± sd pulmonary artery pressure (34 ± 9 versus 14 ± 2 mmHg; p<0.01) and in a lower ventricular-arterial coupling efficiency (0.66 ± 0.18 versus 1.24 ± 0.17; p<0.01) compared with controls at 6 weeks. Dobutamine-induced relative changes in RV stroke volume index (SVI) and end-systolic elastance were lower in the PH group (mean ± SD 47 ± 5% versus 20 ± 5%, p<0.01, and 81 ± 37% versus 32 ± 14%, p<0.01, respectively). Change in SVI was strongly associated with resting ventricular-arterial coupling (R(2)=0.74; p<0.01). RV reserve was associated with ventricular-arterial coupling in a porcine model of chronic pressure overload.

Heart-lung vs. double-lung transplantation for idiopathic pulmonary arterial hypertension.

Patients with idiopathic pulmonary arterial hypertension (IPAH) have improved survival after heart-lung transplantation (HLT) and double-lung transplantation (DLT). However, the optimal procedure for patients with IPAH undergoing transplantation remains unclear. We hypothesized that critically ill IPAH patients, defined by admission to the intensive care units (ICU), would demonstrate improved survival with HLT vs. DLT. All adult IPAH patients (>18 yr) in the Scientific Registry of Transplant Recipients (SRTR) database, who underwent either HLT or DLT between 1987 and 2012, were included. Baseline characteristics, survival, and adjusted survival were compared between the HLT and DLT groups. Similar analyses were performed for the subgroups as defined by the recipients' hospitalization status. A total of 928 IPAH patients (667 DLT, 261 HLT) were included in this analysis. The HLT recipients were younger, more likely to be admitted to the ICU, and have had their transplant in previous eras. Overall, the adjusted survivals after HLT or DLT were similar. For recipients who were hospitalized in the ICU, DLT was associated with worse outcomes (HR 1.827; 95% CI 1.018-3.279). In IPAH patients, the overall survival after HLT or DLT is comparable. HLT may provide improved outcomes in critically ill IPAH patients admitted to the ICU at time of transplantation.

Microvascular disease in chronic thromboembolic pulmonary hypertension: a role for pulmonary veins and systemic vasculature.

Limited numbers of operated patients with chronic thromboembolic pulmonary hypertension (CTEPH) are refractory to pulmonary endarterectomy (PEA) and experience persistent pulmonary hypertension (PH). We retrospectively assessed lung histology available from nine patients with persistent PH (ineffective PEA (inPEA) group) and from eight patients transplanted for distal CTEPH inaccessible by PEA (noPEA group). Microscopically observed peculiarities were compared with the histology of a recently developed CTEPH model in piglets. Pre-interventional clinical/haemodynamic data and medical history of patients from the inPEA and noPEA groups were collected and analysed. Conspicuous remodelling of small pulmonary arteries/arterioles, septal veins and pre-septal venules, including focal capillary haemangiomatosis, as well as pronounced hypertrophy and enlargement of bronchial systemic vessels, were the predominant pattern in histology from both groups. Most findings were reproduced in our porcine CTEPH model. Ink injection experiments unmasked abundant venular involvement in so-called small vessel or microvascular disease, as well as post-capillary bronchopulmonary shunting in human and experimental CTEPH. Microvascular disease is partly due to post-capillary remodelling in human and experimental CTEPH and appears to be related to bronchial-to-pulmonary venous shunting. Further studies are needed to clinically assess the functional importance of this finding.

Protocol for venoarterial ExtraCorporeal Membrane Oxygenation to reduce morbidity and mortality following bilateral lung TransPlantation: the ECMOToP randomised controlled trial.

INTRODUCTION: Lung transplantation (LTx) aims at improving survival and quality of life for patients with end-stage lung diseases. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used as intraoperative support for LTx, despite no precise guidelines for its initiation. We aim to evaluate two strategies of VA-ECMO initiation in the perioperative period in patients with obstructive or restrictive lung disease requiring bilateral LTx. In the control 'on-demand' arm, high haemodynamic and respiratory needs will dictate VA-ECMO initiation; in the experimental 'systematic' arm, VA-ECMO will be pre-emptively initiated. We hypothesise a 'systematic' strategy will increase the number of ventilatory-free days at day 28. METHODS AND ANALYSIS: We designed a multicentre randomised controlled trial in parallel groups. Adult patients with obstructive or restrictive lung disease requiring bilateral LTx, without a formal indication for pre-emptive VA-ECMO before LTx, will be included. Patients with preoperative pulmonary hypertension with haemodynamic collapse, ECMO as a bridge to transplantation, severe hypoxaemia or hypercarbia will be secondarily excluded. In the systematic group, VA-ECMO will be systematically implanted before the first pulmonary artery cross-clamp. In the on-demand group, VA-ECMO will be implanted intraoperatively if haemodynamic or respiratory indices meet preplanned criteria. Non-inclusion, secondary exclusion and VA-ECMO initiation criteria were validated by a Delphi process among investigators. Postoperative weaning of ECMO and mechanical ventilation will be managed according to best practice guidelines. The number of ventilator-free days at 28 days (primary endpoint) will be compared between the two groups in the intention-to-treat population. Secondary endpoints encompass organ failure occurrence, day 28, day 90 and year 1 vital status, and adverse events. ETHICS AND DISSEMINATION: The sponsor is the Assistance Publique-Hôpitaux de Paris. The ECMOToP protocol version 2.1 was approved by Comité de Protection des Personnes Ile de France VIII. Results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT05664204.

Peripheral location of lung cancer is associated with higher local disease recurrence.

OBJECTIVES: Our goal was to evaluate the association between the distance of the tumour to the visceral pleura and the rate of local recurrence in patients surgically treated for stage pI lung cancer. METHODS: We conducted a single-centre retrospective review of 578 consecutive patients with clinical stage IA lung cancer who underwent a lobectomy or segmentectomy from January 2010 to December 2019. We excluded 107 patients with positive margins, previous lung cancer, neoadjuvant treatment and pathological stage II or higher status or for whom preoperative computed tomography (CT) scans were not available at the time of the study. The distance between the tumour and the closest visceral pleura area (fissure/mediastinum/lateral) was assessed by 2 independent investigators who used preoperative CT scans and multiplanar 3-dimensional reconstructions. An area under the receiver operating characteristic curve analysis was performed to determine the best threshold for the tumour/pleura distance. Then multivariable survival analyses were used to assess the relationship between local recurrence and this threshold in relation to other variables. RESULTS: Local recurrence occurred in 27/471 patients (5.8%). A cut-off value of 5 mm between the tumour and the pleura was determined statistically. In the multivariable analysis, the local recurrence rate was significantly higher in patients with a tumour-to-pleura distance ≤5 mm compared to patients with a tumour-to-pleura distance >5 mm (8.5% vs 2.7%, hazard ratio 3.36, 95% confidence interval: 1.31-8.59, P = 0.012). Subgroup analyses of patients with pIA and tumour size ≤2 cm identified local recurrences in 4/78 patients treated with segmentectomy (5.1%), with a significantly higher occurrence with tumour-to-pleura distances ≤5 mm (11.4% vs 0%, P = 0.037), and in 16/292 patients treated with lobectomy (5.5%) without significant higher occurrence in tumour-to-pleura distances of ≤5 mm (7.7% vs 3.4%, P = 0.13). CONCLUSIONS: The peripheral location of a lung tumour is associated with a higher rate of local recurrence and should be taken into account during preoperative planning when considering segmental versus lobar resection.

Effectiveness of Surgeon-Performed Paravertebral Block Analgesia for Minimally Invasive Thoracic Surgery: A Randomized Clinical Trial.

Importance: In minimally invasive thoracic surgery, paravertebral block (PVB) using ultrasound (US)-guided technique is an efficient postoperative analgesia. However, it is an operator-dependent process depending on experience and local resources. Because pain-control failure is highly detrimental, surgeons may consider other locoregional analgesic options. Objective: To demonstrate the noninferiority of PVB performed by surgeons under video-assisted thoracoscopic surgery (VATS), hereafter referred to as PVB-VATS, as the experimental group compared with PVB performed by anesthesiologists using US-guided technique (PVB-US) as the control group. Design, Setting, and Participants: In this single-center, noninferiority, patient-blinded, randomized clinical trial conducted from September 8, 2020, to December 8, 2021, patients older than 18 years who were undergoing a scheduled minimally invasive thoracic surgery with lung resection including video-assisted or robotic approaches were included. Exclusion criteria included scheduled open surgery, any antalgic World Health Organization level greater than 2 before surgery, or a medical history of homolateral thoracic surgery. Patients were randomly assigned (1:1) to an intervention group after general anesthesia. They received single-injection PVB before the first incision was made in the control group (PVB-US) or after 1 incision was made under thoracoscopic vision in the experimental group (PVB-VATS). Interventions: PVB-VATS or PVB-US. Main Outcomes and Measures: The primary end point was mean 48-hour post-PVB opioid consumption considering a noninferiority range of less than 7.5 mg of opioid consumption between groups. Secondary outcomes included time of anesthesia, surgery, and operating room occupancy; 48-hour pain visual analog scale score at rest and while coughing; and 30-day postoperative complications. Results: A total of 196 patients were randomly assigned to intervention groups: 98 in the PVB-VATS group (mean [SD] age, 64.6 [9.5] years; 53 female [54.1%]) and 98 in the PVB-US group (mean [SD] age, 65.8 [11.5] years; 62 male [63.3%]). The mean (SD) of 48-hour opioid consumption in the PVB-VATS group (33.9 [19.8] mg; 95% CI, 30.0-37.9 mg) was noninferior to that measured in the PVB-US group (28.5 [18.2] mg; 95% CI, 24.8-32.2 mg; difference: -5.4 mg; 95% CI, -∞ to -0.93; noninferiority Welsh test, P ≤ .001). Pain score at rest and while coughing after surgery, overall time, and postoperative complications did not differ between groups. Conclusions and Relevance: PVB placed by a surgeon during thoracoscopy was noninferior to PVB placed by an anesthesiologist using ultrasonography before incision in terms of opioid consumption during the first 48 hours. Trial Registration: ClinicalTrials.gov Identifier: NCT04579276.

Pulsatile pulmonary artery pressure in a large animal model of chronic thromboembolic pulmonary hypertension: Similarities and differences with human data.

A striking feature of the human pulmonary circulation is that mean (mPAP) and systolic (sPAP) pulmonary artery pressures (PAPs) are strongly related and, thus, are essentially redundant. According to the empirical formula documented under normotensive and hypertensive conditions (mPAP = 0.61 sPAP + 2 mmHg), sPAP matches ~160%mPAP on average. This attests to the high pulsatility of PAP, as also witnessed by the near equality of PA pulse pressure and mPAP. Our prospective study tested if pressure redundancy and high pulsatility also apply in a piglet model of chronic thromboembolic pulmonary hypertension (CTEPH). At baseline (Week-0, W0), Sham (n = 8) and CTEPH (n = 27) had similar mPAP and stroke volume. At W6, mPAP increased in CTEPH only, with a two- to three-fold increase in PA stiffness and total pulmonary resistance. Seven CTEPH piglets were also studied at W16 at baseline, after volume loading, and after acute pulmonary embolism associated with dobutamine infusion. There was a strong linear relationship between sPAP and mPAP (1) at W0 and W6 (n = 70 data points, r² = 0.95); (2) in the subgroup studied at W16 (n = 21, r² = 0.97); and (3) when all data were pooled (n = 91, r² = 0.97, sPAP range 9-112 mmHg). The PA pulsatility was lower than that expected based on observations in humans: sPAP matched ~120%mPAP only and PA pulse pressure was markedly lower than mPAP. In conclusion, the redundancy between mPAP and sPAP seems a characteristic of the pulmonary circulation independent of the species. However, it is suggested that the sPAP thresholds used to define PH in animals are species- and/or model-dependent and thus must be validated.

Induction and Phenotyping of Acute Right Heart Failure in a Large Animal Model of Chronic Thromboembolic Pulmonary Hypertension.

The development of acute right heart failure (ARHF) in the context of chronic pulmonary hypertension (PH) is associated with poor short-term outcomes. The morphological and functional phenotyping of the right ventricle is of particular importance in the context of hemodynamic compromise in patients with ARHF. Here, we describe a method to induce ARHF in a previously described large animal model of chronic PH, and to phenotype, dynamically, right ventricular function using the gold standard method (i.e., pressure-volume PV loops) and with a non-invasive clinically available method (i.e., echocardiography). Chronic PH is first induced in pigs by left pulmonary artery ligation and right lower lobe embolism with biological glue once a week for 5 weeks. After 16 weeks, ARHF is induced by successive volume loading using saline followed by iterative pulmonary embolism until the ratio of the systolic pulmonary pressure over systemic pressure reaches 0.9 or until the systolic systemic pressure decreases below 90 mmHg. Hemodynamics are restored with dobutamine infusion (from 2.5 µg/kg/min to 7.5 µg/kg/min). PV-loops and echocardiography are performed during each condition. Each condition requires around 40 minutes for induction, hemodynamic stabilization and data acquisition. Out of 9 animals, 2 died immediately after pulmonary embolism and 7 completed the protocol, which illustrates the learning curve of the model. The model induced a 3-fold increase in mean pulmonary artery pressure. The PV-loop analysis showed that ventriculo-arterial coupling was preserved after volume loading, decreased after acute pulmonary embolism and was restored with dobutamine. Echocardiographic acquisitions allowed to quantify right ventricular parameters of morphology and function with good quality. We identified right ventricular ischemic lesions in the model. The model can be used to compare different treatments or to validate non-invasive parameters of right ventricular morphology and function in the context of ARHF.

Benignant and malignant epidemiology among surgical resections for suspicious solitary lung cancer without preoperative tissue diagnosis.

OBJECTIVES: The aim of this study was to describe the epidemiology of patients undergoing diagnostic and/or curative surgical pulmonary resections for lung opacities suspected of being localized primary lung cancers without preoperative tissue confirmation. METHODS: We performed a single-centre retrospective study of a prospectively implemented institutional database of all patients who underwent pulmonary resection between January 2010 and December 2020. Patients were selected when surgery complied with the Fleischner society guidelines. We performed a multivariable logistic regression to determine the preoperative variables associated with malignancy. RESULTS: Among 1392 patients, 213 (15.3%) had a final diagnosis of benignancy. We quantified futile parenchymal resections in 29 (2.1%) patients defined by an anatomical resection of >2 lung segments for benign lesions that did not modified the clinical management. Compared with patients with malignancies, patients with benignancies were younger (57.5 vs 63.9 years, P < 0.001), had lower preoperative risk profile (thoracoscore 0.4 vs 2.1, P < 0.001), had a higher proportion of wedge resection (50.7% vs 12.2%, P < 0.01) and experienced a lower burden of postoperative complication (Clavien-Dindo IV or V, 0.4% vs 5.6%, P < 0.001). Preoperative independent variables associated with malignancy were (adjusted odd ratio [95% confident interval]) age 1.02 [1.00; 1.04], smoking (year-pack) 1.005 (1.00; 1.01), history of cardiovascular disease 2.06 [1.30; 3.30], history of controlled cancer 2.74 [1.30; 6.88] and clinical N involvement 4.20 [1.11; 37.44]. CONCLUSIONS: Futile parenchymal lung resection for suspicious opacities without preoperative tissue diagnosis is rare (2.1%) while surgery for benign lesions represented 15.3% and has a satisfactory safety profile with very low postoperative morbi-mortality.

Epidemiological Study to Assess the Prevalence of Lung Cancer in patients with smoking-associated atherosclerotic cardiovascular diseases: PREVALUNG study protocol.

INTRODUCTION: Eligibility criteria definition for a lung cancer screening (LCS) is an unmet need. We hypothesised that patients with a history of atheromatous cardiovascular disease (ACVD) associated with tobacco consumption are at risk of lung cancer (LC). The main objective is to assess LC prevalence among patients with ACVD and history of tobacco consumption by using low-dose chest CT scan. Secondary objectives include the evaluation LCS in this population and the constitution of a biological biobank to stratify risk of LC. METHODS AND ANALYSIS: We are performing a monocentric 'single-centre' prospective study among patients followed up in adult cardiovascular programmes of vascular surgery, cardiology and cardiac surgery recruited from 18 November 2019 to 18 May 2021. The inclusion criteria are (1) age 45-75 years old, (2) history of ACVD and (3) history of daily tobacco consumption for 10 years prior to onset of ACVD. Exclusion criteria are symptoms of LC, existing follow-up for pulmonary nodule, fibrosis, pulmonary hypertension, resting dyspnoea and active pulmonary infectious disease. We targeted the inclusion of 500 patients. After inclusion (V0), patients are scheduled for a low-dose chest CT and blood and faeces harvesting within 7 months (V1). Each patient is scheduled for a follow-up by telephonic visits at month 3 (V2), month 6 (V3) and month 12 (V4) after V1. Each patient is followed up until 1 year after V1 (14 February 2023). We measure LC prevalence and quantify the National Lung Screening Trial and Dutch-Belgian Randomized Lung Cancer Screening Trial (NELSON) trial eligibility criteria, radiation, positive screening, false positivity, rate of localised LC diagnosis, quality of life with the Short Form 12 (SF-12) and anxiety with the Spielberger State-Trait Anxiety Inventory A and B (STAI-YA and STAI-YB, respectively), smoking cessation and onset of cardiovascular and oncological events within 1 year of follow-up. A case-control study nested in the cohort is performed to identify clinical or biological candidate biomarkers of LC. ETHICS AND DISSEMINATION: The study was approved according the French Jardé law; the study is referenced at the French 'Agence Nationale de Sécurité du Médicament et des Produits de Santé' (reference ID RCB: 2019-A00262-55) and registered on clinicaltrial.gov. The results of the study will be presented after the closure of the follow-up scheduled on 14 February 2023 and disseminated through peer-reviewed journals and national and international conferences. TRIAL REGISTRATION NUMBER: NCT03976804.

Extrapleural cervico-manubriotomy and clavicular swing for the management of a mesenchymal tumour of the middle scalenus: an adapted anterior thoracic inlet approach.

Surgical approach for resection of tumours involving the thoracic inlet has largely been developed in the context of lung cancer of the superior sulcus. Therefore, initial anterior approaches included a thoracotomy associated with a longitudinal cervicotomy. Here, we describe a variation of the previously described anterior surgical approaches of the thoracic inlet that we performed for the resection of a primary mesenchymal tumour of the left middle scalenus muscle secreting fibroblast growth factor-23 responsible for tumour-induced osteomalacia. This approach allowed a safe control of the great vessels phrenic nerve and brachial plexus as well as a comfortable access to the middle scalenus muscle through an L-shaped incision with a cervico-manubriotomy without thoracotomy. The tumour was resected entirely with the middle scalenus. After 3 months of follow-up, the symptoms resolved entirely.

Video-Assisted Thoracoscopic En Bloc Vertebrectomy for Spine Tumors: Technique and Outcomes in a Series of 33 Patients.

BACKGROUND: In en bloc vertebrectomy, the posterior approach is associated with limited access to anterior structures (vertebral body, esophagus, aorta, azygos vein). Video-assisted thoracoscopic surgery (VATS) might prove to be advantageous during thoracic en bloc vertebrectomy by allowing a combined anterior-posterior access in the prone position. We describe the technique and review the outcomes of 33 cases of video-assisted thoracoscopic en bloc vertebrectomy. METHODS: A retrospective, single-center cohort study included all cases of VATS with a minimum follow-up of 1 year. A team of thoracic and orthopaedic surgeons performed the surgical procedure with the patient in a single, prone position. Anterior release was carried out thoracoscopically, followed by posterior en bloc tumor removal. RESULTS: From 2003 to 2019, 33 patients were included. Nine patients underwent total vertebrectomy (8 had single-level and 1 had 3-level), and 24 patients underwent partial vertebrectomy (1 had single-level, 8 had 2-level, 13 had 3-level, and 2 had 4-level). Ten patients had pulmonary resection. Histology revealed 18 cases (55%) of primary bone tumors, 6 cases (18%) of lung cancer invading the spine, 6 cases (18%) of solitary metastasis, and 3 other cases (9%). The margins were tumor-free in 28 cases (85%). The median operative time was 240 minutes (range, 150 to 510 minutes), with a median blood loss of 1,200 mL (range, 400 to 6,700 mL), and there were 2 cases of conversion to thoracotomy. A total of 33 complications occurred in 18 patients (55%), and these were predominantly pulmonary. One death was surgery-related (infection). One patient had a persistent monoplegia. At a median follow-up of 63 months (range, 12 to 156 months), there were 21 surviving patients (64%) with 2 local recurrences and 1 distant recurrence, and 2 patients (6%) were lost to follow-up. The survival rates were 94% at 1 year, 71% at 2 years, and 68% at 5 years. CONCLUSIONS: VATS en bloc vertebrectomy may be indicated for T2-to-T11 spine tumors with the exception of massive tumors, substantial chest wall and/or mediastinal invasion, and lung cancer exceeding 7 cm. The technique yielded satisfactory surgical and oncologic outcomes. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Outcomes after pulmonary lobectomy in patients with history of head and neck carcinoma.

BACKGROUND: We aimed to determine whether video assisted thoracic surgery (VATS) was associated with better short-term outcomes compared to open approach and to determine factors affecting long term survival after lobectomy in patients with history of head and neck carcinoma (HNC). METHODS: We performed a retrospective monocentric analysis of consecutive standard lobectomies performed for lung cancer in patients with history of HNC between 2010 and 2017. Patients' characteristics, surgical approach, lung tumor histology, in-hospital and 90-days morbi-mortality and long term survival were analyzed; VATS and open lobectomy groups were compared. RESULTS: Among 85 patients, 52 underwent an open lobectomy and 33 a VATS lobectomy. There was no significant difference between the two groups regarding age, preoperative characteristics, pathology and stage of lung cancer (All p = NS). In the VATS group, there was a significant decrease in proportion of in-hospital postoperative life-threatening complications requiring hospitalization in intensive care unit (12/52 vs. 1/33, p = 0.01). The 90-days postoperative comprehensive complication index was significantly increased in the open thoracotomy group (median (interquartile range):33.5 (0-53.5) vs. 8.7 (0-34.1), p = 0.018). Long term survival was not significantly different between the 2 groups - Log-rank test comparison, p = NS). Patients with squamous cell histology presented a significantly poorer survival (both Log-rank test comparison, p < 0.01). CONCLUSIONS: Minimally invasive approach improved in-hospital and 90-days outcomes compared to open surgery for lung cancer resection in patients with history of HNC. The poor long-term results in patients with squamous cell carcinoma highlight the need to improve therapeutic strategies for this subset of patients.

Superior vena cava prosthetic replacement for non-small cell lung cancer: is it worthwhile?

OBJECTIVES: Direct involvement of the superior vena cava (SVC) by non-small cell lung cancer (NSCLC) requires en-bloc tumour resection with complete vascular clamping and prosthetic replacement. We report the outcomes of this highly demanding procedure in the largest patient cohort to date. METHODS: We searched our institution's database for patients who underwent complete en-bloc resection of NSCLC invading the SVC followed by prosthetic SVC replacement, between 1980 and 2018. Patients with cN2, cN3 or distant metastases were not eligible. RESULTS: We identified 48 patients (38 males, 10 females; mean age of 57 years; tumour size, 1.9-17 cm). Neoadjuvant therapy was administered to 17 and adjuvant therapy to 31 patients. R0 resection was achieved in 41 (85%) patients; lymph node involvement was pN0 in 8, pN1 in 23, pN2 in 14 and pN3 in 3 patients. Five patients died within 30 days of surgery. Right pneumonectomy was significantly associated with postoperative death (P = 0.02). Postoperative complications developed in 13 other patients. No neurologic events related to SVC clamping occurred. Graft thrombosis developed in 2 patients. Median survival was 24 months; 3-, 5- and 10-year survival rates were 45%, 40% and 35%, respectively; and corresponding disease-free survival rates were 37%, 37% and 30%, respectively. By univariable analysis, only margin-free (R0) resection was associated with better survival (P = 0.02). CONCLUSIONS: In highly selected patients with NSCLC involving the SVC, mortality is acceptable after complete en-bloc resection and prosthetic replacement done in an expert centre. SVC involvement should not preclude consideration of curative resection in selected patients.

Early-stage non-small cell lung cancer beyond life expectancy: Still not too old for surgery?

OBJECTIVE: We investigated on the benefit/risk ratio of surgery in octogenarians with early-stage non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: From 2005-2020, 100 octogenarians were operated on for a clinical stage IA to IIA NSCLC. All patients had undergone whole body PET -scan and brain imaging. Operability was assessed according to current guidelines regarding the cardiopulmonary function. Since 2015, patients followed a dedicated geriatric evaluation pathway. Minimally invasive approaches were used in 66 patients, and a thoracotomy in 34. RESULTS: Clavien-Dindo grade ≥ 4 complications occurred in 15 patients within 90 days, including 7 fatalities. At multivariable analysis, the number of co-morbidities was their single independent prognosticator. Following resection, 24 patients met pathological criteria for adjuvant therapy among whom 3 (12.5 %) received platinum-based chemotherapy. Five-year survival rates were overall (OS) 47 ±â€¯6.3 %, disease-free (DFS) 77.6 ±â€¯5.1 %, and lung cancer-specific (CSS) 74.7 ±â€¯6.3 %. Diabetes mellitus impaired significantly long-term outcomes in these 3 dimensions. OS was improved since the introduction of a dedicated geriatric assessment pathway (72.3 % vs. 6.4 %, P = 0.00002), and when minimally invasive techniques were used (42.3 % vs. 11.3 %; P = 0.02). CSS was improved by the performance of systematic lymphadenectomy (55.3 % vs. 26.9 %; P = 0.04). Multivariable and recursive partitioning analyses showed that a decision tree could be built to predict overall survival on the basis of diabetes mellitus, high co-morbidity index and low ppoDLCO values. CONCLUSIONS: The introduction of a dedicated geriatric assessment pathway to select octogenarians for lung cancer surgery was associated with OS values that are similar to outcomes in younger patients. The use of minimally invasive surgery and the performance of systematic lymphadenectomy were also associated with improved long-term survival. Octogenarians with multiple co-morbid conditions, diabetes mellitus, or low ppo DLCO values may be more appropriately treated with SBRT.