[Early-stage lung cancer: Is there still a role for surgery?] / Tumeurs de petits stades. La chirurgie a-t-elle encore sa place ?

For a patient with stage I or II non-small cell lung cancer (NSCLC) surgical resection remains the treatment of choice on condition that the patient is functionally operable. A complete resection should be obtained. Often lobectomy is feasible by a minimally invasive approach. For patients with compromised cardiopulmonary function stereotactic radiotherapy is an alternative treatment. For patients who are functionally operable, no definite recommendation can be made as no large, randomised studies have been performed with a sufficient number of patients and long-term follow-up. For this reason, it is important to discuss every patient within a multidisciplinary team with participation of thoracic surgeons and radiation oncologists. To provide personalised advice, the primary tumour, its extension, the patient's comorbidities and his respiratory and cardiac function have to be considered.

Circulating cell-free nucleic acids and platelets as a liquid biopsy in the provision of personalized therapy for lung cancer patients.

Lung cancer is the predominant cause of cancer-related mortality in the world. The majority of patients present with locally advanced or metastatic non-small-cell lung cancer (NSCLC). Treatment for NSCLC is evolving from the use of cytotoxic chemotherapy to personalized treatment based on molecular alterations. Unfortunately, the quality of the available tumor biopsy and/or cytology material is not always adequate to perform the necessary molecular testing, which has prompted the search for alternatives. This review examines the use of circulating cell-free nucleic acids (cfNA), consisting of both circulating cell-free (tumoral) DNA (cfDNA-ctDNA) and RNA (cfRNA), as a liquid biopsy in lung cancer. The development of sensitive and accurate techniques such as Next-Generation Sequencing (NGS); Beads, Emulsion, Amplification, and Magnetics (BEAMing); and Digital PCR (dPCR), have made it possible to detect the specific genetic alterations (e.g. EGFR mutations, MET amplifications, and ALK and ROS1 translocations) for which targeted therapies are already available. Moreover, the ability to detect and quantify these tumor mutations has enabled the follow-up of tumor dynamics in real time. Liquid biopsy offers opportunities to detect resistance mechanisms, such as the EGFR T790M mutation in the case of EGFR TKI use, at an early stage. Several studies have already established the predictive and prognostic value of measuring ctNA concentration in the blood. To conclude, using ctNA analysis as a liquid biopsy has many advantages and allows for a variety of clinical and investigational applications.

Dysregulation of the renin-angiotensin system during lung ischemia-reperfusion injury.

UNLABELLED: Aim/Purpose of the Study: Activation of the renin-angiotensin system leading to increased angiotensin-(1-7) (Ang-(1-7)) and decreased angiotensin 2 (Ang 2) levels may be a new therapeutic approach to reduce acute lung injury. Prolylcarboxypeptidase (PRCP) and prolyloligopeptidase (PREP) are capable of hydrolyzing Ang 2 into Ang-(1-7). However, their relation with circulating Ang 2 levels after lung ischemia-reperfusion injury (LIRI) has never been explored. This study determines whether the activity and expression of PRCP and PREP in plasma and lung tissue is related to circulating Ang 2 levels in a murine model of LIRI. MATERIALS AND METHODS: LIRI in Swiss mice (6 animals per group) was induced by temporary left lung hilar clamping (1 h) followed by 0, 1 or 24 h of reperfusion. Animals in the sham group received thoracotomy only. PRCP activity was measured via RP-HPLC, PREP activity using a fluorogenic substrate and plasma Ang 2 levels via ELISA. Western blotting was used to determine the PRCP and PREP protein expression profiles in left lung tissue. RESULTS: Plasma Ang 2 levels significantly rise after lung ischemia and remain increased after 1 h and 24 h of reperfusion compared to the sham group. While a significant decrease in plasma PREP activity was found after 24 h of reperfusion, a transient increase in plasma PRCP activity was observed after ischemia. However, no correlation with plasma Ang 2 levels could be demonstrated. The activity profiles of PRCP and PREP and the protein expression of PRCP in the lung tissues remained unchanged after LIRI. CONCLUSIONS: LIRI causes a dysregulation of circulating Ang 2 levels and plasma PREP activity, although no direct link between both phenomena could be shown. The activity profile of pulmonary PRCP and PREP was not significantly changed after LIRI, which implies a minor role for local PRCP and PREP in the ischemic lung itself.

Aortic Dissection Limited to Abdominal Aorta: an Underrecognized Entity?

BACKGROUND: Aortic dissection limited to the abdominal aorta is a rare clinical entity with non-specific clinical features. Optimal treatment, as well as natural history and progression of the disease, remain unclear. In 1992 we -reported 5 cases of isolated abdominal aortic dissection (IAAD) and in the present paper we update our series with 5 additional patients. A concise literature review is also provided. METHODS: Between 1992 and 2014, we diagnosed 5 patients with IAAD (4 men, mean age 60.6 years, range 45-77). No patient presented with acute onset of symptoms. One patient was diagnosed with a periumbilical bruit, and diagnosis was made with magnetic resonance (MR)-angiography. Other diagnoses were incidental findings on computed tomographic (CT) scanning. Dissection was located infrarenally in four cases and at the celiac trunk in one case. RESULTS: All cases were treated conservatively with hypertension control and close follow-up. Follow-up period ranged from 10 months to 20 years and was performed yearly by CT- or MR-angiography and blood pressure monitoring. All patients remained symptom-free, all dissection lengths remained stable. Slowly increasing post-dissection aneurysmal dilatation was encountered in two patients. We combined results of these five new patients with five previously diagnosed and reported patients at our center. Treatment was surgical in only one out of 10 patients. There was no disease-related mortality during follow-up. CONCLUSIONS: Based on our case series, IAAD remains a rare clinical condition with relative benign clinical course. Treatment was almost exclusively conservative. Recent publications state IAAD might be underrecognized and under-diagnosed compared to thoracic aortic dissections.

Preclose Percutaneous Endurant™ Endografting with the Proglide™ Device: a Safe and Feasible Combination.

BACKGROUND: Endovascular repair of abdominal aortic aneurysms has been revolutionized over the last two decades. Opening the doors for a percutaneous approach by avoiding surgical exposure of the vascular access site. The goal of this report is to analyze the feasibility and efficacy of using Perclose Proglide™ through a preclose technique in a percutaneous approach to Endurant™ endografting for Asymptomatisch infrarenal aortic aneurysms in an elective setting. METHODS: Between April 2011 and April 2014, 45 consecutive patients underwent percutaneous endovascular aortic aneurysm repair (PEVAR) for an asymptomatic infrarenal aortic aneurysm. Closure of percutaneous access sites was ensured with Perclose Proglide in a "preclose" technique. Data were collected in a prospective maintained database with a follow-up period of one month. Patient demographics, aneurysmal characteristics, procedural details and complications were recorded. RESULTS: A total of 170 Proglide devices were used to close 85 access sites. Adequate hemostasis was obtained in 96.5 percent (82 of 85 access sites). Conversion to a femoral cutdown was necessary in 2.4% (2 of 85 access sites). The mean hospitalization was 2.6 days and 86.7 percent of patients were discharged within 2 days. The incidence of post-procedural access-related complications was 2.2%. CONCLUSIONS: PEVAR using the Perclose Proglide in preclosing 14Fr to 20Fr access sites for Endurant endografting in the treatment of asymptomatic infrarenal aortic aneurysms is feasible and effective. Moreover, the percutaneous approach allows for procedures to be performed under local anesthesia, while providing a low risk for access-related complications and a relatively short hospitalization.

2nd ESMO Consensus Conference on Lung Cancer: early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up.

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on early-stage disease.

Malignant Pleural Mesothelioma : Rationale for a New TNM Classification.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare but aggressive thoracic malignancy with a poor prognosis. In this regard, a well-defined staging system is of utmost importance in order to correctly diagnose and assign an appropriate treatment to the patient. METHODS: The current TNM-staging system (7th edition) enables to either clinically or pathologically stage the severity of the disease according to extension of the tumor (T), number of nodes (N) and presence of metastases (M). Patients with stage I-III are considered for surgery, while palliative treatment is indicated for stage IV patients according to the current classification. RESULTS: Despite its widespread use, the validity of this staging system is questioned due to the low prevalence, histological variety and retrospective nature of the previous study design. In addition, the role of specific treatment modalities including surgery, has yet to be determined, especially for treatment of early-stage disease. In this regard, the International Association for the Study of Lung Cancer (IASLC) initiated the multi-centre, prospective "Mesothelioma Staging Project" in order to address limitations of the 7th edition and to optimize the staging system in accordance to current needs. CONCLUSIONS: An improved staging system will contribute to the design of prospective multi-institutional clinical trials investigating novel treatment strategies for mesothelioma. In this way comparison of outcome between different medical centres also becomes feasible.

Intrathymic parathyroid adenoma presenting with seizures.

A 59-year-old diabetic patient was admitted with loss of consciousness and convulsions. Hypercalcaemia and hypoglycaemia were discovered. Computed tomographic and technetium scans revealed a retrosternal paramedian nodule. Radical thymectomy was performed by median sternotomy. Diagnosis of intrathymic parathyroid adenoma was made. One year later the patient had good diabetes control without clinical symptoms.

Surgical implications of the new IASLC/ATS/ERS adenocarcinoma classification.

A new adenocarcinoma classification was recently introduced by a joint working group of the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS) and European Respiratory Society (ERS). A distinction is made between pre-invasive lesions, and minimally invasive and invasive adenocarcinoma. The confusing term "bronchioloalveolar carcinoma" is not used any more and new subcategories include adenocarcinoma in situ and minimally invasive adenocarcinoma. Due to a renewed interest in screen-detected nodules and early-stage lung cancers of <2 cm, this classification also has profound implications for thoracic surgeons. In this article, surgical topics are discussed: the role of a minimally invasive approach, especially video-assisted thoracic surgery, limited resection for early-stage lung cancer, the extent of lymph node dissection, the accuracy of intraoperative frozen section analysis, management of multiple lung nodules and prognostic factors in operated patients. Specific key issues are presented based on the current evidence and areas of surgical uncertainty are defined providing a basis for further studies. Thoracic surgeons will play a major role in the application and global introduction of this new adenocarcinoma classification. The remaining controversies regarding the precise diagnosis and management of early-stage lesions will have to be resolved by multidisciplinary and international collaboration.

Surrogate markers predicting overall survival for lung cancer: ELCWP recommendations.

The present systematic review was performed under the auspices of the European Lung Cancer Working Party (ELCWP) in order to determine the role of early intermediate criteria (surrogate markers), instead of survival, in determining treatment efficacy in patients with lung cancer. Initially, the level of evidence for the use of overall survival to evaluate treatment efficacy was reviewed. Nine questions were then formulated by the ELCWP. After reviewing the literature with experts on these questions, it can be concluded that overall survival is still the best criterion for predicting treatment efficacy in lung cancer. Some intermediate criteria can be early predictors, if not surrogates, for survival, despite limitations in their potential application: these include time to progression, progression-free survival, objective response, local control after radiotherapy, downstaging in locally advanced nonsmall cell lung cancer (NSCLC), complete resection and pathological TNM in resected NSCLC, and a few circulating markers. Other criteria assessed in these recommendations are not currently adequate surrogates of survival in lung cancer.

Endarterectomy combined with retrograde stenting for tandem lesions of the carotid artery.

OBJECTIVES: Due to its location in the chest wall, surgical treatment of lesions at the origin of the brachiocephalic trunk or common carotid artery (CCA) is unattractive. Complete endovascular treatment of lesions at the origin of the common carotid artery or brachiochephalic trunk combined with high-grade lesions at the carotid bifurcation carries a high risk for distal emboli before cerebral protection is installed. Therefore, the combination of open carotid endarterectomy with retrograde stenting of the proximal lesion through one stage is most attractive. METHODS: Eleven patients were treated with a combined procedure for tandem lesions at the origin of the brachiocephalic trunk or common carotid artery (CCA) and the carotid bifurcation. Endpoint of this evaluation was the 30-day MACE (Major Adverse Cardiovascular Events). RESULTS: All procedures were finished as planned and no conversion was necessary. Thirty-day mortality was 0%. One patient developed a restenosis after only 4 days for which he underwent a re-PTA procedure. The 30-day MACE was 0%. None of the patients needed additional treatment during follow-up (mean follow-up 33 months; range: 11 to 60) although one patient developed a non-significant stenosis during follow-up. CONCLUSIONS: Combined treatment of tandem lesions of the carotid artery is safe and effective in the long-term.

Spontaneous pneumothorax: remaining controversies.

Despite many guidelines issued by national and professional societies, a detailed literature survey between the late 1940s and 2010 clearly demonstrates that several aspects of pneumothorax pathogenesis and treatment still remain controversial. Related to pathogenesis of primary pneumothorax, the current manuscript highlights why further studies are needed to explain 1) mechanism of the oxygenation impairment in presence of a large pneumothorax; 2) oxygenation differences between age and sex-matched patients with a pneumothorax of the same size; and 3) sequence of events in tension pneumothorax. Concerning the overall therapeutic approach, video-assisted technology provides a minimally invasive operative treatment. For this reason methods of recurrence prevention are now shared between interventional pulmonologists and thoracic surgeons. Although a significantly higher recurrence rates was reported in patients with primary spontaneous pneumothorax after simple pleural drainage versus thoracoscopic talc poudrage, (34% and 5% respectively), such a policy is still not widely adopted. Certain concerns that relate to the use of talc in relapse prevention are also discussed, showing that they are mostly dependent on the type of the talc used. Concerning secondary pneumothorax, specificities of different forms related to diagnostics and therapeutic approach are also pointed out. Lung tuberculosis as the underlying cause is particularly addressed, due to the challenge of the timely recognition of specific lesions and prompt initiation of the antituberculous medical treatment . Similarly, lung cancer is mentioned as a possible underlying cause in patients with delayed lung expansion.

Restaging the mediastinum in non-small cell lung cancer after induction therapy: non-invasive versus invasive procedures.

OBJECTIVE: Nodal status after induction therapy in patients with stage III non-small cell lung cancer (NSCLC) is an independent prognostic factor for survival. Prognosis is poor in patients with persisting mediastinal lymph node involvement. METHODS: From February 2000 to September 2007, restaging for NSCLC was performed in 25 patients (23 men, 2 women) by computed tomography (CT), positron emission tomography (PET) as well as repeat mediastinoscopy. Initial proof of N2 or N3 disease was obtained by mediastinoscopy. RESULTS: The non-invasive restaging modalities CT and PET had a rather low accuracy of 64% and 72%, respectively. Repeat mediastinoscopy performed better with an accuracy of 84%. CONCLUSION: Histological proof of mediastinal involvement after induction therapy in NSCLC is necessary to select those patients who will benefit from surgical resection. When a first mediastinoscopy has been performed to obtain pathological proof of N2 or N3 disease, repeat mediastinoscopy proves to be more accurate than CT or PET scanning for mediastinal restaging.

TNM-Classification for Lung Cancer: From the 7(th) to the 8(th) Edition.

Most tumors are staged according to the Tumor-Node-Metastasis (TNM) classification. For lung cancer a new edition was introduced in 2009 and generally applied since 2010. This 7(th) TNM-classification is based on a large, international retrospective database. Important changes were made regarding the T, N, M factors and specific subcategories were added. However, this 7(th) edition is still purely based on anatomical information. Other prognosticators such as laboratory results, histology, tumor markers and molecular genetic factors are not yet considered. To prepare the 8(th) TNM classification a prospective database developed by the International Association for the Study of Lung Cancer (IASLC), is currently enrolling patients from all continents. In this way, more precise and reliable data will become available on specific subdivisions of the T, N and M factors. If proven to be prognostically valid, other parameters will be included as histology, demographic data and specific biochemical and molecular predictive and prognostic factors. All centers with a large experience in thoracic oncology are encouraged to participate in this prospective database.