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.

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.

TNM-classification for lung cancer: from the 7th to the 8th 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 7th 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 7th 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 8th 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.

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.

Trimodality therapy for malignant pleural mesothelioma: results from an EORTC phase II multicentre trial.

The European Organisation for Research and Treatment of Cancer (EORTC; protocol 08031) phase II trial investigated the feasibility of trimodality therapy consisting of induction chemotherapy followed by extrapleural pneumonectomy and post-operative radiotherapy in patients with malignant pleural mesothelioma (with a severity of cT3N1M0 or less). Induction chemotherapy consisted of three courses of cisplatin 75 mg·m⁻² and pemetrexed 500 mg·m⁻². Nonprogressing patients underwent extrapleural pneumonectomy followed by post-operative radiotherapy (54 Gy, 30 fractions). Our primary end-point was "success of treatment" and our secondary end-points were toxicity, and overall and progression-free survival. 59 patients were registered, one of whom was ineligible. Subjects' median age was 57 yrs. The subjects' TNM scores were as follows: cT1, T2 and T3, 36, 16 and six patients, respectively; cN0 and N1, 57 and one patient, respectively. 55 (93%) patients received three cycles of chemotherapy with only mild toxicity. 46 (79%) patients received surgery and 42 (74%) had extrapleural pneumonectomy with a 90-day mortality of 6.5%. Post-operative radiotherapy was completed in 37 (65%) patients. Grade 3-4 toxicity persisted after 90 days in three (5.3%) patients. Median overall survival time was 18.4 months (95% CI 15.6-32.9) and median progression-free survival was 13.9 months (95% CI 10.9-17.2). Only 24 (42%) patients met the definition of success (one-sided 90% CI 0.36-1.00). Although feasible, trimodality therapy in patients with mesothelioma was not completed within the strictly defined timelines of this protocol and adjustments are necessary.

Surgical resection of lung metastases including the role of locoregional therapy.

Although no randomized trials are available, surgical resection is a widely accepted treatment for selected patients with pulmonary metastases. Specific criteria have been well defined and a macroscopic complete resection should be obtained. Important prognostic factors include histology, number of metastases and disease-free interval. However, even after complete resection, 5-year survival rates remain disappointingly low and many patients will have recurrent disease confined to the chest. For this reason, locoregional therapies are extensively investigated at the present time. These include biochemical and biophysical methods. Due to toxicity of high doses of intravenous chemotherapy, the main purpose is to deliver high-dose chemotherapy to the lung without systemic side-effects. Chemo-embolization, pulmonary artery infusion and isolated lung perfusion are most intensively studied. These techniques were found to be feasible and are able to deliver a high local concentration of chemotherapeutic drugs. The results of further phase II trials are awaited for to determine their effect on local recurrence and long-term survival.

Emergency endovascular aneurysm repair for ruptured abdominal aortic aneurysms: an institutional experience.

OBJECTIVES: Emergency endovascular aneurysm repair (eEVAR) for ruptured abdominal aortic aneurysms (rAAA) is still under investigation. Since installation of an urgent eEVAR kit in our hospital, all patients with a rAAA or urgent thoracic aortic aneurysm are candidates for eEVAR or eTEVAR (emergency thoracic EVAR), respectively. For this study, we analyzed all rAAA patients treated with eEVAR. METHODS: Data were recorded prospectively. Criteria for an eEVAR were an infrarenal neck > or = 15 mm, acceptable landing zone, angles below 70 degrees and a good femoral approach. We prefer preoperative angio CT-scan but in case of instability, an intra-aortic balloon can stabilize the patient during angiography (in the OR) to decide between open or eEVAR repair. Follow-up was performed on regular intervals by duplex or CT-scan. Thirty-day mortality and overall survival were calculated. RESULTS: Since 2006, nine male rAAA patients with a mean age of 73 years (range : 62-82) had eEVAR repair. Aneurysm diameter was 8 cm (range : 5.8-11). The Hardman index was 1.5 (range : 0-3). In eight patients an aorto-uni-iliac device was placed succesfully followed by a femorofemoral crossover bypass. The 30-day operative mortality was 12.5% (one patient with septic shock). Three patients showed a type 2 endoleak with stable diameter during follow-up but one patient showed expansion 4 years after treatment. CONCLUSIONS: Treating rAAA with eEVAR in selected patients with acceptable anatomy and a kit permanently available in the operating room yielded good results by a surgical team trained for both open and eEVAR repair. The conversion rate was low (11%) and the survival (immediate and 30-days) was excellent (87.5%).