Claudio Caviezel

A strategy to analyse activity-based profiling of tyrosine kinase substrates in OCT-embedded lung cancer tissue

The use of optimal cutting temperature (OCT) medium has served to improve the long-term preservation of surgical tissue specimens. Unfortunately, the presence of polymers in OCT has been found to generate signal interference in proteomic-based techniques. Indeed the presence of OCT medium in tissue lysates precludes the analysis of activity based proteomic profiles obtained from lung adenocarcinoma (LuAdCa) resection specimens. In order to probe this question further tissue lysates were prepared from 47 lung non-neoplastic and tumour, node, metastasis (TNM) stage 1 LuAdCa resection specimens embedded with or without OCT, and data of activity based multiplex profiles of protein tyrosine kinase peptide substrates were obtained. We found that changes in overall phosphorylation level coincided with the use of OCT and subsequently developed an OCT per peptide median correcting strategy by performing median centering on the values of each peptide. Application of this post-analytical strategy not only can identify changes in kinase activity but can also assist in identifying novel targets for therapeutic intervention against LuAdCa.

Left main bronchus sleeve resection with reconstruction of neolobar carina

From the Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland. Disclosures: Authors have nothing to disclose with regard to commercial support. Received for publication Nov 2, 2016; revisions received Dec 21, 2016; accepted for publication Feb 19, 2017; available ahead of print April 1, 2017. Address for reprints: Ilhan Inci, MD, Division of Thoracic Surgery, University Hospital Zurich, Raemistrasse 100, Zurich 8091, Switzerland (E-mail: ilhan.inci@usz.ch). J Thorac Cardiovasc Surg 2017;154:370-2 0022-5223/

Postoperative complications and management after lung volume reduction surgery

36.00 Copyright 2017 by The American Association for Thoracic Surgery http://dx.doi.org/10.1016/j.jtcvs.2017.02.060

Successful lung volume reduction surgery in combined pulmonary emphysema and fibrosis without body-plethysmographic hyperinflation—a case report

The aim of lung volume reduction surgery (LVRS) for patients suffering from severe emphysema is to improve lung function and palliate dyspnea. Careful patient selection in a multidisciplinary approach in a high-volume center is mandatory for a successful outcome. Pulmonary complications including air leak and pneumonia as well as cardiac complications are the most common complications after LVRS. The following article will focus on most common complications observed after LVRS and review the management strategies to improve surgical outcome.

Lung volume reduction surgery beyond the NETT selection criteria

Surgical and bronchoscopic lung volume reduction (LVR) have been demonstrated to improve lung function, dyspnea and quality of life in patients with severe pulmonary emphysema. The most important functional prerequisite for a successful LVR is hyperinflation measured by body plethysmography. A residual volume (RV) of more than 180% predicted and a RV/total lung capacity (TLC) ratio of more than 0.58 were inclusion criteria in major LVR trials. Here we report a successful LVR in a 68-year-old man with advanced, heterogeneous emphysema without plethysmographic evidence of severe hyperinflation (RV/TLC 0.45). Computed tomography (CT) revealed severe, partly bullous upper lobe emphysema and subtle fibrotic changes with volume loss of lower lobes. Since lower lobes appeared compressed by upper lobe emphysema, these target areas were removed by thoracoscopic LVR. Four months later, the patient reported major improvements of dyspnea, FEV1 (by 1.27 L) and 6-minute walking distance (by 150 meters). LVR reduced total lung volume measured by CT-volumetry by 0.5 L and upper lobe volume by 1.85 L while lower lobe volume increased by +1.34 L. Low density volume (-950 HU) reflecting emphysema was reduced by 1.73 L. We conclude that the opposing effects of emphysema and fibrosis resulted in a barely increase in total lung volume that was only slightly reduced by LVR. Nevertheless, resection of emphysematous target areas identified by quantitative CT analysis provided major clinical and physiologic improvements related to decompression of low-compliance lower lobe areas retracted by early fibrosis. Therefore, in the combined presence of severe, heterogeneously distributed emphysema and fibrosis, LVR may improve respiratory mechanics even if RV/TLC, an established body-plethysmographic predictor of LVR success is not severely elevated.

Improved postoperative lung function after sublobar resection of non-small-cell lung cancer combined with lung volume reduction surgery in patients with advanced emphysema

Lung volume reduction surgery (LVRS) for symptomatic patients with advanced emphysema was proven to be successful in a large randomized multi-center trial (NETT) and in several smaller randomized single center trials. This evidence primarily concerns patients with heterogeneous, upper-lobe predominant emphysema and low exercise tolerance within certain selection criteria regarding lung function values. As the most important effect of LVRS is generated by reducing the hyperinflation, even patients with homogeneous emphysema morphology profit from the procedure. Simultaneously, by removing distended and functionless areas in heterogeneous emphysema, also patients with seriously impaired diffusion capacity, moderate pulmonary arterial hypertension, a history of previous LVRS and alpha-1-antitrypsin-deficiency (AATD) can be considered as candidates for (re-)-LVRS. This article summarizes indications for LVRS in these various subtypes of emphysema patients.

Dynamic magnetic resonance imaging as an outcome predictor for lung-volume reduction surgery in patients with severe emphysema

BackgroundnRadiotherapy is recommended as primary local therapy for inoperable patients with non-small cell lung cancer (NSCLC). We hypothesized that selected patients with advanced emphysema could be candidates for surgery and improved functional outcome might result in addition to low mortality and morbidity and successful cancer control when sublobar resection in a lung volume reduction surgery (LVRS) concept is applied.nnnMethodsnAll patients with NSCLC and severe emphysema who underwent cancer resection in a LVRS concept between 2003 and 2015 were included for analysis. Postoperative 90-day mortality, complications, survival and lung function with forced expiratory volume in one second pre-operatively and three months postoperatively served as endpoints.nnnResultsnFourteen patients were included. Three procedures were bilateral and eleven unilateral, eight have been performed with thoracoscopy and six with conversion to an open procedure due to adhesions. In ten patients, tumor resection was atypical and in four patients an anatomic segmentectomy was performed. All patients had lung volume reduction. Prolonged air leak occurred in three patients. Perioperative 90-mortality was zero. Median pre-operative forced expiratory volume in one second was 32.5% and increased to 37% (P=0.002) 3 months following surgery. Three and 5-year survival rates were 50% and 35%, respectively.nnnConclusionsnSublobar resection of NSCLC combined with LVRS in patients with severely impaired lung function due to emphysema can be performed with low mortality and morbidity making it an alternative treatment modality to radiotherapy. This approach allows cancer resection in marginal patients and improves emphysema symptoms simultaneously.

Lung volume reduction surgery in selected patients with emphysema and pulmonary hypertension

OBJECTIVESnWe hypothesize a significant correlation between parameters of preoperative dynamic magnetic resonance imaging (MRI) and postoperative outcomes measured by pulmonary function tests.nnnMETHODSnDynamic MRI of the lungs was prospectively performed during 2 breath cycles 1 day before and 3u2009months after surgery, herein termed as pre- and post-lung-volume reduction surgery (LVRS) MRI. Quantitative measurements were performed on sagittal planes for the left lung and right lung: lung height, anteroposterior diameter, hemidiaphragm height and area as well as perimeter. Additionally, dynamic changes in hemidiaphragmatic area and height were measured. Parameters were normalized by patients height. Pulmonary function test pre-LVRS and post-LVRS was performed. The cut-off value for treatment benefit was defined as a 30% increase in forced expiratory volume in 1 s.nnnRESULTSnThirty-nine consecutive patients (15 women, median age 61u2009years) were included. On expiration, the mean lung area on both sides (Prightu2009=u20090.001 and Pleftu2009=u20090.016) and anteroposterior diameter of the right lung (Prightu2009=u20090.003) improved post-LVRS. Dynamic measurements showed differences pre- and post-LVRS on the right lung but not on the left lung (Prightu2009<u20090.001 and Pleftu2009=u20090.090). There were no significant changes in lung height for both sides, in hemidiaphragmatic height on the right as well as diaphragmatic area pre- and post-LVRS (Pu2009>u20090.05). Except for hemidiaphragmatic height on the left lung (Pu2009=u20090.039), no significant differences were found on inspiration. Considering the 30% cut-off for treatment benefit, the receiver operating curves analysis indicated a height-normalized expiratory lung area ≥35xa0793 mm2 as the most sensitive preoperative outcome predictor (sensitivityu2009=u200986%; specificityu2009=u200961%).nnnCONCLUSIONSnPreoperative dynamic MRI can be used as an additional outcome predictor for patient selection in LVRS. A height-normalized total lung area in expiration ≥35xa0793 mm2 correlates with a 30% increase in forced expiratory volume in 1 s.nnnCLINICAL TRIAL REGISTRATION NUMBERnSNCTP000000480.

Previous lung volume reduction surgery does not negatively affect survival after lung transplantation

OBJECTIVESnPulmonary hypertension (PH) is considered a contraindication for lung volume reduction surgery (LVRS). Because, it has been reported that endobronchial lung volume reduction may have a beneficial effect without increased mortality in patients with emphysema and PH, we evaluated its effect on PH in patients undergoing LVRS.nnnMETHODSnFrom January 2014 until June 2016, 119 LVRSs were performed at Zurich University Hospital. PH was a contraindication for patients with homogeneous emphysema but was acceptable for those with heterogeneous emphysema. Thirty patients underwent echocardiography before and after LVRS, 10 of whom had preoperative systolic pulmonary artery pressures >35u2009mmHg and 20 of whom had normal systolic pulmonary artery pressure. The effect of LVRS on pulmonary artery pressure, lung function and survival was analysed.nnnRESULTSnNinety-day mortality for all 30 patients was 0, and the postoperative course did not differ significantly between the 2 groups. In patients with PH, the median systolic pulmonary artery pressure decreased from 41u2009mmHg [interquartile range (IQR) 39-47] to 37u2009mmHg (IQR 36-38, Pu2009=u20090.04). These patients had an improvement of forced expiratory volume in 1u2009s from the median 27% predicted (IQR 23-34) to 33% (IQR 28-40, Pu2009=u20090.007) 3u2009months postoperatively.nnnCONCLUSIONSnIf further confirmed in other cohorts, mild to moderate PH may no longer be considered a contraindication for LVRS in patients with heterogeneous emphysema.

Outcome After Lung Volume Reduction Surgery in Patients With Severely Impaired Diffusion Capacity

OBJECTIVESnLung volume reduction surgery (LVRS) and lung transplantation (LTx) are the treatments of choice in selected patients with end-stage emphysema. Recently, the history of LVRS has been questioned due to reduced post-transplant survival. We aim to address this question by reviewing our experience, which is the largest single-centre series of LVRS followed by LTx.nnnMETHODSnWe reviewed our prospectively recorded database in patients with emphysema undergoing LTx between 1993 and 2014. Preoperative workup and postoperative outcomes were compared according to previous LVRS status. The Kaplan-Meier test was used for survival analysis and compared with a log-rank test.nnnRESULTSnOne hundred and seventeen patients (66 men; mean age 56u2009±u20097u2009years) underwent LTx during the study period, 52 of whom had previous LVRS (LVRSu2009+u2009LTx). The mean time from LVRS to LTx was 45u2009±u200931u2009months. Patients were slightly older and had extensive smoking history in the LVRSu2009+u2009LTx group. Overall, in-hospital mortality was 10%, which did not differ significantly regardless of the history of LVRS (Pu2009=u20090.8). The median survival for the LTx-only and LVRSu2009+u2009LTx groups was 86 [95% confidence interval (CI) 56-116] and 107 (95% CI 77-137)u2009months, respectively (Pu2009=u20090.6).nnnCONCLUSIONSnPrevious LVRS does not negatively affect short-term and long-term outcomes following LTx in patients with end-stage emphysema. The history of LVRS should not preclude the candidacy for LTx. Considering the limited number of donors available, the LVRS option should be kept in mind for the postponement of LTx in carefully selected patients.