Alessandro Palleschi

Plasmatic extracellular vesicle microRNAs in malignant pleural mesothelioma and Asbestos-Exposed subjects suggest a 2-miRNA signature as potential biomarker of disease

Background Malignant Pleural Mesothelioma (MPM) is an aggressive cancer mainly caused by asbestos exposure and refractory to current therapies. Specific diagnostic markers for early MPM diagnosis are needed. Changes in miRNA expression have been implicated in several diseases and cancers, including MPM. We examined if a specific miRNA signature in plasmatic extracellular vesicles (EV) may help to discriminate between malignant pleural mesothelioma patients (MPM) and subjects with Past Asbestos Exposure (PAE). Methodology/Principal findings We investigated 23 MPM patients and 19 cancer-free subjects with past asbestos exposure (PAE). We screened 754 miRNAs in plasmatic EVs by OpenArray and found 55 differential miRNAs using logistic regression models adjusted for age, sex, BMI, and smoking. Among the top-20 differential miRNAs chosen for validation by Real time PCR, 16 were confirmed. Using receiver operating characteristic (ROC) curve analysis, the most discriminating miRNA combination was given by miR-103a-3p + miR-30e-3p, which generated an AUC of 0.942 (95% CI 0.87–1.00), with a sensitivity of 95.5% and a specificity of 80.0%. Using multivariate Cox regression analysis including gender, age, BMI and smoking we found a Hazard Ratio for miR-103a-3p above the median of 0.37 (95%CI 0.13–1.13) and of 0.51 (95%CI 0.17–1.52) for miR-30e-3p. Conclusions This study suggests EV-associated miR-103a-3p and miR-30e-3p are able to discriminate MPM from PAE subjects. Larger and prospective studies are needed to confirm these two-miRNA signature alone or in combination with other biomarkers as diagnostic tools for MPM.

Clinical Risk Factors for Primary Graft Dysfunction in a Low-volume Lung Transplantation Center

Primary graft dysfunction (PGD) is a severe acute lung injury syndrome following lung transplantation. Previous studies of clinical risk factors, including a multicenter prospective cohort trial, have identified a number of recipient, donor, and operative variables related to Grade 3 PGD. The aim of this study was to validate these risk factors in a lung transplantation center with a low volume of procedures. We conducted a retrospective cohort study of 45 consecutive lung transplantations performed between January 2011 and September 2013. PGD was defined according to the International Society for Heart and Lung Transplantation grading scale. Risk factors were evaluated independently and the significant confounders entered into multivariable logistic regression models. The overall incidence of Grade 3 PGD was 35.5% at T24, 17.7% at T48, and 15.5% at T72. The following risk factors were associated with Grade 3 PGD at the indicated time points: recipient female gender at T24 (P=.034), mixed diagnoses at T72 (P=.047), ECMO bridge-to-lung transplantation at T24 (P=.0004) and at T48 (P=.038), donor causes of death different from stroke and trauma at T24 (P=.019) and T72 (P=.014), blood transfusions during surgery at T24 (P=.001), intraoperative venoarterial ECMO T24 (P<.0001). Multivariate analysis at T24 identified recipient female gender and intraoperative venoarterial ECMO as risk factors (P=.010 and P=.018, respectively). This study demonstrated that risk factors for severe PGD in a low-volume center were similar to international reports in prevalence and type. ECMO bridge-to-lung transplantation emerged as a risk factor previously underestimated.

Graft downsizing during ex vivo lung perfusion: case report and technical notes.

Among patients with respiratory insufficiency awaiting lung transplantation, small adult patients have a lower opportunity of receiving size-matched pulmonary grafts, because of the shortage of donors, particularly those of small size. Reducing the size of an oversized graft is one of the methods to increase the donor pool; similarly, exxa0vivo lung perfusion is an emerging technique aimed toward the same purpose. We describe how we combined the 2 techniques (lobar transplantation plus contralateral nonanatomic graft reduction during exxa0vivo lung perfusion) to overcome graft shortage in a clinical case. For the 1st time, this case report demonstrates that surgical manipulation during exxa0vivo lung perfusion does not affect the functional improvement in a lung previously judged to be not suitable for transplantation. The 6-month follow-up results are similar to those of standard bilateral lung transplantation.

Omentoplasty and Thoracoplasty for treating postpneumonectomy bronchopleural fistula in a patient previously submitted to aortic prosthesis implantation

Bronchopleural fistula following pneumonectomy is a serious and frightening complication in chest surgery with a high mortality rate. The possibility of curing this complication using a conservative treatment is extremely poor. Below we describe a case of a patient affected by left pleural empyema due to a postpneumonectomy bronchopleural fistula. The patient had previously undergone an aortic prosthesis implantation. He was successfully treated using omental pedicle in order to cover the bronchial stump, to fill the pleural space and to protect the aortic prosthesis. He also underwent thoracoplasty to collapse the residual pleural space. The postoperative course was uneventful. During the follow-up, after thirty months, the patient was asymptomatic, and no recurrence of the fistula was present.

Video-assisted pulmonary lobectomy combined with transmanubrial approach for anterior Pancoast tumor resection: case report

BackgroundThe mini-ivasive approach to superior sulcus tumors is an uncommon procedure that is still far from standardization. We describe a hybrid surgical technique to approach “en block” chest resection and pulmonary lobectomy for anterior superior sulcus tumors.Case PresentationA patient affected by right anterior Pancoast tumor surgically staged as cT4N0M0 (suspected anonymous vein invasion) underwent chemo-radiation induction therapy with satisfactory tumor reduction. The surgical operation comprised an initial VATS approach to the hilar structures followed by a limited C-shaped anterior contra-incision; finally, the right upper lobe “en block” with the anterior part of the first and second rib was removed. The whole procedure was conducted with the patient in the supine position; no rib retractors were used. The definitive stage was ypT0N0M0. The patient had an uneventful hospital stay and at the 9 months follow-up she was free from disease and post-thoracotomy syndrome.ConclusionsIn our opinion such hybrid VATS procedure has several advantages: starting with thoracoscopy it is possibleto exclude previously undetected pleural dissemination and to precisely define the tumor location as well as limits of the thoracic wall resection; time could be spared maintaining the patients in the supine position for both surgical times; postoperative pain and post-thoracotomy syndrome could be minimized avoiding the use of any rib retractor.

Color-Doppler sonography patterns in endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph-nodes

BACKGROUNDnEndobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is commonly used for the pathological diagnosis in patients with mediastinal lymphadenopathy. Even though the accuracy of EBUS-TBNA is considered high, several authors have tried to outline characteristic ultrasound criteria for malignant mediastinal lymph-node identification to maximize this accuracy. Recently, a color-Doppler patterns classification has been proposed by Nakajima to target suspected mediastinal lymph-nodes. The aim of this study was to assess such classification.nnnMETHODSnClinical, sonographic and pathological data of patients with suspected malignant mediastinal lymph-nodes on computed tomography (CT) and/or on positron emission tomography (PET) were prospectively recorded. On the basis of color-Doppler patterns, mediastinal lymph-nodes were classified in four grades and the bronchial-artery inflow sign was noted according to the Nakajima classification. The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predicted value (NPV) and accuracy were calculated using standard definitions.nnnRESULTSnSeventy-five patients were enrolled in this prospective study, median age 66 years; 85% of patients had primary lung cancer and 15% had extra-thoracic malignancy. EBUS-TBNA was performed in 87 lymph-nodes (rate 1.16 per patient); 6 lymph-nodes had inadequate samples and were excluded from the analysis; 64 nodes were confirmed as malignant and 17 nodes as benign. Color-Doppler patterns classification was as follow: grade 0-I, 14 lymph-nodes; grade II-III, 67 lymph-nodes; bronchial-artery inflow sign, 8 lymph-nodes. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy of the classification were 0.93, 0.64, 0.84, 0.6 and 0.81 respectively.nnnCONCLUSIONSnThe color-Doppler sonography is a fast, reproducible and effective tool that could help in targeting suspected malignant lymph-nodes during EBUS-TBNA. The current study validates the efficacy of the color-Doppler patterns classification proposed by Nakajima.