Pulmonary artery (PA) can be infiltrated by primary lung cancer or by a metastatic N1 lymph node with extracapsular extension. Lobectomy associated with PA reconstruction has been reported to be a valid option in both situations. However, up to now, no study has been conducted in order to compare results from patients undergoing reconstructive surgery for primary lung cancer PA infiltration with those undergoing PA reconstructions for metastatic single N1 infiltration. Hereby, we report our experience in this setting.

Patients with breast cancer have a relatively favorable long-term prognosis compared with other malignancies. The increase in survival puts these patients at risk of developing other primary tumors, including lung cancer. We hereby present our experience in this setting, reporting characteristics and results of patients who underwent surgery for second primary lung cancer after first primary breast cancer.

The comment from Dr. Ludwig (1) to ore recent paper on lower sleeve lobectomy, the so-called “Y” sleeve (2), is interesting and it deals on some important points related to technical aspects in this setting. It is a pleasure to reply to an author that has published important contributions on sleeve lobectomy, reporting, over time, results from patients that had undergone sleeve lobectomy and pneumonectomy.

s 24th European Conference on General Thoracic Surgery 29 May–1 June 2016, Naples, Italy Session II: Videos I

Objectives: The management of postoperative pain in thoracic surgery is an open issue. The aim of this study is to compare postoperative pain after a videothoracoscopic lobectomy versus a minithoracotomy approach. Methods: Between April 2011 and January 2013 we enrolled in a prospective, non-randomized study, 145 patients undergoing pulmonary lobectomy with lymphadenectomy for stage I lung cancer. In 75 cases (group A), surgery was performed through a videothoracoscopic approach and infiltration with ropivacaine before incision. In 70 cases (group B) surgery was undertaken through a minithoracotomy with intrapleural intercostal nerve block and intercostal muscle flap. Pain was assessed by visual analogue scale (VAS), lung function by spirometry and six-minute walk test before surgery, at 48 h and one month after surgery. Results: Patients were stratified by age, sex, lung function, type and duration of surgery. Mean hospital stay was 4.6 days for group A and 6.7 days for group B (P = 0.01). The differences between mean postoperative pain values were significant at 1 h, 12 h, 24 h and 48 h (P = 0.01). In group A mean preoperative FEV1 values were 2.65 ± 0.61, and 1.83 ± 0.65 and 2.09 ± 0.56 respectively at 48 h and one month; in group B they were 2.70 ± 0.71 preoperatively and 1.33 ± 0.52 and 1.82 ± 0.63 respectively at 48 h and one month. In group A, mean preoperative walking test values (metres) were 426.85 ± 0.51, and 371.23 ± 0.55 and 392.07 ± 0.56 respectively at 48 h and one month; in group B they were 421.75 ± 0.47 preoperatively and 312.03 ± 0.51 and 331.82 ± 0.53 respectively at 48 h and one month. Conclusions: The videothoracoscopic approach in the treatment of stage I lung cancer reduces postoperative pain, allowing patients to rapidly return to normal daily activities.

Although sleeve lobectomy (SL) is considered the best therapeutic option in locally advanced non-small cell lung cancer (LA-NSCLC) patients even when pneumonectomy (PN) is tolerated, its feasibility and long-term results after induction therapy (IT) are very rarely investigated. We present the results of a multicentre experience. From January 1990 to December 2012, patients from 3 tertiary referral centres underwent SL (bronchial, arterial or both) or PN for LA-NSCLC after IT (chemotherapy alone or concurrent radio-chemotherapy). The indication to SL was done whenever technically possible. Clinical and pathological variables were collected and perioperative results were assessed and compared in both groups. Long-term survival was investigated according to clinical and pathological features and calculated by the Kaplan-Meier method and log-rank test as well as by the Cox proportional hazard regression model. There were 119 patients, 94 male/female = 94/25. PN was performed in 68 patients and SL in 51 patients. Overall 30-day mortality and morbidity were 2.9% and 22.1% for PN vs 3.9% and 9.8% for SL, respectively. One-year, 3-year and 5-year survival rates were: 82.4%, 50.9%, 43.1% in PN vs 92.5%, 60.5%, 53.8% in SL, respectively. Overall recurrence rate was 32/66 (47.0%) in PN and 21/49 (42.8%) in SL (P = 0.34) and among these, 8/66 local recurrences in PN (12.1%) vs 11/49 in SL (22.4%) (P = ns). The Cox analysis suggested N-status and right side as independent mortality risk factors (HR = 1.96 [CI 95%: 1.12-3.44], P = 0.018 and HR = 2.96 [CI 95%: 1.13-8.66], P = 0.047, respectively) in SL-group. Also, N status and right side were powerful risk factors of relapse (HR = 2.33 [CI 95%: 1.17-4.64], P = 0.016 and HR = 2.96 [CI 95%: 1.13-8.66], P = 0.046 respectively), in patients who had undergone SL. For LA-NSCLC, a SL represents a safe and effective surgical option when compared to PN even after IT, with comparable early and long-term results. All authors have declared no conflicts of interest.

AIM:Pneumonectomy is the standard surgery for resectable locally advanced lung cancer. Objectives of this study were: 1) to assess the overall survival; 2) to evaluate the pulmonary and cardiac function impairment; 3) to monitor quality of life (QoL) in a consecutive series of patients undergoing pneumonectomy, defining the potential risk factors of a poor prognosis.METHODS:From January 2003 to March 2010, 71 patients undergoing pneumonectomy for lung cancer or mesothelioma were prospectively enrolled in this study. Twenty-six patients underwent right pneumonectomy (2 of them underwent intrapericardial pneumonectomy), 31 left pneumonectomy (3 of them underwent intrapericardial pneumonectomy), 3 extended pneumonectomy, 3 extrapleural pneumonectomy and 5 patients underwent completion pneumonectomy. Three patients were not included in the study for early postoperative deaths (4.3%). All patients underwent complete preoperative assessment and one year after surgery. QoL was assessed by a questionnaire.RESULTS:One and five-year survival rate was 93% (N.=63) and 20% (N.=14), respectively. Mean values of FEV1 decreased from 2.59±0.75 L to 1.8±0.72 L (P<0.001). One year after surgery all patients showed moderate tricuspid valve insufficiency, PASP significantly higher and right ventricular free wall thickness moderately increased. An increased negative effect was recorded in the QoL scores with P<0.001. Three clinical and surgical parameters were identified as risk or protective factors for the survival outcome.CONCLUSION:Postoperative mortality (4.3%) and five-year survival (20%) after pneumonectomy seem to be satisfactory. Late cardiopulmonary insufficiency is uncommon and acceptable QoL is still achievable.

Stage T4 non small cell lung cancer (NSCLC) includes an heterogeneous group of locally advanced tumors. Results of surgery alone and of chemo and/or radiotherapy are disappointing with 5-year survival rates under 10%. Although palliative chemo-radiotherapy is the treatment of choice in most cases, radical resection has shown prognostic benefit in selected groups of patients with tumor infiltrating Superior Vena Cava, carina, aorta, left atrium and vertebral bodies. Completeness of resection and absence of mediastinal nodal involvement are fundamental conditions for the long-term success of surgery. Increased postoperative 30-day mortality and 90-day mortality rates have been reported up to 8% and 18% respectively. Neoadjuvant therapy, in the last decades, has shown to improve survival of T4 NSCLC patients undergoing surgery and to increase the number of patients suitable for surgical resection. Surgical resection is not indicated in patients with neoplastic pleural effusion since it is generally related to a worse prognosis in such cases. Conversely, patients with T4 tumor due to neoplastic satellite nodule in the same lobe are good surgical candidates. In some studies, these patients show a significant survival advantage after surgical treatment with respect to patients with other types of T4 tumors, when no mediastinal nodal involvement is associated.

Postoperative alveolar fistula (AF) associated with pleural cavity (PC) is a serious complication and a therapeutic challenge in thoracic surgery. The purpose of this study was to assess the efficacy of the use of the autologous platelet gel for the treatment of AF and PC. We treated a patient with post lung resection persistent alveolar fistula using a autologous platelet gel, a cellular compose produces at the Division of Immunohaematoligy and Trasfusion. The platelet gel-PRP (Platelet-Rich Plasma) is a biological material made of autologous platelets, extracted from a small amount of the patient's blood, centrifuged at 1100 g for 9 min. The PRP obtained was activated by addition of autologous thrombin and calcium chloride to form a matrix of fibrin (PRFM) thick. The patient presented important air leak after middle lobe wedge resection for solitary lung lesion with standard open decortication for important pleural adhesions post pleuritis. On postoperative day XIII the patient developed a thoracic empyema and consequently underwent a antibiotic pleural irrigation through the chest drainage based on the microbiological analysis of the pleural fluid. After a week we obtained the resolution of the empyema but a residual space remained and air leak persisted. We treated the patient with autologous platelet gel. We administer 7.5 mL of the autologous platelet gel across the chest drainage ever 72 hours for 3 times. After the third application we had the closure of the cavity and the cessation of air leak. Autologous platelet gel is easy to use, safe and inexpensive. It can be considered a valid therapeutic option in selected patients with a alveolar fistula and a lung partial re-expansion. The product consist of a significant amount of cellular components with healing anti-inflammatory an proregenerative properities that permit the body to heal tissue wounds faster and more efficiently. A sterile pleural cavity is fundamental conditions for the final success of the procedure.

We previously developed murine and chimeric antibodies against a specific epithelial ovarian carcinoma (EOC) marker, named folate receptor (FR), and promising results were obtained in phase II trials. More recently, we successfully generated a completely human Fab fragment, C4, by conversion of one of the murine anti-FR antibodies to human antibody using phage display and guided selection. However, subsequent efforts to obtain C4 in a dimer format, which seems especially desirable for EOC locoregional treatment, resulted in a highly heterogeneous product upon natural dimerization and in a very poor production yield upon chemical dimerization by a non-hydrolyzable linker to a di- Fab -maleimide (DFM). We therefore designed, constructed and characterized a large Fab dual combinatorial human antibody phage display library obtained from EOC patients and potentially biased toward an anti-tumor response in an effort to obtain new anti-FR human antibodies suitable for therapy. Using this library and guiding the selection on FR-expressing cells with murine/human antibody chains, we generated four new human anti-FR antibody (AFRA) Fab fragments, one of which was genetically and chemically manipulated to obtain a chemical dimer, designated AFRA-DFM5.3, with high yield production and the capability for purification scaled-up to clinical grade. Overall affinity of AFRA-DFM5.3 was in the 2-digit nanomolar range, and immunohistochemistry indicated that the reagent recognized the FR expressed on EOC samples. 131 I-AFRA-DFM5.3 showed high immunoreactivity, in vitro stability and integrity, and specifically accumulated only in FR-expressing tumors in subcutaneous preclinical in vivo models. Overall, our studies demonstrate the successful conversion of murine to completely human anti-FR antibodies through the combined use of antibody phage display libraries biased toward an anti-tumor response, guided selection and chain shuffling, and point to the suitability of AFRA5.3 for future clinical application in ovarian cancer.

can be the ther-apeutic of choice for solid tumors due to shorter circulat-ing half life and a higher tumor penetration, bothcharacteristics well suited in a radio immunotherapy(RIT) approach.Ovarian cancer is the leading cause of death among gyne-cological tumors. Standard first line therapy consists ofsurgery followed by chemotherapy cycles. About 90% ofpatients relapse with a 5-year survival rate of 5–20% [1].So far, second line chemotherapy after clinical relapse hasshown limited efficacy. With the advancement of therecombinant biotechnology, a novel approach based onhuman monoclonal antibody immunotherapy has beganto be investigated. The alfa folate receptor ( αFR), which isa 38000 Dalton anchored membrane protein, is overexpressed in more than 90% of ovarian carcinoma cells,and in 60% of other gynecological carcinomas [2]. In con-trast to normal epithelial cells, ovarian carcinoma cellsexpress this receptor on their external surface making itaccessible for binding to monoclonal antibodies.The basic concept of our project is to produce a fullhuman F(ab')

The human chemokine CCL2 gene was expressed in the yeast P.pastoris and gave rise to a mixture of differently glycosylated recombinant proteins. In comparison to non-glycosylated E.coli-derived CCL2, glycosylated yeast CCL2L was 4-20 times less active in a chemotactic assay in vitro. However, CCL2L could maintain full activity upon prolonged incubation at 37 degrees C, whereas the non-glycosylated chemokine readily lost activity. It could be hypothesized that glycosylation is a mechanism used by the organism to modulate CCL2 stability. The partial loss of specific activity due to glycosylation is balanced by the advantage of prolonging the effectiveness of chemokine. Thus, differential glycosylation allows one to obtain highly effective short-lived CCL2 or less-effective long-lived CCL2 and may thus represent a novel mechanism of adaptation to pathological versus physiological conditions.

The apoptosis-defective lpr (fas) mutation in MRL mice causes the early onset of a lupus-like autoimmune disease with concomitant inflammation. In order to analyse the consequences of the impaired Fas-dependent apoptosis on inflammation, the susceptibility to apoptosis of polymorphonuclear leukocytes (PMN), obtained from MRL lpr/lpr mice, has been studied. Peritoneal PMN from lpr/lpr and control (+/+) mice were recruited with a mild inflammatory stimulus. The number of cells collected from the peritoneal cavity of young lpr/lpr mice was comparable to that obtained from age-matched control mice, indicating that PMN homeostasis is maintained regardless of the loss-of-function Fas mutation. Recruited neutrophils were exposed in culture to apoptosis-inducing stimuli. Treatment with agonist anti-Fas antibody increased apoptosis of +/+ PMN, but did not affect lpr/lpr PMN which do not express Fas on their surface. However, lpr/lpr PMN could undergo both spontaneous and stimulus-induced apoptosis in a fashion comparable to or higher than that of control +/+ mice. Analysis of mRNA expression revealed that lpr/lpr PMN have reduced expression of IL-18, whereas IL-1beta, IFNgamma, caspase 1 and caspase 3 are expressed at levels comparable to those of +/+ cells. However, caspase-3-like activity was higher in PMN from lpr/lpr mice than in +/+ cells, and correlated with enhanced apoptosis. It could be concluded that in young, uncompromised lpr/lpr mice, PMN homeostasis is still fully regulated through the involvement of Fas-independent, compensatory, apoptotic mechanisms. This could include an increased participation of caspase 3 in the apoptotic pathway, consequent to enhanced activation of the enzyme and to the decreased production of IL-18, which acts as a competitive caspase 3 substrate.

The role of endogenous IL-1 beta in regulating spontaneous and Fas-triggered apoptosis of human PMN has been studied in relation to the activity of the IL-1 beta -generating enzyme ICE (caspase-1), an enzyme also involved in the mechanism of cell death, Upon in vitro culture, PMN undergo spontaneous apoptosis and express increasing levels of IL-1 beta, caspase-1- and caspase-3-like enzymes. Endogenous IL-1 beta protects PMN from apoptosis, since inhibition of either IL-1 beta or caspase-1 activity can accelerate PMN apoptotic death. Thus, in spontaneous PMN apoptosis caspase-1 essentially plays an anti-apoptotic role by inducing maturation of protective IL-1 beta, whereas other molecules are responsible of driving apoptosis, Upon Fas triggering, PMN apoptosis is greatly accelerated, in correlation with increased caspase activity, whereas IL-1 beta production is not augmented. Inhibition of IL-1 beta activity can increase Fas-induced apoptosis, whereas caspase-1 inhibitors are without significant effect, It is hypothesized that in Fas-induced PMN apoptosis caspase-1 has a double role: it can protect from apoptosis through generation of protective IL-1 beta, as in spontaneous apoptosis, and it can also exert pro-apoptotic activity which counterbalances the protective effect and allows accelerated apoptosis.