Advanced medical interventions in pleural disease

The burden of a number of pleural diseases continues to increase internationally. Although many pleural procedures have historically been the domain of interventional radiologists or thoracic surgeons, in recent years, there has been a marked expansion in the techniques available to the pulmonologist. This has been due in part to both technological advancements and a greater recognition that pleural disease is an important subspecialty of respiratory medicine. This article summarises the important literature relating to a number of advanced pleural interventions, including medical thoracoscopy, the insertion and use of indwelling pleural catheters, pleural manometry, point-of-care thoracic ultrasound, and image-guided closed pleural biopsy. We also aim to inform the reader regarding the latest updates to more established procedures such as chemical pleurodesis, thoracentesis and the management of chest drains, drawing on contemporary data from recent randomised trials. Finally, we shall look to explore the challenges faced by those practicing pleural medicine, especially relating to training, as well as possible future directions for the use and expansion of advanced medical interventions in pleural disease

The optimization of the diagnostic work-up in patients with suspected obstructive lung disease

Contains fulltext : 87775.pdf (publisher's version ) (Open Access)BACKGROUND: Pulmonary function testing is a key procedure in the work-up of patients who are suspected of having asthma and chronic obstructive lung disease (COPD). Therein, clinical visits and pulmonary function tests (PFTs) are the major contributors to the overall financial costs.The aim of this study was to assess whether a specific diagnostic test protocol contributes to the optimization of the work-up of patients who are suspected of having asthma and COPD. METHODS: A prospective, single-blind, and randomized controlled study was performed. In the control group (CG), all of the PFTs that were ordered by the lung specialist were carried out. In the experimental group (EG), specific PFTs were selected according to our protocol. The primary end point was the total cost of achieving a final diagnosis. RESULTS: One hundred and seventy-nine patients were included into this study: 86 in the CG and 93 in the EG. The mean number of tests to diagnosis was 3.8 in the CG versus 2.9 in the EG (P < 0.001). The mean number of redundant PFTs before diagnosis was 1.2 in the CG versus 0.08 in the EG (P < 0.001). The number of patients who required an additional outpatient visit to complete diagnosis was higher in the CG in comparison to the EG (P = 0.02). The mean cost of work-up per diagnosis was euro227 in the CG versus euro181 in the EG (P < 0.001). CONCLUSIONS: In this group of patients with suspected obstructive lung disease, protocol-driven, PFT-based selection is more cost-effective than test selection at the discretion of lung physicians

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival