CT-guided percutaneous biopsies of mediastinal and paramediastinal masses in the lateral decubitus position.

BACKGROUND: Percutaneous parasternal puncture is a common procedure that allows sampling of mediastinal lesions. The trans-pulmonary route is sometimes mandatory in the dorsal position and is associated with complications such as pneumothorax. METHODS: Our study explored the efficacy of the lateral decubitus position in avoiding the trans-pulmonary route. Sixteen patients were included between 2005 and 2019. In three patients, the procedure was intended to place fiducial markers. RESULTS: No pneumothorax or hematoma occurred. Access to the lesion was not possible in 1 patient. A histological diagnosis was made for all patients undergoing sampling. This technique seems to be safe and efficient. KEY POINTS: • Parasternal access to mediastinal and paramediastinal lesions whenever a trans-pulmonary crossing is mandatory in the dorsal position is safe, simple, and efficient in the lateral decubitus position.

Video-assisted mediastinoscopy is safe in patients taking antiplatelet or anticoagulant therapy.

BACKGROUND: The aim of this study was to report our experience with video-assisted mediastinoscopy (VAM) in patients taking antiplatelet (AP) or anticoagulant therapies focusing on perioperative complications (especially haemorrhagic). PATIENTS AND METHODS: We have done a retrospective study from a prospectively maintained database with diagnostic VAM (01/2008-06/2012). We included 54 patients with AP (41 patients - Group A) and anticoagulant (13 patients - Group B) therapies. The control group was formed by 263 patients (Group C). Data regarding the clinical records of the patients, operative time, per- and post-operative complications, total numbers of biopsies and the results of the pathologic examination were collected. We compared the groups A+B versus C, and then A versus C. Statistical differences were calculated by Chi-square test. RESULTS: In Group A, we had two minor complications: cardiac arrhythmia and peroperative minor haemorrhage. The mean operative time was 29 min and the mean post-operative stay was 1.08 days. In Group B, we had one minor complication: Peroperative minor haemorrhage. The mean operative time was 35 min and the mean post-operative stay was 1.07 days. In Group C, the mean operative time was 28 min. One death occurred (mortality rate of 0.38%) because of cardiac arrest at the induction of anaesthesia. One major complication occurred (severe respiratory insufficiency needing re-intubation) and eight minor complications. Morbidity rate was 2.28%. Mean post-operative stay was 1.14 days. No statistical difference was noted between groups. CONCLUSION: VAM can be safely performed in patients receiving AP or anticoagulant treatments. There is no increase in peroperative bleeding or post-operative compressive cervico-mediastinal haematoma.

Is There a Place for Thoracoscopic Enucleation of Esophageal Gastrointestinal Stromal Tumors?

BACKGROUND: Esophageal gastrointestinal stromal tumors (E-GISTs) represent less than 1% of all GISTs. The rarity of this lesion precludes the realization of randomized studies, and its treatment remains a matter of debate. We aimed to evaluate the feasibility of enucleation by video-assisted thoracic surgery (VATS) for low- to intermediate-risk E-GIST. METHODS: We performed a retrospective review of patients treated by enucleation through VATS between January 2004 and January 2014 and reviewed the literature. RESULTS: We included five patients (four men and one woman). Mean age was 53 years (range: 49-79). Three patients were diagnosed because of dysphagia and two others incidentally. The diagnosis was made by immunostaining demonstrating CD117 expression on tumor cells. The mitotic index of all E-GISTs was low (≤ 5 per 50 high-power field). Median postoperative follow-up was 5.5 years, and there was no recurrence. CONCLUSION: Thoracoscopic enucleation of E-GIST seems to represent a valuable option as the postoperative morbidity/mortality is low and the oncological outcome is good for low-to-intermediate grade of malignity tumors.This is a retrospective study focused on minimally invasive treatment of E-GIST. We evaluated the feasibility of VATS enucleation of low-to-medium grade of malignity E-GIST.

Use of circulating tumor cells in prospective clinical trials for NSCLC patients - standardization of the pre-analytical conditions.

BACKGROUND: Circulating tumor cells (CTCs) hold potential for noninvasive diagnosis, prognosis and prediction testing in non-small cell lung cancer (NSCLC) patients. Minimizing degradation or loss of CTCs is pivotal for detection and profiling of the low abundance and fragile CTCs, particularly in clinical trials. We prospectively investigated (NCT02372448) whether a new blood collection device performed better compared to commonly used K3EDTA tubes, when subjected to long-term sample storage. METHODS: Blood samples were drawn into K3EDTA and blood collection tubes (BCT) (Streck), and filtered by the Isolation by SizE of Tumor/Trophoblastic Cells (ISET® system), for CTC detection in two study populations of NSCLC patients; the training set of 14 patients with stage II/IV NSCLC, and the validation set of 36 patients with stage IV NSCLC). MET expression was evaluated by immunocytochemistry (ICC) and anaplastic lymphoma kinase (ALK) gene rearrangement by break-apart fluorescence in situ hybridization (FISH) on ISET-enriched CTCs. RESULTS: Blood processed after 24 h and 48 h in BCT tubes showed stable CTCs counts and integrity, whereas CTCs in K3EDTA tubes showed an altered morphology in all patients. CTCs recovered in BCT or K3EDTA tubes at 24 and 48 h were evaluable by ICC for MET expression and by FISH for ALK rearrangement. CONCLUSIONS: The BCT tubes gave a high yield and preserved the integrity of CTCs after 24 and 48 h of storage at room temperature, which facilitate their molecular characterization in NSCLC patients entering clinical trials.

Chemoradiation Therapy Followed by Surgery in the Treatment of Locoregionally Advanced Non-Small Cell Lung Cancer.

BACKGROUND: The aim of this study was to explore the feasibility of surgery after two induction cycles of cisplatin-docetaxel followed by concomitant 40 Gy chemoradiation in the treatment of initially unresectable stage III non-small cell lung cancer (NSCLC; TAXCIS protocol), and to evaluate overall survival (OS) and recurrence-free survival (RFS) and recurrence risk factors over a larger cohort of patients with a subgroup analysis of patients treated by pneumonectomy. METHODS: Between 2004 and 2014, a total of 37 patients were treated. Only patients responding to induction treatment were included. RESULTS: We operated on 32 stage IIIA and 5 stage IIIB patients. We performed 12 pneumonectomies, 1 bilobectomy, and 23 lobectomies. Status ypT0N0 was obtained for 35% of the patients. Surgery was considered R0 in 86% of the cases. Postoperative morbidity was 21.6% with a mortality of 10.8% (25% after pneumonectomy). OS was 50% at 5 years. The median RFS was 50 months. RFS was 47% at 5 years. Local or locoregional recurrence was diagnosed in 10.8% of the patients, and distant metastasis in 35.1%. Recurrence risk factors were pneumonectomy (p = 0.001) and a histologically incomplete response (p = 0.04). CONCLUSION: The TAXCIS protocol followed by surgery is feasible for initially unresectable NSCLC stage IIIA and B patients. Benefit was noted in responding lesions with better OS and PFS, except after pneumonectomy.

PD-L1 expression in basaloid squamous cell lung carcinoma: Relationship to PD-1+ and CD8+ tumor-infiltrating T cells and outcome.

PD-1/PD-L1 inhibitors demonstrated durable clinical responses in patients with lung squamous cell carcinoma. However, the expression pattern of PD-L1 and the presence of CD8+ and PD-1+ tumor-infiltrating T cells in the basaloid variant of squamous cell carcinoma remain unknown. immunohistochemistry analysis of PD-L1 expression, with three recently validated monoclonal antibodies used in clinical trials (clones SP142, SP263, and 28-8), and detection of CD8+ and PD-1+ tumor-infiltrating T cells was performed on whole-tissue sections from 56 patients following surgery for basaloid squamous cell carcinoma. Data were correlated to clinicopathological parameters and outcome. Fair to poor concordance was observed between the SP142 vs SP263 clones, and SP142 vs 28-8 (κ range, 0.018-0.412), while the 28-8 and SP263 demonstrated a strong correlation in both the tumor cell and immune cell compartments (κ=0.883, and κ=0.721). Expression of PD-L1 correlated with a high content of CD8+ and PD-1+ tumor-infiltrating T cells when using SP142 (P=0.012; P=0.022), but not with SP263 or 28-8 (P=0.314; P=0.611). In the multivariate analysis, we found significantly better disease-free and overall survival rates for high PD-L1 expression with SP142, CD8+ and PD-1+ tumor-infiltrating T cells (P=0.003; P=0.007). No significant prognosis value was observed for SP263 and 28-8 clones, except a correlation between improved overall survival and SP263 in the univariate analysis (P=0.039), not confirmed in the multivariate model. In conclusion, we report that the expression of PD-L1 and the content of CD8+ and PD-1+ tumor-infiltrating T cells is an independent indicator of better outcome in basaloid squamous cell carcinoma patients, although the observed effect is dependent on the PD-L1 immunohistochemistry assay.

[Setting up a department of molecular pathology in oncology in a pathology laboratory (LPCE, CHU de Nice)]. / Mise en place d'un secteur de pathologie moléculaire en oncologie au sein d'un laboratoire d'anatomie pathologique (LPCE, CHU de Nice).

The advent of targeted therapies and personalized medicine in oncology has led in France to the settlement and organisation of a network of hospital molecular genetic platforms under the impetus of the National Cancer Institute (INCa). These platforms are, according to the concerned sites, integrated or not in pathology laboratories. The development of molecular biology methods, the choice of the procedures, the establishment of sample workflow, the quality control and the selection of the genomic alterations to be detected on each platform, have been left to the discretion of the different laboratories. Based on calls for project made by the INCa, hospital molecular genetic platforms were able to adapt their activity according to the assigned budgets. While the presence of some genomic alterations (i.e. KRAS gene mutations in metastatic colon adenocarcinoma or EGFR gene mutations in lung adenocarcinomas), may lead to administration of targeted therapies under the Marketing Authorization Application (MAA), others are associated with therapeutic clinical trials. However, increasing number of MAA for new molecules targeting genomic alterations is likely in the near future. In this context, it is necessary to quickly adapt the organisation of work of the hospital pathology laboratories performing molecular biology tests in order to meet the growing demand of oncologists in the field of targeted therapies. The purpose of this article is to describe the different steps of the settlement of a molecular genetic platform in an academic pathology laboratory (LPCE, CHU de Nice) and to show the experience of this laboratory specifically oriented on the support of the morphological and molecular diagnosis of lung cancer, thyroid cancer and malignant melanoma.

Case reports: a variety of clinical presentations and long-term evolution of Bochdalek hernias.

Bochdalek hernias are the most common congenital diaphragmatic hernias, followed by Morgagni hernias. The failure of closure of the pleuroperitoneal membrane results in a posterolateral foramen, which can remain silent until adulthood. They remain a rare pathology with nearly a hundred cases published. Its clinical presentation is variable, making its diagnosis challenging for clinicians. Additionally, its symptoms are not necessarily representative of the content of the hernia. Its management is balanced between the abdominal and the thoracic approaches. However, no guidelines or algorithms are available to help surgeons in the decision-making process. We report here four consecutive cases of symptomatic Bochdalek hernias. Each case has a singular presentation, and we share how they were approached at our institution. In particular, this series shows no reoccurrence in 10+ years of follow-up in two cases and 20+ in one case, underlying the importance of surgical management when Bochdalek hernias are symptomatic.

Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity.

Malignant pleural mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Through a large series of whole-genome sequencing data, integrated with transcriptomic and epigenomic data using multiomics factor analysis, we demonstrate that the current World Health Organization classification only accounts for up to 10% of interpatient molecular differences. Instead, the MESOMICS project paves the way for a morphomolecular classification of MPM based on four dimensions: ploidy, tumor cell morphology, adaptive immune response and CpG island methylator profile. We show that these four dimensions are complementary, capture major interpatient molecular differences and are delimited by extreme phenotypes that-in the case of the interdependent tumor cell morphology and adapted immune response-reflect tumor specialization. These findings unearth the interplay between MPM functional biology and its genomic history, and provide insights into the variations observed in the clinical behavior of patients with MPM.

Predictive clinical outcome of the intratumoral CD66b-positive neutrophil-to-CD8-positive T-cell ratio in patients with resectable nonsmall cell lung cancer.

BACKGROUND: The role of the interaction between tumor cells and inflammatory cells in nonsmall cell lung carcinoma (NSCLC) is unclear. In this study, the authors assessed the prognostic impact of intratumoral cluster of differentiation 66b (carcinoembryonic antigen-related cell adhesion molecule 8 [CD66b])-positive neutrophils and of the intratumoral CD66b-positive neutrophil-to-cluster of differentiation 8 (cell surface antigen T8 [CD8])-positive lymphocytes (the CD66b-positive neutrophil-to-CD8-positive lymphocyte ratio [iNTR]) in patients with resectable NSCLC. METHODS: Expression levels of CD66b and CD8 were evaluated by immunohistochemistry on tissue microarrays consisting of 632 NSCLC specimens from patients who underwent curative surgery. The relation between clinicopathologic variables and patient outcome was assessed. RESULTS: Intratumoral CD66b-positive neutrophils were elevated in 318 patients (50%). In univariate analysis, an increase in CD66b-positive cells was associated with a high cumulative incidence of relapse (CIR) (median CIR, 51 months for low CD66b-positive cell density; 36 months for high CD66b-positive cell density; P = .002) and trended toward worse overall survival (OS) (median OS, 57 months for low CD66b-positive cell density; 54 months for high CD66b-positive cell density; P = .088). The iNTR was elevated in 190 patients (30%). An increased iNTR was strongly associated with both a high CIR (median CIR: 43 months for an iNTR ≤1; 34 months for an iNTR >1; P < .0001) and poor OS (median OS: 60 months for an iNTR ≤1; 46 months for an iNTR >1; P < .0001). In multivariate analysis, independent prognostic factors for a higher CIR were high iNTR (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.56-0.90; P = .005) and tumor stage >I, (HR, 0.39; 95% CI, 0.30-0.52; P < .0001). Independent prognostic factors for worse OS were a high iNTR (HR, 0.70; 95% CI, 0.54-0.91; P = .007) and tumor stage >I (HR, 0.35; 95% CI, 0.26-0.47; P < .0001). CONCLUSIONS: The current results indicated that the iNTR is a novel, independent prognostic factor for a high rate of disease recurrence and poor OS in patients with resectable NSCLC.

The role of clips in preventing migration of fully covered metallic esophageal stents: a pilot comparative study.

BACKGROUND: Migration is the most common complication of the fully covered metallic self-expanding esophageal stent (SEMS). This study aimed to determine the potential preventive effect of proximal fixation on the mucosa by clips for patients treated with fully covered SEMS. METHODS: In this study, 44 patients (25 males, 57%) were treated with fully covered SEMS including 22 patients with esophageal stricture (4 malignant obstructions, 6 anastomotic strictures, and 12 peptic strictures) and 22 patients with fistulas or perforations (10 anastomotic leaks, 4 perforations, and 8 postbariatric surgery fistulas). The Hanarostent (n = 25), Bonastent (n = 5), Niti-S (n = 12), and HV-stent (n = 2) with diameters of 18 to 22 mm and lengths of 80 to 170 mm were used. Two to four clips (mean, 2.35 ± 0.75 clips) were used consecutively in 23 patients to fix the upper flared end of the stent with the esophageal mucosal layer. Stent migration and its consequences were collected in the follow-up assessment with statistical analysis to compare the patients with and without clip placement. RESULTS: No complication with clip placement was observed, and the retrieval of the stent was not unsettled by the persistence of at least one clip (12 cases). Stent migration was noted in 15 patients (34%) but in only in 3 of the 23 patients with clips (13%). The number of patients treated to prevent one stent migration was 2.23. The predictive positive value of nonmigration after placement of the clip was 87%. In the multivariate analysis, the fixation with clips was the unique independent factor for the prevention of stent migration (odds ratio, 2.3; 95% confidence interval, 0.10-0.01; p = 0.03). CONCLUSIONS: Anchoring of the upper flare of the fully covered SEMS with the endoscopic clip is feasible and significantly reduces stent migration.

Detection of circulating tumor cells as a prognostic factor in patients undergoing radical surgery for non-small-cell lung carcinoma: comparison of the efficacy of the CellSearch Assay™ and the isolation by size of epithelial tumor cell method.

Comparison of the efficacy of different enrichment methods for detection of circulating tumor cells (CTCs) before radical surgery is lacking in non-small-cell lung carcinoma (NSCLC) patients. Detection and enumeration of CTCs in 210 consecutive patients undergoing radical surgery for NSCLC were evaluated with the CellSearch Assay™ (CS), using the CellSearch Epithelial Cell Kit, and by the isolation by size of epithelial tumor (ISET) method, using double immunolabeling with anti-cytokeratin and anti-vimentin antibodies. CTCs were detected in 144 of 210 (69%) patients using CS and/or ISET and in 104 of 210 (50%) and 82 of 210 (39%) patients using ISET and CS, respectively. Using ISET, 23 of 210 (11%) patients had vimentin-positive cells with cytological criteria of malignancy. Disease-free survival (DFS) was worse for patients with CTCs compared to patients without CTCs detected by CS alone (p < 0.0001; log rank = 30.59) or by ISET alone (p < 0.0001; log rank = 33.07). The presence of CTCs detected by both CS and ISET correlated even better with shorter DFS at a univariate (p < 0.0001; log rank = 42.15) and multivariate level (HR, 1.235; 95% CI, 1.056-1.482; p < 0.001). CS and ISET are complementary methods for detection of CTCs in preoperative radical surgery for NSCLC. CTC detection in resectable NSCLC patients using CS and/or ISET could be a prognostic biomarker of great interest and may open up new avenues into improved therapeutic strategies for lung carcinoma patients.

Overexpression of carbonic anhydrase XII in tissues from resectable non-small cell lung cancers is a biomarker of good prognosis.

The pattern of protein expression in tumors is under the influence of nutrient stress, hypoxia and low pH, which determines the survival of neoplastic cells and the development of tumors. Carbonic anhydrase XII (CAXII) is a transmembrane enzyme that catalyzes the reversible hydration of cell-generated carbon dioxide into protons and bicarbonate. Hypoxic conditions activate its transcription and translation and enhanced expression is often present in several types of tumors. The aim of our study was to assess the prognostic significance of CAXII tumor tissues expression in patients with NSCLC. Five hundred fifty-five tumors were immunostained for CAXII on tissue microarrays (TMA) and the results were correlated with clinicopathological parameters and outcome of patients. CAXII overexpression was present in 105/555 (19%) cases and was associated with tumors of lower grade (p = 0.015) and histological type (p < 0.001), being significantly higher in squamous cell carcinoma. High CAXII expression correlated with better overall and disease-specific survival of patients with resectable NSCLC in univariate (p < 0.001) and multivariate survival analyses (p < 0.001). In conclusion, this is the first study demonstrating that a high CAXII tumor tissue expression evaluated on TMAs is related to a better outcome in a large series of patients with resectable NSCLC.

[The Nice CHU biobank experience to collect patients' informed consent for research context (2004-2009)]. / L'expérience de la tumorothèque du CHU de Nice pour le recueil des consentements éclairés dans le cadre de la recherche (2004-2009).

Over the last 10 years, significant financial support from the French National Institute of Cancer (INCa), the Ministry of Health (DGOS), and the Health and Research National Institute (Inserm) helped biobanks--of which tumour banks represent a prominent example of hospital-based infrastructures--to improve their operations, and in some instances to adopt the rules of Biological Ressource Centers as defined by OECD. Nowadays, the use of biological samples of human origin is strictly subordinated to regulations that integrate bioethical principles. However, in spite of the establishment of these regulations, requirement to obtain an authorisation and/or to register the biological collections with the Ministry of Research, many uncertainties persist. While French regulations mandate that samples can be used for research as long as patients did not oppose to such use, many biobank curators face practical and theoretical issues when establishing a Material Transfer Agreement with scientists, due to the lack of harmonization between national regulations--particularly due to a different perception of privacy and free will in anglo-american and other countries--and different demands on the side of private industry or editorial boards of scientific journals. The goal of this article is (1) to describe the procedure followed to collect patients' informed consent at the Biobank of CHU de Nice and (2) to assess the number of obtained consents in comparison to the number of collected samples between 01/09/2004 and 31/12/2009, the number of consents obtained before or after collecting the samples, and the number of patients' refusal to collect their biological resources. This balance-sheet is settled for the three major collections (thoracic, thyroid and head and neck tissues) from the Biobank of CHU de Nice. Results show that 88 % of consents were obtained during this period (82 % in a prospective manner and 6 % in a retrospective manner). Refusal was notified by writing in nine cases only. The percentage of consents varies slightly according to the collection involved and is stable from 2004 to 2009. Overall, our procedure is quite efficient at obtaining informed consents from a majority of patients for whom the tumour bank stores biological samples. This situation provides optimal conditions for the use of collected samples in the context of national and international research projects.

Occurrence and number of immune-related adverse events are independently associated with survival in advanced non-small-cell lung cancer treated by nivolumab.

It has been found that occurrence of immune-related adverse events (irAEs) is associated with outcome in the treatment of advanced non-small-cell lung cancer (NSCLC) with anti-programmed cell death (PD)-1 or anti-PDL1 agents. Independent correlation with survival was not consistently demonstrated and correlation with the number of toxicities was also not previously described. All patients treated with nivolumab for advanced NSCLC, in the second line setting, were retrospectively reviewed in a single-center from March 2015 to March 2017. Sixty-nine patients were identified. After a median follow-up of 13 months (95% CI: 10.8; 15.3), there were 46 tumor progressions and 37 deaths. The 6-month and one-year progression-free survival (PFS) and overall survival (OS) rates were 29%/61% and 24%/49%, respectively. Thirty-one patients (44.9%) presented irAEs. Patients presenting tumor response to previous chemotherapy had a higher rate of irAEs (P=0.01) and a better OS (HR=2, P=0.04). Occurrence of irAEs correlated with OS in multivariate analysis (HR=0.4, 95% CI [0.19; 0.8], P=0.02). The number of irAEs correlated with tumor response, PFS and OS in univariate analysis. Having≥2 irAEs correlated with better outcome compared with one irAE, which correlated with better tumor response and PFS in comparison with 0 irAE, in multivariate analysis. In this study, irAEs was associated with a better outcome in patients treated with nivolumab for advanced NSCLC in the second line setting. Interestingly, the number of irAEs correlated with tumor response and PFS.

EGFR and KRAS status of primary sarcomatoid carcinomas of the lung: implications for anti-EGFR treatment of a rare lung malignancy.

Sarcomatoid carcinomas (SC) of the lung are uncommon malignant tumors composed of carcinomatous and sarcomatous cell components and characterized by a more aggressive outcome than other histological subtypes of nonsmall cell lung cancer (NSCLC). Although epidermal growth factor receptor (EGFR)-targeted therapies have emerged as a promising therapeutic approach in patients with advanced typical NSCLC such as adenocarcinoma, the potential clinical activity of these drugs in lung SC is still unknown. To investigate this point, we have analyzed the status of 4 EGFR pathways biomarkers in a series of lung SC. EGFR protein expression, EGFR gene copy number, EGFR mutational status and KRAS mutational status were assessed in a series of 22 consecutive cases of primary lung SC. EGFR protein overexpression was observed in all the cases. High level of polysomy (>or=4 copies of the gene in >40% of cells) was detected in 5 cases (23%). No EGFR mutation was detected. KRAS mutations were found in 8 patients (38%; Gly12Cys in 6 cases and Gly12Val in 2 cases). The consistent EGFR protein overexpression and the high rate of KRAS mutation may contribute to the poorer outcome of lung SC in comparison with typical NSCLC. The rare incidence of increased EGFR gene copy number, the lack of EGFR mutation and the high rate of KRAS mutation observed in our series also suggest that most patients with lung SC are not likely to benefit from anti-EGFR therapies.

Video-assisted mediastinoscopy as a therapeutic tool.

BACKGROUND: Video-assisted mediastinoscopy (VAM) is a well-known method for surgical exploration of superior retrovascular mediastinal disease and for determining the staging of lung cancer. This study aimed to report the authors' experience using VAM therapeutically. METHODS: Between 1998 and 2007, 765 patients had VAM in the authors' service. For 742 of these patients, VAM was used to diagnose or stage a disease. The remaining 23 patients (3%) had VAM as a therapeutic procedure. Two groups of patients were studied: those who had VAM alone and those who had VAM associated with another procedure. These studies focused on indications, results, and specific morbidity and mortality. RESULTS: The VAM alone group (14 patients) underwent mediastinal lymphadenectomy for thyroid cancer (mean number of lymph nodes/positives, 16/6) (n = 4), closure of the left post-pneumonectomy bronchopleural fistula (n = 3), mediastinal cyst resection (n = 5), ectopic hyperfunctioning parathyroid resection (n = 1), and mediastinal hematoma evacuation (n = 1). This group had an operative time of 40 to 160 min and a hospital stay of 2 to 10 days. The group that had VAM associated with another approach (9 patients) had VAM during transhiatal esophagectomy for cancer (mean number of lymph nodes, 8) (n = 7), VAM combined with video-assisted thoracoscopic surgery (n = 1), and minithoracotomy for masses in the aortopulmonary window (unique metastasis from melanoma or thyroid cancer) (n = 1). This group had an operative time of 60 to 135 min and a hospital stay of 7 to 52 days. No specific mortality or morbidity occurred. Meanwhile, three patients died: two after bronchopleural fistula (respiratory insufficiency, severe sepsis) and one because of liver insufficiency. Two patients experienced myocardial ischemia or pneumonia after transhiatal esophagectomy. CONCLUSIONS: "Exploratory" VAM for mediastinal disease is an important training tool that can be applied further for a therapeutic purpose. The authors' experience has shown its potential. Its surgical indications and benefits deserve better identification.

Anatomical pulmonary resections for primary lung cancer in octogenarians within a dedicated care protocol.

BACKGROUND: The aim of this study was to assess the feasibility of major pulmonary resection for a limited non-small cell lung cancer (NSCLC) in octogenarians within a dedicated care protocol. METHODS: We retrospectively analyzed data of 55 octogenarians operated on in a single institution between January 2005 and December 2016. They were all included in a specific care protocol with systematic geriatric assessment and adaptation of the peri-operative care. We describe the results of post-operative morbidity, mortality, and survival after anatomical resection and radical lymphadenectomy. RESULTS: Mean age at the time of surgery was 82.1 years (80-86 years). Median Charlson's comorbidity score was 0 (0-3). All patients were classified Balducci 1 or 2. We performed 2 pneumonectomies (3%), 3 bilobectomies (5%), 47 lobectomies (85%) and 3 segmentectomies (5%). The median hospital stay was 11.5 days (7-31 days). The 30-day mortality rate was 3%. The total of relevant clinical complications (Clavien 3 to 5) was 16% (n=9). The Overall Survival at one, three and five years were, respectively: 83% (95% CI: 75-95%); 70% (95% CI: 56-87%); 58% (95% CI: 43-79%). CONCLUSIONS: Major pulmonary resection for primary lung cancer in octogenarians seems to be safe, with an acceptable morbidity, mortality and long-term survival rate, when processing to rigorous selection of the patients, within a dedicated care protocol.

Redefining malignant pleural mesothelioma types as a continuum uncovers immune-vascular interactions.

BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an aggressive disease related to asbestos exposure, with no effective therapeutic options. METHODS: We undertook unsupervised analyses of RNA-sequencing data of 284 MPMs, with no assumption of discreteness. Using immunohistochemistry, we performed an orthogonal validation on a subset of 103 samples and a biological replication in an independent series of 77 samples. FINDINGS: A continuum of molecular profiles explained the prognosis of the disease better than any discrete model. The immune and vascular pathways were the major sources of molecular variation, with strong differences in the expression of immune checkpoints and pro-angiogenic genes; the extrema of this continuum had specific molecular profiles: a "hot" bad-prognosis profile, with high lymphocyte infiltration and high expression of immune checkpoints and pro-angiogenic genes; a "cold" bad-prognosis profile, with low lymphocyte infiltration and high expression of pro-angiogenic genes; and a "VEGFR2+/VISTA+" better-prognosis profile, with high expression of immune checkpoint VISTA and pro-angiogenic gene VEGFR2. We validated the gene expression levels at the protein level for a subset of five selected genes belonging to the immune and vascular pathways (CD8A, PDL1, VEGFR3, VEGFR2, and VISTA), in the validation series, and replicated the molecular profiles as well as their prognostic value in the replication series. INTERPRETATION: The prognosis of MPM is best explained by a continuous model, which extremes show specific expression patterns of genes involved in angiogenesis and immune response.

Postoperative exacerbation of chronic obstructive pulmonary disease. Does it exist?

BACKGROUND: One of the characteristics of chronic obstructive pulmonary disease (COPD) is the tendency to develop acute exacerbation, defined by the presence of different clinical findings as worsening dyspnea, increase in sputum purulence and volume. This study was designed to verify if definition of acute COPD exacerbation is applicable to patients who underwent pulmonary surgery, and if it has any impact on postoperative morbidity and mortality. METHODS: This study was designed to prospectively enrol 1000 patients undergoing pulmonary resection for lung cancer from five different centres. Postoperative exacerbation of COPD was defined by the concomitant presence of three of the following five signs: deteriorating dyspnea, purulent sputum, bronchial secretion volume >10 ml/24 h, fever without apparent cause, and wheezing. The presence of concomitant pulmonary complications excluded the diagnosis of exacerbation, as they may present one or more of these signs. RESULTS: In the absence of respiratory complications, postoperative stay in exacerbated patients was significantly longer as compared to patients without exacerbation (6.3+/-1.3 vs 8.3+/-1.1, p=0.001). A postoperative exacerbation of COPD was recorded in 276 patients and 152 of them (55%) subsequently developed respiratory complications. Multivariate analysis established that risk factors for postoperative exacerbation are sex (female OR 0.54, CI 0.2-0.8), COPD class (OR 1.5, CI 1.1-8.1), and the postoperative prolonged use of antibiotics (OR 0.6, CI 0.2-0.9). CONCLUSIONS: Postoperative exacerbation of COPD is an existing, frequent clinical entity after lung resection and, when present, it increases the risk of pulmonary complications. The existing guidelines for the treatment of acute exacerbation should be adapted for the management of patients after lung resection in order to test the hypothesis that they could reduce respiratory morbidity.