Air leak and intraoperative bleeding in thoracic surgery: a Delphi consensus among the members of Italian society of thoracic surgery.

Background: Persistent air leak and the management of intraoperative blood loss are common threats in thoracic surgical practice. The availability of new procedures, technology and materials is constantly evolving topical hemostats and surgical sealants must be added to this toolkit. Topical hemostats and surgical sealants differ according to their chemical nature and physical characteristics, to their origin and mechanism of action, regulatory/registration and vigilance paths. A Delphi consensus was set to highlight the different points of view on the use of topical haemostatic products and sealants among the members of Italian Society of thoracic surgery. Methods: The board was formed by a group of five Italian experts; in the first phase after a careful review of the scientific literature and two rounds, the board finally generated 16 consensus statements for testing across a wider audience. During the second phase, the statements were collated into a questionnaire, which was electronically sent to a panel of 46 Italian surgeons, experts in the field. Results: Out of 46 Italian surgeons, 33 (72%) panel members responded to the Delphi questionnaire. All the items reached a positive consensus, with elevated levels of agreement, as demonstrated by the presence of a 100% consensus for nine items. For the remaining 7 statements the minimum level of consent was 88% (29 participants approved the statement and 4 disagreed) and the maximum was 97% (32 participants approved the statement and 1 was in disagreement). Conclusions: The present Delphi analysis shows that air leak and intraoperative bleeding are clinical problems well known among thoracic surgeons. Nevertheless, the aim of the scientific societies and of the group of experts is to execute the education activities in the surgery community. This Delphi survey suggest the need of wider and updated scientific information about technical and registration characteristics of most recent technologic solutions, such as the of topical hemostats and surgical sealants to provide healthcare and administrative staff with the opportunity to work and interact through a common and shared language and eventually to guarantee minimal requirements of assistance.

Coexpression of ΔNp63/p40 and TTF1 Within Most of the Same Individual Cells Identifies Life-Threatening NSCLC Featuring Squamous and Glandular Biphenotypic Differentiation: Clinicopathologic Correlations.

Introduction: Double occurrence of TTF1 and ΔNp63/p40 (henceforth, p40) within the same individual cells is exceedingly rare in lung cancer. Little is known on their biological and clinical implications. Methods: Two index cases immunoreactive for both p40 and TTF1 and nine tumors selected from The Cancer Genome Atlas (TCGA) according to the mRNA levels of the two relevant genes entered the study. Results: The two index cases were peripherally located, poorly differentiated, and behaviorally unfavorable carcinomas, which shared widespread p40 and TTF1 decoration within the same individual tumor cells. They also retained SMARCA2 and SMARCA4 expression, while variably stained for p53, cytokeratin 5, and programmed death-ligand 1. A subset of basal cells p40+/TTF1+ could be found in normal distal airways. Biphenotypic glandular and squamous differentiation was unveiled by electron microscopy, along with EGFR, RAD51B, CCND3, or NF1 mutations and IGF1R, MYC, CCND1, or CDK2 copy number variations on next-generation sequencing analysis. The nine tumors from TCGA (0.88% of 1018 tumors) shared the same poor prognosis, clinical presentation, and challenging histology and had activated pathways of enhanced angiogenesis and epithelial-mesenchymal transition. Mutation and copy number variation profiles did not differ from the other TCGA tumors. Conclusions: Double p40+/TTF1+ lung carcinomas are aggressive and likely underrecognized non-small cell carcinomas, whose origin could reside in double-positive distal airway stem-like basal cells through either de novo-basal-like or differentiating cell mechanisms according to a model of epithelial renewal.

Immunotherapeutic Advances for NSCLC.

Immunotherapy with antibodies against PD-1 or PD-L1, either alone or in combination with chemotherapy, has revolutionized treatment paradigms of non-small cell lung cancer (NSCLC) patients without oncogenic driver alterations. These agents, namely immune checkpoint inhibitors (ICIs), have also widely demonstrated a remarkable efficacy in locally advanced as well as in early-stage NSCLC. Assessment of tumor PD-L1 expression by immunohistochemistry has entered into routine clinical practice to select patients for immunotherapy, even though its predictive role has long been debated. Despite improved survival outcomes over standard chemotherapy, treatment with ICIs is associated with initial low response rate, with a significant proportion of patients not responding to these agents. Hence, novel appealing predictive biomarkers, such as those related to tumor cell signaling pathways, metabolism or the tumor microenvironment, have emerged as potentially useful to select those patients most likely to benefit from immunotherapy. Moreover, most patients ultimately develop acquired resistance to ICI treatment over time and novel therapeutic strategies are urgently needed to overcome or delay resistance. Herein, we provide an overview on recent advances in immunotherapy in NSCLC, focusing on updated results from studies on ICIs in different disease settings and at different lines of treatment. We further describe currently emerging predictive biomarkers, beyond PD-L1, to optimize patient selection and novel strategies to improve clinical outcomes.

Uniportal video-assisted thoracic surgery lobectomy: a consensus report from the Uniportal VATS Interest Group (UVIG) of the European Society of Thoracic Surgeons (ESTS).

OBJECTIVES: Our goal was to report the results of the first consensus paper among international experts in uniportal video-assisted thoracoscopic surgery (UniVATS) lobectomy obtained through a Delphi process, the objective of which was to define and standardize the main procedural steps, optimize its indications and perioperative management and identify elements to assist in future training. METHODS: The 40 members of the working group were convened and organized on a voluntary basis by the Uniportal VATS Interest Group (UVIG) of the European Society of Thoracic Surgeons (ESTS). An e-consensus finding exercise using the Delphi method was applied to require 75% agreement for reaching consensus on each question. Repeated iterations of anonymous voting continued for 3 rounds. RESULTS: Overall, 31 international experts from 18 countries completed all 3 rounds of questionnaires. Although a technical quorum was not achieved, most of the responders agreed that the maximum size of a UniVATS incision should be ≤4 cm. Agreement was reached on many points outlining the currently accepted definition of a UniVATS lobectomy, its indications and contraindications, perioperative clinical management and recommendations for training and future research directions. CONCLUSIONS: The UVIG Consensus Report stated that UniVATS offers a valid alternative to standard VATS techniques. Only longer follow-up and randomized controlled studies will predict whether UniVATS represents a valid alternative approach to multiport VATS for major lung resections or whether it should be performed only in selected cases and by selected centres. The next step for the ESTS UVIG is the establishment of a UniVATS section inside the ESTS databases.

Second-line treatment of non small cell lung cancer by biweekly gemcitabine and docetaxel +/- granulocyte-macrophage colony stimulating factor and low dose aldesleukine.

Background. The antitumor activity of a novel biweekly gemcitabine (G) + docetaxel (D) regimen +/- granulocyte-macrophage colony stimulating factor (GM-CSF) and aldesleukine (IL-2) has been evaluated in a phase II trial in advanced pretreated non-small-cell lung cancer (NSCLC). Results. The treatment was well tolerated. The 42.3% response rate exceeded the predefined target activity, while time to progression (TTP) and overall survival (OS) were 7 and 11.2 months, respectively. A greater objective response rate (58.3% vs 28.6%) and an increased number of eosinophils, basophils and activated mononuclear blood cells were observed in those patients who also received cytokine administration. Methods. Twenty-six NSCLC patients received second line G (1000 mg/m2) and D (75 mg/m2) every 15 days. 12/26 patients also received s.c. GM-CSF (100µg, days 2-6) and s.c. IL-2 (0.5MIU/ twice daily, days 7-14 and 16-29) by random selection. Conclusion. The biweekly GD regimen is a safe and active second-line treatment in NSCLC. Addition of immune-adjuvant cytokines' may enhance the activity of this therapeutic combination.

Protection of right pneumonectomy bronchial sutures with a pedicled thymus flap.

A pedicled flap obtained by mobilizing the right lobe of the thymus was used to protect bronchial sutures in 29 consecutive patients undergoing a right pneumonectomy and in 4 additional patients. Fourteen patients had received preoperative chemotherapy with or without radiotherapy. The flap procedure was, in general, easy to do, required an average time of 20.4 minutes, and did not cause added operative morbidity. Postoperative magnetic resonance imaging, performed in 21 of the 29 patients who had pneumonectomy, showed a viable flap in every instance. One bronchopleural fistula occurred in a pneumonectomy patient after induction chemotherapy plus radiotherapy in a patient in the pneumonectomy group in whom adult respiratory distress syndrome developed postoperatively and who required prolonged mechanical ventilation.

Discordance between predicted postoperative forced expiratory volumes in one second (ppoFEV1) calculated before and after resection of bronchogenic carcinoma.

The aim of this study is to evaluate the concordance between predicted postoperative forced expiratory volumes in 1s (ppoFEV1) calculated on the basis of data known before surgery with ppoFEV1 calculated after completing surgical procedure. We have prospectively studied 66 consecutive patients (55 cases scheduled for lobectomy and 11 for pneumonectomy) operated on for bronchial carcinoma. According to location, 33 tumours were classified as central and 33 as peripheral. In all cases, ppoFEV1 was calculated twice: first (ppoFEV1-A) according to the scheduled surgical procedure; second (ppoFEV1-B) according to the procedure eventually performed. At operation, 43 lobectomies (65.2%) and 23 pneumonectomies (34.8%) were performed. Differences between ppoFEV1 A and B were found in 18 cases (12 central tumours). In three of them (4.5% of 66 cases), ppoFEV1-B was under 40%. Pearson coefficient was 0.85 (P<0.001) for the whole series of cases; 0.83 (P<0.001) for central and 0.87 (P<0.001) for peripheral tumours. On multiple regression analysis, R2 was 0.76 and ppoFEV1-A had the highest influence on the dependent variable. We have found that: (1) there is no perfect correlation between ppoFEV1 calculated with data known before and after surgery; (2) discrepancies are most important in centrally located tumours and (3) in 4.5% of cases, discrepancies could have influenced the preoperative risk estimation.