Noncanonical splicing junctions between exons and transposable elements represent a source of immunogenic recurrent neo-antigens in patients with lung cancer

Although most characterized tumor antigens are encoded by canonical transcripts (such as differentiation or tumor-testis antigens) or mutations (both driver and passenger mutations), recent results have shown that noncanonical transcripts including long noncoding RNAs and transposable elements (TEs) can also encode tumor-specific neo-antigens. Here, we investigate the presentation and immunogenicity of tumor antigens derived from noncanonical mRNA splicing events between coding exons and TEs. Comparing human non-small cell lung cancer (NSCLC) and diverse healthy tissues, we identified a subset of splicing junctions that is both tumor specific and shared across patients. We used HLA-I peptidomics to identify peptides encoded by tumor-specific junctions in primary NSCLC samples and lung tumor cell lines. Recurrent junction-encoded peptides were immunogenic in vitro, and CD8+ T cells specific for junction-encoded epitopes were present in tumors and tumor-draining lymph nodes from patients with NSCLC. We conclude that noncanonical splicing junctions between exons and TEs represent a source of recurrent, immunogenic tumor-specific antigens in patients with NSCLC

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Identification of the intersegmental plane during thoracoscopic segmentectomy: state of the art

During thoracoscopic segmentectomy, where direct palpation of the tumour is not always possible, achieving adequate margins from the cancer is of crucial importance. It is thus mandatory to accurately identify the intersegmental plane (ISP). Indeed, inadequate determination and division of the ISP can lead to unsatisfactory oncological results. Our systematic review focused on the effectiveness of the different techniques for identifying the ISP, highlighting the fact that a 1-size-fits-all method is not feasible. Based on the published evidence, 6 main methods were reported, each with its pros and cons: inflation-deflation technique, selective resected segmental inflation, systemic injection of indocyanine green, injection of endobronchial dye, 3-dimensional simulation using multidetector computed tomography and virtual-assisted lung mapping. In conclusion, ISP demarcation is mandatory to achieve a high rate of success of thoracoscopic segmentectomy, and it is very helpful in surgical planning, especially when preoperative multidetector computed tomography and 3-dimensional reconstructions are routinely performed

How to improve the precision of closed chest sublobar resections.

Abstract: Despite carcinological results awaiting validation, sublobar resections (SLRs) are of increasing interest due to the progressive change in tumour profile and to their lower morbidity when compared to lobectomies. However, this morbidity remains too high in comparison to non-surgical alternatives. Decreasing the complication rate requires greater precision. We present here the different ways to improve the accuracy of the different steps of these interventions: (I) performing these procedures via a closed chest approach; (II) knowing as much as possible about segmental anatomy and studying mapping; (III) performing an intraoperative examination on the intersegmental lymph nodes and on resection margins; (IV) using a preoperative or intraoperative marking method to determine the intersegmental plane (ISP); (V) stapling ISP, an imperfect method but that currently represents the least bad compromise between accuracy and safety

Unplanned Procedures During Thoracoscopic Segmentectomies.

BACKGROUND Thoracoscopic sublobar resections (TSLRs) are gaining popularity, but are challenging. However, despite technical difficulties, the reported rate of adverse events, complications, and unplanned procedures is low. To understand this paradox, we have studied our series of TSLRs. METHODS We reviewed our prospective and intention-to-treat database on videothoracoscopic anatomical resections and extracted all planned thoracoscopic segmentectomies from January 2007 to July 2016. Intraoperative and postoperative data were analyzed. Unplanned procedures were defined as a conversion into thoracotomy or an unplanned additional pulmonary resection. RESULTS During the study period 284 thoracoscopic anatomical segmentectomies were performed in 280 patients. There were 124 men and 156 women with a mean age of 64 years (range, 18 to 86 years). Indication for segmentectomy was a proven or suspected non-small cell lung carcinoma in 184 patients, suspected metastasis in 51 patients, and benign lesion in 49 patients. In total, 23 patients had an unplanned procedure (8%). There were 10 unplanned thoracotomies (9 conversions and 1 reoperation; 3.1%) mainly for vascular injuries, and 15 unplanned additional resections (5.1%) distributed among oncological reasons (n = 7), per operative technical issues (n = 6) and postoperative adverse events (lingular ischemia, n = 2). Considering only the 235 patients operated on for cancer, the unplanned additional pulmonary resection rate for an oncological reason was 3%. CONCLUSIONS Although lower than for thoracoscopic lobectomies, the rate of unplanned procedure during TSLRs is of concern. It could most likely be reduced by technical refinements, such as a better preoperative planning

Oncological results of full thoracoscopic major pulmonary resections for clinical Stage I non-small-cell lung cancer.

OBJECTIVES The full thoracoscopic approach to major pulmonary resections is considered challenging and controversial as it might compromise oncological outcomes. The aim of this work was to analyse the results of a full thoracoscopic technique in terms of nodal upstaging and survival in patients with non-small-cell lung carcinoma (NSCLC). METHODS All patients who underwent a full thoracoscopic major pulmonary resection for NSCLC between 2007 and August 2016 were analysed from an 'intent-to-treat' prospective database. Overall survival and disease-free survival were estimated using the Kaplan-Meier curves and comparisons in survival using the log-rank test. RESULTS A total of 648 patients met the inclusion criteria, of whom 621 patients had clinical Stage I and 27 had higher stages (16 oligometastatic patients were excluded from the analysis, 11 cT3 or cT4). The mean follow-up was 34.5 months. There were 40 conversions to thoracotomy (6.3%). Thirty-day or in-hospital mortality was 0.95%. Complications occurred in 29.3% of patients. On pathological examination, 22.5% of clinical Stage I patients were upstaged. Nodal upstaging to N1 or N2 was observed in 15.8% of clinical Stage I patients. Five-year overall survival of the whole cohort was 75% and was significantly different between clinical Stages IA (76%) and IB (70.9%). For tumours <2 cm, no significant difference in overall survival was found for the segmentectomy group compared to the lobectomy group: 74% versus 78.9% (P = 0.634). CONCLUSIONS Long-term survival is not compromised by a full thoracoscopic approach. Our results compared favourably with those of video-assisted techniques

Full Thoracoscopic Right Basilar Segmentectomy for Carcinoid Tumor

<div>Carcinoid tumors are often located at the origin of a lobar or segmental bronchus. Stapling the bronchus, as is usually done during a thoracoscopic lobectomy or segmentectomy, creates the risk of damaging or crushing the tumor.<br></div><div>This video demonstrates a right basilar segmentectomy for an obstructive carcinoid tumor located at the origin of the basilar bronchial trunk, which required manual cutting and manual suturing of the bronchus. The procedure is performed using a totally thoracoscopic approach with a fissure-based dissection, a deflectable scope, multiple ports, and microinstruments, according to the authors' standard technique.<br></div><div><b>References</b></div><div><ol><li>Gossot D, Lutz JA, Grigoroiu M, Brian E, Seguin-Givelet A. Unplanned procedures during thoracoscopic segmentectomies. <a href="http://www.annalsthoracicsurgery.org/article/S0003-4975(17)30835-4/fulltext"><em>Ann Thorac Surg</em>. 2017;104(5):1710-1717</a>.</li><li>Gossot D, Zaimi R, Fournel L, Grigoroiu M, Brian E, Neveu C. Totally thoracoscopic pulmonary anatomic segmentectomies: technical considerations. <a href="http://jtd.amegroups.com/article/view/1307"><em>J Thorac Dis</em>. 2013;5 Suppl 3:S200-S206</a>.</li></ol></div><div>Dr. Gossot is a consultant for the instrument manufacturer Delacroix-Chevalier.</div

Multicentric evaluation of the impact of central tumour location when comparing rates of N1 upstaging in patients undergoing video-assisted and open surgery for clinical Stage I non-small-cell lung cancer

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