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Tracheal tissue engineering is still facing major challenges: realization of efficient vascularization and mechanical properties comparable to native trachea need to be achieved. In this study, we present a strategy for the manufacturing of a construct for tracheal tissue engineering by conditioning through cell seeding followed by mechanical stimulation in vitro. Scaffolds derived from porcine trachea decellularized with supercritical carbon dioxide were seeded with stem cells of different tissue sources and cultured in a bioreactor for 21 days under mechanical stimulation. Enhanced chondrogenic development was demonstrated, with improved sulphated glycosaminoglycan secretion and cellular alignment which resulted in mechanical properties resembling native trachea. This method may provide a useful addition to tracheal tissue engineering strategies aimed at optimizing cartilage formation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Healthcare systems contribute significantly to CO 2 emissions, accounting for 7 % of emissions in the Netherlands. Understanding the environmental footprint of medical treatments can help identify opportunities for reducing climate impact. We evaluated the climate impact of stereotactic body radiotherapy (SBRT) and Video-Assisted Thoracic Surgery (VATS) when treating T1-2N0M0 Non-Small Cell Lung Cancer (NSCLC)., Materials and Methods: We used life cycle assessment (LCA) to evaluate climate impact in emissions of kilograms of CO 2 equivalent. Care trajectories were inventoried for both VATS and SBRT with the same entry and end point of the paths. We analyzed a range of factors contributing to climate impact, such as patient and staff travel, energy consumption, disposables and medication using direct measurements: questionnaires and waste audits, or retrospective record analysis. As is common in LCA, existing infrastructure was excluded from the analysis. Reductions that can be influenced by individual departments were also modeled., Results: Using LCA we calculated the impact of all categorized contributions for two treatments for NSCLC. In total, VATS generates approximately 547 kg CO 2 equivalent (CO 2 e), whereas SBRT generates 172 kg CO 2 e per treatment. For SBRT, the largest contributors were energy use in the hospital (52 % of total), of which 22 % is from the linac, and patient travel (23 %). For VATS, major contributions were hospital energy use (52 %) and disposables (23 %). Climate impact could be reduced by 20 % (SBRT) by hypofractionation, reduced linac idle time and patient travel impact, and 13 % (VATS) with fast track recovery and a reduction of disposables., Conclusion: When treating T1-2N0M0 NSCLC, surgery has a larger climate impact than SBRT. For both modalities reductions are possible., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Despite the benefits of video-assisted thoracoscopic surgery (VATS), postoperative acute pain and nerve injury are still present and contribute to early persistent and chronic pain. The purpose of this study is to describe the incidence of early persistent pain (EPP) after VATS, which remains unexplored, to enhance patient care and promote awareness among clinicians regarding this clinical condition., Methods: A single-center prospective cohort study that included consecutive patients undergoing VATS between January 2021 and March 2023. The primary outcome was the incidence of EPP, defined as pain experienced at 3 to 4 weeks follow-up. Secondary outcomes were risk factors associated with EPP, characteristics during physical examination, acute postoperative pain scores, the use of additional analgesia and complications between patients with and without EPP., Results: Of 117 patients, 16.2% [95% confidence interval (CI): 9-23%] developed EPP. The presence of acute postoperative pain was the only risk factor for EPP. The pain was mostly localized at the utility and ventral incision. Hyperesthesia, hypoesthesia and a positive pinch test were the most common sensory disturbances. Patients with EPP showed significantly higher acute pain scores until postoperative day (POD) 4, more frequently used additional opioids until POD 2, and had comparable complications., Conclusions: Early persistent postoperative pain is present in 16.2% of patients after VATS. Acute postoperative pain is the strongest risk factor for developing such persistent pain. This underlines that awareness of clinicians for strategies that optimize postoperative pain management is of utmost importance., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-802/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Objective: Harmonized European NSCLC incidence, treatment approach, and survival based on national tumor registries are unclear., Summary Background Data: Surgery has the potential to cure NSCLC and significantly prolong survival. This large-scale international study aimed to investigate treatment variations in Europe and the USA, as well as the determinants for its utilization., Methods: The retrospective cohort study analyzed data from six European national population-based cancer registries (Belgium, Denmark, Estonia, Germany, the Netherlands, and Slovenia) and the US SEER database from 2010-2015., Results: The study computed cancer incidence, survival, and age-standardized proportions of the use of various therapies. Multivariable logistic regression models were used to assess associations between resection and demographic and clinical parameters. A total of 428,107 records were analyzed. Among all countries, Estonia had the highest surgical resection rate (79.3 %) and the lowest radiation rate (7.3 %) for stage I patients. The Netherlands had the highest rate of radiotherapy across all years of investigation and the lowest surgery rate between 2012 and 2015. The primary treatment for early-stage NSCLC showed significant international variation, with the USA having a decrease in surgical rates from 67.6 % to 59.5 %. Resection was less frequently performed as tumor stage increased, patients aged, other lung cancer besides adenocarcinoma was present, and when the tumor site overlapped multiple lobes., Conclusions: Resection rates have declined in some studied European countries and the USA and resection rates vary substantially among countries. Interpretation of current scientific lung cancer evidence and international guidelines results in wide variations in patient treatment., Competing Interests: Declaration of Competing Interest A.F.T.M. Verhagen reports institutional payments from Johnson & Johnson and Bristol Myers Squibb. Kersti Oselin declares research grants from Pfizer to study the role of artificial intelligence and genomic factors in lung cancer recurrence 2021 and an ongoing research collaboration with Optellum to develop an artificial intelligence tool to assess lung cancer prognosis. She reports travel support from MSD, Roche and Astra Zeneca. H. Winter reports consultancy fees, travel support and data safety monitoring honoraria from Astra Zeneca, Roche and Intuitive Surgical. All other authors declare no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: More effective lung sealants are needed to prevent prolonged pulmonary air leakage (AL). Polyoxazoline-impregnated gelatin patch (N-hydroxysuccinimide ester functionalized poly(2-oxazoline)s; NHS-POx) was promising for lung sealing ex vivo. The aim of this study is to confirm sealing effectiveness in an in vivo model of lung injury., Methods: An acute aerostasis model was used in healthy adult female sheep, involving bilateral thoracotomy, amputation lesions (bronchioles Ø > 1.5 mm), sealant application, digital chest tube for monitoring AL, spontaneous ventilation, obduction and bursting pressure measurement. Two experiments were performed: (i) 3 sheep with 2 lesions per lung (N = 4 NHS-POx double-layer, N = 4 NHS-POx single-layer, N = 4 untreated) and (ii) 3 with 1 lesion per lung (N = 3 NHS-POx single-layer, N = 3 untreated). In pooled linear regression, AL was analysed per lung (N = 7 NHS-POx, N = 5 untreated) and bursting pressure per lesion (N = 11 NHS-POx, N = 7 untreated)., Results: Baseline AL was similar between groups (mean 1.38-1.47 l/min, P = 0.90). NHS-POx achieved sealing in 1 attempt in 8/11 (72.7%) and in 10/11 (90.9%) in >1 attempt. Application failures were only observed on triangular lesions requiring 3 folds around the lung. No influences of methodological variation between experiments was detected in linear regression (P > 0.9). AL over initial 3 h of drainage was significantly reduced for NHS-POx [median: 7 ml/min, length of interquartile range: 333 ml/min] versus untreated lesions (367 ml/min, length of interquartile range: 680 ml/min, P = 0.036). Bursting pressure was higher for NHS-POx (mean: 33, SD: 16 cmH2O) versus untreated lesions (mean: 19, SD: 15 cmH2O, P = 0.081)., Conclusions: NHS-POx was effective for reducing early AL, and a trend was seen for improvement of bursting strength of the covered defect. Results were affected by application characteristics and lesion geometry., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Prolonged air leakage (AL) following pulmonary resections leads to prolonged hospital stay and post-operative complications. Intra- and postoperative quantification of AL might be useful for improving treatment decisions, but these measurements have not been characterised. AL calculations based on inspiratory and expiratory tidal volumes were investigated in an Intensive Care Unit mechanical ventilator circuit (Servo-I). AL was also measured by a digital chest drainage system. This study shows that AL measurements increase in accuracy when corrected for baseline deviations (R: 0.904 > 0.997, p  < 0.001). Bland-Altman analysis revealed a funnel-shape, indicative of a detection threshhold. Corrected measurements were most accurate when averaged over five breaths and AL was >500 mL/min, with an estimated mean systemic bias of 7.4% (95%-limits of agreement [LoA]: 1.1%-13.7%) at 500 mL/min air leak. Breath-by-breath analysis showed most accurate results at AL >20 mL/breath (R: 0.989-0.991, p  < 0.001) at tidal volumes between 350-600 mL. The digital drain had a mean systemic bias of -11.1% (95%-LoA: -18.9% to -3.3%) with homogenous scatter in Bland-Altman analysis and a strong correlation to the control measurement over a large range (0-2000mL/min, R: 0.999, p  < 0.001). This study indicates that the Servo-I can be used for air leak quantification in clinically relevant ranges (>500 mL/min), but is unsuited for small leak detection due to a detection threshold. Researchers and clinicians should be aware of varying accuracy and interoperability characteristics between AL measurement devices.

Transesophageal echocardiography (TEE) has become an indispensable part of cardiothoracic surgery at present and is considered to be a safe procedure, rarely associated with complications. However, TEE may cause serious and life threatening complications, as presented in this case report. We describe a patient who developed an empyema after elective cardiac surgery due to an esophageal perforation caused by TEE, without any clinical symptoms. Risk factors for TEE-related complications, identified in recent literature, will be discussed as well as the remarkable absence of clinical symptoms in this particular patient., (© 2024. The Author(s).)

Background: Aortic mycotic aneurysms are a rare but life-threatening condition and may be associated with aorto-bronchial- and aorto-esophageal fistulas. Although both very rare, they carry a high mortality and require (urgent) surgical intervention. Surviving all three conditions concomitantly is extraordinary. We describe a patient who underwent staged repair of such combined defects., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Sealants may provide a solution for pulmonary air leakage (PAL), but their clinical application is debatable. For sealant comparison, standardized animal models are lacking. This systematic review aims to assess methodology and quality of animal models for PAL and sealant evaluation. All animal models investigating lung sealing devices (e.g., staplers, glues, energy devices) to prevent or treat PAL were retrieved systematically from Embase, Pubmed and Web of science. Methodological study characteristics, risk of bias, reporting quality and publication bias were assessed. A total of 71 studies were included ( N   =  75 experiments, N   =  1659 animals). Six different species and 18 strains were described; 92% of experiments used healthy animals, disease models were used in only six studies. Lesions to produce PAL were heterogenous, and only 11 studies used a previously reported technique, encompassing N   =  5 unique lesions. Clinically relevant outcomes were used in the minority of studies (imaging 16%, air leak 10.7%, air leak duration 4%). Reporting quality was poor, but revealed an upward trend per decade. Overall, high risk of bias was present, and only 18.7% used a negative control group. All but one study without control groups claimed positive outcomes (95.8%), in contrast to 84.3% using positive or negative control groups, which also concluded equivocal, adverse or inconclusive outcomes. In conclusion, animal studies evaluating sealants for prevention of PAL are heterogenous and of poor reporting quality. Using negative control groups, disease models and quantifiable outcomes seem important to increase validity and relevance. Further research is needed to reach consensus for model development and standardization.

Background: No validated and standardized animal models of pulmonary air leakage (PAL) exist for testing aerostatic efficacy of lung sealants. Lack of negative control groups in published studies and intrinsic sealing mechanisms of healthy animal lungs might contribute to a translational gap, leading to poor clinical results. This study aims to address the impact of intrinsic sealing mechanisms on the validity of PAL models, and investigate the conditions required for an ovine model of PAL for lung sealant testing., Methods: An ovine acute aerostasis model was developed, consisting of a bilateral thoracotomy with lesion creation, chest tube insertion and monitoring of air leaks using digital drains (≥80 minutes), under spontaneous respiration. Healthy mixed-breed adult female sheep were used and all in vivo procedures were performed under terminal anesthesia. Superficial parenchymal lesions were tested post-mortem and in vivo , extended lesions including bronchioles (deep bowl-shaped and sequential lung amputation lesions) were tested in vivo . Experiment outcomes include air leakage (AL), minimal leaking pressure (MLP) and histology., Results: Two post-mortem (N=4 superficial parenchymal lesions) and 10 in vivo experiments (N=5 superficial parenchymal and N=16 lesions involving bronchioles) were performed. In contrast to the post-mortem model, superficial parenchymal lesions in vivo showed less air leak [mean flow ± standard deviation (SD): 760±693 vs. 42±33 mL/min, P=0.055]. All superficial parenchymal lesions in vivo sealed intrinsically within a median time of 20 minutes [interquartile range (IQR), 10-75 minutes]. Histology of the intrinsic sealing layer revealed an extended area of alveolar collapse below the incision with intra-alveolar hemorrhage. Compared to superficial parenchymal lesions in vivo , lesions involving bronchioles induced significantly higher air leak post-operatively (normalized mean flow ± SD: 459±221 mL/min, P=0.003). At termination, 5/9 (55.6%) were still leaking (median drain time: 273 minutes, IQR, 207-435 minutes), and intrinsic sealing for the remaining lungs occurred within a median of 115 minutes (IQR, 52-245 minutes)., Conclusions: Lung parenchyma of healthy sheep shows a strong intrinsic sealing mechanism, explained pathologically by an extended area of alveolar collapse, which may contribute to a translational gap in lung sealant research. A meaningful ovine model has to consist of deep lesions involving bronchioles of >⌀1.5 mm. Further research is needed to develop a standardized PAL model, to improve clinical effectiveness of lung sealants., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-180/coif). EAR is an employee of GATT Technologies B.V. and HvG was a scientific advisor for GATT Technologies B.V. until 31 December 2021, but not in relation to lung sealing technology. BPH received funding and study materials through the institution for conduction of the study from GATT Technologies B.V. The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Purpose: Resectable non-small-cell lung cancer (NSCLC) with a high probability of mediastinal nodal involvement requires mediastinal staging by endosonography and, in the absence of nodal metastases, confirmatory mediastinoscopy according to current guidelines. However, randomized data regarding immediate lung tumor resection after systematic endosonography versus additional confirmatory mediastinoscopy before resection are lacking., Methods: Patients with (suspected) resectable NSCLC and an indication for mediastinal staging after negative systematic endosonography were randomly assigned to immediate lung tumor resection or confirmatory mediastinoscopy followed by tumor resection. The primary outcome in this noninferiority trial (noninferiority margin of 8% that previously showed to not compromise survival, P noninferior < .0250) was the presence of unforeseen N2 disease after tumor resection with lymph node dissection. Secondary outcomes were 30-day major morbidity and mortality., Results: Between July 17, 2017, and October 5, 2020, 360 patients were randomly assigned, 178 to immediate lung tumor resection (seven dropouts) and 182 to confirmatory mediastinoscopy first (seven dropouts before and six after mediastinoscopy). Mediastinoscopy detected metastases in 8.0% (14/175; 95% CI, 4.8 to 13.0) of patients. Unforeseen N2 rate after immediate resection (8.8%) was noninferior compared with mediastinoscopy first (7.7%) in both intention-to-treat (Δ, 1.03%; UL 95% CIΔ, 7.2%; P noninferior = .0144) and per-protocol analyses (Δ, 0.83%; UL 95% CIΔ, 7.3%; P noninferior = .0157). Major morbidity and 30-day mortality was 12.9% after immediate resection versus 15.4% after mediastinoscopy first ( P = .4940)., Conclusion: On the basis of our chosen noninferiority margin in the rate of unforeseen N2, confirmatory mediastinoscopy after negative systematic endosonography can be omitted in patients with resectable NSCLC and an indication for mediastinal staging.

Background: Sealants are used to prevent prolonged pulmonary air leakage (PAL) after lung resections (incidence 5.6-30%). However, clinical evidence to support sealant use is insufficient, with an unmet need for a more effective product. We compared a novel gelatin patch impregnated with functionalized polyoxazolines (NHS-POx) (GATT-Patch) to commercially available sealant products., Methods: GATT-Patch Single/Double layers were compared to Progel ® , Coseal ® , Hemopatch ® and TachoSil ® in an ex vivo porcine lung model (first experiment). Based on these results, a second head-to-head comparison between GATT-Patch Single and Hemopatch ® was performed. Air leakage (AL) was assessed in three settings using increasing ventilatory pressures (max =70 cmH 2 O): (I) baseline, (II) with 25 mm × 25 mm superficial pleural defect, and (III) after sealant application. Lungs floating on saline (37 ℃) were video recorded for visual AL assessment. Pressure and tidal volumes were collected from the ventilator, and bursting pressure (BP), AL and AL-reduction were determined., Results: Per sealant 10 measurements were performed (both experiments). In the first experiment, BP was superior for GATT-Patch Double (60±24 cmH 2 O) compared to TachoSil ® (30±11 cmH 2 O, P<0.001), Hemopatch ® (33±6 cmH 2 O, P=0.006), Coseal ® (25±13 cmH 2 O, P=0.001) and Progel ® (33±11 cmH 2 O, P=0.005). AL-reduction was superior for GATT-Patch Double (100%±1%) compared to Hemopatch ® (46%±50%, P=0.010) and TachoSil ® (31%±29%, P<0.001), and also for GATT-Patch Single (100%±14%, P=0.004) and Progel (89%±40%, P=0.027) compared to TachoSil ® . In the second experiment, GATT-Patch Single was superior regarding BP (45±10 vs. 40±6 cmH 2 O, P=0.043) and AL-reduction (100%±11% vs. 68%±40%, P=0.043) when compared to Hemopatch ® ., Conclusions: The novel NHS-POx patch shows promise as a lung sealant, demonstrating elevated BP, good adhesive strength and a superior AL-reduction., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1821/coif). ER is employee of GATT Technologies and HG was a Scientific Advisor for GATT Technologies B.V until 31 December 2021, but not in relation to lung sealing technology. BH received funding and study materials through the institution for conduction of the study from GATT-Technologies B.V. The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Background: Early-stage lung cancer is treated with curative intent by surgery or radiotherapy. However, upstaging is frequently seen after surgery in clinical N0 lung cancer patients, and despite curative intent, 2-year recurrence rates of 9-28% are reported. A sentinel lymph node (SLN) procedure could improve the staging accuracy. We explored the feasibility of performing a navigation bronchoscopy based SLN procedure in human ex-vivo lung cancer specimens to optimize procedural parameters and assess a novel injection tool., Methods: Ten lung resection specimens were included and allocated to either peri- or intratumoral injection of a tracer combining 99m Tc-nanocolloid and indocyanine green (ICG) while varying the injection volume. A Pioneer Plus catheter with a pre-angulated 24G needle and an ultrasound (US)-element was used to perform real-time US guided transbronchial injections at multiple locations. Thereafter, single photon emission computed tomography/computed tomography (SPECT/CT)-scanning was performed to image injection depots and to assess their location relative to the tumor., Results: An average volume of 0.7 mL (range, 0.3-1.2 mL) with an average activity of 89.5 MBq 99m Tc (range, 35.4-188.0 MBq) was injected. Intratumoral injections in non-solid and solid tumors were successful in 100% and 64.3% respectively, while 100% of peritumoral injections in solid tumors were successful. The US-element of the catheter allowed real-time imaging and was able to visualize all tumors and 67.4% of all injections. SPECT/CT-scanning visualized 76.7% of the injection depots., Conclusions: A navigation bronchoscopy mediated SLN procedure seems technically feasible. The Pioneer Plus is a suitable catheter to place tracer depots at multiple intra-/peri-tumoral sites, while receiving real-time feedback on the needle localization in relation to the tumor. The next step of in-vivo injections will determine if tracer drainage to the SLN can also be detected on pre- and per-operative imaging., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-984/coif). RLJV reports unrestricted research grants from Philips Medical, Astra Zeneca, Pentax Medical and Johnson & Johnson, consulting fees from Johnson & Johnson and Intuitive Surgical, speaker fees from Medtronic, Travel arrangements from Johnson & Johnson and Intuitive Surgical, is a board member of the Dutch Society of Technical Physicians (NVvTG) and has patents issued, pending and planned in the field of advanced and navigation bronchoscopy; EHFMvdH reports unrestricted research grants from Philips Medical, Astra Zeneca, Pentax Medical and Johnson & Johnson, consulting fees from Johnson & Johnson and Intuitive Surgical, speaker fees from Janssen-Cilag and Pentax Medical, Travel arrangements from Johnson & Johnson and Intuitive Surgical, is a board member of European Association for Bronchology and Interventional Pulmonology (ECBIP) and a board of regents member of the World Association for Bronchology and Interventional Pulmonology (WABIP) and has patents issued, pending and planned in the field of advanced and navigation bronchoscopy. The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Objectives: Pain after thoracoscopic surgery may increase the incidence of postoperative complications and impair recovery. Guidelines lack consensus regarding postoperative analgesia. We performed a systematic review and meta-analysis to determine the mean pain scores of different analgesic techniques (thoracic epidural analgesia, continuous or single-shot unilateral regional analgesia and only systemic analgesia) after thoracoscopic anatomical lung resection., Methods: Medline, Embase and Cochrane databases were searched until 1 October 2022. Patients undergoing at least >70% anatomical resections through thoracoscopy reporting postoperative pain scores were included. Due to a high inter-study variability an explorative meta-analysis next to an analytic meta-analysis was performed. The quality of evidence has been evaluated using the Grading of Recommendations Assessment, Development and Evaluation system., Results: A total of 51 studies comprising 5573 patients were included. Mean 24, 48 and 72 h pain scores with 95% confidence interval on a 0-10 scale were calculated. Length of hospital stay, postoperative nausea and vomiting, additional opioids and the use of rescue analgesia were analysed as secondary outcomes. A common-effect size was estimated with an extreme high heterogeneity for which pooling of the studies was not appropriate. An exploratory meta-analysis demonstrated acceptable mean pain scores of Numeric Rating Scale <4 for all analgesic techniques., Conclusions: This extensive literature review and attempt to pool mean pain scores for meta-analysis demonstrates that unilateral regional analgesia is gaining popularity over thoracic epidural analgesia in thoracoscopic anatomical lung resection, despite great heterogeneity and limitations of current studies precluding such recommendations., Prospero Registration: ID number 205311., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Development of ready-to-use biomaterials and scaffolds is vital for further advancement of scaffold-based tissue engineering in clinical practice. Scaffolds need to mimic 3D ultrastructure, have adequate mechanical strength, are biocompatible, non-immunogenic and need to promote tissue regeneration in vivo. Although decellularization of native tissues seems promising to deliver scaffolds that meet these criteria, adequate decellularization of hard, poorly penetrable and poorly diffusible tissues remains challenging whilst being a very time-consuming process. In this study, a method to decellularize hard, dense tissues using supercritical carbon-dioxide preceded by a freeze/thaw cycle and followed by several washing steps is presented, demonstrating decellularisation efficiency and substantially reduced production/handling time. Additionally, supercritical carbon-dioxide treatment was used as sterilization method, further reducing the time required to produce the final scaffold. Histological evaluation showed that, after fine-tuning of the process, a partially acellular scaffold was obtained, with preservation of glycosaminoglycans and collagen fibers, albeit that the amount of residual dsDNA was still higher then chemically decellularized tissue. Biomechanical properties of the scaffold were similar to the native, non-decellularized tissue. After sterilization with supercritical carbon-dioxide the simulated functional outcome was more similar to native trachea, when compared to sterilization using gamma irradiation. Thus, decellularization and sterilization using supercritical carbon-dioxide with washing steps is an effective method for dense cartilaginous materials, and tuneable to meet different demands in other applications, but further optimization may be required. STATEMENT OF SIGNIFICANCE: Further advancement of the use of tissue engineered tracheal constructs is restricted by the lack of the ideal scaffold. Decellularized trachea is considered a promising scaffold, but the hard, poorly diffusible tissue remains challenging while forming a very time consumable process. Decellularization using supercritical carbon dioxide (scCO 2 ) seems promising, resulting in efficient removal of cellular material while reducing production and handling time. Addition of scCO 2 as a sterilization method resulted in further time reduction while improving functional outcome in comparison with traditional sterilization methods. This study presents an promising alternative method for decellularization and sterilization of dense materials, which can be tuned to meet different demands in other applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Minimally invasive mitral valve surgery is evolving rapidly since the early 1990's and is now increasingly adopted as the standard approach for mitral valve surgery. It has a long and challenging learning curve and there are many considerations regarding technique, planning and patient selection when starting a minimally invasive program. In the current review, we provide an overview of all considerations and the decision-making process during the learning curve.

Background: Adequate pain control after video-assisted thoracoscopic surgery (VATS) for lung resection is important to improve postoperative mobilisation, recovery, and to prevent pulmonary complications. So far, no consensus exists on optimal postoperative pain management after VATS anatomic lung resection. Thoracic epidural analgesia (TEA) is the reference standard for postoperative pain management following VATS. Although the analgesic effect of TEA is clear, it is associated with patient immobilisation, bladder dysfunction and hypotension which may result in delayed recovery and longer hospitalisation. These disadvantages of TEA initiated the development of unilateral regional techniques for pain management. The most frequently used techniques are continuous paravertebral block (PVB) and single-shot intercostal nerve block (ICNB). We hypothesize that using either PVB or ICNB is non-inferior to TEA regarding postoperative pain and superior regarding quality of recovery (QoR). Signifying faster postoperative mobilisation, reduced morbidity and shorter hospitalisation, these techniques may therefore reduce health care costs and improve patient satisfaction., Methods: This multi-centre randomised study is a three-arm clinical trial comparing PVB, ICNB and TEA in a 1:1:1 ratio for pain (non-inferiority) and QoR (superiority) in 450 adult patients undergoing VATS anatomic lung resection. Patients will not be eligible for inclusion in case of contraindications for TEA, PVB or ICNB, chronic opioid use or if the lung surgeon estimates a high probability that the operation will be performed by thoracotomy., Primary Outcomes: (1) the proportion of pain scores ≥ 4 as assessed by the numerical rating scale (NRS) measured during postoperative days (POD) 0-2; and (2) the QoR measured with the QoR-15 questionnaire on POD 1 and 2. Secondary outcome measures are cumulative use of opioids and analgesics, postoperative complications, hospitalisation, patient satisfaction and degree of mobility., Discussion: The results of this trial will impact international guidelines with respect to perioperative care optimization after anatomic lung resection performed through VATS, and will determine the most cost-effective pain strategy and may reduce variability in postoperative pain management. Trial registration The trial is registered at the Netherlands Trial Register (NTR) on February 1st, 2021 (NL9243). The NTR is no longer available since June 24th, 2022 and therefore a revised protocol has been registered at ClinicalTrials.gov on August 5th, 2022 (NCT05491239)., Protocol Version: version 3 (date 06-05-2022), ethical approval through an amendment (see ethical proof in the Study protocol proof)., (© 2022. The Author(s).)

Aims: To investigate the association between the timing of cardiac surgery during pregnancy and both maternal and foetal outcomes., Methods and Results: Studies published up to 6 February 2021 on maternal and/or foetal mortality after cardiac surgery during pregnancy that included individual patient data were identified. Maternal and foetal mortality was analysed per trimester for the total population and stratified for patients who underwent caesarean section (CS) prior to cardiac surgery (Caesarean section (CaeSe) group) vs. patients who did not (Cardiac surgery (CarSu) group). Multivariable logistic regression analysis was performed to evaluate predictors of both maternal and foetal mortality. In total, 179 studies were identified including 386 patients of which 120 underwent CS prior to cardiac surgery. Maternal mortality was 7.3% and did not differ significantly among trimesters of pregnancy (P = 0.292) nor between subgroup CaeSe and CarSu (P = 0.671). Overall foetal mortality was 26.5% and was lowest when cardiac surgery was performed during the third trimester (10.3%, P < 0.01). CS prior to surgery was significantly associated with a reduced risk of foetal mortality in a multivariable model [odds ratio 0.19, 95% confidence interval [0.06-0.56)]. Trimester was not identified as an independent predictor for foetal nor maternal mortality., Conclusion: Maternal mortality after cardiac surgery during pregnancy is not associated with the trimester of pregnancy. Cardiac surgery is associated with high foetal mortality but is significantly lower in women where CS is performed prior to cardiac surgery. When the foetus is viable, CS prior to cardiac surgery might be safe. When CS is not feasible, trimester stage does not seem to influence foetal mortality., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Vocal cord palsy after cervical mediastinoscopy is usually reported at less than 1%. However, its incidence might be underestimated and no follow-up studies are available. Our study aimed to evaluate the incidence of voice changes after cervical mediastinoscopy and report on long-term outcomes, including quality of life, after at least one-year follow-up., Methods: A retrospective cohort study was performed, considering all patients who underwent cervical mediastinoscopy in our center between January 2011 and April 2016. Patients with pre-existing voice changes, voice changes only after pulmonary resection and patients who underwent neoadjuvant chemo(radio)therapy were excluded. Voice changes with full recovery within 14 days were attributed to intubation-related causes. Follow-up questionnaires, including the standardized Voice Handicap Index, were sent to patients with documented voice changes., Results: Of 270 patients who were included for final analysis, 17 (6.3%) experienced voice changes after cervical mediastinoscopy, which persisted > 2 years in 4 patients (1.5%), causing mild to moderate disabilities in daily living. Twelve patients (out of 17, 71%) were referred for otolaryngology consultation, and paresis of the left vocal cord suggesting recurrent laryngeal nerve injury was confirmed in 10 (3.7% of our total study group). Additionally, 83% of the patients who were referred for otolaryngology consultation received voice treatment. Recovery rate after vocal exercises therapy and injection laryngoplasty was respectively 71% and 33%., Conclusions: Voice changes after cervical mediastinoscopy is an underreported complication, with an incidence of at least 6.3% in our retrospective study, with persisting complaints in at least 1.5% of patients, leading to mild to moderate disabilities in daily living. These findings highlight the need for appropriate patient education for this underestimated complication, as well as the exploration of possible preventive measures., (© 2022. The Author(s).)

Objectives: This study assessed whether endobronchial therapy (EBT) for bronchial carcinoid, if not curative, reduces the extent of the surgical resection and whether EBT is associated with increased surgical morbidity., Material and Methods: Analysis was performed in a cohort of patients with bronchial carcinoid who have undergone surgical resection. A group that underwent EBT before the surgery (S + EBT) was compared with a group where no EBT was performed (S-EBT). Postoperative complications were also compared between both groups., Results: A total of 254 patients treated for a bronchial carcinoid tumor between 2003 and 2019 were screened for inclusion. A total of 65 surgically treated patients were included, of whom 41 (63%) underwent EBT prior to surgery. In 5 out of 41 patients (12%) from the S + EBT group, less parenchyma was resected versus 2 out of 24 (8%) from the S-EBT group (OR 1.528, 95% CI 0.273-8.562, p = 1.000). Two patients from the S + EBT group (5%) underwent lobectomy instead of sleeve lobectomy versus 0 from the S-EBT group (OR 1.051, 95% CI 0.981-1.127, p = 0.527). Comparing complications between the S + EBT and S-EBT group did not result in increased postoperative surgical morbidity (15% S + EBT, 24% S-EBT)., Conclusion: EBT, if not curative, does not reduce the extent of the subsequent surgical resection. Therefore, if curative EBT is not anticipated, patients should directly be referred for surgery. If curative EBT seems feasible, it should be attempted not only because surgical resection can be prevented, but also because failure of EBT is not associated with excess surgical morbidity., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: There are discordances in the guidelines regarding the need to acquire histological diagnosis before surgical treatment of (presumed) lung cancer. Preoperative histological confirmation is always encouraged in this setting to prevent unnecessary surgery or when sublobar resection for small-sized tumors is considered. The aim of this retrospective cohort study was to assess the proportion of patients undergoing lung cancer resection in the Netherlands without preoperative pathological confirmation, based on the intraoperative pathological diagnosis (IOD) rate, and to determine characteristics that may influence IOD frequency., Methods: Data on 10,226 patients, who underwent surgical treatment for lung cancer from 2010 to 2015, were retrieved from the Netherlands National Cancer Registry. We registered an IOD when the date of diagnosis equaled the date of the first surgical intervention. Tabulations and multivariable logistic regression were used to identify predictive parameters for IOD., Results: 36% of surgical procedures were classified as IOD, and decreased with increasing tumor size and extent of surgery (57% for segmentectomy, 39% for lobectomy and 11% for pneumonectomy). IOD was more frequently observed in adenocarcinoma (41%), varied between hospitals from 13% to 66% and was less common when patients were referred from a hospital where thoracic surgery was not performed. Previous history of cancer did not affect IOD., Conclusions: More than one-third of patients with suspected lung cancer in the Netherlands was operated without preoperative histological confirmation. There was significant variation in IOD rates between different hospitals, which deserves further detailed analysis when striving for uniform surgical quality of care for patients with lung cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jtd-21-617). van der Heijden EH and Verhagen AF report their department has received unrestricted research grants from Astra Zeneca, Pentax Medical and Philips Medical Systems, as well as speakers fees from Pentax Medical, out the submitted work. The other authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Objective: In patients with NSCLC, lymph node metastases are an important prognostic factor. Despite an accurate pre-operative work up, for optimal staging an intrapulmonary- and mediastinal lymph node dissection (LND) as part of the operation is mandatory. The aim of this study is to assess the completeness of LND in patients undergoing an intended curative resection for NSCLC in the Netherlands and to compare performance between open surgery and minimally invasive surgery (MIS)., Materials and Methods: The intraoperative LND was evaluated in 7460 patients who had undergone a lobectomy for clinically staged N0-1 NSCLC (2013-2018). The LND was considered complete, when three mediastinal (N2) lymph node stations, including station 7, were sampled or dissected, in addition to the lymph nodes from station 10 and 11. A comparison was made between open surgery and MIS., Results: Of 5154 patients, who had MIS, a sufficient intrapulmonary LND was performed in 47.9% and a sufficient mediastinal LND in 58.6%. A complete LND was performed in 31.6%. For 2306 patients who had an open resection, these numbers were 45.0%, 59.0%, and 30.6%, respectively. The overall between-hospital variation in a complete LND ranged between 0 and 72.5%., Conclusion: In the Netherlands, a complete LND of both intrapulmonary- and mediastinal lymph nodes is performed only in a minority of patients with clinically staged N0-1 NSCLC, with substantial between-hospital variation. No differences were seen between open surgery and MIS. Because of poor performance, completeness of lymph node dissection will be recorded as a mandatory performance indicator in our national audit, to improve the quality of resection., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: To develop an interactive tool that estimates what potential benefits are needed for the robot to provide value for money when compared with endoscopic or open surgical interventions., Design: A generic online interactive tool was developed to analyze the (health) effects needed to compensate for the additional costs of using a surgical robotic system from a healthcare perspective. The application of the tool is illustrated with a hypothetical new surgical robotic platform. A synthesis of evidence from different sources was used combined with interviews with surgeons., Setting: Flexible tool that can be adapted to flexible settings., Participants: Any hospital patient group for which robotic, endoscopic or open surgical procedures may be considered as appropriate treatment alternatives (eg, urology, gynecology, and so on)., Intervention: Robotically assisted surgical interventions., Comparator: Endoscopic or open surgical interventions., Main Outcome Measures: Thresholds of how much (health) effect is needed for robot-assisted surgery to provide value for money and to become cost-effective., Results: The utilization rate of the surgical robotic system and a reduction in complications appeared to be important aspects in determining the value for money. To become cost-effective, it was deemed important for new surgical robotic systems to have added clinical benefit and become less costly than the current system., Conclusions: This paper and its assisting interactive tool can be used by clinicians, researchers, and policymakers to gain insight in the benefit needed to provide value for money when using a (new) surgical robotic system or, when the effects are known or can be estimated, to assess the value for money for a specific indication. For robotic surgery to provide most value for money, we recommend assessing for each indication whether the necessary effects seem achievable., Competing Interests: Competing interests: MMR, JPCG and SP have received an unrestricted research grant from Siemens Healthineers for other but related research projects., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Quality assessment is an important element in providing surgical cancer care. The main objective of this study was to develop a new composite measure 'textbook outcome', to evaluate and improve quality of surgical care for patients undergoing a resection for non-small-cell lung cancer (NSCLC)., Methods: All patients undergoing an anatomical resection for NSCLC from 2012 to 2016 registered in the nationwide Dutch Lung Cancer Audit were included in an analysis to assess usefulness of a composite measure as a quality indicator. Based on expert opinion, textbook outcome was defined as having a complete resection (negative resection margins and sufficient lymph node dissection), plus no 30-day or in-hospital mortality, no reintervention in 30 days, no readmission to the intensive care unit, no prolonged hospital stay (<14 days), no hospital readmission after discharge and no major complications. The percentage of patients with a textbook outcome was calculated per hospital. Between-hospital variation in textbook outcome was analysed using case-mix adjustment models., Results: In total, 5513 patients were included in this study. Textbook outcome was achieved in 26.4% of patients. Insufficient lymph node dissection had the most substantial effect on not realizing textbook outcome. If 'sufficient lymph node dissection' was not included as a criterion, textbook outcome would be 60.7%. Case-mix adjusted textbook outcome proportions per hospitals varied between 13.2% and 37.7%., Conclusions: In contrast to focusing on a single aspect, the composite measure textbook outcome provides insight into comprehensive performance in NSCLC surgery. It can be used to evaluate both individual hospitals and national performance and provides the opportunity to give benchmarked feedback to thoracic surgeons., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Objectives: Lymph node staging in patients with non-small cell lung cancer is crucial for determining prognosis and treatment. Our objective was to evaluate the clinical- to pathological agreement of guideline-concordant nodal staging in patients with resectable NSCLC and assess occurrence and distribution of occult lymph node metastases (OLM)., Materials and Methods: In a retrospective single center cohort study (n = 390), we analyzed all surgically treated NSCLC patients from January 2015 until April 2019. Patients were classified into sub-groups (1) mediastinal staging by PET-CT/CT-scan (IMAGE-group) or (2) invasive staging by endobronchial ultrasound and mediastinoscopy (INVAS-group). Agreement between final clinical (cN) and pathological nodal stage (pN) and the presence and location of OLM are analyzed., Results: Agreement between cN- and pN-stage was 86.3 % in the IMAGE-group (n = 117) and 50.9 % in the INVAS-group (n = 167). Occult N1 disease was found in 33 patients (16.6 % in cN0) of which 52 % occurred in LN-regions 12-14. Occult N2 disease was found in 20 cases (6.5 % in cN0 and 12.7 % in cN1). Combined, 23.1 % of all pre-operatively cN0-staged patients (n = 46/199) had OLM (pN+), of which 12.1 % (24/199) had metastases in regions 5-6 and/or 12-14. Of all patients with OLM, 50.0 % (23/46) had primary tumors ≤30 mm., Conclusion: OLM are frequently identified in clinically N0/N1 NSCLC, also in tumors <3 cm, and often in regions beyond reach of current staging techniques. These findings should be addressed when non-surgical treatment or sub-lobar resections are considered for early stage lung cancer., (Copyright © 2020. Published by Elsevier B.V.)

Urgent cardiac surgery was performed in a pregnant woman at 12 weeks of gestation for prosthetic valve thrombosis as result of noncompliance to anticoagulation. With this report we emphasize the importance of proper anticoagulation regimens and follow-up. ( Level of Difficulty: Intermediate. )., (© 2020 The Authors.)

Importance: Resistance of gram-negative bacilli to carbapenems is rapidly emerging worldwide. In 2016, the World Health Organization defined the hospital-built environment as a core component of infection prevention and control programs. The hospital-built environment has recently been reported as a source for outbreaks and sporadic transmission events of carbapenemase-producing gram-negative bacilli from the environment to patients., Objective: To assess risk after the identification of an unexpected, severe, and lethal hospital-acquired infection caused by carbapenemase-producing Pseudomonas aeruginosa in a carbapenemase-low endemic setting., Design, Settings, and Participants: A case series study in which a risk assessment was performed on all 11 patients admitted to the combined cardiothoracic surgery and pulmonary diseases ward and the hospital-built environment in the Radboud University Medical Center, the Netherlands, in February 2018., Exposures: Water and aerosols containing carbapenemase-producing (Verona integron-mediated metallo-β-lactamase [VIM]) P aeruginosa., Main Outcomes and Measures: Colonization and/or infection of patients and/or contamination of the environment after the detection of 1 patient infected with carbapenemase-producing (VIM) P aeruginosa., Results: A total of 5 men (age range, 60-84 years) and 6 women (age range, 55-74 years) were admitted to the combined cardiothoracic surgery and pulmonary diseases ward. The risk assessment was performed after carbapenemase-producing (VIM) P aeruginosa was unexpectedly detected in a man in his early 60s, who had undergone a left-sided pneumonectomy and adjuvant radiotherapy. No additional cases (colonization or infection) of carbapenemase-producing (VIM) P aeruginosa were detected. Plausible transmission of carbapenemase-producing P aeruginosa from the hospital environment to the patient via the air was confirmed by whole-genome sequencing, which proved the relation of Pseudomonas strains from the patient, the shower drains in 8 patient rooms, 1 sink, and an air sample., Conclusions and Relevance: This study suggests that rethinking the hospital-built environment, including shower drains and the sewage system, will be crucial for the prevention of severe and potential lethal hospital-acquired infections.

Background: Quality registries play an important role in the professional quality system for cancer treatment in The Netherlands. This article provides insight into the Dutch Lung Cancer Audit (DLCA); its core principles, initiation and development, first results and what lessons can be learned from the Dutch experience., Methods: Cornerstones of the DLCA are discussed in detail, including: audit aims; the leading role for clinicians; web-based registration and feedback; data handling; multidisciplinary evaluation of quality indicators; close collaborations with all stakeholders in healthcare and transparency of results., Results: In 2012 the first Dutch lung cancer specific sub-registry, focusing on surgical treatment was started. Since 2016 all major treating specialisms (lung oncologists, radiation-oncologists, general- and cardiothoracic surgeons-represented in the DLCA-L, -R and -S sub-registries respectively) have joined. Over time, the number of participating hospitals and included patients has increased. In 2016, the numbers of included patients with a non-small cell lung cancer (NSCLC) were 3,502 (DLCA-L), 2,427 (DLCA-R) and 1,979 (DLCA-S). Between sub-registries mean age varied from 66 to 70 years, occurrence of Eastern Cooperative Oncology Group (ECOG) performance score 2+ varied from 3.3% to 20.8% and occurrence of clinical stage I-II from 27.6% to 81.3%. Of all patients receiving chemoradiotherapy 64.2% was delivered concurrently. Of the surgical procedures 71.2% was started with a minimally invasive technique, with a conversion rate of 18.7%. In 2016 there were 17 publicly available quality indicators-consisting of structure, process and outcome indicators- calculated from the DLCA., Conclusions: the DLCA is a unique registry to evaluate the quality of multidisciplinary lung cancer care. It is accepted and implemented on a nationwide level, enabling participating healthcare providers to get insight in their performance, and providing other stakeholders with a transparent evaluation of this performance, all aiming for continuous healthcare improvement., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: In case of suspicious lymph nodes on computed tomography (CT) or fluorodeoxyglucose positron emission tomography (FDG-PET), advanced tumour size or central tumour location in patients with suspected non-small cell lung cancer (NSCLC), Dutch and European guidelines recommend mediastinal staging by endosonography (endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS)) with sampling of mediastinal lymph nodes. If biopsy results from endosonography turn out negative, additional surgical staging of the mediastinum by mediastinoscopy is advised to prevent unnecessary lung resection due to false negative endosonography findings. We hypothesize that omitting mediastinoscopy after negative endosonography in mediastinal staging of NSCLC does not result in an unacceptable percentage of unforeseen N2 disease at surgical resection. In addition, omitting mediastinoscopy comprises no extra waiting time until definite surgery, omits one extra general anaesthesia and hospital admission, and may be associated with lower morbidity and comparable survival. Therefore, this strategy may reduce health care costs and increase quality of life. The aim of this study is to compare the cost-effectiveness and cost-utility of mediastinal staging strategies including and excluding mediastinoscopy., Methods/design: This study is a multicenter parallel randomized non-inferiority trial comparing two diagnostic strategies (with or without mediastinoscopy) for mediastinal staging in 360 patients with suspected resectable NSCLC. Patients are eligible for inclusion when they underwent systematic endosonography to evaluate mediastinal lymph nodes including tissue sampling with negative endosonography results. Patients will not be eligible for inclusion when PET/CT demonstrates 'bulky N2-N3' disease or the combination of a highly suspicious as well as irresectable mediastinal lymph node. Primary outcome measure for non-inferiority is the proportion of patients with unforeseen N2 disease at surgery. Secondary outcome measures are hospitalization, morbidity, overall 2-year survival, quality of life, cost-effectiveness and cost-utility. Patients will be followed up 2 years after start of treatment., Discussion: Results of the MEDIASTrial will have immediate impact on national and international guidelines, which are accessible to public, possibly reducing mediastinoscopy as a commonly performed invasive procedure for NSCLC staging and diminishing variation in clinical practice., Trial Registration: The trial is registered at the Netherlands Trial Register on July 6th, 2017 ( NTR 6528 ).

Background: In this study we focus on functional outcomes after (laryngo)tracheal resection and reconstruction for acquired benign (laryngo)tracheal stenosis, with a specific interest in the impact of laryngeal involvement on postoperative outcome., Methods: All patients who underwent (laryngo)tracheal surgery for benign pathology between 1996 and 2017 in our centre were included in this retrospective study. Surgical outcomes were procedural success rate, and airway- and voice-related complications. Functional results were assessed using (standardized) questionnaires for quality of life, sensation of dyspnea, swallowing function, and voice perception., Results: Of 119 consecutive patients, 47 underwent laryngotracheal resection and reconstruction and 72 underwent segmental tracheal surgery (78% with an end-to-end tracheal anastomosis and 22% with a cricotracheal anastomosis). Overall success rate was 92% and was similar for all groups, with an overall significant improvement in quality of life when compared to the preoperative situation. However, after laryngotracheal surgery, airway-related complications were more common when compared to segmental resections with an end-to-end tracheal anastomosis (30% versus 7%, P=0.003). Additionally, early voice alterations without recurrent nerve palsy were reported twice as often (34% versus 16%, P=0.034) and voice quality experienced during follow-up was significantly worse when compared to segmental resections. Overall response rate to the questionnaires on functional outcome was 63%., Conclusions: (Laryngo)tracheal surgery is safe and beneficial, with significant functional improvement during mid- and long-term follow-up. However, laryngeal involvement is a predictor for increased surgical airway-related complications. Additionally, voice alterations without recurrent nerve palsy are far more common after laryngotracheal resection and are a serious handicap. This aspect is underexposed in current literature and deserves further attention during preoperative counseling and patient follow-up. However, the results on functional outcome of this current study should be interpreted with caution due to the somewhat low response rate of the questionnaires., Competing Interests: Conflicts of Interest: The abstract of this manuscript was presented at the 31st EACTS Annual Meeting in Vienna, Oct 10, 2017.

Purpose To assess whether dynamic fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET) has added value over static 18 F-FDG PET for tumor delineation in non-small cell lung cancer (NSCLC) radiation therapy planning by using pathology volumes as the reference standard and to compare pharmacokinetic rate constants of 18 F-FDG metabolism, including regional variation, between NSCLC histologic subtypes. Materials and Methods The study was approved by the institutional review board. Patients gave written informed consent. In this prospective observational study, 1-hour dynamic 18 F-FDG PET/computed tomographic examinations were performed in 35 patients (36 resectable NSCLCs) between 2009 and 2014. Static and parametric images of glucose metabolic rate were obtained to determine lesion volumes by using three delineation strategies. Pathology volume was calculated from three orthogonal dimensions (n = 32). Whole tumor and regional rate constants and blood volume fraction (V B ) were computed by using compartment modeling. Results Pathology volumes were larger than PET volumes (median difference, 8.7-25.2 cm 3 ; Wilcoxon signed rank test, P < .001). Static fuzzy locally adaptive Bayesian (FLAB) volumes corresponded best with pathology volumes (intraclass correlation coefficient, 0.72; P < .001). Bland-Altman analyses showed the highest precision and accuracy for static FLAB volumes. Glucose metabolic rate and 18 F-FDG phosphorylation rate were higher in squamous cell carcinoma (SCC) than in adenocarcinoma (AC), whereas V B was lower (Mann-Whitney U test or t test, P = .003, P = .036, and P = .019, respectively). Glucose metabolic rate, 18 F-FDG phosphorylation rate, and V B were less heterogeneous in AC than in SCC (Friedman analysis of variance). Conclusion Parametric images are not superior to static images for NSCLC delineation. FLAB-based segmentation on static 18 F-FDG PET images is in best agreement with pathology volume and could be useful for NSCLC autocontouring. Differences in glycolytic rate and V B between SCC and AC are relevant for research in targeting agents and radiation therapy dose escalation. © RSNA, 2016 Online supplemental material is available for this article.