Search

Jelle E Bousema,1 Fieke Hoeijmakers,2 Marcel GW Dijkgraaf,3 Jouke T Annema,4 Frank JC van den Broek,1 M Elske van den Akker-van Marle5 On behalf of the MEDIASTrial Study Group1Department of Surgery, Máxima MC, Veldhoven, 5500 MB, the Netherlands; 2Department of Surgery, Leiden University Medical Center, Leiden, 2300 RC, the Netherlands; 3Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam, 1100 DE, the Netherlands; 4Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, 1100 DE, the Netherlands; 5Department of Biomedical Data Sciences, Unit Medical Decision Making, LUMC, Leiden, 2300 RC, the NetherlandsCorrespondence: Frank JC van den BroekDepartment of Surgery, Máxima MC, Veldhoven, P.O. BOX 7777, Veldhoven, 5500 MB, the NetherlandsEmail lung.resurge@mmc.nlBackground: Variability in practice and ongoing debate on optimal invasive mediastinal staging of patients with resectable non-small cell lung cancer (NSCLC) are widely described in the literature. Patients’ preferences on this topic have, however, been underexposed so far.Methods: An internet-based questionnaire was distributed among MEDIASTrial participants (NTR6528, randomization of patients to mediastinoscopy or not in the case of negative endosonography). Literature, expert opinion and patient interviews resulted in five attributes: the risk of a futile lung resection (oncologically futile in case of unforeseen N2 disease), the length of the staging period, resection of the primary tumor, complications of staging procedures and the mediastinoscopy scar. The relative importance (RI) of each attribute was assessed by using adaptive conjoint analysis and hierarchical Bayes estimation. A treatment trade-off was used to examine the acceptable proportion of avoided futile lung resections to cover the burden of confirmatory mediastinoscopy.Results: Ninety-seven patients completed the questionnaire (57%). The length of the staging period was significantly the most important attribute (RI 26.24; 95% CI: 25.05– 27.43), followed by the risk of a futile surgical lung resection (RI 23.44; 95% CI: 22.28– 24.60) and resection of the primary tumor (RI 22.21; 95% CI: 21.09– 23.33). Avoidance of 7% (IQR 1– > 14%) futile lung resections would cover the burden of confirmatory mediastinoscopy, with a dichotomy among patients always (39%) or never (38%) willing to undergo confirmatory mediastinoscopy after N2 and N3-negative endosonography.Conclusion: Although a strong dichotomy among patients always or never willing to undergo confirmatory mediastinoscopy was found, the length of the staging period was the most important attribute in invasive mediastinal staging according to patients with resectable NSCLC.Trial Registration: Not applicable.Keywords: patients’ preferences, non-small cell lung cancer, mediastinal nodal staging, endosonography, mediastinoscopy, thoracic surgery

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.

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.)

Background: Routine lymphadenectomy during metastasectomy for pulmonary metastases of colorectal cancer has been recommended by several recent expert consensus meetings. However, evidence supporting lymphadenectomy is limited. The aim of this study was to perform a systematic review of the literature on the impact of simultaneous lymph node metastases on patient survival during metastasectomy for colorectal pulmonary metastases (CRPM)., Methods: A systematic review was conducted according to the PRISMA guidelines of studies on lymphadenectomy during pulmonary metastasectomy for CRPM. Articles published between 2000 and 2020 were identified from Medline, Embase and the Cochrane Library without language restriction. Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to assess the risk of bias and applicability of included studies. Survival rates were assessed and compared for the presence and level of nodal involvement., Results: Following review of 8054 studies by paper and abstract, 27 studies comprising 3619 patients were included in the analysis. All patients included in these studies underwent lymphadenectomy during pulmonary metastasectomy for CRPM. A total of 690 patients (19.1%) had simultaneous lymph node metastases. Five-year overall survival for patients with and without lymph node metastases was 18.2% and 51.3%, respectively (p < .001). Median survival for patients with lymph node metastases was 27.9 months compared to 58.9 months in patients without lymph node metastases (p < .001). Five-year overall survival for patients with N1 and N2 lymph node metastases was 40.7% and 10.9%, respectively (p = .064)., Conclusion: Simultaneous lymph node metastases of CRPM have a detrimental impact on survival and this is most apparent for mediastinal lymph node metastases. Therefore, lymphadenectomy during pulmonary metastasectomy for CRPM can be advised to obtain important prognostic value., 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 © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Guidelines for invasive mediastinal nodal staging in resectable nonsmall cell lung cancer (NSCLC) have changed over the years. The aims of this study were to describe trends in invasive staging and unforeseen N2 (uN2) and to assess a potential effect on overall survival., Methods: A nationwide Dutch cohort study included all clinical stage IA-IIIB NSCLC patients primarily treated by surgical resection between 2005 and 2017 (n=22 555). We assessed trends in invasive nodal staging (mediastinoscopy 2005-2017; endosonography 2011-2017), uN2 and overall survival and compared outcomes in the entire group and in clinical nodal stage (cN)1-3 patients with or without invasive staging., Results: An overall increase in invasive nodal staging from 26% in 2005 to 40% in 2017 was found (p<0.01). Endosonography increased from 19% in 2011 to 32% in 2017 (p<0.01), while mediastinoscopy decreased from 24% in 2011 to 21% in 2017 (p=0.08). Despite these changes, uN2 was stable over the years at 8.7%. 5-year overall survival rate was 41% for pN1 compared to 37% in single node uN2 (p=0.18) and 26% with more than one node uN2 (p<0.01). 5-year overall survival rate of patients with cN1-3 with invasive staging was 44% versus 39% in patients without invasive staging (p=0.12)., Conclusion: A significant increase in invasive mediastinal nodal staging in patients with resectable NSCLC was found between 2011 and 2017 in the Netherlands. Increasing use of less invasive endosonography prior to (or as a substitute for) surgical staging did not lead to more cases of uN2. Performance of invasive staging indicated a possible overall survival benefit in patients with cN1-3 disease., Competing Interests: Conflict of interest: J.E. Bousema has nothing to disclose. Conflict of interest: M.J. Aarts has nothing to disclose. Conflict of interest: M.G.W. Dijkgraaf has nothing to disclose. Conflict of interest: J.T. Annema reports non-financial educational support from Hitachi Medical Systems and Pentax, grants from Cook Medical and Mauna Kea Technologies, outside the submitted work. Conflict of interest: F.J.C. van den Broek has nothing to disclose., (Copyright ©ERS 2021.)

Objectives: Invasive mediastinal staging is advised by guidelines in patients with resectable non-small cell lung cancer (NSCLC) and suspicious lymph nodes (cN1-3) or for central, FDG-non-avid or peripheral tumours >3 cm. Our objective was to assess current guideline adherence and consequent unforeseen N2 disease (uN2) in NSCLC patients having various indications for mediastinal staging., Materials and Methods: We analysed the Dutch Lung Cancer Audit - Surgery data of all patients who underwent a primary lung resection with lymph node dissection for NSCLC in 2017-2018. Based on the 2015 ESTS-ERS-ESGE guideline we assessed the use of initial endosonography and confirmatory mediastinoscopy as well as uN2 rates., Results: A total of 2238 patients were analysed. 43 % (95 %-CI: 41-45) underwent initial endosonography followed by a confirmatory mediastinoscopy in 44 % (95 %-CI:40-47) of them, resulting in a 19 % (95 %-CI: 17-20) rate of properly staged patient according to the guidelines. uN2 was demonstrated in 12.5 % (95 %-CI: 9.7-16.0) of correctly staged patients compared to 10.9 % (95 %-CI: 9.6-12.4) who were not (p = .36). The highest uN2 rate was found in cN1-3 patients who were not staged (23.0 %, 95 %-CI: 16.4-31.2) compared to 13.0 % (95 %-CI: 9.7-17.1) who were (p = .01)., Conclusion: Guideline adherence in Dutch NSCLC patients with an indication for invasive mediastinal staging is poor. The highest uN2 rate was found in unstaged cN1-3 patients, suggesting that this subgroup may benefit from an appropriate staging conform guidelines., Competing Interests: Declaration of Competing Interest Dr. Bousema, Dr. Heineman, Prof. Dr. Dijkgraaf and Dr. Van Den Broek have nothing to disclose. Prof. Dr. Annema reports non-financial support from Hitachi Medical systems, non-financial support from Pentax, grants from Cook medical, outside the submitted work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Sufficient pain control and rapid mobilisation after VATS are important to enhance recovery and prevent complications. Thoracic epidural analgesia (TEA) is the gold standard, but failure rates of 9-30% have been described. In addition, TEA reduces patient mobilisation and bladder function. Subpleural continuous analgesia (SCA) is a regional analgesic technique that is placed under direct thoracoscopic vision and is not associated with the mentioned disadvantages of TEA. The objective of this study was to assess surgical feasibility, pain control and patient satisfaction of SCA., Methods: Observational pilot study in patients who underwent VATS pulmonary resection and received SCA (n = 23). Pain scores (numeric rating scale 0-10) and patient satisfaction (5-point Likert scale) were collected on postoperative day (POD) 0-3. Secondary outcomes were the period of urinary catheter use and period to full mobilisation., Results: Placement of the subpleural catheter took an average of 11 min (SD 5) and was successful in all patients. Pain scores on POD 0-3 were 1.2 (SD 1.2), 2.0 (SD 1.9), 1.7 (SD 1.5) and 1.2 (SD 1.1) respectively. On POD 0-3 at least 79% of patients were satisfied or very satisfied on pain relief and mobilisation. The duration of subpleural continuous analgesia was 4 days (IQR 3-5, range 2-11). Urinary catheters were used zero days (IQR 0-1, range 0-6) and full mobilisation was achieved on POD 2 (IQR 1-2, range 1-6)., Conclusion: Subpleural continuous analgesia in VATS pulmonary resection is feasible and provides adequate pain control and good patient satisfaction., Trial Registration: This pilot study was not registered in a trial register.

Acute abdominal pain is a common symptom in young women. We describe a patient with acute illness and severe lower abdominal pain. Laboratory tests were normal except for mildly deranged inflammatory markers. No abnormalities were reported on abdominal ultrasonography and MRI, whereas diagnostic laparoscopy revealed a tumour located dorsally from the uterus. We resected the tumour and pathology results showed a well-differentiated papillary mesothelioma of the peritoneum (WDPMP). Microscopy showed evidence of acute ischaemia in the resected lesion, which was likely the cause of the acute abdominal pain. WDPMP is a rare disease that arises from the serous membranes which does not seem to have a relation to asbestos exposure. Generally, WDPMP has a mild clinical course and good long-term prognosis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Mediastinal lymph node staging of NSCLC by initial endosonography and confirmatory mediastinoscopy is recommended by the European guideline. We assessed guideline adherence on mediastinal staging, whether staging procedures were performed systematically and unforeseen N2 rates following staging by endosonography with or without confirmatory mediastinoscopy., Material and Methods: We performed a multicentre (n = 6) retrospective analysis of NSCLC patients without distant metastases, who were surgical candidates and had an indication for mediastinal staging in the year 2015. All patients who underwent EBUS, EUS and/or mediastinoscopy were included. Surgical lymph node dissection was the reference standard. Guideline adherence was based on the 2014 ESTS guideline., Results: 330 consecutive patients (mean age 69 years; 61% male) were included. The overall prevalence of N2/N3 disease was 42%. Initial mediastinal staging by endosonography was done in 84% (277/330; range among centres 71-100%; p < .01). Confirmatory mediastinoscopy was performed in 40% of patients with tumour negative endosonography (61/154; range among centres 10%-73%; p < .01). Endosonography procedures were performed 'systematically' in 21% of patients (57/277) with significant variability among centres (range 0-56%; p < .01). Unforeseen N2 rates after lobe-specific lymph node dissection were 8.6% (3/35; 95%-CI 3.0-22.4) after negative endosonography versus 7.5% (3/40; 95% CI 2.6-19.9) after negative endosonography and confirmatory mediastinoscopy., Conclusion: Although adherence to the European NSCLC mediastinal staging guideline on initial use of endosonography was good, 30% of endosonography procedures were performed insufficiently. Confirmatory mediastinoscopy following negative endosonography was frequently omitted. Significant variability was found among participating centres regarding staging strategy and systematic performance of procedures. However, unforeseen N2 rates after mediastinal staging by endosonography with and without confirmatory mediastinoscopy were comparable., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Confirmatory mediastinoscopy after negative endosonography findings is advised by the guidelines on patients with resectable NSCLC and suspected intrathoracic nodes on fludeoxyglucose F 18 positron emission tomography-computed tomography. Its role however is under debate owing to its limited nodal metastasis detection rate, morbidity, associated treatment delay, and unknown impact on survival., Methods: Systematic review and meta-analysis of studies on invasive mediastinal staging in patients with (suspected) NSCLC. The Medline, Embase, and Cochrane databases were searched until September 19, 2018, without year or language restrictions. The Quality Assessment Tool for Diagnostic Accuracy Studies, version 2, was used to evaluate the risk of bias and applicability of the included studies. Rates of unforeseen N2 disease were assessed for endobronchial ultrasound and/or endoscopic ultrasound staging strategies with or without confirmatory mediastinoscopy. Additionally, the complication rates of cervical video mediastinoscopy for mediastinal staging of NSCLC were investigated., Results: A total of 5073 articles were found, of which 42 studies or subgroups (covering a total of 3248 patients undergoing the surgical reference standard of treatment) were considered in the analysis. Random effects meta-analysis of endosonography with or without confirmatory mediastinoscopy showed rates of unforeseen N2 disease of 9.6% (95% confidence interval [CI]: 7.8%-11.7%, I 2  = 30%) versus 9.9% (95% CI: 6.3%-15.2%, I 2  = 73%), respectively. Random effects meta-analysis of mediastinoscopy (eight studies [1245 patients in total]) showed a complication rate of 6.0% (95% CI: 4.8%-7.5%), with laryngeal recurrent nerve palsy accounting for 2.8% (95% CI: 2.0%-4.0%)., Conclusion: The rate of unforeseen N2 disease after negative endosonography findings was similar in patients undergoing immediate lung tumor resection to those undergoing confirmatory mediastinoscopy first, at the cost of 6.0% rate of complications by mediastinoscopy., (Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

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 ).