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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, Pnoninferior < .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%; Pnoninferior = .0144) and per-protocol analyses (Δ, 0.83%; UL 95% CIΔ, 7.3%; Pnoninferior = .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: Accurate diagnosis and staging are crucial to ensure uniform allocation to the optimal treatment methods for non-small cell lung cancer (NSCLC) patients, but may differ among multidisciplinary tumor boards (MDTs). Discordance between clinical and pathologic TNM stage is particularly important for patients with locally advanced NSCLC (stage IIIA) because it may influence their chance of allocation to curative-intent treatment. We therefore aimed to study agreement on staging and treatment to gain insight into MDT decision-making. Research Question: What is the level of agreement on clinical staging and treatment recommendations among MDTs in stage IIIA NSCLC patients? Study Design and Methods: Eleven MDTs each evaluated the same 10 pathologic stage IIIA NSCLC patients in their weekly meeting (n = 110). Patients were selected purposively for their challenging nature. All MDTs received exactly the same clinical information and images per patient. We tested agreement in cT stage, cN stage, cM stage (TNM 8th edition), and treatment proposal among MDTs using Randolph's free-marginal multirater kappa. Results: Considerable variation among the MDTs was seen in T staging (κ, 0.55 [95% CI, 0.34-0.75]), N staging (κ, 0.59 [95% CI, 0.35-0.83]), overall TNM staging (κ, 0.53 [95% CI, 0.35-0.72]), and treatment recommendations (κ, 0.44 [95% CI, 0.32-0.56]). Most variation in T stage was seen in patients with suspicion of invasion of surrounding structures, which influenced such treatment recommendations as induction therapy and type. For N stage, distinction between N1 and N2 disease was an important source of discordance among MDTs. Variation occurred between 2 patients even regarding M stage. A wide range of additional diagnostics was proposed by the MDTs. Interpretation: This study demonstrated high variation in staging and treatment of patients with stage IIIA NSCLC among MDTs in different hospitals. Although some variation may be unavoidable in these challenging patients, we should strive for more uniformity.

Purpose of the Review Although surgical resection is considered the gold standard of curative treatment for bronchial carcinoid, endobronchial treatment (EBT) can serve as a less invasive curative or palliative treatment in a selection of patients. It is unclear whether elderly patients with bronchial carcinoid should be treated in the same way as younger patients. In order to study the characteristics and treatment of elderly patients with bronchial carcinoid, we analyzed data from a cohort of patients that have been treated for bronchial carcinoid with EBT, surgical resection, or a combination of both. We used our existing database of patients referred for EBT and defined two groups of patients: ≥ 65 and Recent Findings Thirty-five patients (19%) were ≥ 65 years. The incidence of atypical carcinoid was the same in both age groups (31%). Thirty-six of 184 patients (20%) were directly referred for surgical resection and 148 (80%) underwent EBT. There was no significant difference in success of EBT between patients p = 0.347). Complication rates were similar in both groups. After unsuccessful EBT, only 70% (14/20) of the elderly patients was operated, whereas 93% (85/91) of the patients p = 0.001). Disease specific mortality was 6% (2/35) in the group ≥ 65 years and 2% (3/149) in the group Summary The incidence of atypical carcinoid is similar between the elderly and younger patients. Success rate and complication rate of EBT do not differ significantly between the age groups. After unsuccessful EBT, elderly patients were less likely to undergo surgical resection, which does not seem associated with excess disease specific mortality, although the number of events in this study is low.

Purpose Recombinant human erythropoietin (rHuEPO) is known to increase thrombotic risk in patients and might have similar effects in athletes abusing the drug. rHuEPO is prohibited by anti-doping legislation, but this risk has not been investigated thoroughly. This analysis was designed to evaluate whether rHuEPO impacts hemostatic profile and endothelial and platelet activation markers in trained subjects, and whether the combination with exercise affects exercise induced alterations. Methods This double-blind, randomized, placebo-controlled trial enrolled healthy, trained male cyclists aged 18–50 years. Participants were randomly allocated (1:1) to receive subcutaneous injections of rHuEPO (epoetin-β; mean dose 6000 IU per week) or placebo (0.9% NaCl) for 8 weeks. Subjects performed five maximal exercise tests and a road race, coagulation and endothelial/platelet markers were measured at rest and directly after each exercise effort. Results rHuEPO increased P-selectin (+ 7.8% (1.5–14.5), p = 0.02) and E-selectin (+ 8.6% (2.0–15.7), p = 0.01) levels at rest. Maximal exercise tests significantly influenced all measured coagulation and endothelial/platelet markers, and in the rHuEPO group maximal exercise tests led to 15.3% ((7.0–24.3%), p = 0.0004) higher E-selectin and 32.1% ((4.6–66.8%), p = 0.0207) higher Platelet factor 4 (PF4) levels compared to the placebo group. Conclusion In conclusion, rHuEPO treatment resulted in elevated E- and P-selectin levels in trained cyclists, indicating enhanced endothelial activation and/or platelet reactivity. Exercise itself induces hypercoagulability, and the combination of rHuEPO and exercise increased E-selectin and PF4 levels more than either intervention alone. Based on this, exercise potentially increases thrombotic risk, a risk that might be enhanced in combination with rHuEPO use.

Background Tumor size and metastatic extent may influence tumor response to immunotherapy in non-small cell lung cancer (NSCLC). The aim of this study was to examine the relationship between both baseline sum of longest diameters (bSLD) and number of metastatic organs (NMO) and the tumor response to pembrolizumab. Secondly, we aimed to analyze the association of baseline SLD and NMO with progression-free survival (PFS) and overall survival (OS). Methods This retrospective study included patients with high PD-L1 expressing tumors (≥50%) and a good performance score (ECOG ≤ 2) that received first-line pembrolizumab monotherapy. Tumor response was calculated as the ‘SLD-change score’ and ‘early treatment discontinuation’ within 3 months on therapy (ETD). The relationship of both bSLD (based on RECIST v1.1) and NMO with tumor response and survival outcome (PFS, OS) was evaluated. Results No significant differences in SLD-change score could be found using bSLD (OR = 1.010, 95%CI = 0.999–1.021), or using NMO at baseline (OR = 1.608, 95%CI = 0.943–2.743). A bSLD cut-off value of 90 mm was found to be most distinctive for ETD. This cut-off value showed a significant difference for PFS (HR = 2.28, 95%CI = 1.12–4.64, p = 0.023) and OS (HR = 2.99, 95%CI = 1.41–6.34, p = 0.004). NMO also showed a difference for PFS and OS, however, not statistically significant. Conclusions Tumor size and metastatic extent could not discriminate for tumor response, however, a bSLD of 90 mm could differentiate for PFS and OS.

ObjectiveRecently, 60% discordancy was reported for distinction between typical carcinoid and atypical carcinoid in preoperative biopsy compared to the resection specimen. This study investigated the impact of biopsy surface size, obtained with flexible and rigid bronchoscopy, on diagnostic accuracy of typical and atypical carcinoid.MethodsBiopsy-resection paired specimens of patients referred for treatment to Amsterdam University Medical Centers were retrieved. Bronchial biopsies were obtained either by flexible or rigid biopsy. The definitive diagnosis was based on the resection specimen. Diagnosis according to the 2015 WHO classification, mitoses and necrosis in biopsy and resection specimen, were independently re-evaluated by two pathologists.ResultsAfter screening 298 patients, 64 biopsy-resection pairs with available tissue were included of which 34 (53%) were biopsied with flexible and 30 (47%) with rigid biopsy. In 35 (55%) patients, the tumor classification between the biopsy and resection specimen was concordant. The discordance in the remaining 29 cases (45%) was caused by misclassification of atypical as typical carcinoid in bronchoscopy specimens, predominantly in small flexible biopsies (59%, p=0.021). Of biopsies measuring 2, 79% were classified as discordant and 52% of the discordant biopsies measured 2.ConclusionHistological classification in central carcinoid tumors is discordant in 45% of the biopsies, with increasing diagnostic accuracy in larger biopsies. Distinguishing carcinoid tumor into typical or atypical carcinoid on biopsies 2 should be discouraged. A cumulative biopsy surface of at least 4 mm2 tumor is preferred to increase the diagnostic accuracy which helps in optimal treatment planning.

IntroductionThe extensive loss of lung parenchyma is a drawback of anatomical resection in bronchial carcinoids. Endobronchial therapy (EBT) has emerged as a safe and effective minimally invasive tissue sparing alternative for small intraluminal tumors. Currently, therapeutic decision making in patients with bronchial carcinoid is mainly based on tumor morphology and patient characteristics. The availability of more accurate biomarkers might help clinicians in selecting low-risk tumors for EBT. Therefore, we investigated radiological (tumor diameter), morphometric (mitotic index) and immunohistochemical (OTP, CD44, Ki-67, Rb and P16) markers as predictors of dissemination.Material and methodsPatients referred to Amsterdam University Medical Centers with available histology were included. Clinical and morphological characteristics relevant for classification such as tumor diameter, mitotic count (MAI) and prognostic immunohistochemical markers as Ki-67, P16, Rb, Orthopedia homebox (OTP) and CD44 were analyzed.ResultsIn a cohort of 171 patients, the vast majority were curatively treated with either EBT (n=61, 36%) or surgery (n=103, 60%). Seven (4%) patients presented with distant metastases at diagnosis. TC was diagnosed in 112 (65%) and AC in 59 (35%) patients. Nine (15%) patients treated with EBT had a local recurrence of disease during follow up and none developed lymph node or distant metastasis. Of all surgically treated patients, 13 (13%) had level 1 or 2 lymph node metastases. Additional 13 (13%) patients developed distant metastases, 11 (85%) were AC and 2 (15%) TC. Patients with tumor stage IA (tumor diameter ≤1cm) irrespective of tumor classification or immunohistochemical results did not develop distant metastases. Patients with typical carcinoid (2) stage ≥IB with Ki67 2), Ki-67 of ≥5% (p=p=5% or loss of CD44 metastasized occasionally (11%).ConclusionAdding tumor diameter, CD44 and Ki-67 to the widely used TC/AC classification, provides a multimodal biomarker that better stratifies patients in prognostically favorable and unfavorable categories than current standards. These findings enable risk stratification allowing a tailored treatment approach for patients with bronchial carcinoid.

Recombinant human erythropoietin (rHuEPO) is used as doping a substance. Anti‐doping efforts include urine and blood testing and monitoring the athlete biological passport (ABP). As data on the performance of these methods are incomplete, this study aimed to evaluate the performance of two common urine assays and the ABP. In a randomized, double‐blinded, placebo‐controlled trial, 48 trained cyclists received a mean dose of 6000 IU rHuEPO (epoetin β) or placebo by weekly injection for eight weeks. Seven timed urine and blood samples were collected per subject. Urine samples were analyzed by sarcosyl‐PAGE and isoelectric focusing methods in the accredited DoCoLab in Ghent. A selection of samples, including any with false presumptive findings, underwent a second sarcosyl‐PAGE confirmation analysis. Hematological parameters were used to construct a module similar to the ABP and analyzed by two evaluators from an Athlete Passport Management Unit. Sensitivity of the sarcosyl‐PAGE and isoelectric focusing assays for the detection of erythropoietin abuse were 63.8% and 58.6%, respectively, with a false presumptive finding rate of 4.3% and 6%. None of the false presumptive findings tested positive in the confirmation analysis. Sensitivity was highest between 2 and 6 days after dosing, and dropped rapidly outside this window. Sensitivity of the ABP was 91.3%. Specificity of the urine assays was high; however, the detection window of rHuEPO was narrow, leading to questionable sensitivity. The ABP, integrating longitudinal data, is more sensitive, but there are still subjects that evade detection. Combining these methods might improve performance, but will not resolve all observed shortcomings., World Anti‐Doping Agency methods for detection of recombinant human erythropoietin were evaluated in cyclists. Detection in urine by sarcosyl‐PAGE had a sensitivity of 63.8% and isoelectric focusing of 58.6%, sensitivity peaked between 2 and 6 days after dosing, rapidly dropping outside this window. False presumptive finding rates were 4.3% and 6%, respectively, but none of the false presumptive findings tested positive in the confirmation analysis. Sensitivity of the athlete biological passport that integrates longitudinal hematological data was 91.3%.

ObjectivesOrganization and governance of national healthcare might play an important role in decision-making and outcomes in patients with lung cancer. Both Denmark and the Netherlands have a high level of healthcare but a different financial coverage, governance and level of centralization. By using both national databases we analyzed the consequences of these differences on patterns of care and outcomes with a focus on morbidity, mortality and clinical staging.Materials and methodsGeneral numbers on both healthcare systems were requested. All patients who had surgery for lung cancer from 2013 to 2016 were included. Mortality, morbidity and clinical staging were analyzed for patients with NSCLC without metastases, only one operation and no neo-adjuvant therapy.ResultsIn 2016 annual budget as share of gross national product was 10.4% for both countries. In Denmark 4 hospitals performed lung surgery in 2016, compared to 43 hospitals in the Netherlands. We included 4030 Danish and 8286 Dutch patients. In the subgroup 30-day mortality was 1.5% in Denmark compared to 1.9% in the Netherlands. The percentage of patients with a complicated course was 24.4% and 34.8% respectively (p ConclusionSurgery for lung cancer is at a high level in both countries, reflected by low mortality-rates. Centralization has been implemented successfully in Denmark, which might explain the lower rate of patients with a complicated post-operative course, although different definitions preclude firm conclusions. In both countries correct clinical staging of lung cancer remains a challenge.

We show a portable third and second harmonic generation microscope in the clinic generating 3D real-time high resolution images of fresh lung tumor tissue providing immediate pathological feedback for clinicians potentially reducing endoscopy/operation time.

Simple Summary High-dose radiotherapy is frequently used to treat lung cancer, however, it can cause serious central airway toxicity. Although radiation toxicity of the lung parenchyma has been studied extensively, relatively little has been published on bronchoscopic findings in the central airways and no standard classification/reporting system exists. With the growing use of high-dose (chemo)radiotherapy and high-dose hypo-fractionated radiotherapy in close proximity to central airways, as well as potential interactions with new systemic therapies, the risks and incidence of central airway toxicity may increase. In this retrospective study, we analyzed patient characteristics and clinical outcomes of 70 patients with central airway toxicity after high-dose radiotherapy. Furthermore, we analyzed the post-radiotherapy bronchoscopic images to identify main patterns of airway toxicity. We identified luminal stenosis and vascular changes as the two main patterns and have proposed a classification system. Preliminary analysis suggests that the pattern and severity of radiation toxicity may be of prognostic value. Abstract The study’s purpose was to identify the bronchoscopic patterns of central airway toxicity following high-dose radiotherapy or chemoradiotherapy, and to look at the consequences of these findings. Our institutional bronchoscopy database was accessed to identify main patterns of airway toxicity observed in a seven-year period. A total of 70 patients were identified with central airway toxicity, and the findings of bronchoscopy were used to derive a classification system. Patient characteristics, time from radiotherapy to toxicity, follow-up and survival were retrospectively analyzed. Results: The main bronchoscopic patterns of airway toxicity were vascular changes (telangiectasia, loss of vascularity, necrosis) and stenosis of the lumen (moderate, severe). Indications for bronchoscopy were airway symptoms (n = 28), assessment post-CRT/surgery (n = 12), (suspected) recurrence (n = 21) or assessment of radiological findings (n = 9). Stenosis was revealed by bronchoscopy at a median time of 10.0 months (IQR: 4–23.5) after radiotherapy and subsequent follow-up after identification was 23 months (IQR: 1.5–55). The corresponding findings for vascular changes were 29 months (IQR: 10.5–48.5), and follow-up after identification was nine months (IQR: 2.5–19.5). There was a statistically significant difference in survival rates between patients with necrosis and telangiectasia (p = 0.002) and loss of vascularity (p = 0.001). Eight out of 10 deceased patients with telangiectasia died of other causes and 4/8 patients with necrosis died of other causes. We identified two main patterns of central airway toxicity visualized with bronchoscopy after high-dose radiotherapy or chemoradiotherapy, and propose a bronchoscopic classification system based on these findings. Preliminary analysis suggests that the pattern and severity of radiation damage might be of prognostic value. Prospective data are required to confirm our findings.

Objectives Treatment patterns in patients with stage III non-small cell lung cancer (NSCLC) vary considerably between countries, for reasons that are not well understood. We studied factors influencing treatment decision-making at thoracic multidisciplinary tumor boards (MDT’s) and outcome for patients treated between 2015–2017, at a regional network comprising 5 hospitals. Materials and methods Details of all patients, including comorbidities, with stage III NSCLC were collected in an ethics-approved database. Weekly MDT’s were conducted. The preferred radical intent treatments (RIT) for suitable patients were assumed to be concurrent chemoradiotherapy and/or surgery and other therapies were non-radical intent treatments (n-RIT). Results Of 197 patients identified, 95 % were discussed at an MDT. RIT were recommended in 61 % of patients, but only 48 % finally received RIT. The estimated median OS was significantly better for patients undergoing RIT (28.3 months, CI-95 % 17.3–39.3), versus those who did not (11.2 months, CI-95 % 8.0−14.3). Patient age ≥70 years and a WHO-PS ≥2 were the most important predictors of not recommending RIT. Deaths due to progressive lung cancer within 2 years were observed in 36, 26 and 29 % of patients who received RIT, sequential chemoradiotherapy or radical radiotherapy. Corresponding comorbidity related deaths within 2 years were 3, 12 and 38 %. Conclusion A large number of patients who underwent MDT review were considered too old or not fit for RIT. More effective and better tolerated systemic treatments are required for patients presenting with stage III NSCLC.

BackgroundWe developed the chronic obstructive pulmonary disease (COPD)-Lower Respiratory Tract Infection-Visual Analogue Score (c-LRTI-VAS) in order to easily quantify symptoms during exacerbations in patients with COPD. This study aimed to validate this score.MethodsIn our study, patients with stable COPD as well as those with an acute exacerbations of COPD (AECOPD) were included. The results of c-LRTI-VAS were compared with other markers of disease activity (lung function parameters, oxygen saturation and two health related quality of life questionnaires (St Georges Respiratory Questionnaire (SGRQ) and Clinical COPD Questionnaire (CCQ)) and validity, reliability and responsiveness were assessed.ResultsEighty-eight patients with clinically stable COPD and 102 patients who had an AECOPD completed the c-LRTI-VAS questionnaire. When testing on two separate occasions for repeatability, no statistically significant difference between total scores was found 0.143 (SD 5.42) (p=0.826). Internal consistency was high across items (Cronbach’s apha 0.755). Correlation with SGRQ and CCQ total scores was moderate to high. After treatment for hospitalised AECOPD, the mean c-LRTI-VAS total score improved 8.14 points (SD 9.13; p≤0.001).Conclusionsc-LRTI-VAS showed proper validity, responsiveness to change and moderate to high correlation with other questionnaires. It, therefore, appears a reliable tool for symptom measurement during AECOPD.Trial registration numberNCT01232140.

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.

Inflammatory myofibroblastic tumours (IMT) are a rare cause of endobronchial masses in adults. Surgery has been the mainstay of treatment of endobronchial IMTs, based on the potential for recurrence. Interventional pulmonology has emerged as a minimally invasive and lung function preserving modality in management of airway obstruction due to tumours. We present a series of three adult patients with IMT treated endobronchially with a short discussion on its potential role. We also discuss how molecular analysis of IMTs for mutations in genes such as ALK and ROS1 might provide insights into clinical behaviour and potential targetable therapy in advanced, unresectable and metastatic cases., Inflammatory myofibroblastic tumours in central airways: bronchoscopic treatment of a “not so pseudo-” tumour https://bit.ly/2KgPntq

During lung cancer operations a rapid and reliable assessment of tumor tissue can reduce operation time and potentially improve patient outcomes. We show that third harmonic generation (THG), second harmonic generation (SHG) and two‐photon excited autofluorescence (2PEF) microscopy reveals relevant, histopathological information within seconds in fresh unprocessed human lung samples. We used a compact, portable microscope and recorded images within 1 to 3 seconds using a power of 5 mW. The generated THG/SHG/2PEF images of tumorous and nontumorous tissues are compared with the corresponding standard histology images, to identify alveolar structures and histopathological hallmarks. Cellular structures (tumor cells, macrophages and lymphocytes) (THG), collagen (SHG) and elastin (2PEF) are differentiated and allowed for rapid identification of carcinoid with solid growth pattern, minimally enlarged monomorphic cell nuclei with salt‐and‐pepper chromatin pattern, and adenocarcinoma with lipidic and micropapillary growth patterns. THG/SHG/2PEF imaging is thus a promising tool for clinical intraoperative assessment of lung tumor tissue., A portable label‐free real‐time ex‐vivo microscope is used to investigate fresh unprocessed lung tumor tissue by generating third harmonic generation (THG), second harmonic generation (THG) and two‐photon excited fluorescence (2PEF) images, and comparing those images with standard HE histology images. Cellular structures (THG), and collagen (SHG) and elastin (2PEF) fibers can be distinguished, revealing important histopathological hallmarks (cell morphology and tissue architecture) for the assessment of lung tumor tissue.

Introduction: Transbronchial lung cryobiopsy (TBCB) is a minimally invasive diagnostic procedure for patients with diffuse parenchymal lung disease. Pneumothorax occurs in approximately 19% of procedures and severe hemorrhage in Methods: We prospectively collected data of patients that underwent TBCB. The decision to perform TBCB was taken in the multidisciplinary ILD meeting. The procedure was performed either under general anesthesia with a rigid bronchoscope or cuffed ET tube, or under propofol sedation with a Rusch Bronchoflex tube. Arndt bronchial blockers were used to block the segmental or lobar bronchus after every biopsy in order to minimize bleeding. Patients were observed for 1 night at the clinic and before discharge a chest X-ray was performed. Results: Ninety-three patients underwent TBCB. The mean number of biopsies was 3,8 ±1,3. The overall pneumothorax rate was 15,1%. The annual rate of pneumothorax declined from 29% in 2015 to 8% in 2018 and 2019 (table 1). Bleeding was controlled in all cases with the bronchial blocker. 30-day moratilty was 1/93 (1%). Conclusions: Although TBCB is a safe procedure, there seems to be a clear learning curve with respect to the incidence of pneumothorax. Careful monitoring of complications is important to learn as a team and to minimize the morbidity. References: 1. Ravaglia C et al. BMC Pulm Med 2019;19:16.

BackgroundThe likelihood of a tumor recurrence in patients with T3-4N0–1 non-small cell lung cancer following multimodality treatment remains substantial, mainly due distant metastases. As pathological complete responses (pCR) in resected specimens are seen in only a minority (28–38%) of patients following chemoradiotherapy, we designed the INCREASE trial (EudraCT-Number: 2019–003454-83; Netherlands Trial Register number: NL8435) to assess if pCR rates could be further improved by adding short course immunotherapy to induction chemoradiotherapy. Translational studies will correlate changes in loco-regional and systemic immune status with patterns of recurrence.Methods/designThis single-arm, prospective phase II trial will enroll 29 patients with either resectable, or borderline resectable, T3-4N0–1 NSCLC. The protocol was approved by the institutional ethics committee. Study enrollment commenced in February 2020.On day 1 of guideline-recommended concurrent chemoradiotherapy (CRT), ipilimumab (IPI, 1 mg/kg IV) and nivolumab (NIVO, 360 mg flat dose IV) will be administered, followed by nivolumab (360 mg flat dose IV) after 3 weeks. Radiotherapy consists of once-daily doses of 2 Gy to a total of 50 Gy, and chemotherapy will consist of a platinum-doublet. An anatomical pulmonary resection is planned 6 weeks after the last day of radiotherapy. The primary study objective is to establish the safety of adding IPI/NIVO to pre-operative CRT, and its impact on pathological tumor response. Secondary objectives are to assess the impact of adding IPI/NIVO to CRT on disease free and overall survival. Exploratory objectives are to characterize tumor inflammation and the immune contexture in the tumor and tumor-draining lymph nodes (TDLN), and to explore the effects of IPI/NIVO and CRT and surgery on distribution and phenotype of peripheral blood immune subsets.DiscussionThe INCREASE trial will evaluate the safety and local efficacy of a combination of 4 modalities in patients with resectable, T3-4N0–1 NSCLC. Translational research will investigate the mechanisms of action and drug related adverse events.Trial registrationNetherlands Trial Registration (NTR):NL8435, Registered 03 March 2020.

ObjectivesResection is the standard treatment for stage I non-small cell lung cancer (NSCLC) in operable patients. Stereotactic body radiotherapy (SBRT) is recommended for inoperable patients. A shift from surgery to SBRT is expected in elderly patients due to increased frailty and competing risks. We assessed the current influence of age on treatment decision-making and overall survival (OS).Materials and methodsWe performed a retrospective cohort study using data from patients with clinical stage I NSCLC diagnosed in 2012–2016 and treated with lobectomy, segmentectomy, wedge resection, or SBRT, retrieved from the Netherlands Cancer Registry. Patient characteristics and OS were compared between SBRT and (sub)lobar resection for patients aged 18−79 and ≥80 years.Results and Conclusion8764 patients treated with lobectomy (n = 4648), segmentectomy (n = 122), wedge resection (n = 272), or SBRT (n = 3722) were included. In 2012–2016, SBRT was increasingly used for octogenarians and younger patients from 75.3% to 83.7% and from 30.8% to 43.2%, respectively. Five-year OS in the whole population was 70% after surgery versus 39% after SBRT and 50% versus 27% in octogenarians. After correction for age, gender, year of diagnosis, and clinical T-stage, OS was equal after lobectomy and SBRT in the first 2 years after diagnosis. However, after >2 years, OS was better after lobectomy than after SBRT.SBRT is the prevailing treatment in octogenarians with stage I NSCLC. While surgery is associated with better OS than SBRT, factors other than treatment modality (e.g. comorbidity) may have had a significant impact on survival. The wider application of SBRT in octogenarians likely reflects the frailty of this group. Registries and trials are required to identify key determinants of frailty in this specific population to improve patient selection for surgery or SBRT.

Rationale: Pleuroparenchymal fibroelastosis (PPFE) is a rare subtype of idiopathic interstitial pneumonias. PPFE mostly affects the upper lung zones and is characterized radiologically by pleural and subpleural fibrotic thickening with a reticular pattern. There is no established treatment for PPFE but lung transplantation can be considered for advanced stage. The gold standard for the diagnosis of PPFE is surgical lung biopsy (SLB) but the bronchoscopic transbronchial cryobiopsy (TBCB) is a less invasive alternative.Patient concerns: We report here two cases in which the diagnosis of PPFE was established with the help of TBCB.Diagnosis and interventions: Bronchoscopy with TBCB was performed under sedation with spontaneous ventilation and the help of an uncuffed ET tube.Outcomes: Histopathology showed intra-alveolar fibroblastic proliferation with elastosis, which confirmed the diagnosis of PPFE.Lessons: The current report demonstrates that TBCB can be a useful and safe tool to confirm the diagnosis of PPFE. According to our knowledge, this is one of few reports that shows successful diagnosis of PPFE by TBCB.

Introduction Treatment patterns in stage III NSCLC can vary considerably between countries. The PACIFIC trial reported improvements in progression-free and overall survival with adjuvant durvalumab after concurrent chemoradiotherapy (CCRT). We studied treatment decision-making by three Dutch regional thoracic multidisciplinary tumor boards between 2015 and 2019, to identify changes in practice when adjuvant durvalumab became available. Methods Details of patients presenting with stage III NSCLC were retrospectively collected. Both CCRT and multimodality schemes incorporating planned surgery were defined as being radical-intent treatment (RIT). Results Of 855 eligible patients, most (95%) were discussed at a thoracic multidisciplinary tumor board, which recommended a RIT in 63% (n = 510). Only 52% (n = 424) of the patients finally received a RIT. Predictors for not recommending RIT were age greater than or equal to 70 years, WHO performance score greater than or equal to 2, Charlson comorbidity index greater than or equal to 2 (excluding age), forced expiratory volume in 1 second less than 80% of predicted value, N3 disease, and period of diagnosis. Between 2015 to 2017 and 2018 to 2019, the proportion of patients undergoing CCRT increased from 34% to 42% (p = 0.02) and use of sequential chemoradiotherapy declined (21%–16%, p = 0.05). Rates of early toxicity and 1-year mortality were comparable for both periods. After 2018, 57% of the patients who underwent CCRT (90 of 159) received adjuvant durvalumab. Conclusions After publication of the PACIFIC trial, a significant increase was observed in the use of CCRT for patients with stage III NSCLC with rates of early toxicity and mortality being unchanged. Since 2018, 57% of the patients undergoing CCRT went on to receive adjuvant durvalumab. Nevertheless, approximately half of the patients were still considered unfit for a RIT.

ObjectiveIn the context of an ongoing debate on the potential risks of hypoxemia and hyperoxemia, it seems prudent to maintain the partial arterial oxygen pressure (PaO2) in a physiological range during administration of supplemental oxygen. The PaO2and peripheral oxygen saturation (SpO2) are closely related and both are used to monitor oxygenation status. However, SpO2values cannot be used as an exact substitute for PaO2. The aim of this study in acutely ill and stable patients was to determine at which SpO2level PaO2is more or less certain to be in the physiological range.MethodsThis is an observational study prospectively collecting data pairs of PaO2and SpO2values in patients admitted to the emergency room or intensive care unit (Prospective Inpatient Acutely ill cohort; PIA cohort). A second cohort of retrospective data of patients who underwent pulmonary function testing was also included (Retrospective Outpatient Pulmonary cohort; ROP cohort). Arterial hypoxemia was defined as PaO2< 60 mmHg and hyperoxemia as PaO2> 125 mmHg. The SpO2cut-off values with the lowest risk of hypoxemia and hyperoxemia were determined as the 95th percentile of the observed SpO2values corresponding with the observed hypoxemic and hyperoxemic PaO2values.Results220 data pairs were collected in the PIA cohort. 95% of hypoxemic PaO2measurements occurred in patients with an SpO2below 94%, and 95% of hyperoxemic PaO2measurements occurred in patients with an SpO2above 96%. Additionally in the 1379 data pairs of the ROP cohort, 95% of hypoxemic PaO2measurements occurred in patients with an SpO2below 93%.ConclusionThe SpO2level marking an increased risk of arterial hypoxemia is not substantially different in acutely ill versus stable patients. In acutely ill patients receiving supplemental oxygen an SpO2target of 95% maximizes the likelihood of maintaining PaO2in the physiological range.

Background Substances that potentially enhance performance (eg, recombinant human erythropoietin [rHuEPO]) are considered doping and are therefore forbidden in sports; however, the scientific evidence behind doping is frequently weak. We aimed to determine the effects of rHuEPO treatment in well trained cyclists on maximal, submaximal, and race performance and on safety, and to present a model clinical study for doping research on other substances. Methods We did this double-blind, randomised, placebo-controlled trial at the Centre for Human Drug Research in Leiden (Netherlands). We enrolled healthy, well trained but non-professional male cyclists aged 18–50 years and randomly allocated (1:1) them to receive abdominal subcutaneous injections of rHuEPO (epoetin β mean dose 6000 IU per week) or placebo (0·9% NaCl) for 8 weeks. Randomisation was stratified by age groups (18–34 years and 35–50 years), with a code generated by a statistician who was not masked to the study. The primary outcome was exercise performance, measured as maximal power output (Pmax), maximal oxygen consumption VO2 max, and gross efficiency in maximal exercise tests with 25 W increments per 5 min, as lactate threshold and ventilatory threshold 1 (VT1) and 2 (VT2) at submaximal levels during the maximal exercise test, and as mean power, VO2, and heart rate in the submaximal exercise tests at the highest mean power output for 45 min in a laboratory setting and in a race to the Mont Ventoux (France) summit, using intention-to-treat analyses. The trial is registered with the Dutch Trial Registry (Nederlands Trial Register), number NTR5643. Findings Between March 7, 2016, and April 13, 2016, we randomly assigned 48 participants to the rHuEPO group (n=24) or the placebo group (n=24). Mean haemoglobin concentration (9·6 mmol/L vs 9·0 mmol/L [estimated difference 0·6, 95% CI 0·4 to 0·8]) and maximal power output (351·55 W vs 341·23 W [10·32, 3·47 to 17·17]), and VO2 max (60·121 mL/min per kg vs 57·415 mL/min per kg [2·707, 0·911 to 4·503]) in a maximal exercise test were higher in the rHuEPO group compared with the placebo group. Submaximal exercise test parameters mean power output (283·18 W vs 277·28 W [5·90, −0·87 to 12·67]) and VO2 (50·288 mL/min per kg vs 49·642 mL/min per kg [0·646, −1·307 to 2·600]) at day 46, and Mont Ventoux race times (1 h 40 min 32 s vs 1 h 40 min 15 s [0·3%, −8·3 to 9·6]) did not differ between groups. All adverse events were grade 1–2 and were similar between both groups. No events of grade 3 or worse were observed. Interpretation Although rHuEPO treatment improved a laboratory test of maximal exercise, the more clinically relevant submaximal exercise test performance and road race performance were not affected. This study shows that clinical studies with doping substances can be done adequately and safely and are relevant in determining effects of alleged performance-enhancing drugs. Funding Centre for Human Drug Research, Leiden.

Rachida Rafiq,1 Hendrik J Prins,2 Wim G Boersma,2 Johannes MA Daniels,3 Martin den Heijer,1 Paul Lips,1 Renate T de Jongh1 1Department of Internal Medicine and Endocrinology, VU University Medical Center, Amsterdam, 2Department of Pulmonary Diseases, Northwest Hospital group, Alkmaar, 3Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, the Netherlands Background: Although vitamin D is well known for its function in calcium homeostasis and bone mineralization, several studies have shown positive effects on muscle strength and physical function. In addition, vitamin D has been associated with pulmonary function and the incidence of airway infections. As vitamin D deficiency is highly prevalent in chronic obstructive pulmonary disease (COPD) patients, supplementation might have a beneficial effect in these patients. Objective: To assess the effect of vitamin D supplementation on respiratory muscle strength and physical performance in vitamin D-deficient COPD patients. Secondary outcomes are pulmonary function, handgrip strength, exacerbation rate, and quality of life. Methods: We performed a randomized, double-blind, placebo-controlled pilot trial. Participants were randomly allocated to receive 1,200 IU vitamin D3 per day (n=24) or placebo (n=26) during 6 months. Study visits were conducted at baseline, and at 3 and 6 months after randomization. During the visits, blood was collected, respiratory muscle strength was measured (maximum inspiratory and expiratory pressure), physical performance and 6-minute walking tests were performed, and handgrip strength and pulmonary function were assessed. In addition, participants kept a diary card in which they registered respiratory symptoms. Results: At baseline, the mean (standard deviation [SD]) serum 25-hydroxyvitamin D (25(OH)D) concentration (nmol/L) was 42.3 (15.2) in the vitamin D group and 40.6 (17.0) in the placebo group. Participants with vitamin D supplementation had a larger increase in serum 25(OH)D compared to the placebo group after 6 months (mean difference (SD): +52.8 (29.8) vs +12.3 (25.1), P

Defects in motile cilia and sperm flagella cause primary ciliary dyskinesia (PCD), characterized by chronic airway disease, infertility, and left-right body axis disturbance. Here we report maternally inherited and de novo mutations in PIH1D3 in four men affected with PCD. PIH1D3 is located on the X chromosome and is involved in the preassembly of both outer (ODA) and inner (IDA) dynein arms of cilia and sperm flagella. Loss-of-function mutations in PIH1D3 lead to absent ODAs and reduced to absent IDAs, causing ciliary and flagellar immotility. Further, PIH1D3 interacts and co-precipitates with cytoplasmic ODA/IDA assembly factors DNAAF2 and DNAAF4. This result has clinical and genetic counseling implications for genetically unsolved male case subjects with a classic PCD phenotype that lack additional phenotypes such as intellectual disability or retinitis pigmentosa.

Summary Background Antibiotics do not reduce mortality or short-term treatment non-response in patients receiving treatment for acute exacerbations of COPD in an outpatient setting. However, the long-term effects of antibiotics are unknown. The aim of this study was to investigate if the antibiotic doxycycline added to the oral corticosteroid prednisolone prolongs time to next exacerbation in patients with COPD receiving treatment for an exacerbation in the outpatient setting. Methods In this randomised double-blind placebo-controlled trial, we recruited a cohort of patients with COPD from outpatient clinics of nine teaching hospitals and three primary care centres in the Netherlands. Inclusion criteria were an age of at least 45 years, a smoking history of at least 10 pack-years, mild-to-severe COPD (Global Initiative of Chronic Obstructive Lung Disease [GOLD] stage 1–3), and at least one exacerbation during the past 3 years. Exclusion criteria were poor mastery of the Dutch language, poor cognitive functioning, known allergy to doxycycline, pregnancy, and a life expectancy of shorter than 1 month. If a participant had an exacerbation, we randomly assigned them (1:1; with permuted blocks of variable sizes [ranging from two to ten]; stratified by GOLD stage 1–2 vs 3) to a 7 day course of oral doxycycline 100 mg daily (200 mg on the first day) or placebo. Exclusion criteria for randomisation were fever, admission to hospital, and current use of antibiotics or use within the previous 3 weeks. Patients in both groups received a 10 day course of 30 mg oral prednisolone daily. Patients, investigators, and those assessing outcomes were masked to treatment assignment. The primary outcome was time to next exacerbation in all randomly allocated patients except for those incorrectly randomly allocated who did not meet the inclusion criteria or met the exclusion criteria. This trial is registered with the Netherlands Trial Register, number NTR2499. Findings Between Dec 22, 2010, and Aug 6, 2013, we randomly allocated 305 (34%) patients from the cohort of 887 patients to doxycycline (152 [50%]) or placebo (153 [50%]), excluding four (1%) patients (two [1%] from each group) who were incorrectly randomly allocated from the analysis. 257 (85%) of 301 patients had a next exacerbation (131 [87%] of 150 in the doxycycline group vs 126 [83%] of 151 in the placebo group). Median time to next exacerbation was 148 days (95% CI 95–200) in the doxycycline group compared with 161 days (118–211) in the placebo group (hazard ratio 1·01 [95% CI 0·79–1·31]; p=0·91). We did not note any significant differences between groups in the frequency of adverse events during the first 2 weeks after randomisation (47 [31%] of 150 in the doxycycline group vs 53 [35%] of 151 in the placebo group; p=0·54) or in serious adverse events during the 2 years of follow-up (42 [28%] vs 43 [29%]; p=1). Interpretation In patients with mild-to-severe COPD receiving treatment for an exacerbation in an outpatient setting, the antibiotic doxycycline added to the oral corticosteroid prednisolone did not prolong time to next exacerbation compared with prednisolone alone. These findings do not support prescription of antibiotics for COPD exacerbations in an outpatient setting. Funding Netherlands Organization for Health Research and Development.

BACKGROUND: The clinical stage of non-small cell lung cancer (NSCLC) determines the initial treatment, whereas the pathologic stage best determines prognosis and the need for adjuvant treatment. In an era in which stereotactic ablative radiotherapy (SABR) has become an alternative modality to surgical intervention, clinical staging is even more important, because pathologic staging is omitted in the case of SABR. The objective of this study was to determine the concordance between clinical and pathologic stage in routine clinical practice for patients with early-stage NSCLC.METHODS: Prospective data were derived from the Dutch Lung Surgery Audit (DLSA) in 2013 and 2014. Patients with clinical stage I NSCLC who underwent surgical resection and had a positron emission tomography-computed tomography (PET-CT) scan in their clinical workup were selected. Clinical and pathologic TNM (cTNM and pTNM) stages were compared.RESULTS: From a total of 1,790 patients with clinical stage I, 1,555 (87%) patients were included in this analysis. Concordance between cTNM and pTNM was 59.9%. Of the patients with clinical stage I, 22.6% were upstaged to pathologic stage II or higher. In total, 14.9% of all patients with clinical stage I had nodal metastases, and 5.5% of all patients had unforeseen N2 disease. In patients with clinical stage T2a tumors, 21.3% had nodal metastases, 14.5% being N1 and 6.7% being N2 disease.CONCLUSIONS: Concordance between clinical and pathologic stage is 59.9%. In patients with clinical stage I NSCLC, 22.6% were upstaged to pathologic stage II or higher, which is an indication for adjuvant chemotherapy. Improvement in accuracy of staging is thus needed, particularly for these patients.

BACKGROUND: Clinical staging of non-small cell lung cancer (NSCLC) determines the initial treatment offered to a patient. The similarity between clinical and pathologic staging in some studies is as low as 50%, and others publish results as high as 91%. The Dutch Lung Surgery Audit is a clinical database that registers the clinical and pathologic TNM of almost all NSCLC patients who undergo operations in the Netherlands. The objective of this study was to determine the accuracy of clinical staging of NSCLC.METHODS: Prospective data were derived from the Dutch Lung Surgery Audit in 2013 and 2014. Patients were included if they had undergone a surgical resection for stage IA to IIIB NSCLC without neoadjuvant treatment and had a positron emission tomography-computed tomography scan as part of the clinical workup. Clinical (c)TNM and pathologic (p)TNM were compared, and whether discrepancy was based on tumor or nodal staging was determined.RESULTS: From 2,834 patients identified, 2,336 (82.4%) fulfilled the inclusion criteria and had complete data. Of these 2,336, 1,276 (54.6%) were staged accurately, 707 (30.3%) were clinically understaged, and 353 (15.1%) were clinically overstaged. In the understaged group, 346 patients had a higher pN stage (14.8%), of which 148 patients had unforeseen N2 disease (6.3%). In the overstaged group, 133 patients had a cN that was higher than the pN (5.7%).CONCLUSIONS: Accuracy of NSCLC staging in the Netherlands is low (54.6%), even in the era of positron emission tomography-computed tomography. Especially accurate nodal staging remains challenging. Future efforts should include the identification of specific pitfalls in NSCLC staging.

It is with great interest that we took notice of the expert knowledge on staging of non-small cell lung cancer (NSCLC) and the implications on adjuvant chemotherapy expressed in the two invited editorials on our previously published article entitled “ Clinical staging of NSCLC: current evidence and implications for adjuvant chemotherapy ” (1).

Remodeling of tissue, such as airway smooth muscle (ASM) and extracellular matrix, is considered a key feature of airways disease. No clinically accepted diagnostic method is currently available to assess airway remodeling or the effect of treatment modalities such as bronchial thermoplasty in asthma, other than invasive airway biopsies. Optical coherence tomography (OCT) generates cross-sectional, near-histological images of airway segments and enables identification and quantification of airway wall layers based on light scattering properties only. In this study, we used a custom motorized OCT probe that combines standard and polarization sensitive OCT (PS-OCT) to visualize birefringent tissue in vivo in the airway wall of a patient with severe asthma in a minimally invasive manner. We used optic axis uniformity (OAxU) to highlight the presence of uniformly arranged fiber-like tissue, helping visualizing the abundance of ASM and connective tissue structures. Attenuation coefficient images of the airways are presented for the first time, showing superior architectural contrast compared to standard OCT images. A novel segmentation algorithm was developed to detect the surface of the endoscope sheath and the surface of the tissue. PS-OCT is an innovative imaging technique that holds promise to assess airway remodeling including ASM and connective tissue in a minimally invasive, real-time manner.

The role of antibiotics in acute exacerbations of chronic obstructive pulmonary disease (COPD) is controversial and a biomarker identifying patients who benefit from antibiotics is mandatory. We performed a randomised, controlled trial in patients with acute exacerbations of COPD, comparing C-reactive protein (CRP)-guided antibiotic treatment to patient reported symptoms in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy, in order to show a reduction in antibiotic prescription.Patients hospitalised with acute exacerbations of COPD were randomised to receive antibiotics based either on the GOLD strategy or according to the CRP strategy (CRP ≥50 mg·L−1).In total, 101 patients were randomised to the CRP group and 119 to the GOLD group. Fewer patients in the CRP group were treated with antibiotics compared to the GOLD group (31.7% versus 46.2%, p=0.028; adjusted odds ratio (OR) 0.178, 95% CI 0.077–0.411, p=0.029). The 30-day treatment failure rate was nearly equal (44.5% in the CRP group versus 45.5% in the GOLD-group, p=0.881; adjusted OR 1.146, 95% CI 0.649–1.187, p=0.630), as was the time to next exacerbation (32 days in the CRP group versus 28 days in the GOLD group, p=0.713; adjusted hazard ratio 0.878, 95% CI 0.649–1.187, p=0.398). Length of stay was similar in both groups (7 days in the CRP group versus 6 days in the GOLD group, p=0.206). On day-30, no difference in symptom score, quality of life or serious adverse events was detected.Use of CRP as a biomarker to guide antibiotic treatment in severe acute exacerbations of COPD leads to a significant reduction in antibiotic treatment. In the present study, no differences in adverse events between both groups were found. Further research is needed for the generalisability of these findings.

The treatment of pulmonary carcinoid has changed over the last decades. Although surgical resection is still the gold standard, minimally invasive endobronchial procedures have emerged as a parenchyma sparing alternative for tumors located in the central airways. This review was performed to identify the optimal treatment strategy for pulmonary carcinoid, with a particular focus on the feasibility and outcome of parenchyma sparing techniques versus surgical resection. A systematic review of the literature was carried out using MEDLINE, Embase and the Cochrane databases, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Two separate searches of publications in endobronchial and surgical treatment in patients with pulmonary carcinoid, were performed. Outcomes were overall survival, disease free survival, recurrence rate, complications, quality of life, and healthcare costs. Combining the two main searches for endobronchial therapy and surgical therapy yielded 3111 records. Finally, 43 studies concerning surgical treatment and 9 studies related to endobronchial treatment for pulmonary carcinoid were included. Assessment of included studies showed that lymph node involvement, histological grade, tumor location and tumor diameter were identified as poor prognostic factors and seem to be important for patients with pulmonary carcinoid. For patients with a more favorable prognosis, tumor location and tumor diameter are important factors that can help decide on the optimal treatment strategy. Centrally located small intraluminal pulmonary carcinoids, without signs of metastasis can be treated with minimally invasive alternatives such as endobronchial treatment or parenchyma sparing surgical resection. Patients with parenchyma sparing resections should be followed with long term follow up to exclude recurrence of disease. In a multidisciplinary setting, it should be determined whether individual patients are eligible for parenchyma sparing procedures or anatomical resection. Overall evidence is of low quality and future studies should focus on prospective trials in the treatment of pulmonary carcinoid.

Background Pulmonary carcinoids are included in the group of neuroendocrine tumors (NET) and derive from pulmonary neuroendocrine cells. The incidence of these tumors is increasing, but disease awareness remains low among clinicians. The synchronous presentation of lung cancer and mycobacterial infection is well known but the combination of pulmonary carcinoid and mycobacterial infection is rare. Case presentation We treated a 45-year-old female who presented with recurrent pneumonia. Chest X-ray showed a consolidation in the left upper lobe. The patient was treated with various courses of antibiotics without full recovery after six months. Computed tomography (CT) scan demonstrated a central mass in the left upper lobe. Bronchoscopy revealed an endobronchial, well-defined lesion that totally obstructed the left upper lobe bronchus. Bronchial biopsy showed typical carcinoid tumor. Rigid bronchoscopy with electrocautery was attempted, but we were unable to radically remove the tumor. Therefore lobectomy was performed. The surgical pathology specimen showed atypical bronchial carcinoid and consolidations in the lung parenchyma with granulomatous inflammation distally of the bronchial obstruction. Ziehl-Neelsen staining demonstrated acid fast bacilli indicative of mycobacterial infection. Conclusions This case history illustrates the importance of careful surgical pathologic examination, not only of the resected tumor, but also of the postobstructive lung parenchyma. Specific postobstructive infections such as tuberculosis or nontuberculous mycobacteria (NTM) can have clinical implications.

PURPOSE: Infectious complications occur following pulmonary resections preceded or not by induction chemoradiotherapy. We aimed to investigate whether bacterial colonization of the bronchial tree at the time of surgery was associated with postoperative complications.PATIENTS AND METHODS: A retrospective analysis of all patients who underwent open anatomical pulmonary resections for malignancies at a single center was performed. Demographical data of the included patients, intraoperative data, and data on the postoperative course of patients were collected. Outcome of patients with a positive intraoperative bronchial culture was compared to patients with a negative bronchial culture. Relations between the presence of potential bacterial pathogens in the bronchial tree and other possible risk factors for the development of postoperative infectious and non-infectious complications, were analyzed using uni- and multivariate analysis.RESULTS: Between January 2010 and January 2012, a total of 121 consecutive patients underwent open anatomical pulmonary resections for malignancy, of whom 45 were preceded by induction chemoradiotherapy and 5 by induction chemotherapy. Intraoperative bronchial cultures were taken from 58 patients (48 %). Patients with a positive bronchial culture developed significantly more infectious (88 % vs. 20 %, p < 0.001) and non-infectious complications (63 % vs. 12 %, p = 0.001). Positive intraoperative bronchial cultures showed the strongest association with the development of infectious and non-infectious postoperative complications (OR 24.8 and 12.2, respectively). After multivariate analysis, only BMI less than 20 kg/m(2) and the presence of a positive intraoperative bronchial culture were found to be independent risk factors for the development of infectious complications. Chemoradiotherapy was not associated with postoperative complications in the present study.CONCLUSIONS: Bacterial colonization of the bronchial tree assessed intraoperatively, appears to be associated with higher rates of infectious and non-infectious complications after pulmonary resection. Whether early starting of appropriate antibiotics based on intraoperative-taken culture findings will reduce the infectious complication rate in a subcategory of patients needs to be investigated.

OBJECTIVE: Optimal treatment selection for patients with non-small cell lung cancer (NSCLC) depends on the clinical stage of the disease. Particularly patients with mediastinal lymph node involvement (stage IIIA-N2) should be identified since they generally do not benefit from upfront surgery. Although the standardized preoperative use of PET-CT, EUS/EBUS and/or mediastinoscopy identifies most patients with mediastinal lymph node metastasis, a proportion of these patients is only diagnosed after surgery. The objective of this study was to identify all patients with unforeseen N2 disease after surgical resection for NSCLC in a large nationwide database and to evaluate the preoperative clinical staging process.METHODS: Data was derived from the Dutch Lung Surgery Audit. Patients with pathological stage IIIA NSCLC after an anatomical resection between 2013 and 2015 were evaluated. Clinical and pathological TNM-stage were compared and an analysis was performed on the diagnostic work-up of patients with unforeseen N2 disease.RESULTS: From 3585 patients undergoing surgery for NSCLC between 2013 and 2015, a total of 527 patients with pathological stage IIIA NSCLC were included. Of all 527 patients, 254 patients were upstaged from a clinical N0 (n = 186) or N1 (n = 68) disease to a pathological N2 disease (7.1% unforeseen N2). In these 254 patients, 18 endoscopic ultrasounds, 62 endobronchial ultrasounds and 67 mediastinoscopies were performed preoperatively.CONCLUSIONS: In real world clinical practice in The Netherlands, the percentage of unforeseen N2 disease in patients undergoing surgery for NSCLC is seven percent. To further reduce this percentage, optimization of the standardized preoperative workup is necessary.

Background: Traditionally, surgical resection is the preferred treatment for typical carcinoids and atypical carcinoids located in the lungs. Recently however, several studies have shown excellent long-term outcome after endobronchial treatment of carcinoid tumors located in the central airways. This study investigates clinical and radiological features as predictors of successful endobronchial treatment in patients with a bronchial carcinoid tumor. Objectives: To identify clinical and radiological features predictive of successful endobronchial treatment in patients with bronchial carcinoid. Methods: This analysis was performed in a cohort of patients with typical and atypical bronchial carcinoid referred for endobronchial treatment. Several patient characteristics, radiological features, and histological grade (typical or atypical carcinoid) were tested as predictors of successful endobronchial treatment. Results: One hundred and twenty-five patients with a diagnosis of bronchial carcinoid underwent endobronchial treatment. On multivariate analysis, a tumor diameter p = p = Conclusions: Purely intraluminal disease and tumor diameter on CT scan seem to be independent predictors for successful endobronchial treatment in patients with bronchial carcinoid. Based on these data, patients with purely intraluminal carcinoid tumors with a diameter

Background: Airway stenting (AS) commenced in Europe circa 1987 with the first placement of a dedicated silicone airway stent. Subsequently, over the last 3 decades, AS was spread throughout Europe, using different insertion techniques and different types of stents. Objectives: This study is an international survey conducted by the European Association of Bronchology and Interventional Pulmonology (EABIP) focusing on AS practice within 26 European countries. Methods: A questionnaire was sent to all EABIP National Delegates in February 2015. National delegates were responsible for obtaining precise and objective data regarding the current AS practice in their country. The deadline for data collection was February 2016. Results: France, Germany, and the UK are the 3 leading countries in terms of number of centres performing AS. These 3 nations represent the highest ranked nations within Europe in terms of gross national income. Overall, pulmonologists perform AS exclusively in 5 countries and predominately in 12. AS is performed almost exclusively in public hospitals. AS performed under general anaesthesia is the rule for the majority of institutions, and local anaesthesia is an alternative in 9 countries. Rigid bronchoscopy techniques are predominant in 20 countries. Amongst commercially available stents, both Dumon and Ultraflex are by far the most commonly deployed. Finally, 11 countries reported that AS is an economically viable activity, while 10 claimed that it is not. Conclusion: This EABIP survey demonstrates that there is significant heterogeneity in AS practice within Europe. Therapeutic bronchoscopy training and economic issues/reimbursement for procedures are likely to be the primary reasons explaining these findings.