Lung volume reduction using one-way endobronchial valves is a bronchoscopic treatment for patients with severe emphysema without collateral ventilation between the treatment target lobe and the ...ipsilateral lobe(s). CT-scan fissure analysis is often used as a surrogate to predict the absence of collateral ventilation. We aimed to evaluate the predictive value of the fissure completeness score (FCS) compared to the functional Chartis measurement of collateral ventilation and to provide cut-off values of the FCS in patient selection.
Multicenter study in patients eligible for treatment with one-way valves. The FCS was calculated by quantitative CT analysis (Thirona, the Netherlands) and compared to status of interlobar collateral ventilation measured with Chartis system (PulmonX, USA). Thresholds were calculated for the predictive values of the presence of collateral ventilation.
An FCS >95% of the left major fissure had a positive predictive value (PPV) of 91%, with 1 in 11 fissures demonstrating collateral ventilation with Chartis measurement, whereas an FCS of ≤80% had a negative predictive value (NPV) of 100% for the presence of collateral ventilation. For the right major fissure, the NPV was 100% for an FCS ≤90%, but 69.7% for the right upper lobe fissure.
Quantitative CT analysis is recommended in all patients evaluated for endobronchial valves. Patients with incomplete fissures (left major fissure: FCS <80%; right major fissure: <90%) can be excluded from Chartis measurement and endobronchial valve treatment. In patients with more complete fissures, the FCS is not specific enough for endobronchial valve treatment decisions. In this case, additional Chartis measurements are always recommended in the right lung. For the left lung, Chartis assessments may be omitted if the FCS is >95%.
Medulloblastoma is the most common malignant brain tumor in childhood. Molecular studies from several groups around the world demonstrated that medulloblastoma is not one disease but comprises a ...collection of distinct molecular subgroups. However, all these studies reported on different numbers of subgroups. The current consensus is that there are only four core subgroups, which should be termed WNT, SHH, Group 3 and Group 4. Based on this, we performed a meta-analysis of all molecular and clinical data of 550 medulloblastomas brought together from seven independent studies. All cases were analyzed by gene expression profiling and for most cases SNP or array-CGH data were available. Data are presented for all medulloblastomas together and for each subgroup separately. For validation purposes, we compared the results of this meta-analysis with another large medulloblastoma cohort (
n
= 402) for which subgroup information was obtained by immunohistochemistry. Results from both cohorts are highly similar and show how distinct the molecular subtypes are with respect to their transcriptome, DNA copy-number aberrations, demographics, and survival. Results from these analyses will form the basis for prospective multi-center studies and will have an impact on how the different subgroups of medulloblastoma will be treated in the future.
Symptomatic airway kinking after bronchoscopic lung volume reduction with endobronchial valves is rare. Owing to the development of the desired lobar atelectasis, the position of the airways of the ...nontreated lobe changes, and that might lead to invalidating symptoms. We present a case of a patient with symptomatic airway kinking after treatment with endobronchial valves, who was successfully treated with a single placement of a biodegradable stent. Placement of a biodegradable stent can be considered for symptomatic patients with airway kinking.
Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, ...suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed 192 ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.
Display omitted
•ATRTs are comprised of three epigenetically distinct subgroups: TYR, SHH, and MYC•H3K27Ac enhancer landscapes reveal ATRT subgroup-specific regulatory networks•Regulatory networks lead to identification of potential therapeutic targets•Epigenetic profiles point at distinct cellular origins of ATRT subgroups
SMARCB1 is the sole highly recurrently mutated gene in atypical teratoid/rhabdoid tumors (ATRTs). Johann et al. show that ATRTs are composed of three epigenetic subgroups that have different clinical characteristics, and identify subgroup-specific regulatory networks that suggest potential therapeutic targets.
Background: Bronchoscopic lung volume reduction using the Zephyr® endobronchial valve (EBV) is a guideline treatment for patients with advanced emphysema. To achieve volume reduction, it is crucial ...that there is absence of collateral ventilation and a complete occlusion of the target lobe. While 3 EBV sizes (4.0; 4.0-LP; and 5.5) are currently available to accommodate all airway sizes, local anatomical variations sometimes warrant a valve with a wide diameter but shorter length. To address this, a new “low profile” 5.5-LP EBV has been introduced. Objective: In this study, we evaluated the feasibility, safety, and efficacy of this new 5.5-LP EBV. Methods: This was a single-center, prospective, open-label study. Patients were included if eligible for valve treatment with a local anatomy suitable to place at least one 5.5-LP EBV. Feasibility of placement of the 5.5-LP EBV was reported. Safety, CT parameters, pulmonary function tests, and St. George’s Respiratory Questionnaire (SGRQ) were assessed at baseline and 6 weeks after treatment. Results: We included 30 patients with severe chronic obstructive pulmonary disease (forced expiratory volume in 1 s FEV 1 29 ± 10%; RV 242 ± 46%; and SGRQ 56 ± 11 points). Besides the regular EBV sizes, a median of 1 (1–3) of the new 5.5-LP EBV was placed. No valve adjustment was needed during the initial procedure. A single asymptomatic small pneumothorax was observed in 1 patient. In 4 patients, a revision bronchoscopy was performed due to absence of clinical benefit. In 1 patient, this was related to a dislocation of the 5.5-LP EBV. Clinically relevant improvements were seen in target lobar volume reduction (–1,554 mL), FEV 1 +39%, RV –960 mL, and SGRQ –18 points. Conclusions: In this first in human study, the 5.5-LP EBV could be placed into wide segments with a shorter landing length without unexpected complications and with good efficacy outcomes.
Bronchoscopic lung volume reduction using one-way endobronchial valves (EBVs) has been proven to be effective in patients with severe emphysema. However, the selection of patients without collateral ...ventilation prior to treatment is critical for procedural success. Collateral ventilation can be assessed directly with the Chartis system or indirectly using computed tomography (CT) fissure analysis.
We retrospectively evaluated the diagnostic value of a combination of the quantitative CT interlobar fissure completeness score (FCS) and Chartis in predicting responders to EBV therapy.
CT data from four prospective studies were pooled and analyzed using semiautomated software to quantify the completeness of interlobar fissures. These FCSs were compared to a reference standard of achieving ≥350 ml of target lobe volume reduction after EBV treatment. Using a receiver operating characteristic curve, optimal thresholds predictive of complete fissures (responders) and incomplete fissures (non-responders) were determined. A subgroup of patients with partially complete fissures was identified, where software had lower accuracy. The complementary value of Chartis was investigated in this group.
A fissure was defined as complete (FCS >95%), incomplete (FCS <80%), or partially complete (80% < FCS < 95%). The positive predictive value (PPV) of complete fissures is 88.1%, and the negative predictive value (NPV) is 92.9%, with an overall accuracy of 89.2%. Chartis was utilized in patients with partially complete fissures, with a PPV of 82.3%, an NPV of 84.6%, and an accuracy of 83.3%.
Combining diagnostic tools could reduce the burden on patients and the healthcare system while providing clinicians with a better means for patient selection for EBV therapy.
Bronchoscopic lung volume reduction treatment with Zephyr one-way valves is an effective guideline-based treatment option for patients with severe emphysema and hyperinflation. However, in some cases ...the treatment response is less than anticipated or there might be a loss of initial treatment effect.
Reasons for the lack of response can include incorrect assessment of collateral ventilation, improper valve placement, or patient related factors. Loss of initial benefit can be due to granulation tissue formation and subsequent valve dysfunction, or there may be side effects such as excessive coughing or infectious problems.
Careful follow-up after treatment with valves is important and evaluation with a CT scan and/or bronchoscopy is helpful if there is no improvement after treatment or loss of initial benefit. This paper aims to describe the most important causes and provide a strategy of how to approach and manage these patients.
•BLVR with endobronchial valves is an important treatment option in carefully selected patients with severe emphysema.•With wide adoption of this procedure, physicians require a systematic approach to troubleshoot when outcomes are not optimal.•Evaluation with CT-scan and/or bronchoscopy is helpful when there is lack of response or loss of initial benefit.•If there is no initial effect after treatment, this may be due to presence of collateral ventilation or displaced valves.•Loss of effect due to valve dislocation or granulation tissue formation can be treated with valve removal and replacement.
•Solitary pulmonary nodules to be evaluated is expected to increase over time.•Virtual bronchoscopy navigation with or without sheet tunnelling has a diagnostic yield of 77%.•Preventing futile ...invasive procedures or receiving treatment without histological confirmation of cancer.•Allows for treatment adaptation in two-third of the analyzed patient population.
The number of solitary pulmonary nodules to be evaluated is expected to increase and therefore we need to improve diagnostic and therapeutic tools to approach these nodules. To prevent patients from futile invasive procedures and receiving treatment without histological confirmation of cancer, we evaluated the value of virtual bronchoscopy navigation to obtain a diagnosis of the solitary pulmonary nodule in a real-world clinical setting.
In the NAVIGATOR single center, prospective, observational cohort study patients underwent a virtual bronchoscopy navigation procedure with or without guide sheet tunnelling to assess a solitary pulmonary nodule. Nodules were considered not accessible if a diagnosis could not be obtained by either by CT-guided transthoracic biopsy or conventional bronchoscopy.
Between February 2021 and January 2022 35 patients underwent the virtual bronchoscopy navigation procedure. The overall diagnostic yield was 77% and was dependent on size of the nodule and chosen path, with highest yield in lesions with an airway path. Adverse events were few and manageable.
Virtual bronchoscopy navigation with or without sheet tunnelling is a new technique with a good diagnostic yield, also in patients in whom previously performed procedures failed to establish a diagnosis and/or alternative procedures are considered not feasible based on expected yield and/or safety. Preventing futile or more invasive procedures like surgery or transthoracic punctures with a higher complication rate is beneficial for patients, and allowed treatment adaptation in two-third of the analyzed patient population.
Background: Bronchoscopic lung volume reduction using one-way endobronchial valves (EBVs) is a valid therapy for severe emphysema patients. However, alpha-1 antitrypsin (AAT)-deficient patients were ...excluded from the majority of clinical trials investigating this intervention. Objectives: The aim of this study was to investigate the feasibility, efficacy, and safety of EBV treatment in patients with AAT deficiency (AATD) or a reduced AAT level. Method: A retrospective analysis was performed of all patients treated with EBV with confirmed AATD or with a reduced AAT serum level at the University Medical Center Groningen between 2013 and 2021. Baseline and 6-month follow-up assessment included chest CT, pulmonary function measurement, 6-min walking distance (6MWD), and St. George’s Respiratory Questionnaire (SGRQ). Results: In total, 53 patients were included, 30 patients in the AATD group (AAT <0.6 g/L or confirmed ZZ phenotype) and 23 patients in the reduced AAT group (AAT 0.6–1 g/L). In both groups, all response variables improved significantly after treatment. There was a median increase in forced expiratory volume in 1 s of 105 mL (12% relative) and 280 mL (31% relative) in the AATD and reduced AAT groups, respectively. 6MWD increased by 62 min and 52 min, and SGRQ decreased by 12.5 patients and 18.7 patients, respectively. A pneumothorax occurred in 10% and 13% of patients, and no patients died. Conclusions: EBV treatment in patients with emphysema and AATD or a reduced AAT level is feasible and results in significant improvements in pulmonary function, exercise capacity, and quality of life and has an acceptable safety profile.
PDF
