The purpose of this study was to describe the use of parallel imaging technique (PAT) using dynam... more The purpose of this study was to describe the use of parallel imaging technique (PAT) using dynamic MRI in lung and tumour mobility during the breathing cycle. 20 patients with stage I non-small cell lung carcinoma were investigated using two dynamic gradient echo sequences with PAT (TrueFISP (fast imaging with steady precession), and fast low angle shot (FLASH). Craniocaudal distance
Flexible bronchoscopy is routinely utilized in the diagnosis and treatment of various lung diseas... more Flexible bronchoscopy is routinely utilized in the diagnosis and treatment of various lung diseases. Nondiagnostic bronchoscopy leads to more invasive interventions, such as transthoracic needle aspiration, mediastinoscopy or even thoracotomy. Electromagnetic navigation is a novel technology that facilitates approaching peripheral lung lesions, which are difficult to sample by conventional means. The navigation system involves creating an electromagnetic field around the chest and localizing an endoscopic tool using a microsensor overlaid upon previously acquired CT images. To determine the practicality, accuracy and safety of real-time electromagnetic navigation, coupled with previously acquired 3D CT images, in locating artificially created peripheral lung lesions in a swine model. Peripheral lung lesions were created in four swine models by insertion of a metal tube (1 x 10 mm) via a transthoracic approach. An electromagnetic field was created by placing the animal on an electromagnetic location board. A position sensor incorporated into the distal tip of a dedicated tool was used to navigate to the various target lesions. Information gathered in real time during bronchoscopy was presented on a monitor simultaneously by displaying previously acquired CT images. Upon reaching the target lesion, biopsies were performed and the functionality and safety of the superDimension/Bronchus System was observed and documented. The registration accuracy expressed by the fiducial target registration error, expressing both the registration quality and the stability of fiducial (registration) points, was 4.5 mm on average. No adverse effects, such as pneumothorax or internal bleeding, were encountered in any of the animals in this study. Real-time electromagnetic positioning technology coupled with previously acquired CT images is an accurate technology added to standard bronchoscopy to assist in reaching peripheral lung lesions and performing biopsies.
This report summarizes initial tests of an emphysematous lung synthetic polymer sealant (ELS) des... more This report summarizes initial tests of an emphysematous lung synthetic polymer sealant (ELS) designed to reduce lung volume in patients with advanced emphysema. The primary study objective was to define a therapeutic strategy to optimize treatment safety and effectiveness. ELS therapy was administered bronchoscopically to 25 patients with heterogeneous emphysema in an open-label, noncontrolled study at 6 centers in Germany. Treatment was performed initially at 2-4 subsegments. After 12 weeks, patients were eligible for repeat therapy to a total of 6 sites. Safety and efficacy were assessed after 6 months. Responses were evaluated in terms of changes from baseline in lung physiology, functional capacity, and health-related quality of life. Follow-up is available for 21 of 25 patients. Treatment was well tolerated. There were no treatment-related deaths (i.e., within 90 days of treatment), and an acceptable short- and long-term safety profile. Physiological and clinical benefits were observed at 24 weeks. Efficacy responses were better among Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III patients [n = 14; change in residual volume/total lung capacity (ΔRV/TLC) = -7.4 ± 10.3%; Δ forced expiratory volume in 1 s (ΔFEV(1)) = +15.9 ± 22.6%; change in forced vital capacity (ΔFVC) = +24.1 ± 22.7%; change in carbon monoxide lung diffusion capacity (ΔDLCO) = +19.3 ± 34.8%; change in 6-min walk test (Δ6MWD) = +28.7 ± 59.6 m; change in Medical Research Council Dyspnea (ΔMRCD) score = -1.0 ± 1.04 units; change in St. George's Respiratory Questionnaire (ΔSGRQ) score = -9.9 ± 15.3 units] than for GOLD stage IV patients (n = 7; ΔRV/TLC = -0.5 ± 6.4%; ΔFEV(1) = +2.3 ± 12.3%; ΔFVC = +2.6 ± 21.1%; ΔDLCO = -2.8 ± 17.2%; Δ6MWD = +28.3 ± 58.4 m; ΔMRCD = 0.3 ± 0.81 units; ΔSGRQ = -6.7 ± 7.0 units). ELS therapy shows promise for treating patients with advanced heterogeneous emphysema. Additional studies to assess responses in a larger cohort with a longer follow-up are warranted.
American Journal of Respiratory and Critical Care Medicine, 1996
We conducted a randomized, controlled trial to prospectively confirm that ultrasound-directed tra... more We conducted a randomized, controlled trial to prospectively confirm that ultrasound-directed transbronchial needle aspiration (USTBNA) results in: (1) improved sensitivity for detecting lymph nodes involved with neoplasm, and (2) a decreased number of aspirates needed to achieve a diagnosis as compared with standard transbronchial needle aspiration (TBNA). The study was conducted in a tertiary medical center on patients undergoing fiberoptic bronchoscopy in the evaluation of enlarged mediastinal lymph nodes. USTBNA or TBNA were followed by rapid, on-site cytopathology examination of the collected specimens. Measurements included the (1) age and sex of the patient, prior diagnosis of cancer, nodal short-axis diameter and node location as determined by computerized tomography (CT), and endobronchial abnormalities at bronchoscopy; (2) number, order, and location of transbronchial aspirates and results of on-site evaluation; (3) results of surgical exploration in patients with negative transbronchial needle aspiration; (4) sensitivity, specificity, and diagnostic accuracy of USTBNA and TBNA; (5) number of aspirates required for successful lymph node aspiration as well as for a diagnosis of cancer for both USTBNA and TBNA; and (6) multiple logistic regression analysis to determine the significance of combinations of clinical predictors and needle aspirate results. Eighty-two bronchoscopic examinations were performed on 80 patients. We found no significant difference between USTBNA and TBNA in sensitivity (82.6% versus 90.5%, respectively), specificity (100% for both), or diagnostic accuracy (86.7% versus 91.7%, respectively). The sensitivity, specificity, and diagnostic accuracy of USTBNA and TBNA were similarly high, regardless of node location (paratracheal or subcarinal). A decrease in the number of aspirates required for lymph node sampling approached statistical significance for all USTBNAs as compared with TBNAs (2.03 +/- 0.19 versus 2.62 +/- 0.25, p = 0.06), but this was not demonstrated for the number required to confirm cancer (1.95 +/- 0.47 versus 2.68 +/- 0.21, p = 0.17). The number of aspirates to successful lymph node aspiration decreased with USTBNA versus TBNA in paratracheal lymph nodes (2.00 +/- 0.20 versus 2.91 +/- 0.34, p = 0.03), but not to a diagnosis of cancer (1.93 +/- 0.25 versus 3.00 +/- 0.58, p = 0.11). No difference was seen in the number of aspirates for subcarinal nodes. The number of TBNA attempts for paratracheal lymph node sampling was inversely correlated with node size (r = 0.48, p = 0.02). No such relation was seen with USTBNA of paratracheal nodes (r = 0.09, p = 0.66), TBNA of subcarinal nodes, or USTBNA of subcarinal nodes. A similar relation was seen between the number of aspirates to a diagnosis of cancer. On multiple logistic regression analysis, a positive transbronchial aspirate was associated only with a larger lymph node and history of prior cancer. We conclude that: (1) in the setting of on-site cytopathology, transbronchial needle aspiration has a high sensitivity, specificity, and diagnostic accuracy in the evaluation of enlarged mediastinal lymph nodes suspected of harboring malignancy; (2) mediastinal anatomy, including vascular structures and lymph nodes, is clearly imaged with endobronchial ultrasonography; (3) a greater short-axis diameter of the mediastinal lymph node and history of a prior malignancy increase the likelihood of a positive transbronchial aspiration; (4) USTBNA exhibits a similarly high diagnostic yield to TBNA in the setting of rapid on-site cytopathology evaluation; (5) USTBNA decreases the number of aspirates required for paratracheal lymph node sampling, which may be particularly useful in sampling smaller paratracheal nodes or at institutions that do not utilize rapid on-site cytopathology evaluation.
International journal of chronic obstructive pulmonary disease, 2015
As well as lung volume reduction surgery, different minimally invasive endoscopic techniques are ... more As well as lung volume reduction surgery, different minimally invasive endoscopic techniques are available to achieve lung volume reduction in patients with severe emphysema and significant hyperinflation. Lung function parameters and comorbidities of the patient, as well as the extent and distribution of the emphysema are factors to be considered when choosing the patient and the intervention. Endoscopic bronchial valve placement with complete occlusion of one lobe in patients with heterogeneous emphysema is the preferred technique because of its reversibility. The presence of high interlobar collateral ventilation will hinder successful treatment; therefore, endoscopic coil placement, polymeric lung volume reduction, or bronchoscopic thermal vapor ablation as well as lung volume reduction surgery can be used for treating patients with incomplete fissures. The effect of endoscopic lung volume reduction in patients with a homogeneous distribution of emphysema is still unclear and th...
NUT (nuclear protein in testis) carcinomas are exceedingly rare neoplasms with specific molecular... more NUT (nuclear protein in testis) carcinomas are exceedingly rare neoplasms with specific molecular alterations and often follow a devastating course. Thus, a precise early diagnosis is of utmost importance. Known from the sinonasal region for years, the new 2015 WHO classification now also recognizes the existence of this entity in the thorax, specifically the lungs and the mediastinum. However, yet available data on this entity are sparse. Here, we report on a 31 years old female patient with an aggressively growing tumor localized in the median line that was initially sampled by endobronchial ultrasound-guided transbronchial biopsies. Pathological assessment of the biopsy specimens revealed a NUT carcinoma with typical morphological characteristics and an uncommon NUT translocation variant with a NSD3-NUT fusion. Diagnosis was further confirmed in the subsequent resection specimen. We describe specific clinical, histomorphological, and molecular characteristics of this tumor and provide a comprehensive review of the current literature on these rare neoplasms.
PPFE is a rare disease characterized by upper lobe pleural fibrosis and parenchymal fibroelastosi... more PPFE is a rare disease characterized by upper lobe pleural fibrosis and parenchymal fibroelastosis. Its aetiology is considered idiopathic, although possible causative factors have been described. An association of PPFE with solid tumours is unknown and has not been considered previously. We identified six patients with PPFE, four of them with a coexisting malignancy. The case series suggests that PPFE might be an implication of varying factors rather than being an exclusively idiopathic condition.
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, Jan 23, 2015
Chronic inflammation and remodeling of the airways remain a hallmark of cystic fibrosis (CF). How... more Chronic inflammation and remodeling of the airways remain a hallmark of cystic fibrosis (CF). However, knowledge of the associated mucosal micro-anatomical changes is limited. We evaluated the potential of optical coherence tomography (OCT) for in vivo imaging of the upper airway mucosa in CF patients. A flexible OCT probe was used for cross-sectional imaging of the nasal mucosa in 25 CF patients and 25 healthy controls. OCT images showed mucosal details including epithelium, basement membrane, lamina propria with seromucinous glands, and underlying cartilaginous structures. Mean nasal mucosa and epithelial layer thickness were increased in CF compared to controls. In CF patients, antibiotic therapy was associated with reduced nasal mucosa thickening. OCT detected mucosal changes associated with upper airway inflammation and response to antibiotic therapy in CF patients. OCT may be a useful tool for quantitative in vivo assessment of structural changes of the airway mucosa.
To investigate the hazard function of tumor recurrence in patients with completely (R0) resected ... more To investigate the hazard function of tumor recurrence in patients with completely (R0) resected non-small cell lung cancer. A total of 1374 patients treated between 2003 and 2009 with complete resection and systematic lymph node dissection were studied. The risk of recurrence at a given time after operation was studied utilizing the cause-specific hazard function. Recurrence was categorized as local recurrence or distant recurrence. The risk distribution was assessed using clinical and pathological factors. The hazard function for recurrence presented an early peak at approximately 10 months after surgery and maintained a tapered plateau-like tail extending up to 8 years. A similar risk pattern was detected for both local recurrence and distant recurrence, while the risk of distant recurrence was higher than that of local recurrence. The double-peaked pattern of hazard rate was present in several subgroups, such as p-stage IA patients. A comparison of histology and status of nodal involvement showed that pN1-2 adenocarcinoma patients demonstrated a high hazard rate of distant recurrence and that pN0 adenocarcinoma patients exhibited a small recurrent risk for a longer time. Squamous cell carcinoma patients showed only little difference in risk. The data may be useful to select patients at high risk of recurrence and may provide information for each patient to decide how to manage the postoperative follow-up individually.
Biomarkers can be subtle tools to aid the diagnosis, prognosis and monitoring of therapy and dise... more Biomarkers can be subtle tools to aid the diagnosis, prognosis and monitoring of therapy and disease progression. The validation of biomarkers is a cumbersome process involving many steps. Serum samples from lung cancer patients were collected in the framework of a larger study for evaluation of biomarkers for early detection of lung cancer. The analysis of biomarker levels measured revealed a noticeable difference in certain biomarker values that exhibited a dependence of the time point and setting of the sampling. Biomarker concentrations differed significantly if taken before or after the induction of anesthesia and if sampled via venipuncture or arterial catheter. To investigate this observation, blood samples from 13 patients were drawn 1-2 days prior to surgery (T1), on the same day by venipuncture (T2) and after induction of anesthesia via arterial catheter (T3). The biomarkers Squamous Cell Carcinoma antigen (CanAG SCC EIA, Fujirebio Diagnostics, Malvern, USA), Carcinoembrio...
To describe changes over time in extent of idiopathic pulmonary fibrosis (IPF) at multidetector c... more To describe changes over time in extent of idiopathic pulmonary fibrosis (IPF) at multidetector computed tomography (MDCT) assessed by semi-quantitative visual scores (VSs) and fully automatic histogram-based quantitative evaluation and to test the relationship between these two methods of quantification. Forty IPF patients (median age: 70 y, interquartile: 62-75 years; M:F, 33:7) that underwent 2 MDCT at different time points with a median interval of 13 months (interquartile: 10-17 months) were retrospectively evaluated. In-house software YACTA quantified automatically lung density histogram (10th-90th percentile in 5th percentile steps). Longitudinal changes in VSs and in the percentiles of attenuation histogram were obtained in 20 untreated patients and 20 patients treated with pirfenidone. Pearson correlation analysis was used to test the relationship between VSs and selected percentiles. In follow-up MDCT, visual overall extent of parenchymal abnormalities (OE) increased in me...
To evaluate lung T2 mapping for quantitative characterization and differentiation of ground-glass... more To evaluate lung T2 mapping for quantitative characterization and differentiation of ground-glass opacity (GGO), reticulation (RE) and honeycombing (HC) in usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). Twelve patients with stable UIP or NSIP underwent thin-section multislice CT and 1.5-T MRI of the lung. A total of 188 regions were classified at CT into normal (n = 29) and pathological areas, including GGO (n = 48), RE (n = 60) and HC (n = 51) predominant lesions. Entire lung T2 maps based on multi-echo single shot TSE sequence (TE: 20, 40, 79, 140, 179 ms) were generated from each subject with breath-holds at end-expiration and ECG-triggering. The median T2 relaxation of GGO was 67 ms (range 60-72 ms). RE predominant lesions had a median relaxation of 74 ms (range 69-79 ms), while for HC pattern this was 79 ms (range 74-89 ms). The median T2 relaxation for normal lung areas was 41 ms (ranged 38-49 ms), and showed significant difference to pathological areas (p < 0.001). A statistical difference was found between the T2 relaxation of GGO, RE and HC (p < 0.05). The proposed method provides quantitative information for pattern differentiation, potentially allowing for monitoring of progression and response to treatment, in interstitial lung disease. • Multi-echo single shot TSE sequence allows for entire lung T2 mapping. • Lung remodelling patterns in ILD show different T2 relaxation. • Quantitative T2 mapping may provide information for monitoring of ILD.
Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 21, 2015
In recent years, immune therapeutic strategies against non-small cell lung cancer (NSCLC) based o... more In recent years, immune therapeutic strategies against non-small cell lung cancer (NSCLC) based on tissue-derived biomarkers, for example PD1/PD-L1 (CD274), have evolved as novel and promising treatment options. However, the crosstalk between tumor and immune cells is poorly understood. Glycodelin (gene name PAEP), initially described in the context of pregnancy and trophoblastic implantation, is a secreted immunosuppressive glycoprotein with an as-of-yet largely unknown function in lung cancer. In this study, we characterized the expression and role of glycodelin in NSCLC through mRNA and protein expression analyses, functional knockdown experiments and correlations with clinicopathological parameters. Glycodelin mRNA expression was significantly elevated in tumors (n=336) compared with matched normal tissue (p<0.0001). Overall survival was significantly reduced in NSCLC with high glycodelin mRNA levels in women but not in men. Glycodelin was detected in the sera of patients, an...
The purpose of this study was to describe the use of parallel imaging technique (PAT) using dynam... more The purpose of this study was to describe the use of parallel imaging technique (PAT) using dynamic MRI in lung and tumour mobility during the breathing cycle. 20 patients with stage I non-small cell lung carcinoma were investigated using two dynamic gradient echo sequences with PAT (TrueFISP (fast imaging with steady precession), and fast low angle shot (FLASH). Craniocaudal distance
Flexible bronchoscopy is routinely utilized in the diagnosis and treatment of various lung diseas... more Flexible bronchoscopy is routinely utilized in the diagnosis and treatment of various lung diseases. Nondiagnostic bronchoscopy leads to more invasive interventions, such as transthoracic needle aspiration, mediastinoscopy or even thoracotomy. Electromagnetic navigation is a novel technology that facilitates approaching peripheral lung lesions, which are difficult to sample by conventional means. The navigation system involves creating an electromagnetic field around the chest and localizing an endoscopic tool using a microsensor overlaid upon previously acquired CT images. To determine the practicality, accuracy and safety of real-time electromagnetic navigation, coupled with previously acquired 3D CT images, in locating artificially created peripheral lung lesions in a swine model. Peripheral lung lesions were created in four swine models by insertion of a metal tube (1 x 10 mm) via a transthoracic approach. An electromagnetic field was created by placing the animal on an electromagnetic location board. A position sensor incorporated into the distal tip of a dedicated tool was used to navigate to the various target lesions. Information gathered in real time during bronchoscopy was presented on a monitor simultaneously by displaying previously acquired CT images. Upon reaching the target lesion, biopsies were performed and the functionality and safety of the superDimension/Bronchus System was observed and documented. The registration accuracy expressed by the fiducial target registration error, expressing both the registration quality and the stability of fiducial (registration) points, was 4.5 mm on average. No adverse effects, such as pneumothorax or internal bleeding, were encountered in any of the animals in this study. Real-time electromagnetic positioning technology coupled with previously acquired CT images is an accurate technology added to standard bronchoscopy to assist in reaching peripheral lung lesions and performing biopsies.
This report summarizes initial tests of an emphysematous lung synthetic polymer sealant (ELS) des... more This report summarizes initial tests of an emphysematous lung synthetic polymer sealant (ELS) designed to reduce lung volume in patients with advanced emphysema. The primary study objective was to define a therapeutic strategy to optimize treatment safety and effectiveness. ELS therapy was administered bronchoscopically to 25 patients with heterogeneous emphysema in an open-label, noncontrolled study at 6 centers in Germany. Treatment was performed initially at 2-4 subsegments. After 12 weeks, patients were eligible for repeat therapy to a total of 6 sites. Safety and efficacy were assessed after 6 months. Responses were evaluated in terms of changes from baseline in lung physiology, functional capacity, and health-related quality of life. Follow-up is available for 21 of 25 patients. Treatment was well tolerated. There were no treatment-related deaths (i.e., within 90 days of treatment), and an acceptable short- and long-term safety profile. Physiological and clinical benefits were observed at 24 weeks. Efficacy responses were better among Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III patients [n = 14; change in residual volume/total lung capacity (ΔRV/TLC) = -7.4 ± 10.3%; Δ forced expiratory volume in 1 s (ΔFEV(1)) = +15.9 ± 22.6%; change in forced vital capacity (ΔFVC) = +24.1 ± 22.7%; change in carbon monoxide lung diffusion capacity (ΔDLCO) = +19.3 ± 34.8%; change in 6-min walk test (Δ6MWD) = +28.7 ± 59.6 m; change in Medical Research Council Dyspnea (ΔMRCD) score = -1.0 ± 1.04 units; change in St. George&#39;s Respiratory Questionnaire (ΔSGRQ) score = -9.9 ± 15.3 units] than for GOLD stage IV patients (n = 7; ΔRV/TLC = -0.5 ± 6.4%; ΔFEV(1) = +2.3 ± 12.3%; ΔFVC = +2.6 ± 21.1%; ΔDLCO = -2.8 ± 17.2%; Δ6MWD = +28.3 ± 58.4 m; ΔMRCD = 0.3 ± 0.81 units; ΔSGRQ = -6.7 ± 7.0 units). ELS therapy shows promise for treating patients with advanced heterogeneous emphysema. Additional studies to assess responses in a larger cohort with a longer follow-up are warranted.
American Journal of Respiratory and Critical Care Medicine, 1996
We conducted a randomized, controlled trial to prospectively confirm that ultrasound-directed tra... more We conducted a randomized, controlled trial to prospectively confirm that ultrasound-directed transbronchial needle aspiration (USTBNA) results in: (1) improved sensitivity for detecting lymph nodes involved with neoplasm, and (2) a decreased number of aspirates needed to achieve a diagnosis as compared with standard transbronchial needle aspiration (TBNA). The study was conducted in a tertiary medical center on patients undergoing fiberoptic bronchoscopy in the evaluation of enlarged mediastinal lymph nodes. USTBNA or TBNA were followed by rapid, on-site cytopathology examination of the collected specimens. Measurements included the (1) age and sex of the patient, prior diagnosis of cancer, nodal short-axis diameter and node location as determined by computerized tomography (CT), and endobronchial abnormalities at bronchoscopy; (2) number, order, and location of transbronchial aspirates and results of on-site evaluation; (3) results of surgical exploration in patients with negative transbronchial needle aspiration; (4) sensitivity, specificity, and diagnostic accuracy of USTBNA and TBNA; (5) number of aspirates required for successful lymph node aspiration as well as for a diagnosis of cancer for both USTBNA and TBNA; and (6) multiple logistic regression analysis to determine the significance of combinations of clinical predictors and needle aspirate results. Eighty-two bronchoscopic examinations were performed on 80 patients. We found no significant difference between USTBNA and TBNA in sensitivity (82.6% versus 90.5%, respectively), specificity (100% for both), or diagnostic accuracy (86.7% versus 91.7%, respectively). The sensitivity, specificity, and diagnostic accuracy of USTBNA and TBNA were similarly high, regardless of node location (paratracheal or subcarinal). A decrease in the number of aspirates required for lymph node sampling approached statistical significance for all USTBNAs as compared with TBNAs (2.03 +/- 0.19 versus 2.62 +/- 0.25, p = 0.06), but this was not demonstrated for the number required to confirm cancer (1.95 +/- 0.47 versus 2.68 +/- 0.21, p = 0.17). The number of aspirates to successful lymph node aspiration decreased with USTBNA versus TBNA in paratracheal lymph nodes (2.00 +/- 0.20 versus 2.91 +/- 0.34, p = 0.03), but not to a diagnosis of cancer (1.93 +/- 0.25 versus 3.00 +/- 0.58, p = 0.11). No difference was seen in the number of aspirates for subcarinal nodes. The number of TBNA attempts for paratracheal lymph node sampling was inversely correlated with node size (r = 0.48, p = 0.02). No such relation was seen with USTBNA of paratracheal nodes (r = 0.09, p = 0.66), TBNA of subcarinal nodes, or USTBNA of subcarinal nodes. A similar relation was seen between the number of aspirates to a diagnosis of cancer. On multiple logistic regression analysis, a positive transbronchial aspirate was associated only with a larger lymph node and history of prior cancer. We conclude that: (1) in the setting of on-site cytopathology, transbronchial needle aspiration has a high sensitivity, specificity, and diagnostic accuracy in the evaluation of enlarged mediastinal lymph nodes suspected of harboring malignancy; (2) mediastinal anatomy, including vascular structures and lymph nodes, is clearly imaged with endobronchial ultrasonography; (3) a greater short-axis diameter of the mediastinal lymph node and history of a prior malignancy increase the likelihood of a positive transbronchial aspiration; (4) USTBNA exhibits a similarly high diagnostic yield to TBNA in the setting of rapid on-site cytopathology evaluation; (5) USTBNA decreases the number of aspirates required for paratracheal lymph node sampling, which may be particularly useful in sampling smaller paratracheal nodes or at institutions that do not utilize rapid on-site cytopathology evaluation.
International journal of chronic obstructive pulmonary disease, 2015
As well as lung volume reduction surgery, different minimally invasive endoscopic techniques are ... more As well as lung volume reduction surgery, different minimally invasive endoscopic techniques are available to achieve lung volume reduction in patients with severe emphysema and significant hyperinflation. Lung function parameters and comorbidities of the patient, as well as the extent and distribution of the emphysema are factors to be considered when choosing the patient and the intervention. Endoscopic bronchial valve placement with complete occlusion of one lobe in patients with heterogeneous emphysema is the preferred technique because of its reversibility. The presence of high interlobar collateral ventilation will hinder successful treatment; therefore, endoscopic coil placement, polymeric lung volume reduction, or bronchoscopic thermal vapor ablation as well as lung volume reduction surgery can be used for treating patients with incomplete fissures. The effect of endoscopic lung volume reduction in patients with a homogeneous distribution of emphysema is still unclear and th...
NUT (nuclear protein in testis) carcinomas are exceedingly rare neoplasms with specific molecular... more NUT (nuclear protein in testis) carcinomas are exceedingly rare neoplasms with specific molecular alterations and often follow a devastating course. Thus, a precise early diagnosis is of utmost importance. Known from the sinonasal region for years, the new 2015 WHO classification now also recognizes the existence of this entity in the thorax, specifically the lungs and the mediastinum. However, yet available data on this entity are sparse. Here, we report on a 31 years old female patient with an aggressively growing tumor localized in the median line that was initially sampled by endobronchial ultrasound-guided transbronchial biopsies. Pathological assessment of the biopsy specimens revealed a NUT carcinoma with typical morphological characteristics and an uncommon NUT translocation variant with a NSD3-NUT fusion. Diagnosis was further confirmed in the subsequent resection specimen. We describe specific clinical, histomorphological, and molecular characteristics of this tumor and provide a comprehensive review of the current literature on these rare neoplasms.
PPFE is a rare disease characterized by upper lobe pleural fibrosis and parenchymal fibroelastosi... more PPFE is a rare disease characterized by upper lobe pleural fibrosis and parenchymal fibroelastosis. Its aetiology is considered idiopathic, although possible causative factors have been described. An association of PPFE with solid tumours is unknown and has not been considered previously. We identified six patients with PPFE, four of them with a coexisting malignancy. The case series suggests that PPFE might be an implication of varying factors rather than being an exclusively idiopathic condition.
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, Jan 23, 2015
Chronic inflammation and remodeling of the airways remain a hallmark of cystic fibrosis (CF). How... more Chronic inflammation and remodeling of the airways remain a hallmark of cystic fibrosis (CF). However, knowledge of the associated mucosal micro-anatomical changes is limited. We evaluated the potential of optical coherence tomography (OCT) for in vivo imaging of the upper airway mucosa in CF patients. A flexible OCT probe was used for cross-sectional imaging of the nasal mucosa in 25 CF patients and 25 healthy controls. OCT images showed mucosal details including epithelium, basement membrane, lamina propria with seromucinous glands, and underlying cartilaginous structures. Mean nasal mucosa and epithelial layer thickness were increased in CF compared to controls. In CF patients, antibiotic therapy was associated with reduced nasal mucosa thickening. OCT detected mucosal changes associated with upper airway inflammation and response to antibiotic therapy in CF patients. OCT may be a useful tool for quantitative in vivo assessment of structural changes of the airway mucosa.
To investigate the hazard function of tumor recurrence in patients with completely (R0) resected ... more To investigate the hazard function of tumor recurrence in patients with completely (R0) resected non-small cell lung cancer. A total of 1374 patients treated between 2003 and 2009 with complete resection and systematic lymph node dissection were studied. The risk of recurrence at a given time after operation was studied utilizing the cause-specific hazard function. Recurrence was categorized as local recurrence or distant recurrence. The risk distribution was assessed using clinical and pathological factors. The hazard function for recurrence presented an early peak at approximately 10 months after surgery and maintained a tapered plateau-like tail extending up to 8 years. A similar risk pattern was detected for both local recurrence and distant recurrence, while the risk of distant recurrence was higher than that of local recurrence. The double-peaked pattern of hazard rate was present in several subgroups, such as p-stage IA patients. A comparison of histology and status of nodal involvement showed that pN1-2 adenocarcinoma patients demonstrated a high hazard rate of distant recurrence and that pN0 adenocarcinoma patients exhibited a small recurrent risk for a longer time. Squamous cell carcinoma patients showed only little difference in risk. The data may be useful to select patients at high risk of recurrence and may provide information for each patient to decide how to manage the postoperative follow-up individually.
Biomarkers can be subtle tools to aid the diagnosis, prognosis and monitoring of therapy and dise... more Biomarkers can be subtle tools to aid the diagnosis, prognosis and monitoring of therapy and disease progression. The validation of biomarkers is a cumbersome process involving many steps. Serum samples from lung cancer patients were collected in the framework of a larger study for evaluation of biomarkers for early detection of lung cancer. The analysis of biomarker levels measured revealed a noticeable difference in certain biomarker values that exhibited a dependence of the time point and setting of the sampling. Biomarker concentrations differed significantly if taken before or after the induction of anesthesia and if sampled via venipuncture or arterial catheter. To investigate this observation, blood samples from 13 patients were drawn 1-2 days prior to surgery (T1), on the same day by venipuncture (T2) and after induction of anesthesia via arterial catheter (T3). The biomarkers Squamous Cell Carcinoma antigen (CanAG SCC EIA, Fujirebio Diagnostics, Malvern, USA), Carcinoembrio...
To describe changes over time in extent of idiopathic pulmonary fibrosis (IPF) at multidetector c... more To describe changes over time in extent of idiopathic pulmonary fibrosis (IPF) at multidetector computed tomography (MDCT) assessed by semi-quantitative visual scores (VSs) and fully automatic histogram-based quantitative evaluation and to test the relationship between these two methods of quantification. Forty IPF patients (median age: 70 y, interquartile: 62-75 years; M:F, 33:7) that underwent 2 MDCT at different time points with a median interval of 13 months (interquartile: 10-17 months) were retrospectively evaluated. In-house software YACTA quantified automatically lung density histogram (10th-90th percentile in 5th percentile steps). Longitudinal changes in VSs and in the percentiles of attenuation histogram were obtained in 20 untreated patients and 20 patients treated with pirfenidone. Pearson correlation analysis was used to test the relationship between VSs and selected percentiles. In follow-up MDCT, visual overall extent of parenchymal abnormalities (OE) increased in me...
To evaluate lung T2 mapping for quantitative characterization and differentiation of ground-glass... more To evaluate lung T2 mapping for quantitative characterization and differentiation of ground-glass opacity (GGO), reticulation (RE) and honeycombing (HC) in usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). Twelve patients with stable UIP or NSIP underwent thin-section multislice CT and 1.5-T MRI of the lung. A total of 188 regions were classified at CT into normal (n = 29) and pathological areas, including GGO (n = 48), RE (n = 60) and HC (n = 51) predominant lesions. Entire lung T2 maps based on multi-echo single shot TSE sequence (TE: 20, 40, 79, 140, 179 ms) were generated from each subject with breath-holds at end-expiration and ECG-triggering. The median T2 relaxation of GGO was 67 ms (range 60-72 ms). RE predominant lesions had a median relaxation of 74 ms (range 69-79 ms), while for HC pattern this was 79 ms (range 74-89 ms). The median T2 relaxation for normal lung areas was 41 ms (ranged 38-49 ms), and showed significant difference to pathological areas (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). A statistical difference was found between the T2 relaxation of GGO, RE and HC (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The proposed method provides quantitative information for pattern differentiation, potentially allowing for monitoring of progression and response to treatment, in interstitial lung disease. • Multi-echo single shot TSE sequence allows for entire lung T2 mapping. • Lung remodelling patterns in ILD show different T2 relaxation. • Quantitative T2 mapping may provide information for monitoring of ILD.
Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 21, 2015
In recent years, immune therapeutic strategies against non-small cell lung cancer (NSCLC) based o... more In recent years, immune therapeutic strategies against non-small cell lung cancer (NSCLC) based on tissue-derived biomarkers, for example PD1/PD-L1 (CD274), have evolved as novel and promising treatment options. However, the crosstalk between tumor and immune cells is poorly understood. Glycodelin (gene name PAEP), initially described in the context of pregnancy and trophoblastic implantation, is a secreted immunosuppressive glycoprotein with an as-of-yet largely unknown function in lung cancer. In this study, we characterized the expression and role of glycodelin in NSCLC through mRNA and protein expression analyses, functional knockdown experiments and correlations with clinicopathological parameters. Glycodelin mRNA expression was significantly elevated in tumors (n=336) compared with matched normal tissue (p<0.0001). Overall survival was significantly reduced in NSCLC with high glycodelin mRNA levels in women but not in men. Glycodelin was detected in the sera of patients, an...
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