J. Hetzel

Transbronchial Cryobiopsy: A New Tool for Lung Biopsies

Background: Specimens from transbronchial lung biopsies lack sufficient quality due to crush artifact and are generally too small for diagnosis of diffuse lung diseases. Flexible cryoprobes have been shown to be useful in therapeutic bronchoscopy. We introduce a novel technique for obtaining lung biopsies bronchoscopically, using a flexible cryoprobe. Objectives: The purpose of this study was to show the feasibility of using a cryoprobe to obtain lung biopsies during flexible bronchoscopy. Methods: Forty-one patients with radiographic signs of diffuse lung disease were selected for transbronchial biopsy. During flexible bronchoscopy, conventional transbronchial biopsies using forceps were done first. Then a flexible cryoprobe was introduced into the selected bronchus under fluoroscopic guidance. Once brought into position, the probe was cooled and then retracted with the frozen lung tissue being attached on the probe’s tip. The tissue was processed for histology. After establishing a diagnosis, the specimen area was measured using a digital morphometry system. Results: We evaluated the biopsy samples of 41 patients. The mean specimen area was 5.82 mm2 (0.58–20.88 mm2) taken by forceps compared to 15.11 mm2 obtained using the cryoprobe (2.15–54.15 mm2, p < 0.01). Two patients had a pneumothorax which resolved with tube thoracostomy. Biopsy-associated bleeding did not require any intervention. Transbronchial cryobiopsy contributed in a substantial number of cases to a definitive diagnosis. Conclusions: Transbronchial cryobiopsy is a novel technique which allows to obtain large biopsy samples of lung parenchyma that exceed the size and quality of forceps biopsy samples. Prospective trials are needed to compare this technique with surgical lung biopsy for diagnosis of diffuse lung diseases.

Rapid Effects of Rosiglitazone Treatment on Endothelial Function and Inflammatory Biomarkers

Background—Antidiabetic thiazolidinediones (TZDs), like rosiglitazone or pioglitazone, improve endothelial function in patients with type 2 diabetes or metabolic syndrome, but it is currently unknown, whether these beneficial effects of TZDs depend on their metabolic action or may be caused by direct effects on the endothelium. Therefore, the present study examined whether short-term rosiglitazone treatment influences endothelium-dependent vasodilation as well as serum levels of vascular disease biomarkers in healthy, nondiabetic subjects. Methods and Results—Short-term treatment (21 days) of healthy subjects (n=10) did not significantly change blood glucose levels or lipid profile. In contrast, rosiglitazone significantly increased flow-mediated, endothelium-dependent vasodilation already within the first day from 5.3±2.7% at baseline to 7.8±2.6%, further increasing it to 9.4±3.0% at day 21. In addition, the early improvement of endothelium-dependent vasodilation was paralleled by a rapid reduction of serum levels of the biomarkers C-reactive protein (CRP), serum amyloid A (SAA), and sE-selectin. Moreover, after drug withdrawal all markers remained suppressed for the whole follow-up period of 7 days. In contrast, rosiglitazone treatment did not significantly affect tumor necrosis factor (TNF)-&agr;, interleukin (IL)-6, sICAM-1, sVCAM-1, and sCD40L levels. Conclusions—Our study suggests a direct effect of TZD treatment on endothelial function and inflammatory biomarkers of arteriosclerosis, promoting the concept that TZDs, independent of their metabolic action, may exhibit protective effects in the vessel wall.

Cryobiopsy increases the diagnostic yield of endobronchial biopsy: a multicentre trial

Forceps, brushes or needles are currently the standard tools used during flexible bronchoscopy when diagnosing endobronchial malignancies. The new biopsy technique of cryobiopsy appears to provide better diagnostic samples. The aim of this study was to evaluate cryobiopsy over conventional endobronchial sampling. A total of 600 patients in eight centres with suspected endobronchial tumours were included in a prospective, randomised, single-blinded multicentre study. Patients were randomised to either sampling using forceps or the cryoprobe. After obtaining biopsy samples, a blinded histological evaluation was performed. According to the definitive clinical diagnosis, the diagnostic yield for malignancy was evaluated by a Chi-squared test. A total of 593 patients were randomised, of whom 563 had a final diagnosis of cancer. 281 patients were randomised to receive endobronchial biopsies using forceps and 282 had biopsies performed using a flexible cryoprobe. A definitive diagnosis was achieved in 85.1% of patients randomised to conventional forceps biopsy and 95.0% of patients who underwent cryobiopsy (p<0.001). Importantly, there was no difference in the incidence of significant bleeding. Endobronchial cryobiopsy is a safe technique with superior diagnostic yield in comparison with conventional forceps biopsy.

Diagnostic yield of transbronchial cryobiopsy in interstitial lung disease: A randomized trial

Transbronchial lung biopsy (TBLB) is required for evaluation in selected patients with interstitial lung disease (ILD). The diagnostic yield of histopathologic assessment is variable and is influenced by factors such as the size of samples and the presence of crush artefacts left by conventional biopsy forceps. We compared the diagnostic yield and safety of TBLB with cryoprobe sampling versus conventional forceps sampling.

Endobronchial tumor debulking with a flexible cryoprobe for immediate treatment of malignant stenosis

OBJECTIVE In addition to use of a laser, argon plasma coagulation, electrocautery, or coring with a rigid bronchoscope, tumor debulking with a flexible cryoprobe is used for therapeutic bronchoscopy with an immediate effect for endobronchial pathologies. We performed this analysis to determine the usefulness, efficacy, and safety of the flexible cryorecanalization in a large population under routine conditions. METHODS We identified 225 bronchoscopic interventions that were done as cryorecanalization with a flexible cryoprobe. All patients had symptomatic airway stenosis. We determined the endoscopic success rate and safety (bleeding and perforation) of the procedure. RESULTS Successful cryorecanalization was achieved in 205 (91.1%) of 225 patients. The flexible cryoprobe was used with all patients, in most patients in combination with flexible bronchoscopy and only in a minority (n = 31, 13.8%) in combination with a rigid bronchoscope. Additional interventional techniques used were endobronchial stents (n = 11, 4.9%) and argon plasma coagulation (n = 37, 16.4%). Mild bleeding (if ice-cold NaCl or epinephrine solution was necessary) occurred in 9 (4.0%) patients, moderate bleeding (if argon plasma coagulation or a bronchus blocker was required) occurred in 18 (8.0%) patients, and severe bleeding (events with hemodynamic instability) never occurred. CONCLUSIONS Cryorecanalization with the flexible cryoprobe for treatment of symptomatic endobronchial tumor stenosis is a safe technique with a high success rate and immediate treatment effect.

Correlation of Simultaneously Acquired Diffusion-Weighted Imaging and 2-Deoxy-[18F] fluoro-2-D-glucose Positron Emission Tomography of Pulmonary Lesions in a Dedicated Whole-Body Magnetic Resonance/Positron Emission Tomography System

ObjectiveHybrid whole-body magnetic resonance/positron emission tomography (MR/PET) systems are a new diagnostic tool enabling the simultaneous acquisition of morphologic and multiple functional data and thus allowing for a diversified characterization of oncological diseases.The aim of this study was to investigate the image and alignment quality of MR/PET in patients with pulmonary lesions and to compare the congruency of the 2 functional measurements of diffusion-weighted imaging (DWI) in MR imaging and 2-deoxy-[18F] fluoro-2-D-glucose (FDG) uptake in PET. Materials and MethodsA total of 15 patients were examined with a routine positron emission tomography/computer tomography (PET/CT) protocol and, subsequently, in a whole-body MR/PET scanner allowing for simultaneous PET and MR data acquisition. The PET and MR image quality was assessed visually using a 4-point score (1, insufficient; 4, excellent). The alignment quality of the rigidly registered PET/CT and MR/PET data sets was investigated on the basis of multiple anatomic landmarks of the lung using a scoring system from 1 (no alignment) to 4 (very good alignment). In addition, the alignment quality of the tumor lesions in PET/CT and MR/PET as well as for retrospective fusion of PET from PET/CT and MR images was assessed quantitatively and was compared between lesions strongly or less influenced by respiratory motion. The correlation of the simultaneously acquired DWI and FDG uptake in the pulmonary masses was analyzed using the minimum and mean apparent diffusion coefficient (ADCmin and ADCmean) as well as the maximum and mean standardized uptake value (SUVmax and SUVmean), respectively. In addition, the correlation of SUVmax from PET/CT data was investigated as well. On lesions 3 cm or greater, a voxelwise analysis of ADC and SUV was performed. ResultsThe visual evaluation revealed excellent image quality of the PET images (mean [SD] score, 3.6 [0.5]) and overall good image quality of DWI (mean [SD] score of 2.5 [0.5] for ADC maps and 2.7 [0.5] for diffusion-weighted images, respectively). The alignment quality of the data sets was very good in both MR/PET and PET/CT without significant differences (overall mean [SD] score of MR/PET, 3.8 [0.4]; PET/CT 3.6 [0.5]). Also, the alignment quality of the tumor lesions showed no significant differences between PET/CT and MR/PET (mean cumulative misalignment of MR/PET, 7.7 mm; PET/CT, 7.0 mm; P = 0.705) but between both modalities and a retrospective fusion (mean cumulative misalignment, 17.1 mm; P = 0.002 and P = 0.008 for PET/CT and MR/PET, respectively). Also, the comparison of the lesions strongly or less influenced by respiratory motion showed significant differences only for the retrospective fusion (21.3 mm vs 11.5 mm, respectively; P = 0.043). The ADCmin and SUVmax as measures of the cell density and glucose metabolism showed a significant reverse correlation (r = −0.80; P = 0.0006). No significant correlation was found between ADCmean and SUVmean (r = −0.42; P = 0.1392). Also, SUVmax from the PET/CT data showed significant reverse correlation to ADCmin (r = −0.62; P = 0.019). The voxelwise analysis of 5 pulmonary lesions each showed weak but significant negative correlation between ADC and SUV. ConclusionsExaminations of pulmonary lesions in a simultaneous whole-body MR/PET system provide diagnostic image quality in both modalities. Although DWI and FDG-PET reflect different tissue properties, there may very well be an association between the measures of both methods most probably because of increased cellularity and glucose metabolism of FDG-avid pulmonary lesions. A voxelwise DWI and FDG-PET correlation might provide a more sophisticated spatial characterization of pulmonary lesions.

Old Meets Modern: The Use of Traditional Cryoprobes in the Age of Molecular Biology

Background: Endobronchial forceps biopsies are often small and are associated with a relevant extent of artifacts. To overcome these limitations is an important task. Especially when considering predictive factors for pharmacological therapies of lung cancer (ERCC1, RRM1) a development of biopsy techniques seems to be essential. This is the first report on a new endobronchial biopsy technique called cryobiopsy. Objectives: In this study the feasibility and the potential advantages of applying cryoprobes for harvesting samples for histological examination in flexible bronchoscopies will be focused on. Methods: In 12 patients suffering from exophytic endobronchial malignancies, a modified flexible cryoprobe was used for immediate recanalization. The extracted tissue was examined histologically regarding sample quality and sample size. Results: Tissue samples obtained using the cryoprobe showed an extraordinary good quality in terms of size (median diameter of 6.7 mm, range 4.2–13 mm) and artifact-free sample area (75% of the samples showed an artifact-free sample area of more than 75%). Additionally molecular markers were shown to be well preserved. Conclusions: The new technique termed cryobiopsy might widen the chest physician’s range of tools for diagnostic bronchoscopies.

Nasal high–flow oxygen therapy in patients with hypoxic respiratory failure: effect on functional and subjective respiratory parameters compared to conventional oxygen therapy and non-invasive ventilation (NIV)

BackgroundAim of the study was to compare the short-term effects of oxygen therapy via a high-flow nasal cannula (HFNC) on functional and subjective respiratory parameters in patients with acute hypoxic respiratory failure in comparison to non-invasive ventilation (NIV) and standard treatment via a Venturi mask.MethodsFourteen patients with acute hypoxic respiratory failure were treated with HFNC (FiO2 0.6, gas flow 55 l/min), NIV (FiO2 0.6, PEEP 5 cm H2O Hg, tidal volume 6–8 ml/kg ideal body weight,) and Venturi mask (FiO2 0.6, oxygen flow 15 l/min,) in a randomized order for 30 min each. Data collection included objective respiratory and circulatory parameters as well as a subjective rating of dyspnea and discomfort by the patients on a 10-point scale. In a final interview, all three methods were comparatively evaluated by each patient using a scale from 1 (=very good) to 6 (=failed) and the patients were asked to choose one method for further treatment.ResultsPaO2 was highest under NIV (129 ± 38 mmHg) compared to HFNC (101 ± 34 mmHg, p <0.01 vs. NIV) and VM (85 ± 21 mmHg, p <0.001 vs. NIV, p <0.01 vs. HFNC, ANOVA). All other functional parameters showed no relevant differences. In contrast, dyspnea was significantly better using a HFNC (2.9 ± 2.1, 10-point Borg scale) compared to NIV (5.0 ± 3.3, p <0.05), whereas dyspnea rating under HFNC and VM (3.3 ± 2.3) was not significantly different. A similar pattern was found when patients rated their overall discomfort on the 10 point scale: HFNC 2.7 ± 1.8, VM 3.1 ± 2.8 (ns vs. HFNC), NIV 5.4 ± 3.1 (p <0.05 vs. HFNC). In the final evaluation patients gave the best ratings to HFNC 2.3 ± 1.4, followed by VM 3.2 ± 1.7 (ns vs. HFNC) and NIV 4.5 ± 1.7 (p <0.01 vs. HFNC and p <0.05 vs. VM). For further treatment 10 patients chose HFNC, three VM and one NIV.ConclusionsIn hypoxic respiratory failure HFNC offers a good balance between oxygenation and comfort compared to NIV and Venturi mask and seems to be well tolerated by patients.Trial registrationGerman clinical trials register: DRKS00005132.

Assessment of tumor vascularity in lung cancer using volume perfusion CT (VPCT) with histopathologic comparison: a further step toward an individualized tumor characterization.

Objective To measure perfusion in different lung cancer subtypes and compare results with histopathological/immunohistochemical results. Methods Seventy-two consecutive untreated patients with lung cancer (40 adenocarcinomas, 20 squamous cell, and 12 small cell lung cancers) were enrolled. A 40-second volume perfusion computed tomography of the tumor bulk was obtained. Blood flow (BF), blood volume (BV), and transit constant were determined. Tumor volume and tumor necrosis were determined on contrast-enhanced computed tomography. Pathologic specimens were assessed for microvessel density (MVD), hypoxia-induced transcription (hif-1/-2), and proliferation (Ki-67). Results Higher MVD is associated with higher BF and BV. Higher tumor grade leads to lower BF but increased necrosis and tumor volume. Markers of hypoxia were independent from perfusion parameters, extent of necrosis or MVD. Blood flow, BV, and MVD were not significantly different among lung cancer subtypes. Transit constant was significantly reduced in small cell lung cancer versus adenocarcinoma. Conclusions Perfusion values are related to MVD and tumor grade but vary considerably among lung cancer subtypes.

Prospective controlled animal study on biopsy sampling with new flexible cryoprobes versus forceps: evaluation of biopsy size, histological quality and bleeding risk.

Background: Cryoextraction is a procedure used for the recanalization of obstructed airways caused by visible exophytic endobronchial tumor. Biopsy samples obtained by this technique have been shown to be useful for histological assessment. Objectives: The aim of the present animal study was to systematically evaluate biopsy size, histological quality and bleeding risk after cryobiopsy with new, flexible cryoprobes in comparison with forceps biopsy, serving as the gold standard. Methods: Biopsies were obtained from anesthetized pigs with the flexible bronchoscopy technique, and evaluated histologically with respect to their size and quality. Bleeding frequency, bleeding duration and histological changes in the biopsy bed were also recorded. Results: Cryobiopsies were significantly larger than forceps biopsies. The size of cryobiopsies was dependent on the freezing time. The histological quality of the cryobiopsy specimenswas not impaired by the freezing process, whereas forceps biopsies showed typical crush artifacts. Despite the larger defects left in the tracheobronchial system after cryobiopsy, bleeding frequency and duration were not higher compared to forceps biopsy. Conclusions: Since cryobiopsy sampling is not associated with a higher bleeding risk compared with forceps biopsy, this new biopsy technique offers – in addition to a good specimen quality – a safe and valuable tool with the potential of improving the outcome of diagnostic endoscopy.