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In our case, a 45-year-old male patient had multiple fractures accompanied by hypophosphatemia. FGF-23 levels were significantly increased, and total body magnetic resonance imaging (MRI) revealed a tumor mass located at the distal tibia leading to the diagnosis of tumor-induced osteomalacia (TIO). After resection of the tumor, hypophosphatemia and the increased levels of FGF-23 normalized within a few days. Subsequent microscopic examination and immunohistochemical analysis revealed a phosphaturic mesenchymal tumor mixed connective tissue variant (PMTMCT) showing a positive expression of somatostatin receptor 2A (SSTR2A), CD68, and Periostin. Electron microscopy demonstrated a poorly differentiated mesenchymal tumor with a multifocal giant cell component and evidence of neurosecretory-granules. However, the resected margins showed no tumor-free tissue, and therefore a subsequent postoperative radiotherapy was performed. The patient is still in complete remission after 34 months. Tumor resection of PMTMCTs is the therapy of choice. Subsequent radiotherapy in case of incompletely resected tumors can be an important option to avoid recurrence or metastasis even though this occurs rarely. The prognostic value of expression of Periostin has to be evaluated more precisely in a larger series of patients with TIO.

Pulmonary involvement in ulcerative colitis may manifest as a variety of disorders. Ulcerative colitis-related interstitial lung disease is exceedingly rare and has been reported to be steroid-responsive. We describe the first case of a patient with acute exacerbation of ulcerative colitis-induced usual interstitial pneumonia, who did not respond to corticosteroid therapy and died 12 weeks after the onset of pulmonary symptoms. Early recognition of pulmonary disease in patients with ulcerative colitis is necessary to initiate further diagnostic work-up and may aid treatment decisions. [ABSTRACT FROM AUTHOR]

Background: The electroencephalographic (EEG) provides the anesthesiologist with information regarding the level of anesthesia. Processed EEG indices are available that reflect the level of anesthesia as a single number. Strong oscillatory EEG activity in the alpha-band may be associated with an adequate level of anesthesia and a lower incidence of cognitive sequelae. So far, we do not know how the processed indices would react to changes in the alpha-band activity. Hence, we modulated the alpha-oscillatory activity of intraoperative EEG to assess possible index changes., Methods: We performed our analyses based on data from 2 studies. Intraoperative EEG was extracted, and we isolated the alpha-band activity by band-pass filtering (8-12 Hz). We added or subtracted this activity to the original EEG in different steps with different amplifications of the alpha signal. We then replayed these signals to the bispectral index (BIS), the Entropy Module (state entropy [SE]), the CONOX (qCON), and the SEDLine (patient state index [PSI]); and evaluated the alpha-band modulation's impact on the respective index., Results: The indices behaved differently to the modulation. In general, indices decreased with stronger alpha-band activity, but the rate of change was different with SE showing the strongest change (9% per step) and PSI and BIS (<5% per step) showing the weakest change. A simple regression analysis revealed a decrease of 0.02 to 0.09 index points with increasing alpha amplification., Conclusions: While the alpha-band in the intraoperative EEG seems to carry information regarding the quality of anesthesia, changes in the alpha-band activity do neither strongly nor uniformly influence processed EEG indices. Hence, to assess alpha-oscillatory activity's strength, the user needs to focus on the raw EEG or its spectral representation also displayed on the monitoring systems., Competing Interests: Conflicts of Interest, Funding: See Disclosures at the end of the article., (Copyright © 2024 International Anesthesia Research Society.)

Background: Spirometry and conventional chest x-ray have limitations in investigating early emphysema, while computed tomography, the reference imaging method in this context, is not part of routine patient care due to its higher radiation dose. In this work, we investigated a novel low-dose imaging modality, dark-field chest x-ray, for the evaluation of emphysema in patients with alpha1-antitrypsin deficiency., Methods: By exploiting wave properties of x-rays for contrast formation, dark-field chest x-ray visualises the structural integrity of the alveoli, represented by a high signal over the lungs in the dark-field image. We investigated four patients with alpha1-antitrypsin deficiency with a novel dark-field x-ray prototype and simultaneous conventional chest x-ray. The extent of pulmonary function impairment was assessed by pulmonary function measurement and regional emphysema distribution was compared with CT in one patient., Results: We show that dark-field chest x-ray visualises the extent of pulmonary emphysema displaying severity and regional differences. Areas with low dark-field signal correlate with emphysematous changes detected by computed tomography using a threshold of -950 Hounsfield units. The airway parameters obtained by whole-body plethysmography and single breath diffusing capacity of the lungs for carbon monoxide demonstrated typical changes of advanced emphysema., Conclusions: Dark-field chest x-ray directly visualised the severity and regional distribution of pulmonary emphysema compared to conventional chest x-ray in patients with alpha1-antitrypsin deficiency. Due to the ultra-low radiation dose in comparison to computed tomography, dark-field chest x-ray could be beneficial for long-term follow-up in these patients., (© 2022. The Author(s) under exclusive licence to European Society of Radiology.)

Background: Intraoperative patient monitoring using the electroencephalogram (EEG) can help to adequately adjust the anesthetic level. Therefore, the processed EEG (pEEG) provides the anesthesiologist with the estimated anesthesia level. The commonly used approaches track the changes from a fast- and a low-amplitude EEG during wakefulness to a slow- and a high-amplitude EEG under general anesthesia. However, besides these changes, another EEG feature, a strong oscillatory activity in the alpha band (8-12 Hz), develops in the frontal EEG. Strong alpha-band activity during general anesthesia seems to reflect an appropriate anesthetic level for certain anesthetics, but the way the common pEEG approaches react to changes in the alpha-band activity is not well explained. Hence, we investigated the impact of an artificial alpha-band modulation on pEEG approaches used in anesthesia research., Methods: We performed our analyses based on 30 seconds of simulated sedation (n = 25) EEG, simulated anesthesia (n = 25) EEG, and EEG episodes from 20 patients extracted from a steady state that showed a clearly identifiable alpha peak in the density spectral array (DSA) and a state entropy (GE Healthcare) around 50, indicative of adequate anesthesia. From these traces, we isolated the alpha activity by band-pass filtering (8-12 Hz) and added this alpha activity to or subtracted it from the signals in a stepwise manner. For each of the original and modified signals, the following pEEG values were calculated: (1) spectral edge frequency (SEF95), (2) beta ratio, (3) spectral entropy (SpEntr), (4) approximate entropy (ApEn), and (5) permutation entropy (PeEn)., Results: The pEEG approaches showed different reactions to the alpha-band modification that depended on the data set and the amplification step. The beta ratio and PeEn decreased with increasing alpha activity for all data sets, indicating a deepening of anesthesia. The other pEEG approaches behaved nonuniformly. SEF95, SpEntr, and ApEn decreased with increasing alpha for the simulated anesthesia data (arousal) but decreased for simulated sedation. For the patient EEG, ApEn indicated an arousal, and SEF95 and SpEntr showed a nonuniform change., Conclusions: Changes in the alpha-band activity lead to different reactions for different pEEG approaches. Hence, the presence of strong oscillatory alpha activity that reflects an adequate level of anesthesia may be interpreted differently, by an either increasing (arousal) or decreasing (deepening) pEEG value. This could complicate anesthesia navigation and prevent the adjustment to an adequate, alpha-dominant anesthesia level, when titrating by the pEEG values., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2021 International Anesthesia Research Society.)

Background: Local anaesthesia of the pharynx (LAP) was introduced in the era of rigid bronchoscopy (which was initially a conscious procedure under local anaesthetic), and continued into the era of flexible bronchoscopy (FB) in order to facilitate introduction of the FB. LAP reduces cough and gagging reflex, but its post-procedural effect is unclear. This prospective multicentre trial evaluated the effect of LAP on coughing intensity/time and patient comfort after FB, and the feasibility of FB under propofol sedation alone, without LAP., Material and Methods: FB was performed in 74 consecutive patients under sedation with propofol, either alone (35 patients, 47.3%) or with additional LAP (39 patients, 52.7%). A primary endpoint of post-procedural coughing duration in the first 10 min after awakening was evaluated. A secondary endpoint was the cough frequency, quality and development of coughing in the same period during the 10 min post-procedure. Finally, the ease of undertaking the FB and the patient's tolerance and safety were evaluated from the point of view of the investigator, the assistant technician and the patient., Results: We observed a trend to a shorter cumulative coughing time of 48.6 s in the group without LAP compared to 82.8 s in the group receiving LAP within the first 10 min after the procedure, although this difference was not significant ( p = 0.24). There was no significant difference in the cough frequency, quality, peri-procedural complication rate, nor patient tolerance or safety. FB, including any additional procedure, could be performed equally well with or without LAP in both groups., Conclusions: Our study suggests that undertaking FB under deep sedation without LAP does to affect post-procedural cough duration and frequency. However, further prospective randomised controlled trials are needed to further support this finding.

Background: Patients suffering from out-of-hospital cardiac arrest (OHCA) frequently receive a bronchoscopy after being admitted to the ICU. We investigated the optimal timing and the outcome in these patients., Methods: All patients who suffered from OHCA and were treated in our ICU from January 2013 to December 2018 were retrospectively analyzed. The data were collected from the patients' medical files, and included duration of mechanical ventilation, antibiotics, microbiological test results and neurological outcome. The outcome was the effect of early bronchoscopy (≤48 h after administration) on the rate of intubated patients on day five and day seven., Results: From January 2013 to December 2018, 190 patients were admitted with OHCA. Bronchoscopy was performed in 111 patients out of the 164 patients who survived the first day. Late bronchoscopy >48 h was associated with higher rates of intubation on day five (OR 4.94; 95% CI 1.2-36.72, 86.7% vs. 55.0%, p = 0.036) and day seven (OR 4.96; 95% CI 1.38-24.69; 80.0% vs. 43.3%, p = 0.019)., Conclusion: This study shows that patients who suffered from OHCA might have a better outcome if they receive a bronchoscopy early after hospital admission. Our data suggests an association of early bronchoscopy with a shorter intubation period.

Purpose: Non-small cell lung cancer (NSCLC) is a fatal disease with poor prognosis. A membrane-bound form of Hsp70 (mHsp70) which is selectively expressed on high-risk tumors serves as a target for mHsp70-targeting natural killer (NK) cells. Patients with advanced mHsp70-positive NSCLC may therefore benefit from a therapeutic intervention involving mHsp70-targeting NK cells. The randomized phase II clinical trial (EudraCT2008-002130-30) explores tolerability and efficacy of ex vivo -activated NK cells in patients with NSCLC after radiochemotherapy (RCT)., Patients and Methods: Patients with unresectable, mHsp70-positive NSCLC (stage IIIa/b) received 4 cycles of autologous NK cells activated ex vivo with TKD/IL2 [interventional arm (INT)] after RCT (60-70 Gy, platinum-based chemotherapy) or RCT alone [control arm (CTRL)]. The primary objective was progression-free survival (PFS), and secondary objectives were the assessment of quality of life (QoL, QLQ-LC13), toxicity, and immunobiological responses., Results: The NK-cell therapy after RCT was well tolerated, and no differences in QoL parameters between the two study arms were detected. Estimated 1-year probabilities for PFS were 67% [95% confidence interval (CI), 19%-90%] for the INT arm and 33% (95% CI, 5%-68%) for the CTRL arm ( P = 0.36, 1-sided log-rank test). Clinical responses in the INT group were associated with an increase in the prevalence of activated NK cells in their peripheral blood., Conclusions: Ex vivo TKD/IL2-activated, autologous NK cells are well tolerated and deliver positive clinical responses in patients with advanced NSCLC after RCT., (©2020 American Association for Cancer Research.)

Competing Interests: T. Greulich erhielt Kongressunterstützung durch AstraZenca, Boehringer-Ingelheim, Chiesi, CSL-Behring, Grifols, GSK, Mundopharma, Novartis sowie Forschungsunterstützung durch CSL-Behring und Grifols. C. Clarenbach erhielt Honorare für Beratertätigkeit von Roche, Novartis, Boehringer, GSK, Astra Zeneca, Sanofi, Vifor und Mundipharma. D. Skowasch erhielt Honorare für Beratertätigkeiten/Vorträge und Kongressteilnahmeunterstützung von Grifols. R. Bals berichtet über persönliche Zahlung (advisory boards) von AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Grifols, Novartis und CSL Behring. Forschung von Prof. Bals wird unterstützt von: Bundesministerium für Bildung und Forschungskompetenznetzwerk (BMBF) Asthma und COPD (ASCONET), Sander Stiftung, Schwiete Stiftung, Boehringer Ingelheim, Novartis und Mukoviszidose e. V. A. R. Koczulla: Vorträge, Advisory Board für CSL und Grifols, Forschungsunterstützung von Grifols und CSL.S. Fähndrich, W. Gleiber, H. Hautmann, R. Heine, M. Idzko, K. Schmidt-Scherzer und R. Wiewrodt geben an, dass kein Interessenkonflikt besteht.

Background: We investigated the correlation and agreement of three depth of anesthesia indices, Bispectral Index (BIS), qCON and state entropy (SE) during propofol sedation, because there is extensive literature that deals with the comparability of these indices during general anesthesia, but not during sedation., Methods: We recorded electroencephalogram (EEG) and SE trend data, using the Entropy Module from 21 patients who underwent elective bronchoscopy with target-controlled infusion of propofol. EEG data were replayed to BIS and qCON with an EEG player. We calculated the Spearman correlation to evaluate similarities in index trend behavior and estimated the general index agreement of displaying the same anesthetic level, i.e., wakefulness, sedation and anesthesia. We used coughing episodes and the bronchoscope placement to investigate the index for possible arousal reactions., Results: We found a high to very high correlation of the indices' trend during the procedure. Furthermore, qCON was significantly lower than BIS and SE. All indices increased significantly after bronchoscope placement and coughing. The agreement of BIS/SE was 68% and around 50% for BIS/qCON and qCON/SE. The median duration of disagreement by >10 points was 39 s for BIS/SE and around 75 s for qCON with BIS and SE., Conclusions: The results indicate a high probability of similar index performance between SE, BIS and qCON with the caveat of a different index scaling for qCON. These results can help the user of these monitoring devices to translate findings from one index to the other.

Objectives: Bronchoscopy is an integral part of pulmonary medicine. In recent years, a series of new technologies have evolved. It is to assume that significant changes have also occurred in clinical practice. We conducted a nationwide survey to evaluate the current status of care and to compare it with earlier reports., Methods: A standard questionnaire was sent to 1875 institutions to assess the clinical practice of bronchoscopy in Germany with respect to general issues, education, sedation/anaesthesia and technical aspects., Results: The returned questionnaires cover 301,965 bronchoscopies, performed by 2158 physicians over 12 months, making it the largest survey to date. The proportion of rigid bronchoscopies has decreased and amounts to 7.3% at present. Atropine as a premedication is hardly used any more. Sedation is routinely applied in 88% of flexible bronchoscopies, for which a combination of propofol and midazolam is preferred by most institutions (41.3%), followed by propofol monotherapy (28.3%). 74.4% of institutions accept aspirin for transbronchial biopsy, 8.1% dual platelet inhibition. 62.4% of all institutions perform airway recanalisation, favouring cryotherapy and argon plasma coagulation. 9.1% of bronchoscopies are supported by endobronchial ultrasound., Conclusion: Compared to preceding surveys, the experience of bronchoscopists, especially regarding interventional procedures, has increased. Endobronchial ultrasound has become a standard of care, as has patient sedation with propofol., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Whole-body plethysmography (WBP) with bronchial challenge testing to measure the (specific) airway resistance, (s)R(AW), is considered to be a more sensitive diagnostic procedure than spirometry, which can only measure the forced expiratory volume in one second (FEV1). The evidence for the added diagnostic value of WBP is not yet conclusive., Methods: In a prospective diagnostic study, we carried out WBP with bronchial challenge testing as well as a bronchodilation test in 400 patients with suspected asthma from June 2010 to October 2011. The bronchial provocation test was considered positive if the FEV1 fell by at least 20% and/or the airway resistance doubled, with an increase of the sR(AW) to at least 2.0 kPA × s and/or of the R(AW) to 0.5 kPA × s/L. Follow-up evaluation was performed one year later., Results: The prevalence of asthma in the 302 patients who completed follow-up was 27.5%. The sensitivity of WBP with sR(AW) measurement for asthma was 95.2% (95% confidence interval [CI] 88.3%-98.1%), and its specificity was 81.7% (95% CI 76.1%-86.3%). The sensitivity of FEV1 was 44.6% (95% CI 34.4%-55.3%), and its specificity was 91.3% (95% CI 86.6%-94.4%). The negative predictive value (NPV) of WBP with sR(AW) measurement was 97.8% (95% CI 94.5%-99.1%), while that of FEV1 was 81.3% (95% CI 76.0%-85.7%). The positive predictive value (PPV) of WBP with sR(AW) measurement was 66.4% (95% CI 57.5%-74.2%), while that of FEV1 was 66.1% (95% CI 53.0%-77.1%)., Conclusion: With sR(AW) measurement, asthma can be ruled out with high certainty. Improving the positive predictive value of testing for asthma remains a challenge, however, as sR(AW) measurement does not yield any increase in specificity.

Heat shock protein 70 (Hsp70) is frequently overexpressed in tumor cells. An unusual cell surface localization could be demonstrated on a large variety of solid tumors including lung, colorectal, breast, squamous cell carcinomas of the head and neck, prostate and pancreatic carcinomas, glioblastomas, sarcomas and hematological malignancies, but not on corresponding normal tissues. A membrane (m)Hsp70-positive phenotype can be determined either directly on single cell suspensions of tumor biopsies by flow cytometry using cmHsp70.1 monoclonal antibody or indirectly in the serum of patients using a novel lipHsp70 ELISA. A mHsp70-positive tumor phenotype has been associated with highly aggressive tumors, causing invasion and metastases and resistance to cell death. However, natural killer (NK), but not T cells were found to kill mHsp70-positive tumor cells after activation with a naturally occurring Hsp70 peptide (TKD) plus low dose IL-2 (TKD/IL-2). Safety and tolerability of ex vivo TKD/IL-2 stimulated, autologous NK cells has been demonstrated in patients with metastasized colorectal and non-small cell lung cancer (NSCLC) in a phase I clinical trial. Based on promising clinical results of the previous study, a phase II randomized clinical study was initiated in 2014. The primary objective of this multicenter proof-of-concept trial is to examine whether an adjuvant treatment of NSCLC patients after platinum-based radiochemotherapy (RCTx) with TKD/IL-2 activated, autologous NK cells is clinically effective. As a mHsp70-positive tumor phenotype is associated with poor clinical outcome only mHsp70-positive tumor patients will be recruited into the trial. The primary endpoint of this study will be the comparison of the progression-free survival of patients treated with ex vivo activated NK cells compared to patients who were treated with RCTx alone. As secondary endpoints overall survival, toxicity, quality-of-life, and biological responses will be determined in both study groups.

Purpose: Flexible fiber-optic bronchoscopy is a widespread medical procedure for the diagnosis and treatment of lung diseases. Navigation systems are needed to track the flexible endoscope within the bronchial tree. Electromagnetic (EM) tracking is currently the only technology used clinically for this purpose. The registration between EM tracking and patient anatomy may become inaccurate due to breathing motion, so the addition of image-based tracking has been proposed as a hybrid EM-image-based system., Methods: When EM tracking is used as an initialization for image registration, small changes in the initialization may lead to different local minima and noise is amplified by hybrid tracking. The tracking output is modeled as continuous and uses splines for interpolation, thus smoothness is greatly improved. The bronchoscope pose relative to computed tomography data is interpolated using Catmull-Rom splines for position and spherical linear interpolation (SLERP) for orientation., Results: The hybrid method was evaluated using ground truth poses manually selected by experts, where mean inter-expert agreement was determined as 1.26 mm. Using four dynamic phantom data sets, the accuracy was 4.91 mm, which is equivalent to previous methods. Compared to state-of-art methods, inter-frame smoothness was improved from 2.77-3.72 to 1.24 mm., Conclusions: Hybrid image and electromagnetic endoscope guidance provides a more realistic and physically plausible solution with significantly less jitter. This quantitative result is confirmed by visual comparison of real and virtual video, where the virtual video output is much more consistent and robust, with fewer occasions of tracking loss or unexpected movement compared with previous methods.

Acute mountain sickness (AMS) is characterized by headache often accompanied by gastrointestinal complaints that vary from anorexia through nausea to vomiting. The aim of this study was to investigate the influence of high altitude on plasma levels of gastroenteropancreatic (GEP) peptides and their association to AMS symptoms. Plasma levels of 6 GEP peptides were measured by radioimmunoassay in 11 subjects at 490 m (Munich, Germany) and, after rapid passive ascent to 3454 m (Jungfraujoch, Switzerland), over the course of three days. In a second study (n = 5), the same peptides and ghrelin were measured in subjects who consumed standardized liquid meals at these two elevations. AMS symptoms and oxygen saturation were monitored. In the first study, both fasting (morning 8 a.m.) and stimulated (evening 8 p.m.) plasma levels of pancreatic polypeptide (PP) and cholecystokinin (CCK) were significantly lower at high altitude as compared to baseline, whereas gastrin and motilin concentrations were significantly increased. Fasting plasma neurotensin was significantly enhanced whereas stimulated levels were reduced. Both fasting and stimulated plasma motilin levels correlated with gastrointestinal symptom severity (r = 0.294, p = 0.05, and r = 0.41, p = 0.006, respectively). Mean O(2)-saturation dropped from 96% to 88% at high altitude. In the second study, meal-stimulated integrated (= area under curve) plasma CCK, PP, and neurotensin values were significantly suppressed at high altitude, whereas integrated levels of gastrin were increased and integrated VIP and ghrelin levels were unchanged. In summary, our data show that acute exposure to a hypobaric hypoxic environment causes significant changes in fasting and stimulated plasma levels of GEP peptides over consecutive days and after a standardized meal. The changes of peptide levels were not uniform. Based on the inhibition of PP and neurotensin release a reduction of the cholinergic tone can be postulated.

Flexible bronchoscopy is a standard examination today and is conducted not only in nearly every hospital but also in privately owned practices. The vast majority of patients want sedation for this examination. Such a procedure is nearly always necessary in complex and interventional procedures, irrespective of the patient's wish. The recommendation at hand to use sedation measures for flexible bronchoscopy is based on the results of numerous clinical studies and also takes account of individual experiences in this area. The structural and procedural requirements and the requirements for staff training are defined and should describe the minimum standard when it comes to conducting a bronchoscopy under sedation. Furthermore the drugs recommended for sedation are discussed and their methods of application shown. Finally the recommendations also include suggestions for patient clarification, monitoring and discharge. They should provide the examiner with concrete operating options and therefore above all increase patient safety., (© Georg Thieme Verlag KG Stuttgart · New York.)

Bronchoscopic training courses are an essential part of the education in bronchoscopy for all kinds of specialisations and professions performing such investigations. All aspects of the application should be mentioned during a course. These recommendations are necessary because the number of bronchoscopies performed in the last years has increased due to the increasing number of patients, improved equipment and better availability. Courses should provide the basic knowledge including main points of indications, preconditions for the procedure and decisions of consequence after bronchoscopy. Participants should be trained in the skills of correct handling and performing flexible bronchoscopies in training dummies. Necessary competence requirements on the course instructor are adequate professional qualifications, paedagogic skills and the availability of appropriate teaching material. Quality assurance of the course should be achieved by consequent evaluation. A widely spread field of bronchoscopic applications can improve patient care in many medical specialisations., (© Georg Thieme Verlag KG Stuttgart · New York.)

We present a novel approach to tracking of flexible bronchoscopes by modeling the output as spatially continuous over time. Bronchoscopy is a widespread clinical procedure for diagnosis and treatment of lung diseases and navigation systems are highly needed. Tracking of the bronchoscope can be regarded as a deformable registration problem. In our approach we use hybrid image-based and electromagnetic tracking, and the bronchoscope pose relative to CT data is interpolated using Catmull-Rom splines for position and SLERP for orientation. We evaluate the method using ground truth poses manually selected by experts, where mean inter-expert agreement was determined as 1.26 mm. For four dynamic phantom data sets, the accuracy of our method is between 4.13 and 5.93 mm and shown to be equivalent to previous methods. We significantly improve inter-frame smoothness from 2.35-3.08 mm to 1.08-1.51 mm. Our method provides a more realistic and physically plausible solution with significantly less jitter. This quantitative result is confirmed by video output, which is much more consistent and robust, with fewer occasions of tracking loss or unexpected movement.

Background and Objective: The diagnostic yield from fluoroscopy-guided bronchoscopic transbronchial biopsy of small solitary pulmonary nodules is low. The hypothesis tested in the present study was that the diagnostic yield can be significantly increased by combining flexible bronchoscopy with CT-guidance using a dedicated low-dose protocol., Methods: CT-guided transbronchial biopsies were performed in 15 patients with a newly diagnosed solitary peripheral pulmonary nodule and negative conventional bronchoscopic biopsies under fluoroscopic guidance. For imaging, a multi-detector helical CT unit, adjusted at 120 kV, 15 mAs/slice, 4 x 5 mm collimation, 10 mm reconstructed slice thickness and a maximal scan length of 150 mm, was used. After advancing the biopsy forceps towards the lesion, a CT scan was obtained. When the tip of the forceps reached or penetrated the lesion a biopsy was taken, otherwise the procedure was repeated with a maximum of eight attempts. The effective radiation dose was calculated., Results: The average diameter of the nodules was 23 +/- 6 mm (mean +/- SD) with a maximum distance to the parietal pleura of 18 mm (mean 6.5 mm). A mean of 4.1 (range 2-8) CT scans was performed to localize the lesion. In four patients, the forceps only reached the periphery of the nodule. In one patient, the nodule was missed in all attempts. Histology was malignant in eight patients and benign in four patients. In three patients, biopsy results were false negative (benign or non-specific instead of malignant). The overall diagnostic yield was 73%. Complications consisted of two pneumothoraces, one of which necessitated a chest tube. Mean effective radiation dose was 0.55 mSv (range 0.3-1.0)., Conclusions: CT-guided transbronchial biopsy can be a valuable diagnostic tool in evaluating solitary pulmonary nodules. This applies for selected patients when other diagnostic methods are either unavailable or inappropriate. The diagnostic yield is high and, when a low-dose protocol is used, radiation exposure can be kept at a minimum.

Background: In the diagnosis of early-stage lung cancer photosensitizer-enhanced fluorescence bronchoscopy with inhaled 5-aminolevolinic acid (5-ALA) increases sensitivity when compared to white-light bronchoscopy. This investigation was to evaluate the in vivo tissue pharmacokinetics of inhaled 5-ALA within the bronchial mucosa in order to define the time optimum for its application prior to bronchoscopy., Methods: Patients with known or suspected bronchial carcinoma were randomized to receive 200 mg 5-ALA via inhalation 1, 2, 3, 4 or 6 hours before flexible fluorescence bronchoscopy was performed. Macroscopically suspicious areas as well as areas with visually detected porphyrin fluorescence and normal control sites were measured spectroscopically. Biopsies for histopathology were obtained from suspicious areas as well as from adjacent normal areas., Results: Fluorescence bronchoscopy performed in 19 patients reveals a sensitivity for malignant and premalignant changes (moderate dysplasia) which is almost twice as high as that of white-light bronchoscopy, whereas specificity is reduced. This is due to false-positive inflammatory lesions which also frequently show increased porphyrin fluorescence. Malignant and premalignant alterations produced fluorescence values that are up to 5 times higher than those of normal tissue. According to the pharmacokinetics of porphyrin fluorescence measured by spectroscopy, the optimum time range for 5-ALA application is 80-270 min prior to fluorescence bronchoscopy, with an optimum at 160 min., Conclusion: According to our results we propose inhalation of 5-ALA 160 min prior to fluorescence bronchoscopy, suggesting that this time difference provides the best tumor/normal tissue fluorescence ratio.

Objective: Staging of bronchial carcinoma presents a diagnostic challenge. In addition to CT scans, endobronchial ultrasound is used. The aim of this study was to compare the diagnostic accuracy of high-resolution multidetector CT (MSCT) with that of endobronchial ultrasound with respect of detection and extension of the bronchial lesions., Methods: 24 patients with lesions in the central bronchial area were examined using both EBUS and MSCT. Multiplanar reconstructions (MPR) as well as virtual endoscopy (VE) were used as adjuncts in this investigation of the comparative diagnostic accuracy of MSCT and EBUS in the imaging of bronchial lesions., Results: No significant difference could be established between EBUS and MSCT in detecting and extension of bronchial lesions. With both procedures, the use of supplementary techniques may be advantageous and helpful in individual cases., Conclusions: When compared with EBUS, MSCT with post-processing has equally high sensitivity with regard to the visualization of malign endobronchial lesions.

Navigated bronchoscopy has been developed by various groups within the last decades. Systems based on CT data and electromagnetic tracking enable the visualization of the position and orientation of the bronchoscope, forceps, and biopsy tools within CT data. Therefore registration between the tracking space and the CT volume is required. Standard procedures are based on point-based registration methods that require selecting corresponding natural landmarks in both coordinate systems by the examiner. We developed a novel algorithm for a fully automatic registration procedure in navigated bronchoscopy based on the trajectory recorded during routine examination of the airways at the beginning of an intervention. The proposed system provides advantages in terms of an unchanged medical workflow and high accuracy. We compared the novel method with point-based and ICP-based registration. Experiments demonstrate that the novel method transforms up to 97% of tracking points inside the segmented airways, which was the best performance compared to the other methods.

Pulmonary involvement in ulcerative colitis may manifest as a variety of disorders. Ulcerative colitis-related interstitial lung disease is exceedingly rare and has been reported to be steroid-responsive. We describe the first case of a patient with acute exacerbation of ulcerative colitis-induced usual interstitial pneumonia, who did not respond to corticosteroid therapy and died 12 weeks after the onset of pulmonary symptoms. Early recognition of pulmonary disease in patients with ulcerative colitis is necessary to initiate further diagnostic work-up and may aid treatment decisions.

Early lung cancer screening failed to reduce lung cancer mortality. New techniques such as autofluorescence bronchoscopy (AF) and the identification of specific genetic alteration might change future outcomes of lung cancer screening. It was the aim of our study to combine p53 analysis with white-light bronchoscopy (WL) or WL and AF to improve the diagnostic yield in a series of 36 patients with histologically proven lung cancer, pulmonary metastasis or suspected lung cancer. - Endobronchial sites were analysed by WL (n = 71), AF (Storz) (n = 34), histopathology (n = 71) and p53 mutations were examined by SSCP analysis on additional biopsies (n = 69). The overall frequency of cancerous lesions was 19, of which 14 were macroscopically visible lesions. The addition of p53 and autofluorescence improved the yield to 17 of 19 cases. In 7 preinvasive lesions (dysplasia/metaplasia) 4 were identified macroscopically and 5 of 7 lesions by all 3 methods. In the WL/p53 group the diagnostic yield was 7 of 9 cancerous lesions compared to 10 of 10 cancerous lesions in the AF group. It should be noted that all methods were associated with false positive results. However, the combination of conventional with autofluorescence bronchoscopy and mutation analysis is a promising approach which is applicable to clinical routine and may be further enhanced by the inclusion of a panel of markers of tumour progression.

Background: Electromagnetic navigation in bronchoscopy is a novel method for assisting in the localization of peripheral lung lesions., Study Objective: To assess the usability, accuracy, and safety of electromagnetic navigation during flexible bronchoscopy in a clinical setting., Design: Prospective evaluation., Patients: Consecutive patients referred to the bronchoscopy unit for the diagnosis of peripheral infiltrates or solitary pulmonary nodules (SPNs)., Methods: Navigation was performed using an electromagnetic tracking system with a position sensor encapsulated in the tip of a flexible catheter that was pushed through the working channel of the bronchoscope. Real-time, multiplanar reconstruction of a previously acquired CT data set provided three-dimensional views for localization of the catheter. To match the position of the sensor with the CT scan, four anatomic landmarks were used for registration. The sensor position generated in the navigation system was controlled by fluoroscopy, and the corresponding error distances were measured. This was performed with all SPNs and at two different peripheral locations of the right upper lobe (RUL)., Results: Sixteen patients (10 men and 6 women; mean age, 63.7 years) were studied. Navigation prolonged bronchoscopy by 3.9 +/- 1.3 min (mean +/- SD). The navigation system identified all lesions. The position sensor achieved a direct hit in three of five SPNs. Fluoroscopy failed to recognize three SPNs (60%) and three infiltrates (38%). The mean error distances between sensor tip position and fluoroscopically verified RUL reference position were 10.4 mm (lateral position) and 12.5 mm (apical position) respectively. The mean error distances between the sensor tip and two endobronchial registration points at the end of the procedure were 4.2 mm and 5.1 mm, respectively., Conclusion: Electromagnetic navigation is useful, accurate, and safe in the localization of peripheral lung lesions and may help to improve the yield of diagnostic bronchoscopic procedures.

Over the last few years various types of metal wire stents have been increasingly employed in the treatment of both malignant and benign tracheobronchial obstruction. To date, however, few studies have investigated the in vivo properties of different stent types. We implanted 26 balloon-expandable tantalum Strecker stents (18 patients) and 18 self-expandable Wallstents (16 patients) into the tracheobronchial system of 30 patients with combined stenting in 4 patients. Mean age was 51 years (range: 0.5-79 years). Malignant disease was present in 23 patients, benign disease in seven patients. Both patients and individual stents were monitored clinically and radiographically. The probability of stents remaining within the tracheobronchial system, and of their remaining undislocated and uncompressed was calculated using Kaplan-Meier analysis for both stent types. Average stent follow-up time was 112 days until explantation and 115 days until patients' death or discharge. Kaplan-Meier analysis revealed a higher probability for the Wallstent to remain within the tracheobronchial system. Dislocation and compression occurred more rarely. Explantation, however, if desired, was more difficult compared to the Strecker stent. The Wallstent also led to the formation of granulation tissue, especially at the proximal stent end, frequently requiring reintervention. Both stent types proved to be effective therapeutic options in the management of obstructive tracheobronchial disease. The mechanical properties of the Strecker stent seem to be less favorable compared to the Wallstent but removal is easy. For benign disease, however, the Wallstent reveals limitations due to significant side effects.

Objective: To determine the response to treatment and the long-term outcome of patients with the antisynthetase syndrome associated with anti-Jo-1-antibodies., Patients and Methods: A total of 12 patients with histologically proven myositis and anti-Jo-1-autoantibodies were evaluated over a mean follow-up period of 66.4 months. In all patients neuromuscular function tests, electromyographic examinations, pulmonary function tests and high-resolution-computed tomography of the lungs were performed regularly., Results: Muscle function improved in all patients with treatment, and a complete clinical response was achieved in 5 patients. Pulmonary function worsened in 1 patient, who died from respiratory failure, but normalised in 4 patients. Arthropathy progressed despite improvement of myositis and pulmonary status in 2 patients. Discontinuation of treatment was facilitated in 1 patient, although long-term therapy was required in 10 patients. In 2 patients with refractory disease, treatment with intravenous immunoglobulins was successful. Severe side effects of treatment occurred in 7 patients and overall mortality rate was one of 12 (8 %)., Conclusion: The antisynthetase syndrome associated with anti-Jo-1-antibodies requires long-term immunosuppressive therapy in most patients. Whereas a complete clinical response of muscular symptoms is frequent, continued deterioration of the pulmonary system may occur despite immunosuppressive treatment, and may lead to fatal outcome. An interdisciplinary therapeutic approach is necessary for best possible results in these patients.

5-ALA-induced protoporphyrin IX (PPIX) fluorescence kinetics was quantified by fluorescence microscopy in three-dimensional organ co-cultures of human bronchial epithelium, which were infiltrated by four different lung tumour cell lines (EPLC-M31, LCLC-103H, NCI-H125 and NCI-H841). Corresponding fluorescence measurements were performed in monolayer cultures of these tumour cell lines and BEAS-2B cells as a model for normal bronchial epithelium by flow cytometry. Significant differences of fluorescence intensities (FI) between the tumours were detected in organ co-cultures as well as in single cell measurements. Relative FI values in organ co-cultures (FI(EPLC-32M1)>FI(LCLC-H103)>FI(NCI-H125)>FI(NCI-H841)) did not correspond to the measurements in single cells (FI(LCLC-H103)>FI(NCI-H125)>FI(NCI-H841)>FI(EPLC-32M1)). Histology of organ co-cultures revealed different patterns of invasion and tumour cell densities depending on the tumour type. After correction of FI in the co-cultures to tumour cell density the correlation coefficient for fluorescence values between both models increased considerably. Thus, additionally to distinctive features of 5-ALA metabolism, patterns of tumour invasion may be a factor determining 5-ALA-induced fluorescence. Considering these results, a pronounced heterogeneity of 5-ALA-induced fluorescence might be expected in different bronchial tumours in vivo. This could interfere with the diagnostic reliability of 5-ALA-induced fluorescence for early tumour detection.

The aim of this study was to evaluate [18F]fluorodeoxyglucose ( F-FDG) imaging of recurrent or inoperable lung cancer using a hybrid positron emission tomography (PET) device of the third generation. Examinations were compared with the results of conventional staging. Thirty-six patients suffering from recurrent or primarily inoperable lung cancer (29 men, seven women; age 64.8+/-12.0 years) were examined using hybrid PET (Marconi Axis gamma-PET ) 60 min after injection of 370 MBq F-FDG. The data obtained were reconstructed iteratively. All patients received a computed tomography (CT) scan using either the spiral or multislice technique. All lesions suspicious for primary or recurrent tumour were verified by biopsy; mediastinal lymph nodes were considered as malignant, when positive histology or a small axis diameter of greater than 1 cm measured with CT in addition to progression of clinical course was found. Distant metastases were diagnosed by CT and bone scintigraphy. Using hybrid PET all lesions showed a focally elevated glucose metabolism. Lymph node involvement of the ipsilateral peribronchial and hilar station (N1) was identified in 24/26 cases (92%), in 26/29 cases (90%) of ipsilateral central manifestation (N2) and in 11/13 (85%) cases of central contralateral or supraclavicular lymphatic infestation (N3). Pulmonary spread in hybrid PET was found in 4/8 cases (50%), whereas mainly lung metastases with a diameter of 1.5 cm and smaller were missed. Pleural involvement diagnosed by CT was verified in 4/5 patients. All four patients with bony metastases in conventional staging also presented with positive findings in hybrid PET (8/9 lesions). Concordance with conventional staging was found in 28/36 of patients (78%). In 4/36 patients (11%) unknown sites of tumour were detected leading to therapeutic consequences in three patients after radiological confirmation. Hybrid PET would have led to an understaging in four cases (11%), resulting theoretically in inefficient treatment in two patients. Hybrid PET for F-FDG imaging in the staging of recurrent or primarily inoperable lung cancer supplied equal (78%) or more information (11%) compared to conventional staging procedures. Using the information of hybrid PET alone, 11% of the patients would have been understaged. We conclude that hybrid PET has the potential for use as an additional staging tool in this subgroup of patients, providing supplementary information compared to conventional staging modalities.

We assessed safety and efficacy of creatine monohydrate (Cr) in myotonic dystrophy (DM1) in a double-blind, cross-over trial. Thirty-four patients with defined DM1 were randomized to receive Cr and placebo for eight weeks (10.6 g day 1-10, 5.3 g day 11-56) in one of 2 treatment sequences. There was no significant improvement using manual and quantitative muscle strength, daily-life activities, and patients' own global assessment comparing verum with placebo administration. Cr supplementation was well tolerated without clinically relevant side effects, but did not result in significant improvement of muscle strength or daily-life activities.

Study Objectives: Assessment of the therapeutic potential of tracheobronchial stenting for obstructive tracheobronchial disease, in-vivo comparison of different stent types and development of helpful criteria for choosing the suitable stent type., Material and Methods: Prospective case analysis. Between 1993 and 1999 53 stents were implanted into the tracheobronchial system of 39 consecutive patients with benign or malignant airway obstruction. Every single stent (26 Strecker Stents, 18 Wallstents, 6 Accuflex Nitinolstents, 1 Dumon-, 1 Rüsch- and 1 Palmazstent) was recorded in an unified database. Analysis comprised clinical effectiveness, lung function if possible, relevant complications and radiologic follow-up parameters. The probability of their remaining within the tracheobronchial system, of their remaining undislocated and uncompressed was calculated using Kaplan-Meier analysis for three stent types., Results: Stent placement proved itself to be an effective treatment in 86 % of the patients. Resistance could be normalized in 9/9 patients. Kaplan-Meier analysis clearly revealed a higher probability for the Wall- and Nitinolstent to remain within the tracheobronchial system and to remain uncompressed. Dislocation also occurred more rarely. Explantation of the Wallstent, however, if desired, was much more difficult compared to the Strecker stent. The Wallstent also occasionally led to the formation of granulation tissue especially at the proximal stent end and, as such, required reintervention., Conclusion: Any of the 3 stent types proved to be an effective therapeutic option in the management of obstructive tracheobronchial disease. Choise of the stent type should be determined through definition of the therapeutic intention. It is useful to distinguish between (a) benign stenosis, (b) malignant stenosis but curative therapeutic situation and (c) malignant stenosis in a palliative therapeutic situation with limited life expectancy. In spite of its superior mechanical properties the Wallstent is rather suited for a palliative situation because explantation may be difficult. The Strecker Stent requires more reinterventions but removal is easy to perform. The Nitinolstent possibly represents a reasonable compromise.

History: A 29-year-old man had finger clubbing since the age of 15 years, and for the last 10 years his hands and feet had grown disproportionately. In addition he suffered from marked whole-body sweating, especially of the hands and feet, as well as persistent pain in the limbs and joints., Investigations: Biochemical and endocrinological tests were normal. Radiology of the hands and lower legs revealed marked periosteal thickening, while the substantia trabeculosa was unremarkable. Secondary causes having been excluded primary hypertrophic osteoarthropathy was diagnosed., Treatment and Course: While there is no causal treatment, physio- and balneotherapy improved the symptoms., Conclusion: Early and accurate diagnosis of primary hypertrophic osteoarthropathy is essential, if only because of its favourable long-term prognosis.

Background: 5-Aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX) fluorescence improves the differentiation of tumor and normal tissue in the bladder, skin and brain., Objective: The kinetics of 5-ALA-induced protoporphyrin IX (PPIX) fluorescence in organ cultures of normal human bronchial epithelium and cocultures of bronchial epithelium and tumor have been studied., Methods: Cultured biopsies of bronchial epithelium were exposed for 5 or 15 min, or continuously to 5-ALA. PPIX fluorescence was quantified for up to 300 min by spectroscopy. Cocultures of normal bronchial epithelium and a non-small-cell lung cancer cell line (EPLC-32M1) were incubated with 5-ALA. Space-resolved fluorescence microscopy was used to quantify PPIX fluorescence kinetics in the tumor and normal epithelium., Results: In cultures of normal epithelium, PPIX fluorescence kinetics were shown to depend on the duration of exposure to 5-ALA. There was a trend to higher fluorescence intensities with longer exposure times. In cocultures of bronchial epithelium and tumor, increases of fluorescence intensity were significantly greater in the tumor. Best tumor/normal tissue fluorescence ratios were found between 110 and 160 min after exposure to 5-ALA., Conclusion: Data obtained in this coculture system of bronchial epithelium and tumor is valuable to optimize modalities of fluorescence bronchoscopy for the diagnosis of early bronchial carcinoma., (Copyright 2002 S. Karger AG, Basel)

Study Objectives: Bronchoscopic balloon dilatation (BBD) has become a valuable tool in the treatment of benign tracheobronchial stenoses. The objective of this study was to assess indications for and results of fiberoptic BBD in treating malignant lesions., Design: One hundred twenty-six balloon dilatation procedures were performed in 78 patients with predominantly bronchial carcinoma. BBD was only performed when alternative modes of local treatment (eg, laser therapy or stent implantation) were not indicated or were inappropriate. Indications were symptomatic stenoses of the tracheobronchial tree: dyspnea or stridor (52%), retention pneumonia (15%), atelectasis (10%), retention of secretions (21%), or lung abscess (2%)., Results: Fifty-five percent of all procedures consisted of dilatations of tracheal or bronchial lesions (group 1). In 22% of procedures, a stent was dilated (group 2). In 13%, BBD was used to facilitate stent placement (group 3), and in 10% to enable the correct positioning of irradiation probes for brachytherapy (group 4). In group 1 and group 2, 2 of 2 lung abscesses resolved, 5 of 8 atelectases resolved, and 11 of 12 retention pneumonias resolved. Dyspnea improved in only 12 of 32 patients. No abscess recurred. Two pneumonias and two atelectases reappeared due to restenosis. Stent implantation and brachytherapy procedures were facilitated in 90% of cases. In 52% of cases, BBD was supported by high-frequency jet ventilation. Complications consisted of one fatal hemoptysis caused by a lacerated pulmonary artery, and minor bleeding not necessitating specific therapy., Conclusions: Fiberoptic BBD is useful in the management of airway stents prior to and postimplantation, as well as in the placement of brachytherapy catheters. BBD is also successful in the resolution of poststenotic lung abscesses, retention pneumonias, and atelectases.

Long segment malacia of the trachea or main stem bronchi in children is not always suitable for surgical correction; patients may therefore remain ventilator-dependent and/or experience severe obstructive crises. We treated 7 children (ages, 4 months to 9 years) with extreme structural central airway obstruction with stent implantations. Six were mechanically ventilated; 5 had frequent life-threatening obstructive spells requiring deep sedation or paralysis. Diagnoses were: syndrome-associated tracheobronchomalacia (n = 4), malignancy infiltrating the carina (n = 1), congenital tracheal stenosis (n = 1), and tracheobronchial compression by a malpositioned aorta (n = 1). Six tracheal and 13 bronchial stents were endoscopically placed. The prostheses included mesh titan (n = 5), the newer shape memory material nitinol (n = 13), and 1 Y-shaped carina stent. Follow-up was reported for 7 weeks to 72 months. All patients showed marked improvement of their respiratory obstruction. Six children were weaned at least temporarily from ventilation. No significant bleeding, stenosis, or perforation was observed. Seven stents were changed after up to 14 months. Three children are well and at home. In 2 children airway stabilization was successful, but they later died from causes unrelated to stent placement, and 2 children died due to generalized airway disease. Soft metal mesh airway stents can offer a therapeutic option in life-threatening inoperable obstruction of the trachea and main stem bronchi in children., (Copyright 2001 Wiley-Liss, Inc.)

The overall prognosis of relapsing Ewing sarcoma is poor and therapeutic options can be limited by extensive chemotherapeutic pretreatment. We report on a case of a 27-year-old male, presenting with a large mediastinal mass and malignant pleural effusions. 5 years prior peripheral Ewing sarcoma had been treated according to the CESS 86 protocol. Relapse chemotherapy was initiated (CESS protocol) but tumor progression led to stenoses of both main bronchi. At this critical point, 2 Strecker tantal stents were placed endoscopically to prevent suffocation and provide the time for further chemotherapy, regardless of the poor overall prognosis. Complete remission was achieved by high-dose ifosfamide, surgery, radiotherapy and adjuvant ifosfamide. In spite of possible complications of long-term stent implantation, the stents were not removed until 4 years later when stent dislocation occurred. After removal, the stents were epithelialized and electron microscopy demonstrated structural integrity of the stent. The patient has remained in complete remission since (6 years).

Background and Objective: Nd-YAG non-contact laser therapy is used to eliminate recurrent tumor tissue within airway stents. This study was performed to determine maximum exposure time until the stent wire is destroyed as well as exposure time necessary to deliberately fracture the wire mesh., Study Design/materials and Methods: Strecker stents, Wallstents, and Nitinol Accuflex stents were implanted into pig bronchi. Then Nd-YAG laser light was directed to the stent wires at different power levels. Portions of the stent surrounded by bronchial tissue as well as bare wires were investigated., Results: The Strecker stent and the Wallstent revealed a considerably higher laser resistance than did the Nitinol Accuflex stent. At 15 W, minimum exposure time until wire destruction was 4.6 and 6.3 s for the Strecker stent and the Wallstent respectively. In contrast, the Nitinol Accuflex stent tolerated only 1.7 s., Conclusions: Laser therapy with bronchial wire stents can be carried out at low power levels. It should, however, be avoided in the case of Nitinol Accuflex stents due to their low heat tolerance., (Copyright 2001 Wiley-Liss, Inc.)

Molecular screening may increase the likelihood to identify early malignant lesions in non-small cell lung cancer. However the presence of gene mutations in non-malignant bronchial tissue has remained controversial. The present study was carried out to investigate systematically the presence of mutations of the K-ras and p53 gene in bronchial biopsies taken during routine bronchoscopy of normal as well as tumour tissues from a series of 40 patients with histologically verified non-small cell lung cancer (NSCLC). K-ras mutations were analysed with specific detection oligonucleotides, p53 mutations were examined by SSCP analysis. In all biopsies the wildtype of both K-ras and p53 could be detected. The overall frequency of mutations was 14 (35%) with 2 K-ras mutations (5%) and 12 mutations of the p53 gene (30%). In 3 cases (1 ras mutation, 2 p53 mutations) the same mutation could be shown in the tumour biopsy and in the distant normal control. In another case only the normal appearing tissue had a mutation of the p53 gene. All other mutations could be detected in the tumour tissue only. Our data confirm that K-ras mutations and p53 can be detected not only in malignant but also in non-malignant bioptic samples from patients with NSCLC. The use of molecular screening for the early detection of lung cancer may be a promising new approach.

Background: Maximal inspiratory mouth pressures are suitable for non-invasive evaluation of respiratory muscle function. Different studies on PIMAX give predicted normal values and their relation to anthropometric data. Due to a large inter-subject variation of PIMAX, predicted values, however, maximal inspiratory mouth pressures are not suitable to define the individual expected normal PIMAX. What is the lower limit of the normal range?, Methods: PIMAX has been prospectively measured in a representative sample of 504 healthy volunteers (248 males and 256 females) between 18 and 82 years of age with normal lung function. Age, height, weight, body mass index (BMI) and smoking status were recorded and incorporated stepwise in a multiple regression analysis to determine prediction equations. Lower limits of the normal range were defined as the fifth percentile of the residuals derived from the regression model., Results: Mean values of PIMAX were 9.95 kPa for men and 7.43 kPa for women. Significant correlations were found with height, weight, BMI, FEV1, PEF and FVC (P<0.01). The strongest correlation appeared with sex and age (P<0.001). Smoking status and smoked pack-years were not independent predictors of inspiratory pressures. Lower limits of normal were 59% for women and 60% for men of the predicted PIMAX., Conclusions: In the interpretation of maximal inspiratory mouth pressures, normal values should represent the lower limit of the normal range derived from the regression model in order to avoid false pathological results. Prediction equations as well as lower limits of normal resulting from a study cohort of healthy 18-82-year-olds are given and are recommended to be used by pulmonary function laboratories in young and old patients.

Unlabelled: High frequency jet ventilation (HFJV) is a well accepted method for securing ventilation in rigid and interventional bronchoscopy. We describe a technique of HFJV using a 14F nylon insufflation catheter placed in the trachea to support stent implantation or endobronchial balloon dilation in endobronchial stenoses with the flexible fiberscope. One hundred sixty-one cases were treated with either a metal wire stent (n = 105) or with balloon dilation (n = 56). In addition to HFJV, IV anesthesia was applied in 132 cases. Driving pressure was 1125-1275 mm Hg, frequency 80-100/min, and inspiratory:expiratory ratio of 1:2. Fraction of inspired oxygen ranged from 0.3-1.0. The effects on alveolar ventilation were assessed by using blood-gas analysis and continuous monitoring of transcutaneous oxygen and carbon dioxide tension (P(tc)CO(2)). Complications consisted of hypertension (n = 8), hypotension (n = 6), bronchospasm (n = 5), and hypoxia (n = 6). In 52% of the cases, mild hypercarbia (P(tc)CO2 50-60mm Hg) was observed. In two cases, a P(tc)CO(2) > 80 mm Hg resolved spontaneously when the patients returned to normal breathing after intermittent superimposed ventilation with a face mask. During placement of stents in the proximal trachea, the jet catheter had to be withdrawn, resulting in displacement of the catheter into the pharynx in one case, which was managed safely with the bronchoscope. In conclusion, HFJV achieves satisfactory operating conditions and provides adequate gas exchange for interventional bronchoscopic procedures with the fiberscope., Implications: Safe ventilation is desired when performing tracheobronchial stent implantation and balloon dilation with the fiberscope. High frequency jet ventilation, applied with a 14F insufflation catheter through the nasotracheal route, offers safe ventilatory support with minimal complications. This was evaluated in 161 procedures treating benign and malignant airway stenoses.

Hypoxic pulmonary vasoconstriction is associated with but may not be sufficient for the development of high-altitude pulmonary oedema (HAPO). Hypoxia is known to induce an inflammatory response in immune cells and endothelial cells. It has been speculated that hypoxia-induced inflammatory cytokines at high altitude may contribute to the development of HAPO by causing capillary leakage in the lung. We were interested if such an inflammatory response, possibly involved in a later development of HAPO, is detectable at high altitude in individuals without HAPO. We examined the plasma levels of interleukin 6 (IL-6), interleukin 1 receptor antagonist (IL-1ra) and C-reactive protein (CRP) in two independent studies: study A, Jungfraujoch, Switzerland, three overnight stays at 3458 m, n=12; study B: Capanna Regina Margherita, Italy, 3 overnight stays at 3647 m and one overnight stay at 4559 m, n=10. In both studies, probands showed symptoms of acute mountain sickness but no signs of HAPO. At the Jungfraujoch, IL-6 increased from 0.1+/-0.03 pg/ml to 2. 0+/-0.5 pg/ml (day 2, P=0.03), IL-1ra from 101+/-21 to 284+/-73 pg/ml (day 2, P=0.01), and CRP from 1.0+/-0.4 to 5.8+/-1.5 micrograms/ml (day 4, P=0.01). At the Capanna Margherita, IL-6 increased from 0. 5+/-0.2 pg/ml to 2.0+/-0.8 pg/ml (P=0.02), IL-1ra from 118+/-25 to 213+/-28 pg/ml (P=0.02), and CRP from 0.4+/-0.03 to 3.5+/-1.1 micrograms/ml (P=0.03). IL-8 was below the detection limit of the ELISA (<25 pg/ml) in both studies. The increase of IL-6 and IL-1ra in response to high altitude was delayed and preceded the increase of CRP. We conclude that: (1) circulating IL-6, IL-1ra and CRP are upregulated in response to hypobaric hypoxic conditions at high altitude, and (2) the moderate systemic increase of these inflammatory markers may reflect considerable local inflammation. The existence and the kinetics of high altitude-induced cytokines found in this study support the hypothesis that inflammation is involved in the development of HAPO., (Copyright 2000 Academic Press.)

Background: Endoscopic bronchoplastic procedures, such as metal stent implantation, are for safety reasons and mainly performed using rigid bronchoscopy. Major complications, such as bleeding and accidental airway occlusion, are thought to be better managed with the rigid device. An increasing number of pneumologists, however, use the flexible fiberscope for endobronchial stenting., Methods: Sixty-five stent implantations were performed in 51 patients with flexible fiberoptic bronchoscopy. We implanted 27 Tantalum Strecker stents (Boston Scientific Co, Watertown, MA), 20 Nitinol Accuflex stents (Boston Scientific Co) and 18 Wallstents (Schneider, Zurich, Switzerland). Underlying conditions were malignant disease in 84% and benign bronchial collapse in 16%. Sites of implantation were the trachea (45%), the main bronchi (35%), and other locations (20%). In 47 cases the patients received intravenous sedation combined with high frequency jet ventilation, and in 18 cases the patients were treated with topical anesthesia alone., Results: Mean examination time was 58.3 (standard deviation 29.1) minutes. Eighty percent of patients experienced immediate clinical improvement in respiratory symptoms. Spirometric parameters (forced expiratory volume in one second, peak expiratory flow rate, forced vital capacity) increased. Complications included hypertension (17%), hypotension (12%), hypoxia (5%), bronchospasm (4%), initial displacement of the prosthesis (11%), and diameter mismatch between stent and bronchus (5%). All complications were managed safely. Relevant bleeding or asphyxia during the procedure has not been observed. Late stent migration was observed in 12% of cases. There were 3 fatalities within 30 days of stent placement which, however, were not attributed to the implantation technique., Conclusions: Flexible fiberoptic bronchoscopy is a safe and suitable method to perform endobronchial metal stent implantation. Complications were rare and not serious. Initial misplacement of the prosthesis occurred in some cases and necessitated removal and replacement within the same procedure.

A randomized two-part study was conducted in order to determine the efficacy of theophylline in the treatment of acute mountain sickness during fast ascent to altitudes >2,500 m. Fourteen healthy male subjects participated in a randomized single-blind placebo-controlled crossover study carried out in a decompression chamber (simulated altitude 4,500 m). A second randomized single-blind, placebo-controlled study was conducted at a high-altitude research laboratory (3,454 m) and included 21 healthy male subjects. The study medication was either 375 mg oral slow-release theophylline (250 mg if <70 kg) or a matched placebo tablet taken twice daily. The acute mountain sickness score (AMSS) was assessed three times a day, beginning 18 h prior to altitude exposure and continuing for 18 h after altitude exposure. In addition, measurements of respiratory frequency, pulse rate, oxygen saturation and arterial blood gas levels were performed. Acute mountain sickness was significantly reduced by theophylline during the decompression chamber study (mean+/-SD 1.2+/-0.9) with placebo versus 3.6+/-0.8 with theophylline; p=0.03). During the high-altitude study, subjects with theophylline showed a significantly lower AMSS on arrival and after 18 h at altitude (0.6 versus 2.3, p=0.03). Oxygenation was improved in both parts of the study. In conclusion, oral slow-release theophylline improves acute mountain sickness.

Purpose: To evaluate the long-term mechanical behavior in vivo of expandable endobronchial wire stents, we imaged three different prostheses in the treatment of tracheobronchial disease., Methods: Six patients with bronchial stenoses (three benign, three malignant) underwent insertion of metallic stents. Two self-expandable Wallstents, two balloon-expandable tantalum Strecker stents and two self-expandable nitinol Accuflex stents were used. Measurements of deformation properties were performed during voluntary cough by means of fluoroscopy, at 1 month and 7-10 months after implantation. The procedures were videotaped, their images digitized and the narrowing of stent diameters calculated at intervals of 20 msec., Results: After stent implantation all patients improved with respect to ventilatory function. Radial stent narrowing during cough reached 53% (Wallstent), 59% (tantalum Strecker stent), and 52% (nitinol Accuflex stent) of the relaxed post-implantation diameter. Stent compression was more marked in benign compared with malignant stenoses. In the long term permanent deformation occurred with the tantalum Strecker stents; the other stents were unchanged., Conclusion: Endobronchial wire stents can be helpful in the treatment of major airway collapse and obstructing bronchial lesions. However, evidence of material fatigue as a possible effect of exposure to recurrent mechanical stress on the flexible mesh tube may limit their long-term use. This seems to be predominantly important in benign bronchial collapse.