Cross-Sectional Survey on Bronchoscopy in Germany--The Current Status of Clinical Practice.

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.

[Recommendations for sedation during flexible bronchoscopy]. / Empfehlung zur Sedierung in der flexiblen Bronchoskopie.

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.

[Recommendations for training courses in bronchoscopy]. / Empfehlungen zu Trainingskursen in der Bronchoskopie.

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.

Visualization of bronchial lesions using multidetector CT and endobronchial ultrasound (EBUS).

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.

Case report: Fatal acute exacerbation of usual interstitial pneumonia in ulcerative colitis.

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.

Detection of cancerous endobronchial lesions by autofluorescence bronchoscopy combined with mutation analysis of p53.

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.

Does additional brachytherapy improve the effect of external irradiation? A prospective, randomized study in central lung tumors.

PURPOSE: Endobronchial brachytherapy has become more widely used to increase the total local dose of irradiation ("boost") applied for the treatment of lung cancer. Apart from treatment for local stenosis, endobronchial brachytherapy in combination with external irradiation (EI) has the potential to improve local tumor control and perhaps prolong survival, but the real benefit has not been proven yet. To evaluate the possible effects of external irradiation with an additional boost of high dose rate (HDR) brachytherapy, we conducted a prospective randomized study. METHODS AND MATERIALS: Design-two groups were compared: Group 1 was treated with external radiotherapy alone (planned dose 60 Gy); Group 2 received an additional boost of HDR brachytherapy of scheduled 4.8 Gy each (at 10 mm from the source axis) before and after external irradiation. Patients-98 patients with advanced inoperable lung cancer were included in the study, 42 in Group 1 and 56 in Group 2. Both groups were comparable with respect to age, sex, tumor stage, Karnofsky performance status (KPS), and histology. RESULTS: A mean total external irradiation dose of 50.5 +/- 14.1 Gy in Group 1 and 50 +/- 12.5 Gy in Group 2 was applied. Group 2 received an additional dose of 7.44 +/- 2.6 Gy (at 10 mm depth) through brachytherapy. The median survival time in both groups was comparable (28 weeks and 27 weeks, respectively). In patients with squamous cell carcinoma (68 patients) Group 2 showed an advantage in median survival with borderline significance (40 vs. 33 weeks, p = 0.09). Group 2 showed also a better local tumor control in all patients; patients with squamous cell carcinoma had a significantly longer period of local tumor control. Fatal hemoptysis was the cause of death in 6 (14.2%) patients in Group 1 and 11 (18.9%) in Group 2 (p = 0.53). CONCLUSIONS: High dose rate brachytherapy in patients with inoperable lung cancer increased local control in our randomized study when used in combination with external irradiation. Survival time was also longer, but with no clear statistical significance. This applied especially to patients with squamous cell carcinomas. There was no statistically significant difference in the incidence of fatal hemoptysis between the two groups.

Fiberoptic bronchoscopic balloon dilatation in malignant tracheobronchial disease: indications and results.

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.

Palliative endobronchial brachytherapy for central lung tumors. A prospective, randomized comparison of two fractionation schedules.

AIM OF THE STUDY: Remote high dose rate brachytherapy is an effective local treatment modality for central lung tumors and has the potential to improve survival time. Optimal dose and fractionation schemes have not been identified yet. We conducted a prospective randomized study to compare two treatment schedules in terms of survival time, local tumor control, and possible complications. DESIGN: Group 1 received 4 brachytherapies with a dose of 3.8 Gy (at a 10-mm depth) on a weekly basis, and group 2 received 2 treatments with 7.2 Gy (at a 10-mm depth) at a 3-week interval. At a depth of 5 mm, the calculated doses would be 8 and 15 Gy. This study is still ongoing. Here we report interim results. PATIENTS: Ninety-three patients with advanced cancer were included in the study; 44 were in group 1 and 49, in group 2. Both groups were comparable regarding age, sex, tumor stage, Karnofsky performance status, and histologic findings. INTERVENTIONS: A mean total irradiation dose of 13.4 +/- 5.2 Gy for group 1 and 13.7 +/- 4.4 for group 2 were applied (calculated at 10 mm from the source axis, equivalent to 27.9 Gy in group 1 and 28.5 Gy in group 2 at a 5-mm depth). RESULTS: The 1-year survival rate was 11.4% in group 1 and 20.4% in group 2. No significant difference in survival time was found, but mean survival was longer in group 2 (49 weeks) than in group 1 (26 weeks). Local control after 3 months was comparable in both groups. Fatal hemoptysis occurred at a similar rate in group 1 (22.2%) and in group 2 (21.1%). CONCLUSION: High-dose rate brachytherapy with 2 x 7.2 Gy with a 3-week interval is equivalent to a 4 x 3.8-Gy regimen on a weekly basis. The shorter treatment schedule is more convenient for patients, does not cause more side effects, and provides an equal local tumor control.

Flexible bronchoscopy: a safe method for metal stent implantation in bronchial disease.

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.

Metal airway stent implantation in children: follow-up of seven children.

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.

Maximal inspiratory mouth pressures (PIMAX) in healthy subjects--what is the lower limit of normal?

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.

5-Aminolevulinic acid-induced fluorescence in bronchial tumours: dependency on the patterns of tumour invasion.

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.

[Interdisciplinary interventional therapy for tracheobronchial stenosis with modern metal net stents]. / Interdisziplinäre interventionelle Therapie tracheobronchialer Stenosen mit modernen Metallmaschenstents.

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.

Staging of recurrent and advanced lung cancer with 18F-FDG PET in a coincidence technique (hybrid PET).

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.

Detection of K-ras and p53 mutations in bronchoscopically obtained malignant and non-malignant tissue from patients with non-small cell lung cancer.

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.