[The Role of Bronchoalveolar Lavage in the Diagnosis of Idiopathic Pulmonary Fibrosis: An Investigation of the Relevance of the Protein Content]. / Der Stellenwert der bronchoalveolären Lavage bei der Diagnostik der idiopathischen Lungenfibrose - eine Analyse unter Berücksichtigung des Proteingehaltes.

Although bronchoalveolar lavage (BAL) is often used in the diagnosis of interstitial lung diseases (ILDs), its importance in investigating, in particular, idiopathic pulmonary fibrosis (IPF) is controversial. The cell distributions in the BAL are taken into account in the clinical routine, non-cellular characteristics of the BAL play no role.Using mathematical modeling of data, the present work investigated the extent to which BAL features enable drawing conclusions about the underlying ILK or help exclude IPF. Included in the calculation are cellular findings of the BAL, in addition the protein and albumin content of the BAL, the nicotine history (pack years), and spirometry (FEV1, IVC).Using linear discriminant analysis and creating classification trees, the relevance of the characteristics of 806 patients with ILK was examined (183 IPF, 191 cryptogenic organizing pneumonia, 147 lung involvement in autoimmune disease, 97 respiratory bronchiolitis interstitial lung disease, 118 extrinsic allergic alveolitis, 41 lymphocytic interstitial pneumonia (LIP), 23 non-specific interstitial pneumonia (NSIP), 88 controls).There was a close positive relationship between protein levels and lymphocytes in the group as a whole. No such correlations were seen in IPF and NSIP. Albumin was closely correlated with the protein content in all groups.The lymphocytes are best suited to distinguish between different ILDs. Yet, a reliable calculation of the ILD is not possible on the basis of the investigated factors, the classification error ranged from 23.5 % (IPF) to 100 % (LIP, NSIP).Constellations that likely (> 99 %) speak against an IPF are lymphocytosis > 34 % or protein content > 347 mg/l. The same applies to the constellation: lymphocytes > 25 % together with protein > 250 mg/l.In ILD, BAL findings can narrow the diagnosis, but they are seldom diagnostic. BAL can make an important contribution to excluding of IPF.

[Nitric oxide in exhaled breath of patients with interstitial lung diseases]. / Stickstoffmonoxyd in der Atemluft von Patienten mit interstitiellen Lungenkrankheiten.

BACKGROUND: Nitric oxide (NO) in exhaled breath is a marker of inflammation in bronchial asthma. Its role in interstitial lung disease has so far not been established. OBJECTIVES: The present study investigates exhaled NO in patients with interstitial lung diseases using constant flow and flow independent NO exchange parameters. These parameters were compared with clinical, lung function and BAL data. METHODS: 83 patients with the following diagnoses were included into the study: 33 patients with sarcoidosis, 14 patients with idiopathic pulmonary fibrosis, 12 patients with connective tissue disease affecting the lungs, 10 with extrinsic allergic alveolitis, 8 patients with cryptogenic organizing pneumonitis, 6 patients with respiratory bronchiolitis with interstitial lung disease and 17 control patients. NO was analysed using a chemiluminescence-analyser. NO-concentration in the exhaled breath was measured at a constant flow of 50 ml/s according the ATS/ERS-standard (FENO50) and additionally at three different flow rates of 30, 100 and 300 ml/s to analyse the following flow independent NO parameters: NO alveolar concentration (CANO), airway wall NO concentration (CAWNO), maximum airway wall NO flux (JAWNO) and airway NO diffusing capacity (DAWNO). BAL was performed during flexible bronchoscopy with an irrigation volume of 100 ml 0.9 % saline solution in 5 aliquots of 20 ml each. RESULTS: CANO (p = 0.012), CAWNO (p = 0.008) and DAWNO (p = 0.031) varied between the diagnostic groups. CANO was positively correlated with age (p < 0.05) and negatively correlated with inspiratory vital capacity (%pred.; p < 0.01). CAWNO was positively correlated with the relative proportion of CD8 cells in BAL (p < 0.01) and negatively correlated with smoking history (p < 0.05). DAWNO was negatively correlated with the relative proportion of CD8 cells in BAL (p < 0.05). FENO50 was positively correlated with age (p < 0.01) and negatively correlated with smoking history (p < 0.05). CONCLUSIONS: In patients with interstitial lung diseases there were correlations of flow independent NO exchange parameters with diagnoses, lung function parameters and BAL-variables.

Bronchoalveolar lavage in interstitial lung diseases: does the recovery rate affect the results?

BACKGROUND: Bronchoalveolar lavage (BAL) is an established diagnostic tool in interstitial lung diseases. BAL frequently yields findings of diagnostic value and at times even confirmatory diagnostic results. OBJECTIVES: The present study has been designed to investigate whether the recovery rate affects BAL results relative to the instilled volume. METHODS: Six hundred and eighteen patients with the following diagnoses were included into the study: 236 with sarcoidosis, 85 with idiopathic pulmonary fibrosis, 83 with cryptogenic organizing pneumonitis, 64 with connective tissue disease affecting the lungs, 54 with respiratory bronchiolitis with interstitial lung disease, 51 with extrinsic allergic alveolitis and 45 control patients. BAL was performed during flexible bronchoscopy with an irrigation volume of 100 ml 0.9% saline solution in 5 aliquots of 20 ml each. Only patients with a recovery of at least 30 ml were evaluated. Initially, the entire patient population was analysed, followed by an analysis within the different diagnostic groups and a comparison between patients with a high (>50 ml) and low (< or =50 ml) recovery rate. RESULTS: The recovery rate varied between the diagnostic groups (p < 0.001) and was negatively correlated with age (r = -0.21, p < 0.001) and smoking history (r = -0.11, p < 0.035). There were no correlations with inspiratory vital capacity (%pred.; p = 0.26) and forced expiratory volume in 1 s (%pred.; p = 0.15), but a positive correlation with the index (forced expiratory volume in 1 s/inspiratory vital capacity) x 100 (r = 0.23, p < 0.001). The cellular and non-cellular constituents of BAL were not affected by the recovery: cells/millilitre BAL (p = 0.71), relative proportion of macrophages (p = 0.92), lymphocytes (0 = 0.33), neutrophils (p = 0.14) and eosinophils (p = 0.11), albumin concentration (p = 0.13), and proportion of albumin in total protein (p = 0.06). The same applied for the lymphocyte surface markers CD4 (p = 0.72) and CD8 (p = 0.53). In the group with a high recovery rate, patients with sarcoidosis had a lower proportion of eosinophils (p = 0.04) and patients with cryptogenic organizing pneumonitis a higher concentration of albumin (p = 0.02) and lymphocytes (p = 0.007). Otherwise, no further differences were detected. CONCLUSIONS: The recovery rate hardly affected the cellular and non-cellular constituents of BAL at a lower limit of 30% of the instilled volume.

[Guidance of the pulmonary artery catheter by echocardiography]. / Echokardiographische Katheterführung beim Rechtsherzkatheter.

BACKGROUND: Pulmonary artery catheterisation plays an important role in the diagnosis of and therapy for pulmonary hypertension. Usually the pressure waveforms show the actual position of the catheter. In the case of inadequate waveforms X-ray fluoroscopy is recommended to avoid complications such as catheter malpositioning or knotting. Disadvantages of X-ray fluoroscopy are the costs of the X-ray devices and the radiation itself. METHODS: We demonstrate a special method of guiding the catheter by ultrasonic imaging that has not been published until now. This procedure combines the right heart catheterisation with the echocardiography performed through the subcostal axis. PATIENTS: 19 patients with pulmonary hypertension have been assessed/evaluated prospectively by this method. RESULTS: It was possible to trace the passage of the catheter from the upper right atrium through the right ventricle into the main stem of the pulmonary artery in all 19 patients. In 14 patients (74 %) it was even possible to show the exact position of the catheter in the right or left pulmonary artery. Malpositioning of the catheter such as knotting or intubation of the vena cava inferior were discovered very early and with ease. X-ray fluoroscopy was not necessary in any of the reported cases. CONCLUSIONS: Echocardiography is a non-invasive, easily available method for tracing the right heart catheter, that does not interfere with the catheterisation itself and matches it perfectly. Major advantages of this method in contrast to the standard X-ray fluoroscopy are the lack of radiation, the cost-effectiveness, the ubiquitous availability and the ease of use.

[Pulmonary sarcoidosis -- clinical and bronchoscopic findings in relation to the radiographic stage]. / Sarkoidose der Lunge -- klinische und bronchoskopische Befunde in Abhängigkeit vom radiologischen Stadium.

UNLABELLED: The classification of pulmonary involvement in sarcoidosis is based upon the radiographic stage of disease. We investigated 170 patients with new detected sarcoidosis (stage I / II / III: 79 / 39 / 52) for differences between the stages in demographic data, lung function values and results of BAL. With a multinomial logistic regression model to estimate probabilities, we found an increased probability for stage I with lower age (p < 0.001), higher IVC and FEV1 (p < 0.001), a less intensive smoking history (p<0.035), in BAL with a lower count of eosinophils (p < 0.014), mast cells (p < 0.004), CD8 lymphocytes (p < 0.015) and a less content of alkaline phosphatase (p < 0.004). For stage III the opposite results apply. With higher cell counts in BAL the probability of stage II increased, of stage III decreased (p < 0.013). The most relevant diagnostic BAL parameter in sarcoidosis, i.e. the count of lymphocytes and CD4 cells, was not different between the radiographic stages. CONCLUSION: Between patients with different radiographic stages of sarcoidosis there are differences in demographic data, lung function values and the pattern of alveolitis.

[The influence of smoking on clinical manifestation and composition of bronchoalveolar lavage in sarcoidosis]. / Der Einfluss des Inhalationsrauchens auf die Klinik und die bronchalveoläre Lavage bei Sarkoidose.

Sarcoidosis is defined as an inflammatory systemic disease; the characteristic morphological feature is the noncaseating granuloma. Typical finding in bronchoalveolar lavage (BAL) is a lymphocytic alveolitis with an increased CD4/CD8-quotient. A higher frequency of sarcoidosis in non-smokers (NS) than in smokers (S) has been reported. The influence of inhalative smoking on demographical data, lung function and results of BAL in prospectively selected patients with sarcoidosis was investigated. 111 NS (Sarcoidosis stage I/II+III 48/63) and 44 S (23/21) were included in the study. 16 patients without provable pulmonary disease (9 NS, 7 S) served as controls. Patients with sarcoidosis ware less often S than NS (28 vs. 72%, p = 0,0001) Controls 44 vs. 56%, p = 0.6 [chi(2)]). Sarcoidosis S were younger than NS (40.4 +/- 11.9 vs. 45.6 +/- 14.7 years, p = 0.009). There were no differences in the IVC (in % predicted). There was a negative effect of smoking on the course of the IVC (% predicted) with incremental age, not seen in the non smoking group (S vs. NS: r = -0.54, p = 0.001 vs. r = -0.13, p = 0.22). In BAL of Sarcoidosis S there was a lower concentration of albumin than of NS (in mg/dl), S vs. NS: 9.5 +/- 5.9 vs. 14.5 +/- 13.4, p = 0.012 and a trend to a less intensive lymphocytic alveolitis (in % of BAL-cells, S vs. NS: 29.2 +/- 21.1 vs. 34.1 +/- 18.6, p = 0.099). Influences of the smoking on the populations of T-lymphocytes could not be seen. (CD4/CD8-ratio S vs. NS 10.0 +/- 11.4 vs. 7. 2 +/- 7.1, p = 0, 25). In conclusion patients with sarcoidosis were more often NS than S. S were younger than NS. A protective effect of smoking on the course of lung function in sarcoidosis could be excluded. In the BAL S demonstrated a lower content of albumin and a trend to a less pronounced lymphocytosis and therefore a less pronounced alveolitis than NS. Influences of smoking on the distribution of the lymphocytic populations were not seen.

[Mast cells in bronchoalveolar lavage fluid of patients with interstitial lung diseases]. / Die Mastzelle in der bronchoalveolären Lavage bei interstitiellen Lungenerkrankungen.

Mast cells play an important role in tissue inflammation, fibrosis and remodelling. They are found in bronchoalveolar lavage fluid (BAL) of healthy persons only in small numbers. We investigated the number of mast cells in interstitial lung diseases and analysed our data for correlations with clinical parameters, cellular and non-cellular parameters of BAL. We found following counts of mast cells in % of total BAL cells: Sarcoidosis (n = 123); 0.22 +/- 0,04 %, idiopathic pulmonary fibrosis (IPF) (n = 35); 0.39 +/- 0.47 %, cryptogenic organising pneumonia (COP) (n = 27); 2.05 +/- 2.19 %, hypersensitivity pneumonitis (HP) (n = 24); 1.02 +/- 1.05 %, rheumatoid lung (n = 20); 0.21 +/- 0.21 %, respiratory bronchiolitis-associated interstitial lung disease (RBILD) (n = 11); 0.16 +/- 0.29 %) and control group (n = 16); 0.06 +/- 0.16 %. Compared to controls mast cells were increased in COP (p < 0.001) and HP (p < 0,01). Correlation analysis showed that an increased mast cell count correlated with: Higher age (sarcoidosis (p = 0.03); smaller vital capacity (sarcoidosis (p = 0.01)), smaller FEV 1 (sarcoidosis (p = 0.04), RBILD (p = 0.04)); higher alkaline phosphatase in BAL (sarcoidosis (p = 0.004), HP (p = 0.02), COP (p = 0.04); higher albumin level in BAL (sarcoidosis (p = 0.000), IPF (p = 0.003); higher cell counts in BAL (sarcoidosis (p = 0.013), COP (p = 0.04)); lower portion of macrophages in BAL cells (sarcoidosis (p = 0.001), HP (p = 0.02), COP (p = 0.02)); higher portion of lymphocytes in BAL cells (sarcoidosis (p = 0.03)); higher portion of neutrophils in BAL cells (sarcoidosis (p = 0.007)); higher portion of eosinophils in BAL cells (sarcoidosis (p = 0.001), HP (p = 0.006)). Correlations to smoking history in pack years and to lymphocyte surface markers CD3, CD4, CD8 were not found. In conclusion comparing different interstitial lung diseases we found significantly increased mast cell counts in COP and HP. Moreover there were correlations of increased mast cell counts with more intensive alveolitis and exudation.

[Airway challenge testing - accuracy of the interrupter technique]. / Die Bestimmung der bronchialen Sensitivität - ist die Widerstandsmessung mittels Unterbrechermethode ein zuverlässiges Verfahren?

According to national and international recommendations the bronchial sensitivity should be determined based on the decrease of the FEV1 by 20 % (FEV1 - 20) or the increase of the airway resistance by means of body plethysmography by 100 % (Raw + 100). Measurement of airway resistance by interrupter technique (Rint) is a simple method and needs no active cooperation of the patient, but is not recommended in airway challenge testing. We investigated the role of the increase of Rint by 100 % (Rint + 100) compared to Raw + 100 and FEV1 - 20 during carbachol airway challenge testing by means of dosimetry. We examined 123 patients with following symptoms: 85 x coughing, 31 x coughing and dyspnea, 7 x medical opinion. Significant correlations between Rint and Raw were found before and after the challenge tests (Rint before/after 0,3 +/- 0,13/0,36 +/- 0,25 kPa*s/l; Raw before/after 0,24 +/- 0,09/0,50 +/- 0,41 kPa*s/l; r = 0,504/0,672; p < 0,001 [Pearson]). The median values of Rint and Raw were significantly different (p < 0,001 [Wilcoxon]). Moreover Rint systematically overestimated airway resistance in the normal range and underestimated the increase of airway resistance during challenge testing (r = 0,783; p < 0,001 [Pearson]). In 58 patients an increased airway responsiveness was found. In 21 oft these patients there was no increase of Rint above the initial value. Sensitivity/specificity/positive predictive value/negative predictive value in % to the detection of airway hyperresponsiveness were in Rint + 100 9/95/63/54, in FEV1 - 20 61/100/100/66 and in Raw + 100 98/100/100/98. In conclusion we found significant correlations between Rint and Raw, but the median values were systematically and significantly different. Rint + 100 had a low sensitivity to detect airway hyperresponsiveness and is not comparable with FEV1 - 20 or Raw + 100.

[Successful treatment of benign tracheal stenosis with a silicone stent (Polyflex-Stent) over 5 years]. / Erfolgreiche Behandlung einer benignen Trachealstenose durch einen Silikonstent (Polyflex-Stent) über 5 Jahre.

Inoperable, functional relevant stenoses of the airways can be effectively treated short-termed and medium-termed by means of bronchoscopic stenting occasionally, silicone stents cause problems after long-term periods, such as migration and retention of bronchial secretions. Metallic stents can lead to obstructing granulomas or even bronchial wall perforation. As regards long-term treatment with airway stents over several years, there is little experience and no uniform recommendations are known. We report on a 76-year old female patient with a severe benign subglottic tracheostenosis after tracheostomy who was successfully treated by means of bronchoscopic dilatation and stenting with a silicone stent (POLYFLEX stent). POLYFLEX Stent is a self-expanding silicone stent with an encapsulated monofilament network made of polyester. The network is completely covered by a silicone layer with a smooth inner surface (protecting against incrustation) and a structured outer surface of the stent (protecting against migration). The ends of the monofilaments were provided with a special protection to avoid tissue granulation and to yield x-ray contrast. During a follow-up of almost 5 years the stent is well tolerated and there is no restenosis. Complications such as migration, obstructing secretions and obstructing granulomas did not occur. A slight bronchial hypersecretion presented no problem under regular inhalation therapy with isotonic NaCl solution. 21 and 56 months after stenting there were two episodes of minor haemoptysis. There was no demonstrable source of haemorrhage by bronchoscopy. After 56 months, biopsy at the distal opening of the stent showed a squamous cell metaplasia, but no granulation tissue. Microbiological analysis of bronchial secretions revealed an increasing, but clinically silent colonisation with potentially pathogenic microorganisms.

[Concentration of alkaline phosphatase (AP) and AP/albumin ratio in bronchoalveolar lavage (BAL) for the diagnosis of interstitial lung diseases]. / Wert der Bestimmung der alkalischen Phosphatase (AP) und des AP/Albumin-Quotienten in der bronchoalveolären Lavage (BAL) für die Diagnostik interstitieller Lungenkrankheiten.

As a result of several studies with different animal models there is evidence that the concentration of AP in BAL is produced in the pneumocyte II and that an increase of AP in the BAL is a marker of tissue damage. By measuring AP in the BAL of patients with interstitial lung diseases we investigated its potential role as a diagnostic tool. To detect plasma leakage we also measured the concentration of albumin in the BAL. We studied 85 patients with following diagnoses: Sarcoidosis in 34 patients (Stage 1/2/3 14/7/13), idiopathic pulmonary fibrosis (IPF) in 14, bronchiolitis obliterans with organizing pneumonia (BOOP) in 7, hypersensitivity pneumonitis (HP) in 6. The control group consisted in 24 patients (13 nonsmokers, 11 smokers). In IPF and BOOP we observed significantly higher concentrations of AP than in controls and sarcoidosis (42.4 +/- 36.6 and 35.6 +/- 16 vs. 15.8 +/- 12.7 and 15.0 +/- 9.8 U/l, p < 0.05, ANOVA). Compared with controls in sarcoidosis higher concentrations of albumin (5.7 +/- 4 vs. 13.2 +/- 10 mg/dl, p < 0.05, ANOVA) and a lower AP/albumin-ratio (3.6 +/- 3.0 vs. 1.3 +/- 0.9 U/10 mg, p < 0.05, ANOVA) were seen. This result is an argument against plasma leakage as the source of AP in BAL. There were no differences in AP and albumin between the different stages of sarcoidosis and between smokers and nonsmokers in the control group. We conclude, that there are different concentrations of AP and albumin in BAL in different interstitial lung diseases. Compared with controls we observed higher concentrations of AP and an AP/albumin-ratio in the normal range in IPF, a normal concentration of AP and a lowered AP/albumin-ratio in sarcoidosis.

[Bronchial cancer and asbestos: comparison of anamnestic exposure to asbestos, detection of asbestos bodies in bronchoalveolar lavage and in lung tissue]. / Bronchialkarzinom und Asbest: Vergleich zwischen anamnestischer Asbestexposition, Nachweis von Astbestkörperchen (AK) in der bronchoalveolären Lavage (BAL) und im Lungengewebe.

The histories of 19 surgical patients with carcinomas of the lungs were examined for exposure to asbestos, and the patients investigated with BAL and lung tissue analysis for the presence of AB. In 63% there was a history of occupational exposure to asbestos; in 47% there was an above-average asbestos load in the lung tissue. In 22% of the patients with exposure to asbestos, the BALF was positive. The asbestos content of lung tissue was appreciably higher than that of a published control group with no carcinoma of the lungs, on the basis of post-mortem material.

[Prognostic factors in diffuse malignant mesothelioma of the pleura]. / Prognostische Faktoren beim diffusen malignen Mesotheliom der Pleura.

Diffuse malignant pleural mesothelioma (DMM) is associated with a very poor prognosis and is only partially accessible to treatment. On the basis of a retrospective analysis, we made an attempt to identify possible factors that influence the prognosis. Between 1964 and 1986, 84 evaluable patients were treated: the ratio of male to female patients was 4.3:1, their average age being 58.5 +/- 11.9 (range: 21-82 years). The tumour types included 50% epithelial, 38% biphasic, and 12% mesenchymal tumours. The classification in accordance with the suggestions of Butchart revealed: I 10%, II 89%, III 0%, IV 1%. In 32% of the patients, treatment was purely symptomatic, in 42% a palliative surgical procedure with decortication of the tumour and tumour-pleurectomy was performed, while in 26% the palliative procedure was followed by adjuvant chemotherapy using doxorubicin and cisplatin. The median survival for the patients overall was 253 days. Parameters that were found not to correlate with the prognosis were: age, sex, exposure to asbestos, use of tobacco, pleural effusion, and growth behaviour in the thymus aplastic nude mouse. A significant influence was found for the histological type of the tumour and therapy administered, epithelial and biphasic tumour forms, as also surgical and combined surgical/chemotherapeutic treatment resulting in a more prolonged survival. On the basis of these results, surgical therapy should always be employed, despite the fact that there is almost always no curative option; postoperative adjuvant therapy is capable of further improving the prognosis.

[The effect of mass chest x-ray on early detection of bronchial cancer]. / Der Einfluss der Röntgenreihenuntersuchung auf die Früherkennung des Bronchialkarzinoms.

On 30.6.1983, mass radiographic screening was abandoned despite objections to the effect that it offered the only chance of detecting carcinoma of the lung at an early stage. In a retrospective analysis of our patient material comprising 1.010 patients with bronchial carcinomas seen within the period between 1.1.1980 to 31.12.1986, we investigated the question as to whether these objections might not be justified. Four hundred and thirty-seven patients seen prior to 30.6.1983 were compared with 537 patients examined after this date, on the basis of the following parameters: age - sex - symptomatology - cancer stage - histology - treatment. After stopping mass radiographic screening, an increase in age and symptomatic tumour findings was observed, and thus a shift towards more advanced stages of carcinoma. A relative decrease in the number of squamous cell carcinomas, and a relative increase in the number of adenocarcinomas were observed. All the parameters in the patients identified at mass radiographic screening were comparable with those seen in patients identified incidentally. In comparison with symptomatic patients, those identified by mass radiography screening more frequently presented with earlier tumour stages, and the lesions were more frequently resectable. All in all, over a period of three and one-half years, mass radiographic screening revealed 23.8% of all cancers of the lung, and 36.8% of all resectable lesions. After the abandonment of mass radiographic screening, an increase in more advanced and symptomatic tumours was observed.

[Stent implantation as a palliative measure in an inoperable bronchial tumor. Initial experiences with an endoscopically implanted stent]. / Stentimplantation als Palliativmassnahme beim inoperablen Bronchialtumor. Erste Erfahrungen über eine endoskopisch implantierte Stentapplikation.

Imminent asphyxia due to tracheal or bronchial compression by inoperable tumors in the mediastinum and the central bronchi is serious, particularly if alternative treatments, i.e., radiation or chemotherapy, have been exhausted. For that reason, stents of different diameters and lengths were developed that could be dilated. With the patient under general anesthesia these stents can be introduced into the stenotic bronchus or trachea through a rigid bronchoscope. The appropriate stent is mounted on a 3-mm balloon catheter, which is inflated after the stent is in the correct position. Positioning is done under direct bronchoscopic and fluoroscopic control. After deflation of the balloon, the stent maintains its cross-sectional shape and keeps the airway open. The first clinical application was in a 53-year-old patient with end-stage small-cell carcinoma. The patient had had a relapse after combined chemo- and radiotherapy and had severe stridor. Stent insertion led to a significant relief of symptoms. The second patient, a 53-year-old woman who suffered from collapse of the bronchus caused by a radionecrosis, was treated by the same method. Nine months later, ventilation is excellent in the left lung, and the patient can tolerate the stent without any clinical symptoms. A 69-year-old woman suffered from a tracheal carcinoma with severe tracheal stenosis. It was possible to maintain the stability of the collapsed tracheal wall by insertion of a tracheal stent. This new technique can provide good palliative treatment and is sometimes even the main therapy in such cases.

Effects of human bone marrow stroma on the growth of human tumor cells.

As some tumors metastasize frequently to marrow we modified the clonogenic assay for human tumor cell growth by culturing tumor cells in the presence of human bone marrow stromal cells. In a bilayer soft agar assay, human tumor cells which had been passaged in nude mice were plated in the agar overlayer on an underlayer containing a suspension of trypsinized human bone marrow stromal cells. These marrow stromal cells stimulated the growth of tumor cells in a dose-dependent fashion, with a growth peak at a stromal cell density of 5-10 x 10(5)/ml. The maximal stimulation of tumour cell growth was 13-fold. We evaluated clonal growth of six separate tumors of five different histological types (small and large cell bronchogenic carcinoma; mammary carcinoma; malignant melanoma; pleural mesothelioma) and demonstrated that in 9 of 11 experiments tumor cell colonies formed in the absence of stromal cells, but colony growth was markedly stimulated by stromal cells in every case. Stromal stimulation persisted after irradiation of the stromal cells with 10 Gy. Growth of five fresh human tumor samples was similarly stimulated by the presence of human bone marrow stromal cells. Tumor cell colonies were characterized morphologically by Pappenheim stain and immunologically for surface antigens by peroxidase-antiperoxidase immunostaining utilizing monoclonal antibodies (carcinoembryonic antigen 26/3/13 and 26/5/1, EMA, HEA125, Sam 2 and Sam 10) which detected epithelial cell antigens. Colonies consisted of cytologically malignant cells which expressed epithelial cell antigens. Thus, the tumor cell origin of colonies from mammary carcinoma and bronchogenic small cell, large cell, and adenocarcinoma was proven. This tumor stem cell assay permits further analyses of human tumor cell biology and may be useful for testing drug sensitivity.

Phase-II study with the combination of cisplatin and doxorubicin in advanced malignant mesothelioma of the pleura.

The effectiveness of combination chemotherapy with doxorubicin and cisplatin was studied in patients with advanced malignant pleuramesothelioma. 19 patients were treated intravenously with cisplatin 60 mg/m2/day on days 1 and 2, and with adriamycin 40 mg/m2 on day 3 every 4 weeks. 8/19 patients (46%) responded to chemotherapy; 2 achieved complete remissions (CR), and 6 went into partial remissions (PR). Median duration of response was 222 days. Median survival time of all patients was 370 days compared to a median survival of 273 days in a historical control group consisting of 30 patients treated by surgery only. Substantial toxicity was observed, mainly gastrointestinal. We conclude that the combination of cisplatin and adriamycin is effective in malignant pleuramesothelioma. However, the duration of treatment is limited by gastrointestinal toxicity.