Endobronchial-ultrasound needle aspiration and endoscopic ultrasound-fine-needle aspiration in thoracic diseases.

EBUS-TBNA and EUS-FNA are minimally invasive techniques rapidly gaining ground in the non-surgical invasive diagnostic approach to thoracic diseases due to their high accuracy and low morbidity and mortality compared to surgical techniques. Moreover, in the diagnosis and staging of lung cancer the combination of the two techniques is superior to either test alone. In this review we focus on the role of EBUS-TBNA and EUS-FNA in both malignant and non-malignant thoracic diseases.

Reliable and valid assessment of competence in endoscopic ultrasonography and fine-needle aspiration for mediastinal staging of non-small cell lung cancer.

BACKGROUND AND STUDY AIMS: Fine-needle aspiration (FNA) guided by endoscopic ultrasonography (EUS) is important in mediastinal staging of non-small cell lung cancer (NSCLC). Training standards and implementation strategies of this technique are currently under discussion. The aim of this study was to explore the reliability and validity of a newly developed EUS Assessment Tool (EUSAT) designed to measure competence in EUS - FNA for mediastinal staging of NSCLC. PATIENTS AND METHODS: A total of 30 patients with proven or suspected NSCLC underwent EUS - FNA for mediastinal staging by three trainees and three experienced physicians. Their performances were assessed prospectively by three experts in EUS under direct observation and again 2 months later in a blinded fashion using digital video-recordings. Based on the assessments, intra-rater reliability, inter-rater reliability, and construct validity were explored. RESULTS: The intra-rater reliability was good (Cronbach's α = 0.80), but comparison of results based on direct observations and blinded video-recordings indicated a significant bias favoring consultants (P = 0.022). Inter-rater reliability was very good (Cronbach's α = 0.93). However, one rater assessing five procedures or two raters each assessing four procedures were necessary to secure a generalizability coefficient of 0.80. The assessment tool demonstrated construct validity by discriminating between trainees and experienced physicians (P = 0.034). CONCLUSIONS: Competency in mediastinal staging of NSCLC using EUS and EUS - FNA can be assessed in a reliable and valid way using the EUSAT assessment tool. Measuring and defining competency and training requirements could improve EUS quality and benefit patient care.

A comparison of endoscopic ultrasound guided biopsy and positron emission tomography with integrated computed tomography in lung cancer staging.

BACKGROUND AND STUDY AIMS: Exact staging of patients with non-small-cell lung cancer (NSCLC) is important to improve selection of resectable and curable patients for surgery. Positron emission tomography with integrated computed tomography (PET/CT) and endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNA) are new and promising methods, but indications in lung cancer staging are controversial. Only few studies have compared the 2 methods. The aim of this study was to assess and compare the diagnostic values of PET/CT and EUS-FNA for diagnosing advanced lung cancer in patients, who had both procedures performed. PATIENTS AND METHODS: 27 patients considered to be potential candidates for resection of NSCLC underwent PET/CT and EUS-FNA. Diagnoses were confirmed either by open thoracotomy, mediastinoscopy or clinical follow-up. Advanced lung cancer was defined as tumour-stage ≥ IIIA(N2), corresponding to T4- and/or N2-N3- and/or M1 disease. Diagnostic values of PET/CT and EUS-FNA, with regard to the diagnosis of advanced lung cancer, were assessed and compared. RESULTS: The sensitivity of PET/CT and EUS-FNA were respectively 60% and 60% for T4 disease, 56% versus 100% for N2-N3 disease (p=0.12) and 100% versus 33% for M1 disease (p=0.50). For diagnosing advanced lung cancer PET/CT had a sensitivity of 79%, specificity of 61%, positive predictive value (PPV) of 69%, negative predictive value (NPV) of 73%, and an accuracy of 70%. EUS-FNA had a sensitivity of 79%, specificity of 100%, PPV of 100%, NPV of 81%, and an accuracy of 89% for advanced lung cancer. CONCLUSIONS: PET/CT and EUS-FNA had a comparable sensitivity and NPV for diagnosing advanced lung cancer, but EUS-FNA had superior specificity and PPV. The two methods seem to complement each other.

Transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) biopsy: a combined approach in the evaluation of mediastinal lesions.

BACKGROUND AND STUDY AIMS: It would be desirable to develop minimally invasive methods of tissue diagnosis from lymph nodes as well as solid lesions in the mediastinum. The aim of the present study was to test the combined method of transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the evaluation of mediastinal lesions. PATIENTS AND METHODS: EUS-FNA and EBUS-TBNA were compared in 33 patients, for the staging of lung cancer in patients with an established diagnosis of non-small-cell lung cancer (n = 20) or for diagnosis of a suspicious mediastinal lesion in patients with suspected lung cancer (n = 13). EBUS-TBNA and EUS-FNA were unsuccessful in one patient each. The diagnoses were verified in 28 of the remaining 31 patients either at thoracotomy (n = 9) or during the clinical follow-up (n = 19). RESULTS: A total of 119 lesions were sampled by EUS-FNA (n = 59) and EBUS-TBNA (n = 60). EUS-FNA and EBUS-TBNA demonstrated cancer in 26 and 28 lesions, respectively, and benign cytology in 30 and 28 lesions, respectively. Suspicious cells were found in three and four lesions by EUS-FNA and EBUS-TBNA, respectively. When the 60 EBUS-TBNA samples were compared with the 59 EUS-FNA samples, 11 additional cancer diagnoses and three samples with suspicious cells were obtained by EBUS-TBNA that had not been obtained by EUS-FNA. Conversely, EUS-FNA diagnosed 12 additional cancer diagnoses, one suspicious and one specific benign diagnosis (sarcoidosis) in addition to EBUS-TBNA. With a combined approach (EUS-FNA + EBUS-TBNA) in 28 of the 31 patients in whom a final diagnosis was obtained in the evaluation of mediastinal cancer, 20 patients were found to have mediastinal involvement, whereas no mediastinal metastases were found in eight patients. The accuracy of EUS-FNA and EBUS-TBNA, in combination, for the diagnosis of mediastinal cancer was 100 % (95 % CI, 83 - 100 %). CONCLUSIONS: EUS-FNA and EBUS-TBNA appear to be complementary methods. A combined approach with both EUS-FNA and EBUS-TBNA may be able to replace more invasive methods for evaluating lung cancer patients with suspected hilar or mediastinal metastases, as well as for evaluating unclear mediastinal or hilar lesions.

Transesophageal endoscopic ultrasound/fine-needle aspiration diagnosis of a malignant adrenal gland in a patient with non-small cell lung cancer and a negative CT scan.

Adrenal metastasis is only seen on CT scan is less than 5% of patients with otherwise resectable NSCLS, but this diagnosis has a major impact on treatment and prognosis. We present a case of a patient with NSCLC and an adrenal metastasis, which was diagnosed by EUS/FNA of an enlarged adrenal gland, who had false-negative CT scan for adrenal metastasis. PET was not performed. Prospective studies are needed to assess the incremental yield of EUS/FNA over upper abdominal CT scan and PET for detecting left adrenal metastasis in patients with suspected or proven otherwise respectable NSCLC.

4. Preliminary Findings of a Prospective Study of FDG-PET in Patients with Possible Lung Cancer.

Purpose: To examine the value of PET in diagnosis and staging of suspected lung cancer.Methods: 20 (13 male; mean age: 56 yr., range: 22-83 yr.) patients with chest X-ray findings suspicious of malignancy were staged a) "clinically" (X-ray, history/physical examination, lung function), b) by chest CT of thorax/upper abdomen, and c) by whole-body PET (GE Advance, visual analysis). The CT and PET studies were performed within 2 weeks of admission and read blinded to all information except the chest X-ray report. The decision to refer to mediastinoscopy/thoracotomy was made by a tumor board using clinical information, CT and PET findings. In principle, suspected metastatic lesions were biopsied before surgery. The gold standard was histology from biopsy or thoracotomy, or resolution of the X-ray findings and symptoms.Results: One patient was excluded because of uncertain diagnosis. In 3 (15%) patients surgery was avoided mainly because of the PET findings. In one SCLC patient and one lymphoma patient, PET showed extensive disease, which changed the chemotherapy regime. Accuracy was 83% for clinical stage, 79% for CT and 77% for PET. Four (20%) false positive PET findings were caused by granuloma, pneumonia and BOOP. These nodules were only 1 to <3 cm, while malignant nodules were 2-8 cm. There were no false negative PET or CT studies.Conclusion: FDG-PET is valuable in patients suspected for pulmonary malignancy, since thoracotomy was avoided in 15% of patients and in 10% of patients more extensive disease was found which changed the chemotherapy regime.

Chlamydia pneumoniae and possible relationship to asthma. Serum immunoglobulins and histamine release in patients and controls.

Chlamydia pneumoniae (C.pn.) is claimed to be of importance for the development of bronchial asthma in previously healthy individuals. This is a new and speculative theory. Earlier studies have mainly focused on C.pn. and exacerbation of asthma. If this new theory were true, one would expect titres of C.pn.-specific IgG to be higher or more common in patients compared with controls. It would also seem probable that pathobiological mechanisms as found in connection with other microorganisms could be demonstrated, i.e. presence of C.pn.-specific IgE and the capability of C.pn. to induce or enhance histamine release from basophil leukocytes. We therefore examined C.pn.-specific IgE, IgG and IgM in sera from 22 adults with bronchial asthma and 25 healthy controls. IgE was verified by passive sensitization of basophils from umbilical cord blood. The prevalence of IgE was approx. 69% and IgG approx. 23% in both groups. IgG-titres were between 1:16 and 1:64 in both groups. No IgM was found. Further, C.pn. could neither induce nor enhance histamine release from basophil leukocytes of patients or controls. We conclude that patients with bronchial asthma and healthy controls do not differ in relation to 1) C.pn.-specific IgE in sera, 2) the capability of C.pn. to induce or enhance histamine release from basophil leukocytes, since no such effect was found, or 3) previous C.pn. infection judged by the presence of specific IgG antibodies. Our results cannot support the theory that C.pn. is a cause of adult-onset asthma.

Treatment of malignant pleural effusion: pleurodesis using a small percutaneous catheter. A prospective randomized study.

The aim of this prospective, randomized study was to investigate the possibility of performing pleurodesis using a small percutaneous catheter (Cystofix catheter, CH10, 65 cm) inserted at bedside in patients with recurrent malignant pleural effusion and to compare this catheter with a conventional large bore chest tube (CH24) placed in connection with diagnostic thoracoscopy. After drainage pleurodesis was performed with tetracycline as sclerosing agent. Of 18 evaluable consecutive patients (mean age 67.8 years) nine were randomized for pleurodesis with the small and nine for the large catheter. In the former group, the majority (seven of nine) did not find insertion of the catheter more unpleasant than thoracentesis. In the latter group only a few (two of nine) found insertion comparable with thoracentesis (P < 0.05). All patients found the presence of the large catheter very or somewhat unpleasant (two and seven patients), whereas this was only the case for a few (no and two patients) treated with the small catheter (P < 0.05). In the former group three patients required new thoracentesis, whereas this was only the case for two patients in the latter group (P > 0.05). No complications were seen. We conclude that pleurodesis in patients with recurrent malignant pleural effusion can be performed with a small percutaneous catheter (Cystofix) with an effect similar to that obtained with a large-bore chest tube and with less discomfort for the patient.

Medical thoracoscopy, results and complications in 146 patients: a retrospective study.

In a retrospective study the results of medical thoracoscopy in 147 patients were reviewed; 136 of the patients had pleural effusion and 11 patients had diffuse pulmonary infiltration. All the pleural exudates were initially screened three times successively and found to be sterile and without tumour cells. All thoracoscopies were performed with local anaesthesia, with the 'open technique', and nine different doctors performed the thoracoscopies. The overall diagnostic sensitivity was 90.4%. The results demonstrated 62% with malignancy of the pleura, and 38% revealed benign pleural diseases, among them 2% with tuberculosis. The sensitivity for malignancy was found to be 88% and the specificity 96%. The most common primary lung cancer with involvement of the pleura was the adenocarcinoma (62%), and the most common metastatic tumour originated from the breast (28%). The sensitivity for tuberculosis was 100% and the specificity 100%. No mortality was found, and the morbidity was low at about 0.6% (empyema, pleuro-cutaneous fistula, transcutaneous growth of tumour (mesothelioma)). In 64% of the patients the thoracoscopy resulted in treatment (pleurodesis, antituberculous treatment, chemotherapy and peroral steroid therapy). The medical diagnostic thoracoscopy in local anaesthesia is a simple, low-cost investigation with a relatively high diagnostic accuracy, no mortality and a low morbidity.

The in vivo and in vitro effects of rhG-CSF on allergic, haematological and biochemical variables.

UNLABELLED: The objective was to evaluate the influence of treatment with rhG-CSF on allergic indexes. This was done by open trial of 5 days' treatment with rhG-CSF (5 microg/kg/day s. c.). 10 patients (6 men), aged 28 to 54 years, with rhinoconjunctivitis due to grass pollen allergy, participated in the investigation. Main measures were blood count, basophil histamine release, skin test and conjunctival provocation test. RESULTS: The treatment resulted in significant increases in numbers of neutrophils (590%), basophils (280%), eosinophils (250%) and lymphocytes (71%). Total blood histamine was increased, but basophil histamine releasability was decreased. Serum alkaline phosphatase increased 92% and serum lactate dehydrogenase increased 35% (both significant). There were no significant changes in the skin tests and the conjunctival provocation tests. Two months after the treatment all tests had returned to baseline levels. Five of the patients (50%) reported side effects, one withdrew. In conclusion treatment with rhG-CSF increases the number of circulating blood cells other than neutrophils without causing changes in indexes of allergic reactivity.

[Intestinal tuberculosis]. / Intestinal tuberkulose.

Since the symptoms and clinical presentation of intestinal tuberculosis is nonspecific, the diagnosis is frequently delayed and may be achieved at autopsy only. Intestinal tuberculosis is very rare in Denmark, but may now be seen more often because of increasing numbers of immigrants from countries of the third world with a high prevalence of tuberculosis. A case of intestinal tuberculosis in a 28 year old Somalian female is reported. Methods of diagnosing intestinal tuberculosis are commented, and the frequent necessity of starting medical treatment before a bacteriological diagnosis is reached is emphasized.

Nurse-conducted smoking cessation with minimal intervention in a lung clinic: a randomized controlled study.

This study aimed to evaluate the effect of a motivational, minimal intervention approach to smoking cessation in an open, randomized design conducted by nurses as routine work in a lung clinic. Subjects who smoked less than 10 cigarettes x day(-1), and subjects who smoked > or = 10 cigarettes x day(-1) and who had refused to participate in a smoking cessation trial with nicotine replacement therapy, were randomly allocated to a motivational approach to smoking cessation or to a control group. The motivational approach consisted of a nurse-conducted 5 min consultation concerning reasons to quit smoking, brochures about smoking cessation and advice about how to quit. After 4-6 weeks, subjects in the motivational group received a letter encouraging them to quit smoking. After 1 year, all subjects were contacted by phone and smoking status reported. Subjects claiming to be abstinent attended the clinic for carbon monoxide verification. A total of 507 subjects were enrolled, 254 in the motivational group and 253 in the control group. The mean age of the motivational group was 51 yrs, 50% were males and they smoked a mean of 13 cigarettes x day(-1). The mean age of the control group was 53 yrs, 61% were males and they smoked a mean of 12 cigarettes x day(-1). At the 1 year follow-up, the success rate for point prevalence (no smoking at 1 year and during the preceding month) was 8, 7% in the motivational group versus 3.6% in the control group (p=0.025). The 12 months sustained success rate (no smoking at all during the year) was 3.1 versus 1.2% (p=0.22). The point prevalence for light smokers (<10 cigarettes x day(-1)) was 13.9% in the motivational group versus 6.3% in control group (p=0.12), and for heavy smokers (10 or more cigarettes x day(-1)) 5.2% versus 1.9% (p=0.20). In conclusion, the effect of this nurse-conducted, minimal intervention, motivational approach seems promising as the quit rate at 1 year follow-up had doubled.

[Diagnostic procedures in artificially ventilated patients with pneumonia]. / Diagnostiske procedurer hos respiratorpatienter med pneumoni.

Pneumonia is a common complication in patients requiring mechanical ventilation and the mortality is high. The diagnosis is difficult to establish in spite of many available diagnostic techniques: Aspiration from endotracheal tube or tracheostomy, fiberbronchoscopy with bronchial aspiration, protected specimen-brush (PSB), bronchoalveolar lavage (BAL), transbronchial biopsy or percutaneous lung needle aspiration or open lung biopsy. A review of the literature is given. It is concluded that PSB and BAL combined with quantitative cultures are valid tools, but there is no conclusion as to the superiority of one over the other. With the use of prior antibiotics the rate of false negatives increases and the specificity and sensitivity are lowered. However, we do need a prospective, randomized trial in order to demonstrate that invasive methods in fact decrease morbidity and mortality in the patients compared with clinical judgement alone.

The indoor microfungus Trichoderma viride potentiates histamine release from human bronchoalveolar cells.

Trichoderma viride (Tv) is often found in damp and mouldy buildings where people complain of adverse health effects including mucosal/respiratory symptoms. Inhaled spores can reach the alveoli and may interact with the airway epithelium. An interaction with the mucosal mast cells was studied in cells obtained by bronchoalveolar lavage (BAL) from 18 individuals. The fungal spores were found to trigger histamine release from the BAL cells, but relatively high concentrations (0.1-2 mg/ml) were needed. A similar dose response was obtained in basophil histamine release. The Tv-induced mediator release was caused by non-immunological (non-IgE-dependent) mechanisms since the histamine release was not changed by removal of IgE from the basophils before exposure of the cells to the spores. However, in very low concentrations (0.1 ng/ml) the fungal spores were found to potentiate IgE-mediated histamine release triggered by anti-IgE antibody in suspensions of BAL cells. Potentiation was also obtained in basophil histamine release, but relatively high concentrations of Tv (10(-2) mg/ ml) were needed. Our in vitro experiments show that mucosal mast cells from the airways are highly sensitive to the potentiating effect of Tv. Although inhalation studies are needed to determine the in vivo effect of the spores, the results suggest reinforcement of mediator release to be a mechanism in the adverse health implications observed in mouldy buildings.

[DNA-fingerprinting and tuberculosis]. / DNA-fingerprinting og tuberkulose.

DNA-fingerprinting or RFLP (Restriction Fragment Length Polymorphism) is a molecular biological technique which allows differentiation between tuberculosis strains. The technique is based on the occurrence of repetitive elements in the mycobacterial genome and is a powerful tool in epidemiological studies. DNA-fingerprinting is also of value in tracking the spread of infection in patients with tuberculosis. The latter is illustrated in two case stories.