Epidermal growth factor receptor and anaplastic lymphoma kinase testing and mutation prevalence in patients with advanced non-small cell lung cancer in Switzerland: A comprehensive evaluation of real world practices.

In order to improve outcomes, identification of the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) genes has become crucial in advanced non-small-cell lung cancer (NSCLC). The aim of the present study is to analyse time trends and frequency of testing, factors affecting testing as well as prevalence of mutations in the Swiss population. We analysed EGFR and ALK testing in a cohort of patients with newly diagnosed metastasised non-squamous NSCLC in the catchment area of the cancer registry Eastern Switzerland in the years 2008-2014. We analysed prevalence of mutations and studied clinicopathological characteristics and survival of tested and non-tested patients and of patients with and without mutations. Among 718 patients identified, 11% (51/447) harboured an EGFR mutation in the exons 18, 19 or 21 and further 12% (31/265) showed a positive test result for ALK rearrangements. In non-smokers the proportions of mutations were 31% and 23% respectively. Testing rates increased over time and reached 79% in 2014. We observed significantly lower testing rates and poorer survival in elderly, patients with limited life expectancy and patients treated at hospitals not involved in clinical research. Outcomes can be further improved in a considerable proportion of patients with advanced non-squamous NSCLC.

[Methods for detection of changes in muscle tonus]. / Nachweismethoden von Tonusveränderungen der Muskulatur.

Muscular spasm is a frequent symptom which is difficult to record precisely. On the basis of literature on the subject and of own studies, we undertook to describe various methods of examination which could be used to demonstrate such changes. Up to now, palpation is still the most important and most exact method for the experienced examiner. In this way local as well as extended muscular spasms can be made evident. The disadvantage however is the lack of objective proof. The easy-to-use Tissue-Compliance-Meter of Fischer, which measures the consistency of soft tissue, documents the intraindividual difference rather than the interindividual difference. This is due to the individually variable thickness of the subcutaneous fatty tissue. However, on the whole there is a good correlation to the findings of palpation. The pendulous-test and badismography allow especially the conclusion with regard to unilateral changes of tonus in the gluteal and upper leg muscles. This method also very well suits the intraindividual comparison, but less so the interindividual one. The continuous electromyogram is able to show the enhanced activity in spasmotic muscles also during sleep. The evaluation of enhanced muscle activity remains uncertain when using plain electromyogram. Recording of muscle tissue oxygen pressure is of little use to evaluate muscle spasm. Nonetheless, it provides interesting insights into pathogenetic questions. Thermography, measuring the blood circulation at the skin surface, is especially suited for perceiving intraindividual differences in case of muscle spasm. Nuclear magnetic resonance spectroscopy allows for noninvasive pH measurements in the muscle and therewith renders certain data concerning the degree of tension of this tissue. It is not yet suited for routine examination. The value of positron emission tomography for registering muscle spasm remains uncertain. Hopefully, this method, which documents the muscle energy metabolism, will enable us to more clearly evaluate muscle spasm than previous methods have done. Light and electron microscopic studies have provided contradictory results concerning histological changes in muscle biopsy in case of muscle spasm.

[Recording muscle spasm in the musculus erector spinae using in vivo 31P magnetic resonance spectroscopy in patients with chronic lumbalgia and generalized tendomyopathies]. / Die Erfassung von Muskelverspannungen im Musculus erector spinae mit Hilfe der in vivo 31P Magnetresonanzspektroskopie (31P MRS) bei Patienten mit chronischen Lumbalgien und generalisierten Tendomyopathien.

Using 31P nuclear magnetic resonance, the following parameters were determined in the resting musculus erector spinae of five patients suffering from chronic low back pain, five patients with fibromyalgia, and five healthy controls: Inorganic phosphate (Pi), phosphocreatine (PCr), ATP gamma, ATP alpha, ATP beta. The intracellular pH was derived from the chemical shift of Pi referenced to the PCr resonance. In addition, the Pi-Index was calculated according to the formula: Pi/(Pi + PCr). We discovered a tendency towards a shift of the Pi resonance in the alcalic direction, which was the larger, the stronger muscle spasm was found on palpation. The pH showed the most reliable relationship to the clinical status of muscle spasm. The surprising finding that there is no acidification within the spasmed muscle indicates that generalized hypoxia does not exist in this tissue. This has already been shown with PO2 measurements. An intracellular acidification is only recorded during maximal isometric contraction. Thus, ischemia cannot be responsible for pain experienced during muscle spasm.

Tissue oxygen measurement and 31P magnetic resonance spectroscopy in patients with muscle tension and fibromyalgia.

Muscle tissue oxygen tension was measured by a polarographic oxygen fine-needle probe, and inorganic phosphate and creatine phosphate spectra were recorded using magnetic resonance spectroscopy in patients with chronic low back pain and in patients with fibromyalgia. Results were compared with healthy controls. The tissue oxygen tension was markedly higher in those with tense muscles than in normal subjects. Magnetic resonance spectra for inorganic phosphate were higher in patients demonstrating muscle contraction, and intracellular pH was shifted in the alkaline direction in cases with increased muscle tension. Results show that hypoxia is not the result of increased muscle tension, as was thought previously, but results from oversupply of oxygen demanded by the muscle, leading to increased capillary perfusion and rising oxygen tension.

Imaging of lung cancer with fluorine-18 fluorodeoxyglucose: comparison of a dual-head gamma camera in coincidence mode with a full-ring positron emission tomography system.

Dual-head gamma cameras operated in coincidence mode are a new approach for tumour imaging using fluorine-18 fluorodeoxyglucose (FDG). The aim of this study was to assess the diagnostic accuracy of such a camera system in comparison with a full-ring positron emission tomography (PET) system in patients with lung cancer. Twenty-seven patients (1 female, 26 males, age 62+/-9 years) with lung cancer or indeterminate pulmonary nodules were studied on the same day with a full-ring PET scanner (Siemens ECAT EXACT) and a coincidence gamma camera system (ADAC Vertex MCD). Sixty minutes after injection of 185-370 MBq FDG, a scan of the chest was performed with the full-ring system. Approximately 2 h p.i., the coincidence camera study was performed. Coincidence gamma camera (CGC) and PET images with (PETac) and without attenuation correction (PETnac) were analysed independently by two blinded observers. In addition, FDG uptake in primary tumours and involved lymph nodes was quantified relative to normal contralateral lung (T/L ratios). All primary tumours were histologically proven. The lymph node status was histologically determined in 23 patients. In four patients, no lymph node sampling was performed because of extensive disease or concurrent illnesses. In the 27 patients, 25 primary lung cancers and two metastatic lesions were histologically diagnosed. The number of coincidences per centimetre axial field of view was 3.33+/-0. 93x10(5) for the CGC and 1.09+/-0.36x10(6) for the dedicated PET system. All primary tumours (size: 4.6+/-2.6 cm) were correctly identified in the CGC and dedicated PET studies. T/L ratios were 4. 7+/-2.5 for CGC and 6.9+/-2.8 for PETnac (P <0.001). Histopathological evaluation revealed lymph node metastases in 11 of 88 sampled lymph node stations (size: 2.3+/-1.0 cm). All lymph node metastases were identified in the PETac studies, while PETnac detected 10/11 and CGC 8/11. For positive lymph nodes that were visible in CGC and PETnac studies, T/L ratios were 3.7+/-2.3 for CGC and 6.6+/-3.1 for PETnac (P=0.02). The diameters of false-negative lymph nodes in the CGC studies were 0.75, 1.5 and 2 cm. False-positive FDG uptake in lymph nodes was found in two patients with all three imaging methods. For all lesions combined, T/L ratios in CGC relative to PETnac studies decreased significantly with decreasing lesion size (r=0.62; P<0.001). In conclusion, compared with a full-ring PET system the sensitivity of CGC imaging for detection of lung cancer is limited by a lower image contrast which deteriorates with decreasing lesion size. Nevertheless, the ability of CGC imaging to detect pulmonary lesions with a diameter of at least 2 cm appears to be similar to that of a full-ring system. Both systems provide a similar specificity for the evaluation of lymph node involvement.