Blood immune cell biomarkers in lung cancer.

Characterization of host immune cell parameters prior to treatment is expected to identify biomarkers predictive of clinical outcome as well as to elucidate why some patients fail to respond to immunotherapy. We monitored blood immune cells from 58 patients with non-small- cell lung cancer (NSCLC) undergoing surgery of the primary tumor and from 50 age-matched healthy volunteers. Complete leukocyte blood count, the number of circulating dendritic cells (DC), HLA-DRlow monocytes and several lymphocytic subpopulations were determined by eight-color flow cytometry. Furthermore, the prognostic value of the immune cell parameters investigated was evaluated by patients' survival analysis. Compared to the control group, blood of NSCLC patients contained more neutrophils resulting in a higher neutrophil-to-lymphocyte ratio (NLR), but a lower number of blood DC, in particular of plasmacytoid DC (pDC), natural killer (NK) cells and naive CD4+ and CD8+ T cells. Furthermore, a higher frequency of CD4+ regulatory T cells (Treg) and HLA-DRlow monocytes was detected, and smoking had a significant impact on these values. HLA-DRlow monocytes were positively correlated to the number of neutrophils, monocytes and NLR, but negatively associated with the number of pDC and naive CD4+ T cells. The frequency of Treg, HLA-DRlow monocytes and naive CD4+ and CD8+ T cells as well as the ratios of CD4/HLA-DRlow monocytes and HLA-DRlow monocytes/pDC correlated with patient's overall survival. Next to Treg, HLA-DRlow monocytes and naive T cells represent prognostic markers for NSCLC patients and might be useful for monitoring of patients' responses to immunotherapies in future studies.

[Rebiopsy for Patients with Lung Cancer - Joint Opinion from both the Endoscopic and Thoracic Oncology Sections of the German Society of Pneumology (DGP)]. / Empfehlung der Sektionen 2 und 11 der DGP zur Rebiopsie bei Lungenkarzinomen.

Performing rebiopsies for primary lung cancer and/or their metastases is becoming more and more prominent in daily practice, as the therapeutical spectrum increases and some newer strategies are dependent on immunohistochemical and/or molecular factors. In general, nearly all recurrent lesions or metastases can be reached. However, frequently invasive procedures are necessary with the need to carefully weigh risks and benefits of rebiopsies for the patient in each case. In this review indications for recurrent and progressive disease as well as risks are discussed and alternatives to rebiopsies are shown. This work is the joint opinion from both the endoscopic and thoracic oncology sections of the German Society of Pneumology (DGP).

[Implementation of the German guideline for the prevention, diagnosis, treatment and follow-up of non-small cell lung cancer at the Diakoniekrankenhaus Halle/Saale]. / Umsetzung der aktuellen S3-Leitlinie zur Prävention, Diagnostik, Therapie und Nachsorge des nicht-kleinzelligen Lungenkarzinoms am Diakoniekrankenhaus Halle/Saale.

BACKGROUND: More than three years since the release of the german guideline for the prevention, diagnosis, treatment and follow-up of lung cancer the database in terms of the implementation of guideline recommendations is deficient. The aim of this article is to analyze the implementation of the recommended algorithms for first-line therapy of non-small cell lung cancer. PATIENTS AND METHODS: On the basis of the patients records we determined all cases of newly diagnosed non-small cell lung cancer which received a first-line therapy at the Diakoniekrankenhaus Halle/Saale between January 2010 and December 2011. The demographic data, tumor stage, time of diagnosis and performed first-line therapy were documented. Each case was assigned to the groups "guideline-adherent treatment" or "deviation from guideline recommendation" in dependency of its tumor stage. For this assignment the corresponding algorithms from guideline chapter "Therapy of non-small lung cancer" were used. RESULTS: A total of 126 from 148 cases (85%) received guideline-adherent treatment. Deviation from guideline recommendation was found in 22 cases (15%). The categories "poor performance status", "technical factors", "patient decision" and "others" were determined as the main reasons for non guideline-adherent treatment. CONCLUSIONS: Based on the analyzed population this study determined a high grade of guideline adherence at the period of investigation. Otherwise it shows that guideline recommendations cannot include each individual factor of the complex lung cancer disease. It could be found a wide range of reasons for deviation from the guideline recommendations.

[Prognostic Relevance of the Metastatic Localisation in Patients with Stage IV NSCLC - Results of a Prospective Epidemiological Study]. / Prognostische Relevanz der Metastasenlokalisation bei nicht kleinzelligem Bronchialkarzinom im Tumorstadium IV - Ergebnisse einer prospektiven epidemiologischen Studie.

Patients with non-small cell lung cancer (NSCLC) frequently suffer from stage IV disease at the time of presentation. Survival of these patients is disadvantageous although they may benefit from chemotherapy. The main purpose of this investigation was to evaluate the prognostic relevance of the metastatic localisation in unselected patients. The second purpose was to evaluate the impact of clinical characteristics on the kind of decision-making in patients with stage IV NSCLC in an epidemiological manner.[nl]Clinical data as well as survival of 336 patients with stage IV NSCLC were analysed. The recruitment period was 3? years, mean follow-up was 24 months. This investigation was part of the HALLUCA studies which were sponsored by the German Ministry of Health.[nl]Localisation-dependent median and 1-year survivals were significantly different and varied between 2.2 months and 4.7 % (liver metastases) and 11.0 months and 44.5 % (lung metastases). The different survival remained significant in the multivariate analyses with age, performance status, treatment and histology as co variables. The chemotherapy rate of all patients with stage IV NSCLC was 39 %. Patients with liver, bone and multiple metastases received less often chemotherapy compared to patients with other metastases although the performance status was not different to the other groups.[nl]Although there are some limitations in this investigation, these epidemiological data demonstrate the prognostic heterogeneity of stage IV NSCLC patients which should be considered for stratification in controlled clinical trials. Regional treatment decision-making is different from guidelines and controlled clinical trials. Further regionally orientated trials are necessary to improve the transformation from clinical trials to regional medical care.

[Treatment of respiratory papillomatosis--a case report on systemic treatment with bevacizumab]. / Behandlung der respiratorischen Papillomatose--Kasuistik zur systemischen Therapie mit Bevacizumab.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a known but rare disease, caused by human papilloma virus and characterised by multiple exophytic lesions and uncontrolled growth of papilloma in the respiratory tract. The most common complication of RRP is stenosis of the trachea. Medical therapeutic options have so far been less effective. However, inhibition of vascular endothelial growth factor (VEGF) by bevacizumab does appear to be an effective treatment option for RRP. CASE REPORT: The case of a 32-year-old male patient with RRP who has been treated for his symptomatic tracheal stenosis four times a year since 1996 is described. Only treatment by laser ablation showed any efficacy. Alternative treatment options did not show any effect. In May 2006 intrapulmonary lesions of RRP were also diagnosed but without any malignancy. From December 2007 to June 2008 the patient has been treated with bevacizumab. A visible regression of RRP and markedly less symptoms were observed. During this treatment no further laser ablation was necessary. CONCLUSION: Inhibition of VEGF by bevacizumab seems to offer a new and effective option in the medical management of RRP.

[Palliative care in respiratory medicine]. / Palliativmedizin in der Pneumologie.

Palliative care should be part of respiratory medicine for two reasons: first, many respiratory diseases--besides thoracic tumours--need palliative care in the late stages of the disease. Second, dyspnoea is a common symptom in advanced, primary extrapulmonary diseases and the knowledge of respiratory specialists can be beneficial in the treatment of this symptom. In this paper we describe frequent symptoms of advanced pulmonary diseases and their treatment. Moreover, we focus on the structure of palliative care in Germany.

[Second-line treatment of malignant pleural mesothelioma with Pemetrexed (Alimta) -- a case report]. / Second-line-Behandlung des malignen Pleuramesothelioms mit Pemetrexed (Alimta) -- eine Kasuistik.

Malignant Pleural Mesothelioma is regarded as a tumour, which lacks chemo-sensitivity. However, patients are able to benefit from a first line chemotherapy, as indicated in a currently published randomised study. Here the case of a 75 year old patient will be reported, who has been diagnosed with malignant pleural mesothelioma for 4 years. After a first line therapy with Gemcitabine/Oxaliplatin, partial remission was assessed. 15 months later a distinct progress was detected. After a second line therapy with Pemetrexed a sound partial response could be determined radiologically and clinically. This case history is supposed to exemplify that patients with malignant pleural mesothelioma should not only be considered for a first line therapy, but that a second line therapy may also be offered to a certain group of patients. The new substance Pemetrexed (Alimta) offers an excellent alternative with a very good efficacy profile and a favourable spectrum of side effects.

Gabapentin potentiation of the antiepileptic efficacy of vigabatrin in an in vitro model of epilepsy.

1. An enhancement of promoted release of gamma-aminobutyric acid (GABA) and a change in GABA-metabolism have been suggested as mechanisms of action of gabapentin. Vigabatrin is supposed to act mainly via inhibition of GABA-transaminase but it also interferes with GABA-release and GABA-uptake. On the basis of these mechanisms of action, a pharmacodynamic interaction of the two antiepileptic drugs could be supposed which might be of relevance in the sense of a rational polypharmacy. 2. To address the aforementioned hypothesis, experiments were carried out on hippocampal slices (n=107) of guinea-pigs (n=70). Epileptiform field potentials (e.f.p.) were induced by omission of magnesium from the bath solution and recorded in the stratum pyramidale of the CA3 region. Gabapentin (30-600 microM; 5.1-102.72 microg ml(-1)), vigabatrin (50-200 microM, 6.45-25.8 microg ml(-1)) and the GABA(A)-receptor antagonist bicuculline (100 microM) were added to the bath solution for 3 h. 3. Gabapentin, in concentrations up to 600 microM, failed to decrease the repetition rate or duration of e.f.p. (n=19). However, vigabatrin, evoked a dose-dependent reduction of the repetition rate of e.f.p. For a concentration of 100 microM (12.9 microg ml(-1)) there was a reduction down to 48+/-5% (mean+/-s.e.mean) of the initial value within 3 h (n=11). With simultaneous administration of vigabatrin (100 microM) and gabapentin (60 microM) for 3 h (n=15), the repetition rate of e.f.p. decreased down to 8+/-3%, which is significantly different from the values obtained after administration of 100 microM vigabatrin alone (P<0.0001). Both, the antiepileptic effect of vigabatrin alone and the enhancement by gabapentin were blocked by the GABA(A)-receptor antagonist bicuculline (100 microM, n=16). 4. These results demonstrate that gabapentin is able to augment the antiepileptic effects of vigabatrin significantly. It is possible that a change in the GABA-release machinery is induced by vigabatrin which then can be augmented by gabapentin.

[Paraneoplastic IgA nephritis as the initial symptom of bronchial carcinoma]. / Paraneoplastische IgA-Nephritis als Erstsymptom eines Bronchialkarzinoms.

We report on a 45-year old patient who was treated for IgA-Nephritis for 9 months. During treatment he developed coughing and dyspnoea which led to diagnose a central stenosing NSCLC at the tracheobronchial angle. Cancer treatment by x-ray showed a good response, e.g. significant reduction of cancer volume and a remarkably improved renal function. In the course of tumour progression (3 months after initial treatment) retention parameter deteriorated again and the patient needed to be dialysed. Palliative laser therapy had no influence on renal function. The close linkage between tumour regression and the extent of IgA nephritis suggest that the preceding IgA nephritis was paraneoplastic and hence a primary symptom of the NSCLC.

Very low temperature formaldehyde reactions and the build-up of organic molecules in comets and interstellar ices.

We have investigated thermally promoted reactions of formaldehyde (H2CO) in very low temperature ices. No such reactions occurred in ices of pure formaldehyde. However, addition of trace amounts of ammonia (NH3) were sufficient to catalyze reactions at temperatures as low as 40 K. Similar reactions could take place in interstellar ices and in Comets and produce considerable amounts of organic molecules.

Formaldehyde and organic molecule production in astrophysical ices at cryogenic temperatures.

Thermally promoted formaldehyde (H2CO) reactions in cryogenic ices have been studied to test their importance as a source of organic molecules in comets and interstellar ices. Ices containing H2CO, H2O, CH3OH, CO, and NH3 were investigated by using infrared spectroscopy. Small traces of NH3 (NH3/H2CO > or = 0.005) are sufficient to convert significant fractions (> or = 40%) of the H2CO into more complex organics. However, H2CO reactions do not proceed without NH3. Spectral evidence for reaction onset appeared between 40 and 80 kelvin, depending on the ice. Five distinct products were formed. These principally consist of polyoxymethylene and related derivatives. Polyoxymethylene itself was not made in significant amounts in cometary analogs. These products differ from those produced by ultraviolet and particle irradiation. The nature and relative amounts of the products depend on the initial composition, making these materials excellent tracers of a comet's history. About 3% of the organics in p-Halley's coma could have been produced by thermal H2CO reactions.

An experimental study of the organic molecules produced in cometary and interstellar ice analogs by thermal formaldehyde reactions.

Thermally promoted formaldehyde (H2CO) reactions in very low temperature ices have been studied to test their importance as a source of organic molecules in astrophysical environments such as comets and interstellar ices. The infrared absorption strengths of a number of the H2CO bands were measured in 10 K ices of pure H2CO and H20:H2CO = 100:3. Infrared spectroscopy was used to monitor the formaldehyde chemistry during warm-up of ices containing H2CO and one or more of the molecules H2O, CH3OH, CO, CO2, O2, and NH3. Formaldehyde reactions do not proceed at low temperatures in the absence of NH3. However, even small traces of NH3 (NH3/H2CO > or = 0.005) are sufficient to induce conversion of a considerable fraction (> 40%) of the H2CO into organic residues. Formaldehyde reactions were observed to start at temperatures as low as 40 K for NH3:H2CO binary ices and at approximately 80 K in astrophysically relevant (i.e., H2O-dominated) ices. A total of five different organic products of these reactions can be distinguished by infrared spectroscopy. One of them is polyoxymethylene (POM), a well-known H2CO polymerization product, whereas the others are reaction products of H2CO with H20, CH3OH and NH3. These all seem to be derivatives of polyoxymethylene. The nature of the components and their relative abundances depend strongly on the initial composition of the ice mixture as well as on the ice's irradiation history. We estimate that about 1% of the organics found in the coma of Comet Halley could have been produced by thermal formaldehyde reactions taking place in the nucleus.

[Pancreatico-biliary secretion in enteral hyperoxaluria]. / Die pankreatobiliäre Sekretion bei enteraler Hyperoxalurie.

The increased oxalic acid absorption is a well documented finding in gastroenterological diseases. The malabsorption of bile acids and fat is important in the pathogenesis of the hyperoxaluria. The enteric absorption of 14C-labelled oxalic acid was measured in 49 patients with different diseases. The dihydroxy-trihydroxy-ratio of bile acids is significantly decreased in patients with hyperoxaluria over 20% of the ingested dosage. We didn't find any correlation between the excretion of oxalic acid and the intraduodenal pancreatic lipase activity.

[Oxalic acid resorption in patients with resection of the small intestine, jejunoileal bypass, Crohn disease and chronic pancreatitis]. / Oxalsäureresorption bei Patienten mit Dünndarmresektion, jejunoilealem Bypass, Morbus Crohn und chronischer Pankreatitis.

The enteric absorption of oxalic acid with 14C-labelled oxalic acid was determined in patients with small bowel resection, jejunoileal bypass, Crohn's disease and chronic pancreatitis in comparison to the control group. Extreme hyperoxaluria were found in small bowel resections above 100 cm, after bypass operations and in ileocolitis Crohn with signs of clinical activity. Small bowel resections and relapses of Crohn's disease increase the absorption of oxalic acid. The significance of 14C-oxalic acid absorption test is the recognition of enteric hyperoxaluria.

Formaldehyde levels in homes insulated with urea-formaldehyde foam.

Twenty seven UFFI homes in Colorado and Wisconsin were sampled for formaldehyde levels. The formaldehyde concentrations found in these homes averaged 0.059 ppm. Two homes were monitored for an extended period to determine the impact of ambient climatic conditions.