[Joint Statement of the German Respiratory Society and German Society of Thoracic Surgery in Cooperation with the German Radiological Society: Structural Prerequisites of Centers for Interventional Treatment of Emphysema]. / Positionspapier der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin und der Deutschen Gesellschaft für Thoraxchirurgie in Kooperation mit der Deutschen Röntgengesellschaft: Strukturvoraussetzungen von Zentren für die interventionelle Emphysemtherapie.

Interventional treatment of emphysema offers a wide range of surgical and endoscopic options for patientes with advanced disease. Multidsciplinary collaboration of pulmonology, thoracic surgery and imaging disciplines in patient selection, therapy and follow up ensures treatment quality. The present joint statement describes the required structural and quality prerequsites of treatment centres.

Clinical reactivity of celery cultivars in allergic patients: Role of Api g 1.

BACKGROUND: Celery (Apium graveolens L.) is a vegetable consumed world-wide. Celery stalks and celeriac roots are often ingredients in convenient food products like spice blends and soups. OBJECTIVE: In this study, we examined the allergenicity of distinct celeriac cultivars. METHODS: Sixteen celery-allergic patients were identified using a double-blind, placebo-controlled food challenge. Ten different celeriac cultivars were used for skin prick testing in the patients. Two cultivars were further applied for oral food challenges; their protein composition was analysed by immunoblotting, and contents of major allergen Api g 1 were quantified. RESULTS: From the 10 investigated celeriac cultivars, two cultivars elicited significantly different skin reactivity ("Anita": 5.0 [2.0-12.0] mm vs "Prinz": 7.0 [3.0-9.5] mm; P = .047). Moreover, "Anita" induced fewer symptoms after a controlled oral-celeriac challenge in 14 patient (P < .001). The protein profiles on 2DE protein gels showed distinct protein patterns and higher protein amounts of Api g 1 in "Prinz" than in "Anita." CONCLUSIONS AND CLINICAL RELEVANCE: Taken together, the data from this study suggest that cultivar Anita is better tolerated in celery-allergic patients than "Prinz." Differences in the protein expression profile between the cultivars, particularly the different content of Api g 1, could cause the different allergenicity.

Rapid diversification of sexual signals in Hawaiian Nesosydne planthoppers (Hemiptera: Delphacidae): the relative role of neutral and selective forces.

Changes in sexual signals have the potential to promote rapid divergence and reproductive isolation among populations of animals. Thus, identifying processes contributing to variation in signals is key to understanding the drivers of speciation. However, it is difficult to identify the processes initiating changes in signals in empirical systems because (1) the demographic history of populations under study is usually unclear, and (2) there is no unified hypothesis-testing framework for evaluating the simultaneous contribution of multiple processes. A unique system for study in the Hawaiian Islands, the planthopper species Nesosydne chambersi, offers a clear demographic context to disentangle these factors. By measuring variation in male vibratory sexual signals across different genetic populations on the island of Hawaii, we found that that multiple signal traits varied significantly between populations. We developed a mixed modelling framework to simultaneously test competing hypotheses about which processes contribute to changes in signal traits: genetic drift, sensory drive or reproductive character displacement. Our findings suggest that signal divergence proceeds along different axes for different signal traits under the influence of both neutral and selective processes. They are the first, to our knowledge, to document the relative importance of multiple processes on divergence in sexual signals.

Assessment of SHOX2 methylation in EBUS-TBNA specimen improves accuracy in lung cancer staging.

BACKGROUND: Endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) is a well-established method to assess mediastinal lymph nodes for lung cancer. However, a proportion of patients require further investigation, due to the low negative predictive value (NPV). The objective of this study was to determine whether the assessment of short stature homeobox 2 (SHOX2) DNA methylation level in lymph node tissue obtained by EBUS-TBNA improves the accuracy of mediastinal staging. PATIENTS AND METHODS: EBUS-TBNA was carried out for suspicious lymph nodes of 154 patients. Negative or ambiguous histological results were confirmed by surgical means and clinical follow-up over 6 months. EBUS-TBNA was assessed on 80 positive and 85 negative classified lymph nodes and compared with the result of the SHOX2 DNA methylation real-time PCR analysis. Relative methylation measured by delta-delta cycle threshold (ΔΔCt) was used to classify the samples. Clinical performance of the EBUS-TBNA procedure with and without the additional SHOX2 assessment was calculated against the final classification according to the gold standard. RESULTS: Based on data from 105 patients, an average 80-fold increase in the SHOX2 methylation level was measured for positive compared with negative lymph nodes. SHOX2 results with a ΔΔCt value of <6.5 indicate positive lymph nodes. Applying this molecular analysis to EBUS-TBNA cases, not diagnosed by pathologic assessment, the sensitivity of staging was improved by 17%-99%. The NPV increased from 80% to 99%. CONCLUSIONS: The combination of EBUS-TBNA and SHOX2 methylation level strongly improves the assessment of the nodal status by identifying additional malignant lesions and confirming benign nodes and therefore avoiding invasive follow-up procedures.

Identification of putative new tomato allergens and differential interaction with IgEs of tomato allergic subjects.

BACKGROUND: Tomato became one of the world-wide most consumed vegetables, unfortunately accompanied by an increasing risk of tomato allergy affecting certain people. As tomato allergic subjects show highly variable reactions in clinical allergy tests, it is difficult to identify cultivars or differentially treated tomato plants where a significant reduction in the allergenic potential over all subjects of a cohort can be detected. OBJECTIVE: This study was carried out to test the hypothesis that individual variability is based on differential reactions of single subjects to particular allergens in tomato fruits of plants with certain genetic background or cultivated under distinct conditions. METHODS: Proteins were extracted from tomato fruits of the previously investigated genotypes 76R, its mycorrhizal mutant RMC, and the cultivar Counter, fertilized with different forms of nitrogen in deficit or excess. 2-D immunoblots were carried out with sera of nine tomato allergic subjects, beforehand analysed in skin prick tests. RESULTS: In total, ten putative tomato allergens were identified in these immunoblots. No correlation was detected between individual skin prick test results and the quantity of positive reactions to putative allergens. IgEs of each subject showed reactions to nearly every identified putative allergen, but reactions were dependent on genotype and growth conditions. Among the ten putative tomato allergens, five new candidates were identified as follows: an endo-ß-mannanase, a pectinacetylesterase, a pectinesterase inhibitor, an aspartyl protease family protein and a protein of unknown function. CONCLUSION AND CLINICAL RELEVANCE: The hypothesis that high interindividual differences in allergic reactions are based on the interactions between the IgEs of allergic subjects with particular allergens has to be rejected. However, five proteins with putative clinical relevance as tomato allergens could be newly identified.

Cannibalism as an interacting phenotype: precannibalistic aggression is influenced by social partners in the endangered Socorro Isopod (Thermosphaeroma thermophilum).

Models for the evolution of cannibalism highlight the importance of asymmetries between individuals in initiating cannibalistic attacks. Studies may include measures of body size but typically group individuals into size/age classes or compare populations. Such broad comparisons may obscure the details of interactions that ultimately determine how socially contingent characteristics evolve. We propose that understanding cannibalism is facilitated by using an interacting phenotypes perspective that includes the influences of the phenotype of a social partner on the behaviour of a focal individual and focuses on variation in individual pairwise interactions. We investigated how relative body size, a composite trait between a focal individual and its social partner, and the sex of the partners influenced precannibalistic aggression in the endangered Socorro isopod, Thermosphaeroma thermophilum. We also investigated whether differences in mating interest among males and females influenced cannibalism in mixed sex pairs. We studied these questions in three populations that differ markedly in range of body size and opportunities for interactions among individuals. We found that relative body size influences the probability of and latency to attack. We observed differences in the likelihood of and latency to attack based on both an individual's sex and the sex of its partner but found no evidence of sexual conflict. The instigation of precannibalistic aggression in these isopods is therefore a property of both an individual and its social partner. Our results suggest that interacting phenotype models would be improved by incorporating a new conditional ψ, which describes the strength of a social partner's influence on focal behaviour.

[Glandular papilloma of the right main bronchus. Detection of an exon 2 mutation of the KRAS gene (c.35G>A)]. / Glanduläres Papillom des rechten Hauptbronchus. Nachweis einer Exon-2-Mutation des KRAS-Gens (c.35G>A).

Benign epithelial tumors of the tracheobronchial system and the lungs are exceedingly rare. These entities encompass squamous and glandular papillomas (as well as their mixed forms) and adenomas (alveolar adenoma, papillary adenoma, salivary gland-like pleomorphic and mucinous adenomas and mucinous cystadenomas). These tumors are considered to be biologically benign neoplasms; however, they can pose considerable diagnostic difficulties, especially during frozen section evaluation, as they can mimic malignant tumors and in particular they can resemble well differentiated papillary adenocarcinomas. As a result of the extreme rarity of these tumors only a few descriptive diagnostic series exist and a systematic investigation including molecular data does not exist. This article presents the case of a 64-year-old patient with a glandular papilloma of the right main bronchus including the immunohistochemical and molecular work-up as well as a review of the current literature.

[Injuries to the tracheo-bronchial tree]. / Verletzungen des Tracheobronchialbaums.

Tracheobronchial injuries are rare events but often life-threatening. A great expertise in the field of thoracic surgery is necessary to manage these events. The aetiology of the injury - traumatic or iatrogenic - allows immediate considerations about the pattern of damage. The flexible or rigid bronchoscopy is the central diagnostic procedure to classify the injury. Whereas iatrogenic tracheal lacerations can be treated by conservative or operative means depending on severity, traumatic injuries of the tracheo-bronchial system need technically challenging operative reconstructions in almost every case.

ßV-tubulin expression is associated with outcome following taxane-based chemotherapy in non-small cell lung cancer.

BACKGROUND: Tubulin-binding agents (TBAs) are effective in non-small cell lung cancer (NSCLC) treatment. Both ßIII- and ßV-tubulins are expressed by cancer cells and may lead to resistance against TBAs. METHODS: Pre-treatment samples from 65 locally advanced or oligometastatic NSCLC patients, who underwent uniform induction chemotherapy with paclitaxel and platinum followed by radiochemotherapy with vinorelbine and platinum were retrospectively analysed by immunohistochemistry. Protein expression of ßIII- and ßV-tubulin was morphometrically quantified. RESULTS: Median pre-treatment H-score for ßIII-tubulin was 110 (range: 0-290), and 160 for ßV-tubulin (range: 0-290). Low ßIII-tubulin expression was associated with improved overall survival (OS) (P=0.0127, hazard ratio (HR): 0.328). An association between high ßV-tubulin expression and prolonged progression-free survival (PFS, median 19.2 vs 9.4 months in high vs low expressors; P=0.0315, HR: 1.899) was found. Further, high ßV-tubulin expression was associated with objective response (median H-score 172.5 for CR+PR vs 120 for SD+PD patients, P=0.0104) or disease control following induction chemotherapy (170 for CR+PR+SD vs 100 for PD patients, P=0.0081), but not radiochemotherapy. CONCLUSION: Expression of ßV-tubulin was associated with treatment response and PFS following paclitaxel-based chemotherapy of locally advanced and oligometastatic NSCLC patients. Prolonged OS was associated with low levels of ßIII-tubulin. Prospective evaluation of ßIII/ßV-tubulin expression in NSCLC is warranted.

Colorectal cancer pulmonary oligometastases: pooled analysis and construction of a clinical lung metastasectomy prognostic model.

BACKGROUND: Although resecting colorectal cancer (CRC) pulmonary metastasis is associated with long-term survival, identification of prognostic groups is needed for future randomized trials, and construction of a lung metastasectomy prognostic model (LMPM) is warranted. PATIENTS AND METHODS: We searched the PubMed database for retrospective studies evaluating prognostic factors following resecting CRC lung metastasis. Individual patient data were analyzed. Independent prognostic factors were used to construct an LMPM. RESULTS: Between 1983 and 2008, 1112 metastasectomies were carried out on 927 patients included in eight studies. Five-year survival rate was 54.3% following the first lung resection. Multivariate analysis identified three independently poor prognostic factors: pre-thoracotomy carcinoembryonic antigen ≥5 ng/ml, disease-free interval <36 months, and more than one metastatic lesion. Patients with good-, intermediate-, and high-risk groups according to the LMPM had a 5-year survival of 68.2%, 46.4%, and 26.1%, respectively (P < 0.001). Perioperative chemotherapy and previously resected liver metastasis had no influence on survival. CONCLUSIONS: The low- and intermediate-risk groups have a good chance of long-term survival following metastasectomy. However, more studies are needed to investigate whether surgery offers any advantage over systemic therapy for the poor-risk group.

Lung segment geometry study: simulation of largest possible tumours that fit into bronchopulmonary segments.

BACKGROUND: Segmental resection in stage I non-small cell lung cancer (NSCLC) has been well described and is considered to have similar survival rates as lobectomy but with increased rates of local tumour recurrence due to inadequate parenchymal margins. In consequence, today segmentectomy is only performed when the tumour is smaller than 2 cm. METHODS: Three-dimensional reconstructions from 11 thin-slice CT scans of bronchopulmonary segments were generated, and virtual spherical tumours were placed over the segments, respecting all segmental borders. As a next step, virtual parenchymal safety margins of 2 cm and 3 cm were subtracted and the size of the remaining tumour calculated. RESULTS: The maximum tumour diameters with a 30-mm parenchymal safety margin ranged from 26.1 mm in right-sided segments 7 + 8 to 59.8 mm in the left apical segments 1-3. CONCLUSIONS: Using a three-dimensional reconstruction of lung CT scans, we demonstrated that segmentectomy or resection of segmental groups should be feasible with adequate margins, even for larger tumours in selected cases.

[Lung cancer staging: what is the actual role of mediastinoscopy?]. / Staging des Lungenkarzinoms: Welche Rolle spielt die Mediastinoskopie heute?

Today several methods for invasive mediastinal staging of lung cancer are available. Whereas mediastinoscopy and anterior mediastinotomy had been the gold standard in every situation several years ago, today EBUS-TBNA has been developed as an alternative to mediastinoscopy concerning the status of lymph node positions 2 L / R, 4 L / R and 7. Actually mediastinoscopy is accepted as the gold standard only in special situations such as negative cytology of suspicious lymph nodes after EBUS-TBNA and mediastinal evaluation after neoadjuvant treatment.

Factors influencing the usage of complementary and alternative medicine by patients with cancer.

INTRODUCTION: The interest in CAM among cancer patients is constantly growing and about 50% already used CAM alongside cancer therapy. Little is known on the factors influencing patients' choice of type of CAM used. METHODS: A questionnaire consisting of two validated instruments (the ASKU (Allgemeine Selbstwirksamkeit Kurzskala), the PAM 13-D (Patient Activation Measure) and the structured AKKOM questionnaire on CAM usage was distributed at a German university hospital. RESULTS: 639 patients (male 32.9%, female 63.2%; gynecological cancer 41%, gastrointestinal 19.2%, urogenital 15.6%) took part. 60% had used CAM in the last 3 months (biological 73%, holistic 63%, mind-body-methods 62%). Participants up to 30 years preferred biologically (p = 0.001), while women with gynecological cancer favored holistic based methods (p < 0.0001). There was no association between patients' beliefs on cancer causes and the chosen CAM method. CONCLUSION: Improving knowledge in patients on cancer etiology and treatments could facilitate the understanding of additional complementary treatments.

[Tracheal injuries, fistulae from bronchial stump and bronchial anastomoses and recurrent laryngeal nerve paralysis : management of complications in thoracic surgery]. / Tracheaverletzungen, Insuffizienz von Bronchusstumpf/-anastomose und Rekurrensparese : Management der Komplikationen in der Thoraxchirurgie.

BACKGROUND: Complications cannot always be avoided and their treatment is an integral component of a high quality medical treatment. Complications of the central airways are rare but necessitate supportive treatment by an experienced thoracic surgeon. OBJECTIVE: The reader should become acquainted with measures to prevent complications, to recognize and treat complications early and should understand the necessity for an interdisciplinary approach. MATERIAL AND METHODS: A selective literature research was supplemented by personal experiences and complemented with prospectively collected photographs. RESULTS: There are risk constellations for the appearance of all the mentioned complications which the surgeon needs to know in order to be able to take measures for early detection of complications. Iatrogenic tracheal injuries and bronchial stump fistulae are rare (< 5 %) whereas recurrent laryngeal nerve palsy after left-sided pneumonectomy occurs in up to 30 % of cases. DISCUSSION: After the occurrence of complications at the latest, it is very important to include experienced thoracic surgeons and other specialists when necessary to protect the patient from further damage.

HER2 expression and markers of phosphoinositide-3-kinase pathway activation define a favorable subgroup of metastatic pulmonary adenocarcinomas.

OBJECTIVES: Pulmonary adenocarcinomas (ADC) can be sub-grouped based on dominant oncogenic drivers. EGFR mutations define an entity of metastatic ADC with favorable prognosis and high susceptibility to EGFR tyrosine kinase inhibition. In contrast, the clinical impact of additional ERBB family members in ADC is less defined. To this end we prospectively studied HER2 expression, gene amplification, and mutation in relation to outcome of patients with advanced or metastatic ADC. MATERIALS AND METHODS: Diagnostic tumor biopsies from 193 sequential patients with stage III/IV ADC were prospectively studied for HER2 expression by immunohistochemistry (IHC). Cases with IHC scores 2+ or 3+ were analyzed by HER2 chromogenic in situ hybridization (CISH), and sequencing of HER2 exons 20 and 23. Additional prospectively determined biomarkers included PTEN, cMET, pAKT, and pERK expression, KRAS, EGFR, BRAF and PIK3CA mutations, and ALK fluorescence ISH (FISH). RESULTS AND CONCLUSION: HER2-IHC was feasible in 176 (91.2%) cases. Of 53 (30%) cases with IHC scores 2+/3+, 45 (85%) could be studied by CISH and 34 (64%) by sequencing. The lower number of HER2-mutational analyses resulted from exhaustion of tumor tissue and DNA following mutational analysis of KRAS, EGFR, BRAF and PIK3CA. HER2 amplification was detected in 4 cases (2.3%), while no mutation was found. HER2 expression correlated with expression of pAKT and cMET. Expression of HER2 and pAKT was associated with favorable overall survival in stage IV disease. HER2-expressing ADC more frequently harbored KRAS mutations, while HER2 expression was absent in all 4 cases with BRAF mutation. HER2-IHC was not predictive of HER2 gene amplification or mutation, which both were rare events in prospectively studied patients with advanced or metastatic ADC. Expression of HER2 and pAKT define a population of patients with stage IV ADC with a distinct disease course, who could benefit from specifically tailored pharmacotherapies.

Factors predicting successful labor induction.

OBJECTIVE: To evaluate maternal parity, the sonographic measurement of cervical length, and the five components of the Bishop score to determine which factors best predict the length of latent-phase labor in women undergoing labor induction. METHODS: Cervical position, cervical consistency, cervical effacement, cervical dilation, station of fetal presenting part, maternal parity, and sonographic measurement of cervical length were studied prospectively in 109 women undergoing labor induction. A multiple regression model was used to determine which factors best predict the length of latent-phase labor. RESULTS: A model using these seven factors was predictive in determining the number of hours of latent-phase labor (F = 32.1, P < .001). Backward stepwise multiple linear regression indicated that only cervical dilation independently predicted the length of latent-phase labor. There was a significant correlation between the clinical assessment of cervical effacement and the sonographic estimation of cervical length, (r = -0.523, P < .001). CONCLUSION: Only cervical dilation appears to predict the length of latent-phase labor. The sonographic evaluation of cervical length and maternal parity do not add significant independent information.

Tolerance to herbivory by a stemboring caterpillar in architecturally distinct maizes and wild relatives.

In a screenhouse experiment in southwest Mexico, we infested two maize cultivars, a land-race and a modern high-yielding variety, and two wild teosintes, Zea diploperennis and Zea mays parviglumis, with newly hatched larvae of the stemborer, Diatraea grandiosella. While subsequent damage levels, when corrected for differences in plant size, were highest in the wild perennial, Zea diploperennis, this taxon showed the lowest absolute and proportional reductions in growth and reproduction, i.e., it was most tolerant to the damage. Higher growth rates were not associated with tolerance. Rather, a greater number of tillers and leaves in the wild taxa allowed for compartmentalization of damage and greater developmental plasticity. These results, when combined with previous findings on effective defense patterns, indicate that tolerance in maizes and wild relatives may be positively associated with defense against stemboring by the same insect. Because the probable mechanisms for defense (tissue fiber) and tolerance (plant architecture) are unrelated, a positive association is contrary to the predictions of some optimal defense theories, which posit a negative relationship between tolerance and defense.

High-risk obstetric patients. Maternal morbidity after cesareans.

OBJECTIVE: To assess maternal morbidity associated with cesarean delivery among high-risk obstetric patients in a private practice setting. STUDY DESIGN: Maternal outcome parameters were prospectively studied in 1,000 consecutively delivered patients over a one-year period. RESULTS: Three hundred forty-one patients (34%) delivered by cesarean; 194 of the procedures were performed without labor. The incidence of febrile morbidity and wound infection in patients undergoing cesarean delivery without labor, 0.5%, was no greater than that of patients who delivered vaginally (P = 1.0). There was a higher incidence of transfusion in patients delivered by cesarean without labor, but these patients were more likely to have preoperative anemia (P = .036). Patients undergoing cesarean with labor or ruptured membranes had an increased incidence of both febrile morbidity (P = .023) and wound seroma (P = .008). CONCLUSION: Maternal morbidity following cesarean delivery in high-risk obstetric patients in a private practice setting is low.

Correlated insecticide cross-resistance in azinphosmethyl resistant codling moth (Lepidoptera: Tortricidae).

Resistance to several classes of insecticides was correlated with azinphosmethyl resistance in codling moth, Cydia pomonella (L.), in California. In tests of laboratory and field populations, cross-resistance was positively correlated with azinphosmethyl and two organophosphates (diazinon, phosmet), a carbamate (carbaryl), a chlorinated hydrocarbon (DDT), and two pyrethroids (esfenvalerate and fenpropathrin). Additionally, negatively correlated cross-resistance was identified between azinphosmethyl and two other organophosphates, chlorpyrifos and methyl parathion. Patterns of resistance observed in laboratory colonies were confirmed with field bioassays. In bioassays of field populations, azinphosmethyl resistance was observed to increase from 1991 to 1993, although levels of resistance remained < 13-fold. Because orchards with azinphosmethyl resistance have had difficulties with suppression of codling moth, and cross-resistance was found for all tested classes of insecticides, strategies for managing resistance will need to be developed so as to protect current and future control tactics. The two insecticides with negatively correlated cross-resistance are discussed as potential tools for resistance management.

Potential for outbreaks of leafrollers (Lepidoptera: Tortricidae) in California apple orchards using mating disruption for codling moth suppression.

Two species of leafrollers, Argyrotaenia citrana (Fernald) and Pandemis pyrusana Kearfott, represent serious obstacles to the implementation of mating disruption for control of codling moth in coastal California apple orchards. Larval and adult densities of A. citrana and P. pyrusana and subsequent fruit damage were compared under different codling moth control treatments. Leafroller larval counts and levels of fruit damage were significantly higher in most plots that were untreated or treated only with codling moth pheromone. Leafroller fruit damage levels in these plots were commonly between 10 and 15% at harvest. As summer larval counts were good predictors of fruit damage levels, larval sampling could be a useful tool for predicting leafroller outbreaks. Use of pheromone trapping for A. citrana to detect localized outbreaks within an orchard was not useful and failed to correlate with larval numbers, whereas adult monitoring for P. pyrusana appears more promising. Efforts to implement a codling moth mating-disruption program in California must include changes in strategies for monitoring and controlling leafroller species.