Revised ESTS guidelines for preoperative mediastinal lymph node staging for non-small-cell lung cancer†

Accurate preoperative staging and restaging of mediastinal lymph nodes in patients with potentially resectable non-small-cell lung cancer (NSCLC) is of paramount importance. In 2007, the European Society of Thoracic Surgeons (ESTS) published an algorithm on preoperative mediastinal staging integrating imaging, endoscopic and surgical techniques. In 2009, the International Association for the Study of Lung Cancer (IASLC) introduced a new lymph node map. Some changes in this map have an important impact on mediastinal staging. Moreover, more evidence of the different mediastinal staging technique has become available. Therefore, a revision of the ESTS guidelines was needed. In case of computed tomography (CT)-enlarged or positron emission tomography (PET)-positive mediastinal lymph nodes, tissue confirmation is indicated. Endosonography [endobronchial ultrasonography (EBUS)/esophageal ultrasonography (EUS)] with fine-needle aspiration (FNA) is the first choice (when available), since it is minimally invasive and has a high sensitivity to rule in mediastinal nodal disease. If negative, surgical staging with nodal dissection or biopsy is indicated. Video-assisted mediastinoscopy is preferred to mediastinoscopy. The combined use of endoscopic staging and surgical staging results in the highest accuracy. When there are no enlarged lymph nodes on CT and when there is no uptake in lymph nodes on PET or PET-CT, direct surgical resection with systematic nodal dissection is indicated for tumours ≤3 cm located in the outer third of the lung. In central tumours or N1 nodes, preoperative mediastinal staging is indicated. The choice between endoscopic staging with EBUS/EUS and FNA or video-assisted mediastinoscopy depends on local expertise to adhere to minimal requirements for staging. For tumours >3 cm, preoperative mediastinal staging is advised, mainly in adenocarcinoma with high standardized uptake value. For restaging, invasive techniques providing histological information are advisable. Both endoscopic techniques and surgical procedures are available, but their negative predictive value is lower compared with the results obtained in baseline staging. An integrated strategy using endoscopic staging techniques to prove mediastinal nodal disease and mediastinoscopy to assess nodal response after induction therapy needs further stud

Technique of the transcervical-subxiphoid-videothoracoscopic maximal thymectomy

Background: The aim of this study is to present the new technique of transcervical-subxiphoid-videothoracoscopic "maximal"thymectomy introduced by the authors of this study for myasthenia gravis. Materials and Methods: Two hundred and sixteen patients with Osserman scores ranging from I-III were operated on from 1/9/2000 to 31/12/2006 for this study. The operation was performed through four incisions: a transverse 5-8 cm incision in the neck, a 4-6 cm subxiphoid incision and two 1 cm incisions for videothoracoscopic (VTS) ports. The cervical part of the procedure was performed with an open technique while the intrathoracic part was performed using a video-assisted thoracoscopic surgical (VATS) technique. The whole thymus with the surrounding fatty tissue containing possible ectopic foci of the thymic tissue was removed. Such an operation can be performed by one surgical team (the one team approach) or by two teams working simultaneously (two team approach). The early and late results as well as the incidence and localization of ectopic thymic foci have been presented in this report. Results: There were 216 patients in this study of which 178 were women and 38 were men. The ages of the patients ranged from 11 to 69 years (mean 29.7 years). The duration of myasthenia was 2-180 months (mean 28.3 months). Osserman scores were in the range of I-III. Almost 27% of the patients were taking steroids or immunosuppressive drugs preoperatively. The mean operative time was 201.5 min (120-330 min) for a one-team approach and it was 146 (95-210 min) for a two-team approach (P < 0.05). While there was no postoperative mortality, the postoperative morbidity was 12%. The incidence of ectopic thymic foci was 68.4%. The rates of complete remission after one, two, three, four and five years of follow-up were 26.3, 36.5, 42.9, 46.8 and 50.2%, respectively. Conclusion: Transcervical-subxiphoid-VTS maximal thymectomy is a complete and highly effective treatment modality for myasthenia gravis. The need for sternotomy is avoided while the completeness of the operation is retained

Technique of the transcervical-subxiphoid-videothoracoscopic maximal thymectomy

<b>Background</b>: The aim of this study is to present the new technique of transcervical-subxiphoid-videothoracoscopic "maximal"thymectomy introduced by the authors of this study for myasthenia gravis. <b>Materials and Methods</b>: Two hundred and sixteen patients with Osserman scores ranging from I-III were operated on from 1/9/2000 to 31/12/2006 for this study. The operation was performed through four incisions: a transverse 5-8 cm incision in the neck, a 4-6 cm subxiphoid incision and two 1 cm incisions for videothoracoscopic (VTS) ports. The cervical part of the procedure was performed with an open technique while the intrathoracic part was performed using a video-assisted thoracoscopic surgical (VATS) technique. The whole thymus with the surrounding fatty tissue containing possible ectopic foci of the thymic tissue was removed. Such an operation can be performed by one surgical team (the one team approach) or by two teams working simultaneously (two team approach). The early and late results as well as the incidence and localization of ectopic thymic foci have been presented in this report. <b>Results</b>: There were 216 patients in this study of which 178 were women and 38 were men. The ages of the patients ranged from 11 to 69 years (mean 29.7 years). The duration of myasthenia was 2-180 months (mean 28.3 months). Osserman scores were in the range of I-III. Almost 27&#x0025; of the patients were taking steroids or immunosuppressive drugs preoperatively. The mean operative time was 201.5 min (120-330 min) for a one-team approach and it was 146 (95-210 min) for a two-team approach (<i>P</i> &lt; 0.05). While there was no postoperative mortality, the postoperative morbidity was 12&#x0025;. The incidence of ectopic thymic foci was 68.4&#x0025;. The rates of complete remission after one, two, three, four and five years of follow-up were 26.3, 36.5, 42.9, 46.8 and 50.2&#x0025;, respectively. <b>Conclusion</b>: Transcervical-subxiphoid-VTS maximal thymectomy is a complete and highly effective treatment modality for myasthenia gravis. The need for sternotomy is avoided while the completeness of the operation is retained

Technique of the transcervical-subxiphoid-videothoracoscopic maximal thymectomy

BACKGROUND: The aim of this study is to present the new technique of transcervical-subxiphoid-videothoracoscopic “maximal”thymectomy introduced by the authors of this study for myasthenia gravis. MATERIALS AND METHODS: Two hundred and sixteen patients with Osserman scores ranging from I–III were operated on from 1/9/2000 to 31/12/2006 for this study. The operation was performed through four incisions: a transverse 5–8 cm incision in the neck, a 4–6 cm subxiphoid incision and two 1 cm incisions for videothoracoscopic (VTS) ports. The cervical part of the procedure was performed with an open technique while the intrathoracic part was performed using a video assisted thoracoscopic surgical (VATS) technique. The whole thymus with the surrounding fatty tissue containing possible ectopic foci of the thymic tissue was removed. Such an operation can be performed by one surgical team (the one team approach) or by two teams working simultaneously (two team approach). The early and late results as well as the incidence and localization of ectopic thymic foci have been presented in this report. RESULTS: There were 216 patients in this study of which 178 were women and 38 were men. The ages of the patients ranged from 11 to 69 years (mean 29.7 years). The duration of myasthenia was 2–180 months (mean 28.3 months). Osserman scores were in the range of I–III. Almost 27% of the patients were taking steroids or immunosuppressive drugs preoperatively. The mean operative time was 201.5 min (120–330 min) for a one-team approach and it was 146 (95–210 min) for a two-team approach (P < 0.05). While there was no postoperative mortality, the postoperative morbidity was 12%. The incidence of ectopic thymic foci was 68.4%. The rates of complete remission after one, two, three, four and five years of follow-up were 26.3, 36.5, 42.9, 46.8 and 50.2%, respectively. CONCLUSION: Transcervical-subxiphoid-VTS maximal thymectomy is a complete and highly effective treatment modality for myasthenia gravis. The need for sternotomy is avoided while the completeness of the operation is retained

Inter-annual and inter-habitat variation in breeding performance of Blue Tits (Cyanistes caeruleus) in central Poland

Studies at various locations in Europe show that nest-box populations of tits in urban areas lay earlier and produce fewer eggs than do birds in rural areas. Long-term data on laying date and clutch size were studied for Blue Tit (Cyanistes caeruleus) populations in two, structurally and floristically contrasting sites (an urban parkland and a rich decidu-ous forest, located only 10 km apart) in central Poland. The peak abundance of caterpillars, the optimal food of breeding tits, was also studied at both breeding areas. We focused on four environmental factors; year, site, insect availability and ambient temperature. Birds initiated breeding earlier in the urban area compared to the forest area and the laying date was highly correlated with air temperature during the period between 15 March and 15 April. At both study areas there was a similar negative temporal trend – birds started breeding earlier with later years. The number of eggs laid per breeding pair tended to be lower in the parkland than in the forest and it is likely that this is due to the habitat-specific pattern of food abundance and patchy environment in the parkland. This study provides new data on the reproductive biology of a model species and also fills up some knowledge gaps concerning inter-habitat and macro-geographic patterns

Spatial and temporal variation in heterophil-to-lymphocyte ratios of nestling passerine birds: comparison of blue tits and great tits.

Environmental factors affecting trophic conditions act as stressors on nestling altricial birds. Access of parental birds to a sufficient supply of food in a limited period of the nestling stage differ in time and space, depending on nesting habitat, prey density and weather conditions. Heterophil-to-lymphocyte ratio (H/L) is considered as a reliable indicator of prolonged stress reaction in birds. In this study we examine if variation in H/L shows consistent spatio-temporal patterns in nestlings of two parids, blue tit Cyanistes caeruleus and great tit Parus major. We found that blue tit nestlings had on average higher H/L than great tit nestlings, which corresponds with the ecological sensitivity of these species. In both species H/L was higher in a poor parkland habitat than in a high quality forest habitat. In nestling blue tits, higher H/L values occurred in years characterized by more extreme weather conditions and worse caterpillar availability. Such consistent patterns of variation in the H/L ratio of nestling blue tits and great tits suggest that, when age-dependent effects are controlled, the ratio can be used as an indicator of physiological stress that is generated by food-related stressors differing in space and time. In particular, elevated H/L ratios are indicative of human-induced changes in the structure of breeding habitats

ERα36-High Cancer-Associated Fibroblasts as an Unfavorable Factor in Triple-Negative Breast Cancer

Background: Cancer-associated fibroblasts (CAFs) are the most abundant cell type in the tumor microenvironment (TME). Estrogen receptor alpha 36 (ERα36), the alternatively spliced variant of ERα, is described as an unfavorable factor when expressed in cancer cells. ERα can be expressed also in CAFs; however, the role of ERα36 in CAFs is unknown. Methods: Four CAF cultures were isolated from chemotherapy-naïve BC patients and characterized for ERα36 expression and the NanoString gene expression panel using isolated RNA. Conditioned media from CAF cultures were used to assess the influence of CAFs on triple-negative breast cancer (TNBC) cells using a matrigel 3D culture assay. Results: We found that ERα36high CAFs significantly induced the branching of TNBC cells in vitro (p low CAFs, among which hepatocyte growth factor (HGF) was the main inducer of TNBC cell invasive phenotype in vitro (p high CAFs was correlated with high Ki67 expression (p = 0.041) and tumor-associated macrophages markers (CD68 and CD163, p = 0.041 for both). HGF was found to be an unfavorable prognostic factor in TCGA database analysis (p = 0.03 for DFS and p = 0.04 for OS). Conclusions: Breast cancer-associated fibroblasts represent distinct subtypes based on ERα36 expression. We propose that ERα36high CAFs could account for an unfavorable prognosis for TNBC patients

ER&alpha;36-High Cancer-Associated Fibroblasts as an Unfavorable Factor in Triple-Negative Breast Cancer

Background: Cancer-associated fibroblasts (CAFs) are the most abundant cell type in the tumor microenvironment (TME). Estrogen receptor alpha 36 (ER&alpha;36), the alternatively spliced variant of ER&alpha;, is described as an unfavorable factor when expressed in cancer cells. ER&alpha; can be expressed also in CAFs; however, the role of ER&alpha;36 in CAFs is unknown. Methods: Four CAF cultures were isolated from chemotherapy-na&iuml;ve BC patients and characterized for ER&alpha;36 expression and the NanoString gene expression panel using isolated RNA. Conditioned media from CAF cultures were used to assess the influence of CAFs on triple-negative breast cancer (TNBC) cells using a matrigel 3D culture assay. Results: We found that ER&alpha;36high CAFs significantly induced the branching of TNBC cells in vitro (p &lt; 0.001). They also produced a set of pro-tumorigenic cytokines compared to ER&alpha;36low CAFs, among which hepatocyte growth factor (HGF) was the main inducer of TNBC cell invasive phenotype in vitro (p &lt; 0.001). Tumor stroma rich in ER&alpha;36high CAFs was correlated with high Ki67 expression (p = 0.041) and tumor-associated macrophages markers (CD68 and CD163, p = 0.041 for both). HGF was found to be an unfavorable prognostic factor in TCGA database analysis (p = 0.03 for DFS and p = 0.04 for OS). Conclusions: Breast cancer-associated fibroblasts represent distinct subtypes based on ER&alpha;36 expression. We propose that ER&alpha;36high CAFs could account for an unfavorable prognosis for TNBC patients