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div>More generally, the current analysis suggests that epithelial MPM progresses from the diaphragmatic pleura to the apex of the chest. Pathologists have previously observed that the bases are more extensively involved with disease than the apices.14 To the extent that the disease may depend on pleural fluid as a vehicle of intrapleural dissemination of inhaled asbestos fibers and/or shed tumor cells, this finding is consistent selleck with a gravitational influence on the tumor's natural history. The current study documents a worsening prognosis as tumor involves lymph nodes and surgical margins at superior thoracic levels. These observations also support the utility of mediastinoscopy to assess superior N2 and N3 nodal involvement21 and careful radiographic assessment of the apical chest when considering EPP as primary therapy. Staging systems must evolve to account for the interaction between tumor biology and the therapeutic intervention being applied. The adjustments to classification and stage grouping criteria suggested here improved survival stratification in this cohort of patients with epithelial tumor histology who received definitive surgical therapy by EPP. Application of other therapeutic strategies, including pleurectomy/decortication, will address the generic extent of the proposed adjustments. We suspect that one would be able to use this procedure with mediastinoscopy to establish stage with a level of confidence, although the use Romidepsin of such procedures, and the strong divergence of clinical outcomes among histologic subtypes, selleck screening library may require further adjustments or annotation of the staging of MPM. The prognostic significance of individual TNM factors may be affected as nonepithelial disease is considered and as new therapies are developed that interact with tumor biology. The authors acknowledge Carl Alsup and Jordan Mueller for assistance in establishing the Patient Data Registry, Dr. John A. Mannick for critical review of the manuscript, and Ann S. Adams for editorial assistance. Supported by the International Mesothelioma Program. The authors made no further disclosures. ""Thrombocytopenia is very common in myelodysplastic syndrome (MDS); however, its clinical impact in low-risk patients remains controversial. The authors analyzed the incidence and prognostic significance of thrombocytopenia at diagnosis in 2565 de novo MDS patients included in the Spanish MDS Registry. Thrombocytopenia (platelet count <100 �� 109/L) was identified in 842 patients (32.8%). Severe thrombocytopenia (platelet count <30 �� 109/L) was observed in 7.1% of patients and was significantly associated with a higher-risk World Health Organization subtype (P = .</div>