Worldwide Esophageal Cancer Collaboration : clinical staging data

Peer reviewe

Early pregnancy peripheral blood gene expression and risk of preterm delivery: a nested case control study

<p>Abstract</p> <p>Background</p> <p>Preterm delivery (PTD) is a significant public health problem associated with greater risk of mortality and morbidity in infants and mothers. Pathophysiologic processes that may lead to PTD start early in pregnancy. We investigated early pregnancy peripheral blood global gene expression and PTD risk.</p> <p>Methods</p> <p>As part of a prospective study, ribonucleic acid was extracted from blood samples (collected at 16 weeks gestational age) from 14 women who had PTD (cases) and 16 women who delivered at term (controls). Gene expressions were measured using the GeneChip^®Human Genome U133 Plus 2.0 Array. Student's T-test and fold change analysis were used to identify differentially expressed genes. We used hierarchical clustering and principle components analysis to characterize signature gene expression patterns among cases and controls. Pathway and promoter sequence analyses were used to investigate functions and functional relationships as well as regulatory regions of differentially expressed genes.</p> <p>Results</p> <p>A total of 209 genes, including potential candidate genes (e.g. PTGDS, prostaglandin D2 synthase 21 kDa), were differentially expressed. A set of these genes achieved accurate pre-diagnostic separation of cases and controls. These genes participate in functions related to immune system and inflammation, organ development, metabolism (lipid, carbohydrate and amino acid) and cell signaling. Binding sites of putative transcription factors such as EGR1 (early growth response 1), TFAP2A (transcription factor AP2A), Sp1 (specificity protein 1) and Sp3 (specificity protein 3) were over represented in promoter regions of differentially expressed genes. Real-time PCR confirmed microarray expression measurements of selected genes.</p> <p>Conclusions</p> <p>PTD is associated with maternal early pregnancy peripheral blood gene expression changes. Maternal early pregnancy peripheral blood gene expression patterns may be useful for better understanding of PTD pathophysiology and PTD risk prediction.</p

The role of the amygdala in face perception and evaluation

Faces are one of the most significant social stimuli and the processes underlying face perception are at the intersection of cognition, affect, and motivation. Vision scientists have had a tremendous success of mapping the regions for perceptual analysis of faces in posterior cortex. Based on evidence from (a) single unit recording studies in monkeys and humans; (b) human functional localizer studies; and (c) meta-analyses of neuroimaging studies, I argue that faces automatically evoke responses not only in these regions but also in the amygdala. I also argue that (a) a key property of faces represented in the amygdala is their typicality; and (b) one of the functions of the amygdala is to bias attention to atypical faces, which are associated with higher uncertainty. This framework is consistent with a number of other amygdala findings not involving faces, suggesting a general account for the role of the amygdala in perception

Chronology of the Pueblo Viejo epithermal gold-silver deposit, Dominican Republic: formation in an Early Cretaceous intra-oceanic island arc and burial under ophiolite.

The Pueblo Viejo deposit (production to 1996:166 t Au, 760 t Ag) is located in the Dominican Republic on the Caribbean island of Hispaniola and ranks as one of the largest high-sulfidation/acid-sulfate epithermal deposits (reserves in 2007: 635 t Au, 3,648 t Ag). One of the advanced argillic ore bodies is cut by an inter-mineral andesite porphyry dike, which is altered to a retrograde chlorite-illite assemblage but overprinted by late-stage quartz-pyrite-sphalerite veins and associated low-grade Au, Ag, Zn, Cd, Hg, In, As, Se, and Te mineralization. The precise TIMS U-Pb age (109.6±0.6 Ma) of the youngest zircon population in this dike confirms that the deposit is part of the Early Cretaceous Los Ranchos intraoceanic island arc. Intrusion-related gold-sulfide mineralization took place during late andesite-dacite volcanism within a thick pile (>200 m) of carbonaceous sand- and siltstones deposited in a restricted marine basin.The high-level deposit was shielded from erosion after burial under a late Albian (109-100 Ma) ophiolite complex (8 km thick), which was in turn covered by the volcano-sedimentary successions (>4 km) of a Late Cretaceous-Early Tertiary calc-akaline magmatic arc. Estimates of stratigraphic thickness and published alunite, illite, and feldspar K-Ar ages and closure temperatures (alunite 270±20C, illite 260±30C, K-feldspar 150C) indicate a burial depth of about 12 km at 80 Ma. During peak burial metamorphism (300C and 300 MPa), the alteration assemblage kaolinite + quartz in the deposit dehydrated to pyrophyllite. Temperature-time relations imply that the Los Ranchos terrane then cooled at a rate of 3-4C/Ma during slow uplift and erosion

Worldwide esophageal cancer collaboration

The aim of this study is to report assemblage of a large multi-institutional international database of esophageal cancer patients, patient and tumor characteristics, and survival of patients undergoing esophagectomy alone and its correlates. Forty-eight institutions were approached and agreed to participate in a worldwide esophageal cancer collaboration (WECC), and 13 (Asia, 2; Europe, 2; North America, 9) submitted data as of July 1, 2007. These were used to construct a de-identified database of 7884 esophageal cancer patients who underwent esophagectomy. Four thousand six hundred and twenty-seven esophagectomy patients had no induction or adjuvant therapy. Mean age was 62±11 years, 77% were men, and 33% were Asian. Mean tumor length was 3.3±2.5 cm, and esophageal location was upper in 4.1%, middle in 27%, and lower in 69%. Histopathologic cell type was adenocarcinoma in 60% and squamous cell in 40%. Histologic grade was G1 in 32%, G2 in 33%, G3 in 35%, and G4 in 0.18%. pT classification was pTis in 7.3%, pT1 in 23%, pT2 in 16%, pT3 in 51%, and pT4 in 3.3%. pN classification was pN0 in 56% and pN1 in 44%. The number of lymph nodes positive for cancer was 1 in 12%, 2 in 8%, 3 in 5%, and >3 in 18%. Resection was R0 in 87%, R1 in 11%, and R2 in 3%. Overall survival was 78, 42, and 31% at 1, 5, and 10 years, respectively. Unlike single-institution studies, in this worldwide collaboration, survival progressively decreases and is distinctively stratified by all variables except region of the world. A worldwide esophageal cancer database has been assembled that overcomes problems of rarity of this cancer. It reveals that survival progressively (monotonically) decreased and was distinctively stratified by all variables except region of the world. Thus, it forms the basis for data-driven esophageal cancer staging. More centers are needed and encouraged to join WECC. © 2008 Copyright the Authors Journal compilation © 2008, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.link_to_subscribed_fulltex

Optimum lymphadenectomy for esophageal cancer

OBJECTIVE: Using Worldwide Esophageal Cancer Collaboration data, we sought to (1) characterize the relationship between survival and extent of lymphadenectomy, and (2) from this, define optimum lymphadenectomy. SUMMARY BACKGROUND DATA: What constitutes optimum lymphadenectomy to maximize survival is controversial because of variable goals, analytic methodology, and generalizability of the underpinning data. METHODS: A total of 4627 patients who had esophagectomy alone for esophageal cancer were identified from the Worldwide Esophageal Cancer Collaboration database. Patient-specific risk-adjusted survival was estimated using random survival forests. Risk-adjusted 5-year survival was averaged for each number of lymph nodes resected and its relation to cancer characteristics explored. Optimum number of nodes that should be resected to maximize 5-year survival was determined by random forest multivariable regression. RESULTS: For pN0M0 moderately and poorly differentiated cancers, and all node-positive (pN+) cancers, 5-year survival improved with increasing extent of lymphadenectomy. In pN0M0 cancers, no optimum lymphadenectomy was defined for pTis; optimum lymphadenectomy was 10 to 12 nodes for pT1, 15 to 22 for pT2, and 31 to 42 for pT3/T4, depending on histopathologic cell type. In pN+M0 cancers and 1 to 6 nodes positive, optimum lymphadenectomy was 10 for pT1, 15 for pT2, and 29 to 50 for pT3/T4. CONCLUSIONS: Greater extent of lymphadenectomy was associated with increased survival for all patients with esophageal cancer except at the extremes (TisN0M0 and ≥7 regional lymph nodes positive for cancer) and well-differentiated pN0M0 cancer. Maximum 5-year survival is modulated by T classification: resecting 10 nodes for pT1, 20 for pT2, and ≥30 for pT3/T4 is recommended. Copyright © 2009 by Lippincott Williams & Wilkins.link_to_subscribed_fulltex