Policies and reporting guidelines for small biopsy specimens of mediastinal masses

目前，胸腺恶性肿瘤治疗方案大多是根据术\ud 后病理确定，然而，多数临床治疗决策需要在术前\ud 通过活检小标本的病理报告来制定。所以，术前活\ud 检小标本的正确获取和病理解读对治疗决策的制定\ud 显得非常重要[1]。这些标本包括细针活检标本，带\ud 芯穿刺活检标本和手术切取活检标本[2-7]。由于胸\ud 腺肿瘤的病理诊断对组织的获取方法和获取量都有较高\ud 的要求，加之对病理的描述也没有统一的标准，使得小\ud 标本在诊断胸腺瘤方面存在诸多问题。为此，ITMIG在\ud 病理科医生和外科医生回顾相关文献和提出初步建议的\ud 基础上，经集体讨论制定了活检规范操作流程，提出了\ud 对纵隔肿物小活检标本处理和病理报告的建议。旨在为\ud 术前患者的治疗提供一个统一和具有循证医学证据的方\ud 法；同时，将有利于全球数据之间的比较和开展合作研\ud 究，充分利用医疗资源

An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors.

To address the biological heterogeneity of lung cancer, we studied 199 lung adenocarcinomas by integrating genome-wide data on copy number alterations and gene expression with full annotation for major known somatic mutations in this cancer. This showed non-random patterns of copy number alterations significantly linked to EGFR and KRAS mutation status and to distinct clinical outcomes, and led to the discovery of a striking association of EGFR mutations with underexpression of DUSP4, a gene within a broad region of frequent single-copy loss on 8p. DUSP4 is involved in negative feedback control of EGFR signaling, and we provide functional validation for its role as a growth suppressor in EGFR-mutant lung adenocarcinoma. DUSP4 loss also associates with p16/CDKN2A deletion and defines a distinct clinical subset of lung cancer patients. Another novel observation is that of a reciprocal relationship between EGFR and LKB1 mutations. These results highlight the power of integrated genomics to identify candidate driver genes within recurrent broad regions of copy number alteration and to delineate distinct oncogenetic pathways in genetically complex common epithelial cancers

Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: Results in 663 patients

ObjectiveThe optimal procedure for resection of malignant pleural mesothelioma is controversial, partly because previous analyses include small numbers of patients. We performed a multi-institutional study to increase statistical power to detect significant differences in outcome between extrapleural pneumonectomy and pleurectomy/decortication.MethodsPatients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy or pleurectomy/decortication at 3 institutions were identified. Survival and prognostic factors were analyzed by the Kaplan–Meier method, log-rank test, and Cox proportional hazards analysis.ResultsFrom 1990 to 2006, 663 consecutive patients (538 men and 125 women) underwent resection. The median age was 63 years (range, 26–93 years). The operative mortality was 7% for extrapleural pneumonectomy (n = 27/385) and 4% for pleurectomy/decortication (n = 13/278). Significant survival differences were seen for American Joint Committee on Cancer stages 1 to 4 (P < .001), epithelioid versus non-epithelioid histology (P < .001), extrapleural pneumonectomy versus pleurectomy/decortication (P < .001), multimodality therapy versus surgery alone (P < .001), and gender (P < .001). Multivariate analysis demonstrated a hazard rate of 1.4 for extrapleural pneumonectomy (P < .001) controlling for stage, histology, gender, and multimodality therapy.ConclusionPatients who underwent pleurectomy/decortication had a better survival than those who underwent extrapleural pneumonectomy; however, the reasons are multifactorial and subject to selection bias. At present, the choice of resection should be tailored to the extent of disease, patient comorbidities, and type of multimodality therapy planned

Suitability of Thoracic Cytology for New Therapeutic Paradigms in Non-small Cell Lung Carcinoma: High Accuracy of Tumor Subtyping and Feasibility of EGFR and KRAS Molecular Testing

Introduction:The two essential requirements for pathologic specimens in the era of personalized therapies for non-small cell lung carcinoma (NSCLC) are accurate subtyping as adenocarcinoma (ADC) versus squamous cell carcinoma (SqCC) and suitability for EGFR and KRAS molecular testing. The aim of this study was to comprehensively review the performance of cytologic specimens for the above two goals in a high-volume clinical practice.Methods:Subtyping of primary lung carcinomas by preoperative cytology was correlated with subsequent resection diagnoses during a 1-year period (n = 192). The contribution of various clinicopathologic parameters to subtyping accuracy and utilization of immunohistochemistry (IHC) for NSCLC subtyping were analyzed. In addition, the performance of cytologic specimens submitted for EGFR/KRAS molecular testing during a 1-year period (n = 128) was reviewed.Results:Of the 192 preoperative cytology diagnoses, tumor subtype was definitive versus favored versus unclassified in 169 (88%) versus 15 (8%) versus 8 (4%) cases, respectively. Overall accuracy of cytologic tumor subtyping (concordance with histology) was 93% and accuracy of definitive diagnoses 96%. For a group of patients with ADC and SqCC (n = 165), the rate of unclassified cytologic diagnoses was 3% and overall accuracy 96%. IHC was used for subtyping of 9% of those cases, yielding 100% accuracy. The strongest predictors of difficulty in subtyping of ADC and SqCC were poor differentiation (p = 0.0004), low specimen cellularity (p = 0.019), and squamous histology (p = 0.003). Of 128 cytologic specimens submitted for molecular testing, 126 (98%) were suitable for analysis, revealing EGFR and KRAS mutations in 31 (25%) and 25 (20%) cases, respectively.Conclusions:Cytologic subtyping of NSCLC is feasible and accurate, particularly when morphologic assessment is combined with IHC. Furthermore, routine cytologic specimens can be successfully used for EGFR/KRAS mutation analysis. Our data strongly support the suitability of cytologic specimens for the new therapeutic paradigms in NSCLC

Genetic counselling and the intention to undergo prophylactic mastectomy: effects of a breast cancer risk assessment

Scientific reports suggest that women at risk for familial breast cancer may benefit from prophylactic mastectomy. However, few data are available about how women decide upon this clinical option, and in particular, what role an objective risk assessment plays in this. The purpose of the present study is to assess whether this objective risk information provided in genetic counselling affects the intention for prophylactic mastectomy. Additionally, the (mediating) effects of breast cancer worry and perceived risk are investigated. A total of 241 women completed a questionnaire before and after receiving information about their familial lifetime breast cancer risk in a genetic counselling session. Path analysis showed that the objective risk information had a corrective effect on perceived risk (β=0.38; P=0.0001), whereas the amount of breast cancer worry was not influenced by the counselling session. The objective risk information did not directly affect the intention for prophylactic mastectomy. The intention was influenced by perceived risk after counselling (β=0.23; P=0.002), and by the precounselling levels of perceived risk (β=0.27; P=0.00025) and breast cancer worry (β=0.32; P=0.0001), that is, higher levels of perceived risk and breast cancer worry imply a stronger intention for prophylactic mastectomy. A personal history of breast cancer did not directly influence the intention for prophylactic mastectomy, but affected women who had undergone a mastectomy as surgical treatment were more positively inclined to have a prophylactic mastectomy than women who had had breast-conserving therapy. The impact of objective risk information on the intention for prophylactic mastectomy is limited and is mediated by perceived risk. Important determinants of the intention for prophylactic mastectomy were precounselling levels of breast cancer worry and perceived risk, suggesting that genetic counselling is only one event in the entire process of decision making. Therefore, interventions aimed at improving decision making on prophylactic mastectomy should explicitly address precounselling factors, such as personal beliefs and the psychological impact of the family medical history

High Expression Levels of Total IGF-1R and Sensitivity of NSCLC Cells In Vitro to an Anti-IGF-1R Antibody (R1507)

© 2009 Gong et al

Employment status and work-related difficulties in stomach cancer survivors compared with the general population

Little was known about work situation and work-related difficulties, including housework after stomach cancer diagnosis. We aimed to compare employment status and work-related difficulties between stomach cancer survivors and the general population. We enrolled 408 stomach cancer survivors from two hospitals 28 months after diagnosis and 994 representative volunteers from the general population from 15 geographic districts. Working was defined as being employed (including self-employed) and nonworking as being retired or a homemaker. Nonworking was significantly higher among stomach cancer survivors (46.6%) than in the general population (36.5%). Compared with the general population, the survivors had more fatigue in performing both housework (adjusted odds ratio (aOR)=2.08; 95% confidence interval (95% CI)=1.01–4.29) and gainful work (aOR=4.02; 2.55–6.33). More cancer survivors had reduced working hours (aOR=1.42; 95% CI=4.60–28.35) and reduced work-related ability (aOR=6.11; 95% CI=3.64–10.27) than did the general population. The association of nonworking with older age and being female was significantly more positive for survivors than for the general population. Among survivors, poorer Eastern Cooperation Oncology Group Performance Status and receiving total gastrectomy were positively associated with nonworking. Stomach cancer survivors experienced more difficulties in both housework and gainful employment than did the general population. Our findings on stomach cancer survivors' work-related difficulties and the predictors of nonworking will help physicians guide patients towards more realistic postsurgical employment plans

Rhabdovirus Matrix Protein Structures Reveal a Novel Mode of Self-Association

The matrix (M) proteins of rhabdoviruses are multifunctional proteins essential for virus maturation and budding that also regulate the expression of viral and host proteins. We have solved the structures of M from the vesicular stomatitis virus serotype New Jersey (genus: Vesiculovirus) and from Lagos bat virus (genus: Lyssavirus), revealing that both share a common fold despite sharing no identifiable sequence homology. Strikingly, in both structures a stretch of residues from the otherwise-disordered N terminus of a crystallographically adjacent molecule is observed binding to a hydrophobic cavity on the surface of the protein, thereby forming non-covalent linear polymers of M in the crystals. While the overall topology of the interaction is conserved between the two structures, the molecular details of the interactions are completely different. The observed interactions provide a compelling model for the flexible self-assembly of the matrix protein during virion morphogenesis and may also modulate interactions with host proteins