Diagnostic challenges in a child with early onset desmoplastic medulloblastoma and homozygous variants in MSH2 and MSH6

International audienceConstitutional mismatch repair deficiency (CMMRD) is an autosomal recessively inherited childhood cancer susceptibility syndrome caused by biallelic germline mutations in one of the mismatch repair (MMR

Erfolgsfaktoren umsetzbarer Entscheidungen im Projekt

Die Forschungsfrage dieser Masterarbeit wird beantwortet, indem die Erfolgsfaktoren umsetzbarer Entscheidungen im Projekt herausgearbeitet und mittels Checkliste für die Projektleitung anwendbar werden. Die Checkliste unterstützt, dass das definierte Projektziel unter effizienter Ressourcennutzung erreicht wird, indem das Zustandekommen von Entscheidungen prozesshaft ausgestaltet wird. Die Checkliste baut auf einer managementorientierten Sicht der BWL auf und berücksichtigt die Erkenntnisse des aktuellen Sankt Galler Management-Modells mit seiner Aufgaben- und Praxisperspektive. Durch die Einsicht in die Rhomberg Bahntechnik GmbH soll dem/der Leser/in aufgezeigt werden, welche Rahmenbedingungen und Ziele ein Projekt hat und wie ein Projektmanagement in der Praxis gestaltet werden kann. Die wesentliche Erkenntnis ist, dass komplexe Entscheidungen nur von Menschen getroffen werden können. Die personale Existenzanalyse enthält anwendungsfähige Methoden, mit derer sich die Menschen zu umsetzbaren Entscheidungen führen können. Deshalb wird im Ausblick auf die personale Existenzanalyse kurz eingegangen.The research question of this master thesis is answered by working out the success factors of implementable decisions in the project and applying them to the project management using a checklist. The checklist supports that the defined project goal is achieved with efficient use of resources by structuring the process of making decisions. The checklist is based on a management-oriented view of business administration and takes into account the findings of the current Sankt Gallen management model with its task and practical perspective. By viewing Rhomberg Bahntechnik GmbH, the reader should be shown what framework conditions and goals a project has and how project management can be designed in practice. The key finding is that complex decisions can only be made by people. The personal existence analysis contains usable methods with which people can lead to implementable decisions. That is why the personal existence analysis is cured in the outlook

CXCR4-A Prognostic and Clinicopathological Biomarker for Pancreatic Ductal Adenocarcinoma: A Meta-Analysis

<div><p>Adenocarcinomas of the pancreatic duct (PDAC) are characteristically aggressive tumors that are extremely challenging to treat as curative surgical resection, the definitive treatment, is seldom possible. Regretably, most patients are diagnosed with metastatic disease at the time of initial presentation. In addition, current chemotherapeutic concepts that are used for advanced disease stages show frustrating results. Thus, there is an urgent need to identify novel therapeutic molecular targets that are associated with PDAC disease. Recently, the chemokine receptor CXCR4 has been demonstrated to be highly expressed in metastatic PDAC. However, the results of the published data on CXCR4 and its association with clinicopathological variables and prognosis in PDAC seem to be heterogeneous. Consequently, to clarify the relevance of CXCR4 as a biomarker in PDAC we performed a comprehensive literature search by using PubMed and Web of Science databases to identify articles that focused on the expression of CXCR4 in PDAC by using immunohistochemistry. Subsequently, data from nine relevant studies, encompassing 1183 patients were extracted, qualitatively assessed, and entered into a meta-analysis. By using a random effects model, the pooled hazard ratio of the seven studies that reported on patients overall survival revealed a correlation between expression of CXCR4 and poor prognosis (HR 1.49; 95% CI: 1.04-2.14; <i>P</i> = 0.03; I² = 74%). Although heterogeneity became evident, subgroup analyses confirmed the prognostic value of CXCR4 in PDAC, especially in high-quality studies that performed multivariate analysis. In addition, meta-analysis revealed a strong association of CXCR4 expression with the UICC stage (OR: 3.40; 95% CI: 1.67-6.92; <i>P</i> = 0.0007; I² = 0%) and metastatic disease (N-status: OR: 2.55; 95% CI: 1.56-4.15; <i>P</i> = 0.0002; I² = 26%; recurrence to the liver: OR: 2.80; 95% CI: 1.48-5.29; <i>P</i> = 0.001; I² = 0%). Taken together, our meta-analysis suggests that CXCR4 represents a useful prognostic biomarker in PDAC and might therefore be evaluated as a potential therapeutic target in the treatment of metastatic cancer disease of the pancreas.</p></div

Association between CXCR4 and hepatic metastasis during follow up.

<p>Forest plot reflects the individual and pooled OR with CI to assess the association between CXCR4 and hepatic metastasis during follow up. Heterogeneity was quantified by the Cochrane Q test (Chi-squared test; Chi²) and inconsistency (I²).</p

Clinical and methodological characteristics of included studies.

<p>Abbreviation: A, age; D, differentiation; Lvi, lymphovascular invasion; Le, lymphatic embolus; M, distant metastasis; N, lymph node metastasis; Pn, perineural invasion; S, sex; T, depth of invasion; U, UICC stage; Ve, vascular embolus; NS, not specified</p><p>* liver metastasis specified as recurrence</p><p>^$, distant recurrence without organ specification</p><p>^# 428 patients in multivariate analysis</p><p>^§ 249 patients evaluable</p><p>UV, univariate; MV, multivariate</p><p>^Ф, only for 17 patients without recurrence or dead.</p><p>Clinical and methodological characteristics of included studies.</p

Association between CXCR4 and clinicopathological variables.

<p>The Forest plot reflects the individual and pooled OR with CI for the relationship between expression of CXCR4 and <b>(A)</b> sex, <b>(B)</b> depth of invasion (T-stage), <b>(C)</b> lymph node metastasis (N-status), <b>(D)</b> UICC tumor stage or <b>(E)</b> grade of differentiation. Heterogeneity was verified by the Cochrane Q test (Chi-squared test; Chi²) and inconsistency (I²).</p

Study quality assessment according to the ELCWP Scale.

<p>Abbreviation: NA, not assessed</p><p>^# p-value not calculated because of low study number</p><p>*included 2 studies without survival analysis</p><p>Study quality assessment according to the ELCWP Scale.</p