https://www.um.es/biomybiotec/web/Seminarios/2010/papers/Cano_2.pdf

Epithelial-Mesenchymal Transitions in Development and Disease

Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

Tumors are cellularly and molecularly heterogeneous, with subsets of undifferentiated cancer cells exhibiting stem cell-like features (CSCs). Epithelial to mesenchymal transitions (EMT) are transdifferentiation programs that are required for tissue morphogenesis during embryonic development. The EMT process can be regulated by a diverse array of cytokines and growth factors, such as transforming growth factor (TGF)-β, whose activities are dysregulated during malignant tumor progression. Thus, EMT induction in cancer cells results in the acquisition of invasive and metastatic properties. Recent reports indicate that the emergence of CSCs occurs in part as a result of EMT, for example, through cues from tumor stromal components. Recent evidence now indicates that EMT of tumor cells not only causes increased metastasis, but also contributes to drug resistance. In this review, we will provide potential mechanistic explanations for the association between EMT induction and the emergence of CSCs. We will also highlight recent studies implicating the function of TGF-β-regulated noncoding RNAs in driving EMT and promoting CSC self-renewal. Finally we will discuss how EMT and CSCs may contribute to drug resistance, as well as therapeutic strategies to overcome this clinically.

/pdf/emt-cancer-stem-cells-and-drug-resistance-an-emerging-axis-3ztp4dopjd.pdf

EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer

Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

Integrative Genomics Viewer

Primre aortoduodenale Fistel als Sptkomplikation nach paraaortaler Radiatio Ein Fallbericht

Introduction: Apart from immunological rejection, ischemia/reperfusion injury (IRS) still remains a serious complication following pancreas transplantation. The present study was designed to investigate the influence of FTY720 on pancreatic IRS. FTY720, a sphingosine 1-phosphate (S1P) analog, acts as an immunosuppressant through trapping of T cells in secondary lymphoid tissues. FTY720 was also shown to prevent tumor growth and to inhibit vascular permeability probably through a VEGF- dependent pathway [1]. Material and methods: Male Sprague-Dawley-Rats were anaesthetized and randomly assigned to three experimental groups: (I) sham (n = 7), (II) 60 min ischemia by temporary occlusion of the pancreas-supplying arteries followed by 60 min of reperfusion (ischemia-control, I/R, n = 7), (III) 60 min I/R and FTY720-treatment (2 mg/kg BW p. o. FTY720 6 h before ischemia, n = 5). Quantification of the effective microvascular permeability (P) was achieved by digital dynamic intravital-epifluorescence- microscopy; functional capillary density (FCD) and leukocyte-endothelial-interaction (LEI) were measured using intravital video-epifluorescence-microscopy. Results: Sham compared with I/R [P (*10-7 cm/s) 0.052 ± 0.067 vs. 1.487 ± 0.281; FCD (cm/cm2) 360 ± 13 vs. 258 ± 12; LEI (cells/mm2) 147 ± 23 vs. 310 ± 39] demonstrates a significant degradation of microcirculation with increased permeability, decreased capillary perfusion and increased number of adherent leukocytes. Except leucocyte endothelium interaction [LEI 311 ± 103] I/R + FTY720 led to a significant improvement of substantially raised parameters [P 0.361 ± 0.355, FKD 331 ± 8]. Statistical significance p < 0.05, MEAN ± SD, ANOVA on ranks and Student-Newman-Keuls-test. Conclusion: In this study we were able to show for the first time that FTY720 exhibits a protective effect in a model of pancreatic I/R-injury. Compared with conventional immunosuppressants — such as mTOR inhibitors — FTY720 as a sphingosine 1-phosphate analog (S1P) functions over a completely new signal mechanism. Possibly the protective effect of FTY720 directly correlates with its plasma concentration. In which way FTY720 detailly improves pancreatic microcirculation in ischemia/reperfusion, has yet to be examined in further experiments.

FTY720 als Sphingosin-1-Phosphat-Rezeptor (S1P-R) Agonist verbessert partiell die Mikrozirkulation des Pankreas nach Ischämie/Reperfusion

Die intraoperative Radiotherapie (IORT) kann bei lokal weit fortgeschrittenen Tumoren und zu erwartender bzw. nicht vermeidbarer R1-Situation erganzend zur chirurgischen Resektion eingesetzt werden. Ziel ist eine verbesserte lokale Tumorkontrolle und damit ein besseres Langzeituberleben. Indikationen sind sowohl primare intraabdominelle und retroperitoneale Tumoren als auch Rezidivtumoren. Im Rahmen der vorliegenden Arbeit werden die eigenen Erfahrungen mit der Durchfuhrung einer IORT bei viszeralchirurgischen Resektionen zusammengefasst. Patienten, die von Januar 2008 bis Dezember 2018 eine IORT kombiniert mit abdomineller Tumorresektion in der Klinik fur Allgemein- und Viszeralchirurgie des Universitatsklinikums Freiburgs erhalten hatten, wurden in diese Arbeit eingeschlossen und hinsichtlich Kurz- und Langzeitergebnisse evaluiert. Die haufigste Indikation zur Durchfuhrung einer IORT stellten Sarkome gefolgt von Rektum- und Analkarzinomen dar. Die mediane angewandte Strahlendosis der IORT betrug 15 Gy (8–19 Gy). Bei einem medianen „comprehensive complication index“ (CCI) von 11,9 traten bei 24 % der Patienten Komplikationen (Dindo-Clavien ≥ °III) auf. Die 90-Tage-Mortalitat betrug 0 %. Besonders fur Analkarzinomrezidive war die lokale Kontrolle nach einem Jahr trotz R0-Resektion unzureichend. In unserem Patientenkollektiv war die IORT mit vertretbarer Morbiditat einsetzbar. Dennoch sind Indikationsstellung und Patientenselektion kritische Punkte fur die Durchfuhrung der Behandlung. Der Effekt der IORT zur Verbesserung der lokalen Kontrolle und damit auch des Langzeituberlebens sollte in weiteren Studien evaluiert werden.

https://link.springer.com/content/pdf/10.1007/s00104-020-01165-z.pdf

[Intraoperative radiotherapy in abdominal surgery-Own experiences].

Pankreaschirurgie ist anspruchsvoll und komplikationstrachtig. Klare Standards fur den Routineablauf beinhalten Ernahrung, Infusionsregime, Mobilisierung, Schmerztherapie sowie endokrine und exokrine Substitution. Den meisten Patienten kann erfolgreich ein FastTrack-Konzept angeboten werden. Typische Probleme sind postoperative Pankreasfisteln, verzogerte Magenentleerung und Blutungen. Ein konsequentes Management von Komplikationen ermoglicht heute eine Letalitat von

Ulrich T. Hopt

Papers

Primre aortoduodenale Fistel als Sptkomplikation nach paraaortaler Radiatio Ein Fallbericht

FTY720 als Sphingosin-1-Phosphat-Rezeptor (S1P-R) Agonist verbessert partiell die Mikrozirkulation des Pankreas nach Ischämie/Reperfusion

[Intraoperative radiotherapy in abdominal surgery-Own experiences].

Perioperatives Management bei Pankreasresektionen

The Inflammatory Pancreatic Head Mass