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

Objectives Perioperative morbidity after pancreatoduodenectomies is still high. One potentially responsible factor is the insertion of bile duct stents before surgery. In our single-center study, we evaluated the influence of preoperative bile duct stenting combined with perioperative antibiotic therapy versus primary surgery in carcinoma patients. Methods Clinical data of 973 patients undergoing pancreatoduodenectomy at the University Hospital Freiburg from 2002 to 2018 were explored retrospectively. Postoperative pancreatic fistula, delayed gastric emptying (DGE), and postpancreatectomy hemorrhage (PPH) were graded by current international definitions. Patients with pancreatic ductal adenocarcinoma or periampullary carcinoma were included. Results We included 634 patients of whom 372 (58.7%) were treated with preoperative bile duct stenting. No difference concerning postoperative pancreatic fistula was observed (P = 0.479). We found more wound infections (stent 18.4%, no stent 11.1%, P = 0.008) but a significantly lower rate of PPH and DGE in stented patients (PPH 7.5% vs 11.9%, P = 0.044; DGE 16.5% vs 22.5%, P = 0.039). Surprisingly, intra-abdominal abscesses were reduced in stented patients (9.4% vs 15.0%, P = 0.022), just as insufficiencies of the biliodigestive anastomosis (P = 0.021). Conclusions Perioperative antibiotic therapy seems to reduce the risk for severe intra-abdominal infectious complications in stent-bearing patients.

Stent-Associated Infectious Complications After Pancreatoduodenectomies Can Be Prevented by Perioperative Antibiotic Therapy

Kapitel 23 – Pankreastransplantation

Mit dieser Studie konnte erstmals gezeigt werden, dass Everolimus einen protektiven Einfluss auf das postischamische Pankreas besitzt. Neben einer verminderten Expression von VEGF mit deutlicher Abnahme der Permeabilitat nach Ischamie/Reperfusion fuhrt Everolimus zusatzlich zu einer verbesserten Funktionellen Kapillardichte mit zugleich verminderter leukozytenbedingter inflammatorischer Aktivitat. Ein zeitgleicher Abfall der pankreasspezifischen Entzundungsmarker Amylase und Lipase als Ausdruck eines minder geschadigten Parenchymgewebes lasst auch hier eine protektive Funktion von Everolimus auf das postischamische Pankreas erkennen. Everolimus konnte durch seine Ischamie/-Reperfusions spezifischen Effekte eine interessante Alternative zu bisherigen Immunsuppressiva bei Pankreastransplantation darstellen.

Protektive Wirkung von RAD001 (Everolimus) bei postischämischer Pankreatitis

Hintergrund
Wahrend die Pankreasschwanzresektion sicher und routiniert in zahlreichen Institutionen praktiziert wird, wurden laparoskopische Pankreaskopfresektionen nur von sehr wenigen Chirurgen weltweit und bisher nicht in Deutschland durchgefuhrt.

Laparoskopische Pankreaskopfresektion

Pulmonary injury caused by polymorphonuclear leukocytes (PMN) is a common complication in necrotizing pancreatitis. This study was designed to test the hypothesis that immature PMN released from the bone marrow during severe acute pancreatitis are preferentially sequestered in lung microvessels and are important contributors to lung injury. Material and Methods: The thymidin analogue 5′-bromo-2′-desoxyuridine (BrdU) was used to label dividing PMN in the bone marrow of rats. Their appearance in the circulation after induction of pancreatitis was evaluated by flow-cytometry. Their sequestration in the lung was determined by immunohistochemistry against PMN and BrdU. Sham-operated animals served as control (n = 7). Severe acute pancreatitis (n = 7) was induced by intraductal infusion of glycodeoxycholic acid (GDOC 10 mmol/l). Blood was analyzed for BrdU positive cells at 6, 12, 18, 24, 48 and 72 h in both groups. Sequestration of bone marrow released PMN was evaluated at the maximum of systemic release. Lung injury was evaluated by H & E histology. Results: In control animals BrdU positive PMN were released starting from 48 h. Animals with severe acute pancreatitis showed a premature release of PMN from the bone marrow starting at 18 h with a maximum at 24 h (19 ± 4 vs 5 ± 1% BrdU positive PMN; p < 0.01). At 48 h the release of bone marrow derived PMN in the pancreatitis group decreased whereas in the sham operated group an increase was observed. There were significantly more PMN sequestered in lungs 24 h after induc-tion of pancreatitis with over a third of these cells prematurely released from the bone marrow (35 ± 6%). Histologic lung injury paralleled the PMN sequestration. Conclusion: We conlude that younger PMN released from the bone marrow after induction of severe acute pancreatitis preferen-tially sequester in pulmonary microvessels paralleling lung injury and speculate that therapies preventing this release may prove useful in the prevention of pancreatitis induced lung injury.

Ulrich T. Hopt

Papers

Stent-Associated Infectious Complications After Pancreatoduodenectomies Can Be Prevented by Perioperative Antibiotic Therapy

Kapitel 23 – Pankreastransplantation

Protektive Wirkung von RAD001 (Everolimus) bei postischämischer Pankreatitis

Laparoskopische Pankreaskopfresektion

Induktion Pankreatitis-assoziierten Lungenschadens durch Freisetzung unreifer Leukozyten aus dem Knochenmarkspool