Die pyloruserhaltende Whipple-Operation: eine Alternative oder heutiger Standard beim Pankreaskarzinom?

Zusammenfassung: Grundlagen: Während die pyloruserhaltende Whipple-Operation eine gute Alternative zur klassischen Operation bei periampullären Tumoren darstellt, ist das Verfahren beim Pankreaskopfkarzinom umstritten. Methodik: Wir haben die Daten von 70 Patienten mit Pankreaskopfkarzinom prospektiv im Hinblick auf die Vorteile des operativen Vorgehens und in bezug auf Lebensqualität und Überlebenszeit untersucht. Ergebnisse: Bei 44 Patienten wurde eine pyloruserhaltende Resektion durchgeführt, bei 26 Fällen eine klassische Whipple-Operation (WO) mit Lymphadenektomie. Es gab bezüglich Alter, Geschlecht und Tumorstadium keine Unterschiede in den beiden Patientengruppen. Die Mittelwerte für die Operationszeit, Blutverlust und Hospitalisationsdauer betrugen bei der pyloruserhaltenden WO 382 min, 1125 ml und 18,3 Tage und bei der klassischen WO 460 min (p<0,05), 1650 ml (p<0,05) und 22 Tage. Die mediane Überprüfzeit betrug 17 Monate (Range 2 bis 28 Monate). In den ersten 3 Monaten postoperativ war der Gewichtsverlauf bei den Patienten mit pyloruserhaltender WO deutlich besser. Die mediane Überlebenszeit war nicht signifikant verschieden mit 12,2 Monaten für die Patienten mit pyloruserhaltender WO und 12,9 Monaten bei den Patienten mit klassischer WO. Schlußfolgerungen: Bei Patienten mit Pankreaskarzinom war die Lebensqualität und Gewichtszunahme postoperativ besser bei solchen mit pyloruserhaltender partieller Duodenopankreatektomie im Vergleich zur klassischen WO. Aufgrund dieser Ergebnisse, der intraoperativen Vorteile und bei gleicher Überlebenszeit sollte dieses Operationsverfahren beim Pankreaskarzinom, wenn immer möglich, bevorzugt werde

Rectal Bleeding Associated With Chronic Pancreatitis

Pseudocyst formation, with its attendant complications of compression, rupture, bleeding and fistula formation, is a well known complication of chronic pancreatitis. In 1966 Berne and Edmondson drew attention to the often fatal outcome of pancreatico-colonic fistula complicated by hemorrhage. We present two cases of this rare complication of chronic pancreatitis as defined by the Marseille classification

CRASH2 in Germany [ISRCTN86750102]

ABSTRACT: In June 2005, the Study Centre of the German Surgical Society (SDGC) in Heidelberg, Germany, agreed to participate in the investigator initiated trial CRASH2. Regulatory and administrative affairs within Germany were assigned to the Coordination Centre for Clinical Trials (KKS) at the University of Heidelberg, Germany. For more than nine months the KKS and the SDGC have been trying to procure a separate insurance for CRASH2 in Germany. Unfortunately, these attempts have not been successful, yet. One major reason is the way in which German authorities and authorities of some other countries have interpreted the EU Directive (Directive 2001/20/EC) with regards to the need for "adequate" indemnity for clinical trials. The indemnity insurance for CRASH2 procured by the LSHTM for all participating hospitals throughout the world (except for the USA) did not comply with the limits required by the federal German drug law (AMG)

A new approach to the modelling of local defects in crystals: the reduced Hartree-Fock case

This article is concerned with the derivation and the mathematical study of a new mean-field model for the description of interacting electrons in crystals with local defects. We work with a reduced Hartree-Fock model, obtained from the usual Hartree-Fock model by neglecting the exchange term. First, we recall the definition of the self-consistent Fermi sea of the perfect crystal, which is obtained as a minimizer of some periodic problem, as was shown by Catto, Le Bris and Lions. We also prove some of its properties which were not mentioned before. Then, we define and study in details a nonlinear model for the electrons of the crystal in the presence of a defect. We use formal analogies between the Fermi sea of a perturbed crystal and the Dirac sea in Quantum Electrodynamics in the presence of an external electrostatic field. The latter was recently studied by Hainzl, Lewin, S\'er\'e and Solovej, based on ideas from Chaix and Iracane. This enables us to define the ground state of the self-consistent Fermi sea in the presence of a defect. We end the paper by proving that our model is in fact the thermodynamic limit of the so-called supercell model, widely used in numerical simulations.Comment: Final version, to appear in Comm. Math. Phy

The CD34-Related Molecule Podocalyxin Is a Potent Inducer of Microvillus Formation

BACKGROUND: Podocalyxin is a CD34-related transmembrane protein involved in hematopoietic cell homing, kidney morphogenesis, breast cancer progression, and epithelial cell polarization. Although this sialomucin has been shown to block cell adhesion, the mechanisms involved remain enigmatic. It has, however, been postulated that the adaptor proteins NHERF-1 and 2 could regulate apical targeting of Podocalyxin by linking it to the actin cytoskeleton. PRINCIPAL FINDINGS: Here, in contrast, we find that full-length Podocalyxin acts to recruit NHERF-1 to the apical domain. Moreover, we show that ectopic expression of Podocalyxin in epithelial cells leads to microvillus formation along an expanded apical domain that extends laterally to the junctional complexes. Removal of the C-terminal PDZ-binding domain of Podocalyxin abolishes NHERF-1 recruitment but, surprisingly, has no effect on the formation of microvilli. Instead, we find that the extracellular domain and transmembrane region of Podocalyxin are sufficient to direct recruitment of filamentous actin and ezrin to the plasma membrane and induce microvillus formation. CONCLUSIONS/SIGNIFICANCE: Our data suggest that this single molecule can modulate NHERF localization and, independently, act as a key orchestrator of apical cell morphology, thereby lending mechanistic insights into its multiple roles as a polarity regulator, tumor progression marker, and anti-adhesin

Dispersal and reproductive careers of male mountain gorillas in Bwindi Impenetrable National Park, Uganda

Dispersal is a key event in the life of an animal and it influences individual reproductive success. Male mountain gorillas exhibit both philopatry and dispersal, resulting in a mixed one-male and multimale social organization. However, little is known about the relationship between male dispersal or philopatry and reproductive careers in Bwindi mountain gorillas. Here we analyze data spanning from 1993 to 2017 on social groups in Bwindi Impenetrable National Park, Uganda to examine the proportion of males that disperse, age of dispersal, pathways to attaining alpha status, fate of dispersing males and philopatric males, and male tenure length as well as make comparisons of these variables to the Virunga mountain gorilla population. We report previously undocumented cases of dispersal by immature males and old males and we also observed the only known case of a fully mature male immigrating into a breeding group. We used genetic tracking of known individuals to estimate that a minimum of 25% of males that disperse to become solitary males eventually form new groups. No differences were found between the Bwindi and Virunga population in the age of male dispersal, the proportion of males that disperse, the age of alpha male acquisition, and dominance tenure length. The lack of differences may be due to small sample sizes or because the observed ecological variability does not lead to life history differences between the populations. Males in both populations follow variable strategies to attain alpha status leading to the variable one-male and multimale social organization, including dispersal to become solitary and eventually form a group, via group fissioning, usurping another alpha male, or inheriting the alpha position when a previous group leader dies

Neutrophils Promote Mycobacterial Trehalose Dimycolate-Induced Lung Inflammation via the Mincle Pathway

Trehalose 6,6′-dimycolate (TDM), a cord factor of Mycobacterium tuberculosis (Mtb), is an important regulator of immune responses during Mtb infections. Macrophages recognize TDM through the Mincle receptor and initiate TDM-induced inflammatory responses, leading to lung granuloma formation. Although various immune cells are recruited to lung granulomas, the roles of other immune cells, especially during the initial process of TDM-induced inflammation, are not clear. In this study, Mincle signaling on neutrophils played an important role in TDM-induced lung inflammation by promoting adhesion and innate immune responses. Neutrophils were recruited during the early stage of lung inflammation following TDM-induced granuloma formation. Mincle expression on neutrophils was required for infiltration of TDM-challenged sites in a granuloma model induced by TDM-coated-beads. TDM-induced Mincle signaling on neutrophils increased cell adherence by enhancing F-actin polymerization and CD11b/CD18 surface expression. The TDM-induced effects were dependent on Src, Syk, and MAPK/ERK kinases (MEK). Moreover, coactivation of the Mincle and TLR2 pathways by TDM and Pam3CSK4 treatment synergistically induced CD11b/CD18 surface expression, reactive oxygen species, and TNFα production by neutrophils. These synergistically-enhanced immune responses correlated with the degree of Mincle expression on neutrophil surfaces. The physiological relevance of the Mincle-mediated anti-TDM immune response was confirmed by defective immune responses in Mincle−/− mice upon aerosol infections with Mtb. Mincle-mutant mice had higher inflammation levels and mycobacterial loads than WT mice. Neutrophil depletion with anti-Ly6G antibody caused a reduction in IL-6 and monocyte chemotactic protein-1 expression upon TDM treatment, and reduced levels of immune cell recruitment during the initial stage of infection. These findings suggest a new role of Mincle signaling on neutrophils during anti-mycobacterial responses