Molecular absorbent recirculating system for the treatment of acute liver failure in surgical patients

The Molecular Adsorbent Recirculating System (MARS) represents an attractive artificial liver support system for the treatment of liver insufficiency. However, neither indications for MARS treatment (i.e., after extended liver resection) nor criteria for discontinuation of therapy have been evaluated. Therefore, we analyzed the clinical data of all our surgical patients who received MARS treatment for acute liver failure (n = 7). The aim of the study was to identify prognostic indicators for survival. Four of 174 patients resected for hepatic malignancy at our institution received a total of 13 MARS treatments. Two additional patients were successfully bridged to orthotopic liver transplantation with seven MARS treatments and one patient was MARS supported after liver transplantation of a steatotic graft with three MARS treatments. Five of the seven patients survived and were dismissed an average of 31 days, ranging from 17 to 47 days, after the final MARS treatment. No technical complications or adverse effects were observed during the MARS treatments. Important prognostic factors for hepatic recovery and survival were indocyanin green plasma disappearance rates greater than 5%/min and an increase in clotting factor V levels after each MARS treatment. We conclude that MARS therapy can be an effective treatment of postoperative liver insufficiency in the surgical hepatobiliary uni

[Surgical proctology - what is common is common]

Proktologische Erkrankungen sind ausgesprochen häufig und werden von den Patienten oft verdrängt oder aus Scham verschwiegen und von den Chirurgen leider auch meist vernachlässigt. Dies mag damit zusammenhängen, dass die Genese dieser Krankheitsbilder völlig unterschiedlich sein kann und von neurologischen Störungen über embryonale Fehlentwicklungen bis zu traumatisch bedingten Defekten reichen kann. Wohl aus diesem Grund wurde in der Vergangenheit die Proktologie von unterschiedlichen Disziplinen mit uneinheitlichen Therapieansätzen und nicht standardisierten Methoden angegangen. Die Interdisziplinarität ist in diesem Bereich der Medizin aber von äusserster Wichtigkeit. Denn nur durch ein gutes Zusammenspiel der verschiedenen Disziplinen in der Diagnostik und Therapie kann das bestmögliche Ergebnis für unsere Patienten erzielt werden. Das höchste Gut für das Leben der Betroffenen und einer der wichtigsten Faktoren in der Therapie ist der Erhalt der Kontinenz. Im Folgenden wollen wir hier auf die häufigsten Krankheitsbilder und deren chirurgische Therapieansätze eingehen.Proctological diseases are extremely common and are often suppressed or concealed by the patients out of shame and unfortunately mostly neglected by the surgeons. This may have to do with the fact that the genesis of these clinical pictures can be completely different and can range from neurological disorders to embryonic maldevelopment to traumatically caused defects. Probably for this reason, in the past proctology was approached by different disciplines with inconsistent therapeutic approaches and non-standardized methods. However, interdisciplinarity is of utmost importance in this field of medicine. Only through a good interaction of the different disciplines in diagnostics and therapy can the best possible outcome be achieved for our patients. The highest good for the life of those affected and one of the most important factors in therapy is the preservation of continence

GPR15 facilitates recruitment of regulatory T cells to promote colorectal cancer.

Colorectal cancer (CRC) is one of the most frequent malignancies worldwide. Despite considerable progress in early detection and treatment, there is still an unmet need for novel anti-tumor therapies, particularly in advanced CRC. Regulatory T cells (Tregs) are increased in the peripheral blood and tumor tissue of CRC patients. Recently, transient ablation of tumor-associated Tregs was shown to foster CD8+ T cell-mediated anti-tumoral immunity in murine CRC models. However, before considering therapies, targeting Tregs in cancer patients and detailed knowledge of the phenotype and features of tumor-associated Tregs is indispensable. Here we demonstrate in a murine model of inflammation-induced CRC that tumor-associated Tregs are mainly of thymic origin and equipped with a specific set of molecules strongly associated with enhanced migratory properties. Particularly, a dense infiltration of Tregs in mouse and human CRC lesions correlated with increased expression of the orphan chemoattractant receptor GPR15 on these cells. Comprehensive gene expression analysis revealed that tumor-associated GPR15+ Tregs have a Th17-like phenotype, thereby producing IL-17 and TNF-α. Gpr15 deficiency repressed Treg infiltration in CRC, which paved the way for enhanced anti-tumoral CD8+ T cell immunity and reduced tumorigenesis. In conclusion, GPR15 represents a promising novel target for modifying T cell-mediated anti-tumoral immunity in CRC

The IL-33/ST2 pathway shapes the regulatory T cell phenotype to promote intestinal cancer.

The composition of immune infiltrates strongly affects the prognosis of patients with colorectal cancer (CRC). Interleukin (IL)-33 and regulatory T cells (Tregs) in the tumor microenvironment have been separately implicated in CRC; however their contribution to intestinal carcinogenesis is still controversial. Here, we reveal that IL-33 signaling promotes CRC by changing the phenotype of Tregs. In mice with CRC, tumor-infiltrating Tregs preferentially upregulate IL-33 receptor (ST2), and IL-33/ST2 signaling positively correlates with tumor number and size. Transcriptomic and flow cytometry analyses demonstrate that ST2 expression induces a more activated and migratory phenotype in FOXP3 Tregs, which favors their accumulation in the tumor environment. Consequently, genetic ablation of St2 reduces Treg infiltration and concomitantly enhances the frequencies of effector CD8 T cells, thereby restraining CRC. Mechanistically, IL-33 curtails IL-17 production by FOXP3 Tregs and inhibits Th17 differentiation. In humans, numbers of activated ST2-expressing Tregs are increased in blood and tumor lesions of CRC patients, suggesting a similar mode of regulation. Together, these data indicate a central role of IL-33/ST2 signaling in shaping an immunosuppressive environment during intestinal tumorigenesis. Blockade of this pathway may provide a strategy to modulate the composition of CRC immune infiltrates