[What does the general and abdominal surgeon need to know about oncologically oriented radiotherapy?] / Was muss der Allgemein- und Viszeralchirurg von der onkologisch ausgerichteten Strahlentherapie wissen?

BACKGROUND: Radiotherapy is an integral component of most modern multimodal tumor treatment concepts, both in palliative and curative situations and intentions. This also applies to many tumor entities relevant in general as well as abdominal surgery. This can give rise to new challenges in the context of the daily clinical routine and interdisciplinary tumor conferences. AIM: Practice relevant overview, based on selective references from the current scientific literature in medicine and own experiences obtained in daily work, for the oncological surgeon on radiotherapy-associated options for visceral tumor lesions. A particular focus is on rectal cancer, esophageal cancer, anal cancer and liver metastases. METHOD: A narrative review is given. RESULTS (SELECTED CORNER POINTS): In total neoadjuvant therapy it is possible to avoid resection in rectal cancer if a good response is achieved and close monitoring can be provided. In esophageal cancer neoadjuvant chemoradiotherapy followed by resection can be considered the therapeutic regimen of choice for all suitable patients. If surgery is not an option, definitive chemoradiotherapy is an appropriate and favorable alternative, especially with respect to squamous cell carcinoma. Even taking the latest data on the topic into account, definitive chemoradiotherapy remains undisputedly recommended for anal cancer. Liver tumors can be locally ablated by stereotactic radiotherapy. CONCLUSION: Close cooperation between disciplines in the context of tumor therapy remains essential for the best possible treatment and outcome of patients.

Polyunsaturated Fatty Acids Induce ROS Synthesis in Microvascular Endothelial Cells.

In sepsis, endothelial dysfunction is a crucial driver known to limit the survival rate of affected patients. For this, ROS-mediated signaling plays an important role in endothelial communication and functionality. In the management of sepsis, polyunsaturated fatty acids (PUFA) have received increasing attention regarding their anti-inflammatory potential neglecting the oxidative properties of these substances. Therefore, in the present study we examined the capacity of PUFA to interfere with the expression of major ROS-producing enzymes, as well as endothelial ROS production itself. The human microvascular endothelial cells TIME (ATCC number: CRL-4025) were used. Cells were cultured in medium enriched with LNA (C18:3n3), EPA (C20:5n3), DHA (C22:6n3), LA (C18:2n6), or AA (C20:4n6) in concentrations of 15 µM totaling 144 h. Stimulation of cells was performed in the last 24 h of fatty acid supplementation by addition of the cytokines TNF-α + IL-1ß + IFN-γ (5 ng/ml each). Gene expression of eNOS, COX-2, and NOX-4 was evaluated by qPCR. ROS synthesis was analyzed by means of a flow cytometry-based rhodamine 123 assay. Cytokine stimulation was found to differentially affect gene expression of major ROS synthesizing enzymes: eNOS was decreased whereas COX-2 and NOX-4 were increased. As a consequence, cytokine stimulation had no effect on rhodamine accumulation in endothelial cells. PUFA supplementation alone did not affect the gene expression of eNOS, COX-2, and NOX-4. Nevertheless, an increasing action of PUFA on the stimulation-induced reduction in eNOS expression was found. More importantly, the number of rhodamine positive endothelial cells almost doubled following enrichment with the PUFA EPA, DHA or AA. This effect was independent of the stimulation status of the cells but seemed to be related to the number of double bonds of a supplemented fatty acid. Our data warrant further studies to ensure that increased endothelial cell oxidative stress is not boosted by PUFA in septic patients.

Impact of Unsaturated Fatty Acids on Cytokine-Driven Endothelial Cell Dysfunction.

Polyunsaturated fatty acids (PUFA) are reported to exert prophylactic and acute therapeutic effects in diseases linked to endothelial dysfunction. In the present study, the consequences of a PUFA enrichment of endothelial cells (cell line TIME) on cell viability, expression of the cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte-macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein 1 (MCP-1), synthesis of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and vascular adhesion molecule 1 (VCAM-1), and production of the coagulation factors plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF), and tissue factor (TF) was analyzed in parallel. PUFA of both the n3 and the n6 family were investigated in a physiologically relevant concentration of 15 µM, and experiments were performed in both the presence and the absence of the pro-inflammatory cytokines interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). Supplementation of the culture medium with particular fatty acids was found to have a promoting effect on cellular production of the cytokines IL-6, IL-8, GM-CSF, and MCP-1. Further on, PUFA treatment in the absence of a stimulant diminished the percentage of endothelial cells positive for ICAM-1, and adversely affected the stimulation-induced upregulation of VCAM-1. Cell viability and production of coagulation factors were not or only marginally affected by supplemented fatty acids. Altogether, the data indicate that PUFA of either family are only partially able to counterbalance the destructive consequences of an endothelial dysfunction.