The Interplay between Perioperative Oxidative Stress and Hepatic Dysfunction after Human Liver Resection: A Prospective Observational Pilot Study.

Post-hepatectomy liver failure (PHLF) remains the major contributor to death after liver resection. Oxidative stress is associated with postoperative complications, but its impact on liver function is unclear. This first in-human, prospective, single-center, observational pilot study evaluated perioperative oxidative stress and PHLF according to the ISGLS (International Study Group for Liver Surgery). Serum 8-isoprostane, 4-hydroxynonenal (4-HNE), total antioxidative capacity, vitamins A and E, and intraoperative, sequential hepatic tissue 4-HNE and UCP2 (uncoupling protein 2) immunohistochemistry (IHC) were assessed. The interaction with known risk factors for PHLF and the predictive potential of oxidative stress markers were analyzed. Overall, 52 patients were included (69.2% major liver resection). Thirteen patients (25%) experienced PHLF, a major factor for 90-day mortality (23% vs. 0%; p = 0.013). Post-resection, pro-oxidative 8-isoprostane significantly increased (p = 0.038), while 4-HNE declined immediately (p < 0.001). Antioxidative markers showed patterns of consumption starting post-resection (p < 0.001). Liver tissue oxidative stress increased stepwise from biopsies taken after laparotomy to post-resection in situ liver and resection specimens (all p < 0.001). Cholangiocarcinoma patients demonstrated significantly higher serum and tissue oxidative stress levels at various timepoints, with consistently higher preoperative values in advanced tumor stages. Combining intraoperative, post-resection 4-HNE serum levels and in situ IHC early predicted PHLF with an AUC of 0.855 (63.6% vs. 0%; p < 0.001). This was also associated with grade B/C PHLF (36.4% vs. 0%; p = 0.021) and 90-day mortality (18.2% vs. 0%; p = 0.036). In conclusion, distinct patterns of perioperative oxidative stress levels occur in patients with liver dysfunction. Combining intraoperative serum and liver tissue markers predicts subsequent PHLF. Cholangiocarcinoma patients demonstrated pronounced systemic and hepatic oxidative stress, with increasing levels in advanced tumor stages, thus representing a worthwhile target for future exploratory and therapeutic studies.

Miles down for lunch: deep-sea in situ observations of Arctic finned octopods Cirroteuthis muelleri suggest pelagic-benthic feeding migration.

Deep-sea cephalopods are diverse, abundant, and poorly understood. The Cirrata are gelatinous finned octopods and among the deepest-living cephalopods ever recorded. Their natural feeding behaviour remains undocumented. During deep-sea surveys in the Arctic, we observed Cirroteuthis muelleri. Octopods were encountered with their web spread wide, motionless and drifting in the water column 500-2600 m from the seafloor. Individuals of C. muelleri were also repeatedly observed on the seafloor where they exhibited a repeated, behavioural sequence interpreted as feeding. The sequence (11-21 s) consisted of arm web spreading, enveloping and retreating. Prey capture happened during the enveloping phase and lasted 5-49 s. Numerous traces of feeding activity were also observed on the seafloor. The utilization of the water column for drifting and the deep seafloor for feeding is a novel migration behaviour for cephalopods, but known from gelatinous fishes and holothurians. By benthic feeding, the octopods benefit from the enhanced nutrient availability on the seafloor. Drifting in the water column may be an energetically efficient way of transportation while simultaneously avoiding seafloor-associated predators. In situ observations are indispensable to discover the behaviour of abundant megafauna, and the energetic coupling between the pelagic and benthic deep sea.

Associations of Oxidative Stress and Postoperative Outcome in Liver Surgery with an Outlook to Future Potential Therapeutic Options.

Several types of surgical procedures have shown to elicit an inflammatory stress response, leading to substantial cytokine production and formation of oxygen-based or nitrogen-based free radicals. Chronic liver diseases including cancers are almost always characterized by increased oxidative stress, in which hepatic surgery is likely to potentiate at least in the short term and hereby furthermore impair the hepatic redox state. During liver resection, intermittent inflow occlusion is commonly applied to prevent excessive blood loss but resulting ischemia and reperfusion of the liver have been linked to increased oxidative stress, leading to impairment of cell functions and subsequent cell death. In the field of liver transplantation, ischemia/reperfusion injury has extensively been investigated in the last decades and has recently been in the scientific focus again due to increased use of marginal donor organs and new machine perfusion concepts. Therefore, given the intriguing role of oxidative stress in the pathogenesis of numerous diseases and in the perioperative setting, the interest for a therapeutic antioxidative agent has been present for several years. This review is aimed at giving an introduction to oxidative stress in surgical procedures in general and then examines the role of oxidative stress in liver surgery in particular, discussing both transplantation and resection. Results from studies in the animal and human settings are included. Finally, potential therapeutic agents that might be beneficial in reducing the burden of oxidative stress in hepatic diseases and during surgery are presented. While there is compelling evidence from animal models and a limited number of clinical studies showing that oxidative stress plays a major role in both liver resection and transplantation and several recent studies have suggested a potential for antioxidative treatment in chronic liver disease (e.g., steatosis), the search for effective antioxidants in the field of liver surgery is still ongoing.