The use of laparoscopy for liver surgery is increasing rapidly. The Second International Consensus Conference on Laparoscopic Liver Resections (LLR) was held in Morioka, Japan, from October 4 to 6, 2014 to evaluate the current status of laparoscopic liver surgery and to provide recommendations to aid its future development. Seventeen questions were addressed. The first 7 questions focused on outcomes that reflect the benefits and risks of LLR. These questions were addressed using the Zurich-Danish consensus conference model in which the literature and expert opinion were weighed by a 9-member jury, who evaluated LLR outcomes using GRADE and a list of comparators. The jury also graded LLRs by the Balliol Classification of IDEAL. The jury concluded that MINOR LLRs had become standard practice (IDEAL 3) and that MAJOR liver resections were still innovative procedures in the exploration phase (IDEAL 2b). Continued cautious introduction of MAJOR LLRs was recommended. All of the evidence available for scrutiny was of LOW quality by GRADE, which prompted the recommendation for higher quality evaluative studies. The last 10 questions focused on technical questions and the recommendations were based on literature review and expert panel opinion. Recommendations were made regarding preoperative evaluation, bleeding controls, transection methods, anatomic approaches, and equipment. Both experts and jury recognized the need for a formal structure of education for those interested in performing major laparoscopic LLR because of the steep learning curve.

Laparoscopic hepatic resection is a growing option in the field of hepatic surgery. Nearly 3000 laparoscopic hepatic resections have been reported in the literature for both benign and malignant tumors with a reported perioperative mortality of 0.3% and morbidity of 10.5%.^1,2 Multiple series^3-21 have attested to the feasibility and safety of laparoscopic liver resections; however, to our knowledge, no randomized controlled trial has been reported comparing laparoscopic with open liver resection. Further, the overall benefits of a minimally invasive approach to hepatic resection have not been systematically defined.

Hypoxia is often found in solid tumors and is associated with tumor progression and poor clinical outcomes. The exact mechanisms related to hypoxia-induced invasion and metastasis remain unclear. We elucidated the mechanism by which the nuclear-damage–associated molecular pattern molecule, high-mobility group box 1 (HMGB1), released under hypoxic stress, can induce an inflammatory response to promote invasion and metastasis in hepatocellular carcinoma (HCC) cells. Caspase-1 activation was found to occur in hypoxic HCC cells in a process that was dependent on the extracellular release of HMGB1 and subsequent activation of both Toll-like receptor 4 (TLR4)- and receptor for advanced glycation endproducts (RAGE)-signaling pathways. Downstream from hypoxia-induced caspase-1 activation, cleavage and release of proinflammatory cytokines interleukin (IL)-1β and -18 occurred. We further demonstrate that overexpression of HMGB1 or treatment with recombinant HMGB1 enhanced the invasiveness of HCC cells, whereas stable knockdown of HMGB1 remarkably reduced HCC invasion. Moreover, in a murine model of HCC pulmonary metastasis, stable knockdown of HMGB1 suppressed HCC invasion and metastasis. Conclusion: These results suggest that in hypoxic HCC cells, HMGB1 activates TLR4- and RAGE-signaling pathways to induce caspase-1 activation with the subsequent production of multiple inflammatory mediators, which, in turn, promote cancer invasion and metastasis.

Ischemia reperfusion injury (IRI) is a major obstacle in liver resection and liver transplantation. The initial step of IRI is mediated through ischemia which promotes the production of reactive oxygen species in Kupffer cells. This furthermore promotes the activation of pro-inflammatory signaling cascades, including tumor necrosis factor-alpha, IL-6, interferon, inducible nitric oxide synthase, TLR9/nuclear-factor kappa B pathway, and the production of damage-associated molecular patterns (DAMPs), such as ATP, histone, high mobility group box 1 (HMGB1), urate, mitochondrial formyl peptides and S100 proteins. With ongoing cell death of hepatocytes during the ischemic phase, DAMPs are built up and released into the circulation upon reperfusion. This promotes a cytokines/chemokine storm that attracts neutrophils and other immune cells to the site of tissue injury. The effect of IRI is further aggravated by the release of cytokines and chemokines, such as epithelial neutrophil activating protein (CXCL5), KC (CXCL1) and MIP-2 (CXCL2), the complement proteins C3a and C5a, mitochondrial-derived formyl peptides, leukotriene B4 and neutrophil extracellular traps (NETs) from migrating neutrophils. These NETs can also activate platelets and form Neutrophil-platelet microthrombi to further worsen ischemia in the liver. In this review we aim to summarize the current knowledge of mediators that promote liver IRI, and we will discuss the role of neutrophils and neutrophil extracellular traps in mediating IRI.