The Influence of Two Different Hepatectomy Methods on Transection Speed and Chemokine Release From the Liver

The CUSA (cavitron ultrasound surgical aspirator) is the method of choice for hepatic resection in our center. Recently a stapler-hepatectomy methods has been developed and approved for liver surgery using Covidien Endo-Gia stapler. The potential benefit of this method is a potential shorter transection time compared to the CUSA technique. Thus the investigators will perform a randomized controlled trial including 20 patients in the stapler-group and 20 patients in the CUSA control group. Primary endpoint will be transection speed. Secondary endpoints will be peri-operative (d-1, d0, d1, d3) cytokines concentration, T cell subsets, blood loss, morbidity, and a cost analysis.

Many different techniques of parenchymal transection are used in hepatic surgery. In a systematic review, there were no significant differences in morbidity (including bile leak), mortality, routine markers of liver parenchymal injury or dysfunction and length of hospital stay irrespective of the method used for parenchymal transection. This Cochrane review analyzed studies comparing the following transection devices: CUSA (cavitron ultrasound surgical aspirator) versus clamp-crush (two trials); radiofrequency dissecting sealer versus clamp-crush (two trials); sharp dissection versus clamp-crush technique (one trial); and hydrojet versus CUSA (one trial). The clamp-crush technique appeared to have the lowest blood loss and lowest transfusion requirements compared to the other techniques.

However, even in specialized centers morbidity and mortality rates of hepatic resections are still in the range of 45% and 3% respectively and uncertainty persists regarding the optimal technique of transection. Local experience seems to be the most important factor for the choice of the transection method. An innovative technique is stapler hepatectomy using Covidien Endo-Gia™ Ultra Handle Short Staplers and Endo Gia™ TRI staple 60mm or 45 mm AVM/AMT loading units (Covidien). A randomized controlled trial (CRUNSH trial) to evaluate the intraoperative blood loss of stapler hepatectomy compared to the clamp-crushing technique is currently under way.

The CUSA technique is well established in many centers including ours with excellent morbidity and mortality rates. However, it has been shown that CUSA has a longer transection speed than the clamp-crush technique (with vascular occlusion). The investigators of the CRUNSH trial hypothesize that stapler hepatectomy technique might also be comparable or more favorable to clamp-crushing regarding transection time with the advantage of avoiding vascular occlusion. Therefore stapler hepatectomy should also be faster than CUSA.

It has been shown that the release of cytokines, chemokines, and stress hormones correlates with postoperative infection and organ dysfunction. Chemokines are critically involved in the process of leukocyte recruitment and activation in the liver. Major surgery causes inflammation reflected in the production of pro-inflammatory cytokines. In various studies IL-6, for instance, was a valid predictor for post-operative sepsis, complications or mortality. Besides, the levels of these cytokines are expected to correlate with the degree of surgical trauma. Therefore differences in cytokine levels between the two study groups will be assessed, including pro- (INF-γ, IL-1β, IL-5, IL-6, IL12p70, TNFα) and anti-inflammatory (IL-4, IL-10, IL-13) cytokines.

Monocyte chemotactic protein-1 (MCP-1) production is elevated in Kupffer cells following ischemia / reperfusion in response to free radicals and neutrophil elastase, as well as in animal oxidative liver injury models (e.g. carbon tetrachloride) Macrophage inflammatory protein-3-alpha (MIP3-alpha) is constitutively expressed in the liver. It is strongly chemotactic for cytokine-stimulated neutrophils, immature dendritic cells and memory/effector T and B lymphocytes by utilizing chemokine receptor (CCR) 6.

sCD163 (soluble haemoglobin scavenger receptor) is a novel marker of activated macrophages, like neopterin it can be determined in serum or plasma.

The effect of the transection speed in respect to chemokine release has never been investigated. The investigators hypothesize that a shorter transection time leads to a reduced release of these molecules potentially resulting in improved postoperative outcome.

Additionally the interaction between adaptive and innate immunity plays a significant role in liver ischemia-reperfusion (I/R) injury. Notably, activation of T cells in the absence of TCR ligation seems to be a predominant factor in the initial phase of I/R injury. Therefore as a pilot study, peripheral T cell subsets (including naïve T cells, effector and central memory T cells, regulatory T cells, early activated T cells) will be determined by flow cytometry in a subgroup of study patients (i.e. patients undergoing hepatic resection for other than oncological reasons).

The supposedly slower technique of CUSA resection shall therefore be compared with the novel technique of stapler hepatectomy.

Eligibility Criteria:
Inclusion Criteria:

* Patients scheduled for elective major hepatic resection at the Department of General Surgery, Medical University of Vienna
* Stapler hepatectomy and CUSA resection feasible based on preoperative imaging
* Age equal or greater than 18 years
* Informed consent

Exclusion Criteria:

* Minor hepatectomy
* Hepatitis B, Hepatitis C, HIV infection, autoimmune disease
* Inflammatory conditions of the bowel such as Crohn's Disease
* Pregnancy