The Influence of Two Different Hepatectomy Methods on Transection Speed and Chemokine Release From the Liver
Condition: Liver Neoplasms; Liver Metastasis; Liver Hemangioma; Echinococcosis, Hepatic
MeSH terms: Echinococcosis; Echinococcosis, Hepatic; Hemangioma; Liver Neoplasms
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Stapler; CUSA (Cavitron ultrasonic aspirator; Valleylab, Boulder, CO)
Intervention type(s): Device; Device
Intervention description(s): stapler hepatectomy; CUSA is a well established device used for hepatic resection using ultrasound
Other intervention name(s): Covidien Endo-Gia™ Ultra Handle Short Staplers(Covidien)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment