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

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ClinicalTrials.gov Identifier: NCT01785212
Recruitment Status : Completed
First Posted : February 7, 2013
Last Update Posted : April 7, 2015
Sponsor:
Information provided by (Responsible Party):
Klaus Kaczirek, Medical University of Vienna

Tracking Information
First Submitted Date  ICMJE January 23, 2013
First Posted Date  ICMJE February 7, 2013
Last Update Posted Date April 7, 2015
Study Start Date  ICMJE March 2013
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 4, 2013)
transection speed [ Time Frame: during surgery ]
The transection time will be recorded by the anesthesiological team during surgery. The transection phase starts with opening the liver parenchyma after the transection line has been marked by electrocautery. It ends after complete division of the liver parenchyma. The cut surface of the resected liver will be photographed together with a 4 cm² reference scale in an exact 90° angle. The area of the liver transection surface will be calculated in cm² by setting the measured pixels of the cut surface in relation to the reference scale using Adobe Photoshop. The transection speed will expressed in cm²/min
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 4, 2013)
  • Perioperative cytokine concentrations [ Time Frame: day -1, d0, d1, d3 ]
  • Intraoperative blood loss in ml [ Time Frame: during surgery ]
  • Postoperative laboratory markers of liver damage [ Time Frame: first week after surgery ]
    Postoperative routine laboratory markers of liver damage (aspartate aminotransferase (AST), alanine aminotransferase (ALT)), and markers of liver function (bilirubin, prothrombin time) measured on first and third postoperative day
  • Morbidity and Mortality [ Time Frame: participants will be followed for the duration of hospital stay, an expected average of 2 weeks ]
  • Perioperative T-cell subsets [ Time Frame: Day -1, 0, 1, 3 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: February 4, 2013)
Costs and health economics [ Time Frame: participants will be followed for the duration of hospital stay, an expected average of 2 weeks ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE The Influence of Two Different Hepatectomy Methods on Transection Speed and Chemokine Release From the Liver
Official Title  ICMJE The Influence of Two Different Hepatectomy Methods on Transection Speed and Chemokine Release From the Liver
Brief 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE
  • Liver Neoplasms
  • Liver Metastasis
  • Liver Hemangioma
  • Echinococcosis, Hepatic
Intervention  ICMJE
  • Device: Stapler
    stapler hepatectomy
    Other Name: Covidien Endo-Gia™ Ultra Handle Short Staplers(Covidien)
  • Device: CUSA (Cavitron ultrasonic aspirator; Valleylab, Boulder, CO)
    CUSA is a well established device used for hepatic resection using ultrasound
Study Arms  ICMJE
  • Stapler-hepatectomy
    The liver parenchyma is crushed with a Pean clamp and subsequently divided using Covidien Endo-Gia™ Ultra Handle Short Staplers and Endo Gia™ TRI staple 60 mm or 45 mm AVM/AMT loading units (Covidien). Hepatic veins and portal pedicles clamped and suture ligated.
    Intervention: Device: Stapler
  • CUSA-hepatectomy
    The liver parenchyma is divided along the transection line by CUSA (Cavitron ultrasonic aspirator; Valleylab, Boulder, CO) and bipolar forceps in a two surgeon technique. Vessels of less than 2 mm in diameter are coagulated with bipolar forceps. The remaining vessels are clipped or ligated. Hepatic veins and portal pedicles clamped and suture ligated.
    Intervention: Device: CUSA (Cavitron ultrasonic aspirator; Valleylab, Boulder, CO)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 4, 2013)
40
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 2015
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01785212
Other Study ID Numbers  ICMJE Version 1.0
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Klaus Kaczirek, Medical University of Vienna
Study Sponsor  ICMJE Medical University of Vienna
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Klaus Kaczirek, M.D. Medical University of Vienna
PRS Account Medical University of Vienna
Verification Date April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP