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

April 6, 2015 updated by: Klaus Kaczirek, Medical University of Vienna
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria, 1090
        • Dept. of Surgery/Div. of General Surgery Medical University of Vienna

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 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.
Device: Stapler
stapler hepatectomy
Other Names:
  • Covidien Endo-Gia™ Ultra Handle Short Staplers(Covidien)
Other: 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.
Device: CUSA (Cavitron ultrasonic aspirator; Valleylab, Boulder, CO)
CUSA is a well established device used for hepatic resection using ultrasound

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
during surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Perioperative cytokine concentrations
Time Frame: day -1, d0, d1, d3
day -1, d0, d1, d3
Intraoperative blood loss in ml
Time Frame: during surgery
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
first week after surgery
Morbidity and Mortality
Time Frame: participants will be followed for the duration of hospital stay, an expected average of 2 weeks
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
Day -1, 0, 1, 3

Other Outcome Measures

Outcome Measure
Time Frame
Costs and health economics
Time Frame: participants will be followed for the duration of hospital stay, an expected average of 2 weeks
participants will be followed for the duration of hospital stay, an expected average of 2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Vienna

Investigators

  • Principal Investigator: Klaus Kaczirek, M.D., Medical University of Vienna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2013

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

April 1, 2015

Study Registration Dates

First Submitted

January 23, 2013

First Submitted That Met QC Criteria

February 4, 2013

First Posted (Estimate)

February 7, 2013

Study Record Updates

Last Update Posted (Estimate)

April 7, 2015

Last Update Submitted That Met QC Criteria

April 6, 2015

Last Verified

April 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Version 1.0

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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