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Study of the Protective Effect of Mechanism of Pentoxyfilline After Major Liver Resection Under Inflow Occlusion (Pringle Manoeuvre)

Phase 4
Completed
Conditions
Liver Regeneration
Interventions
Drug: pentoxyfilline
Drug: Placebo
Registration Number
NCT00957619
Lead Sponsor
University of Zurich
Brief Summary

The investigators hypothecate that pentoxyfilline increase significantly the liver regeneration and reduces significantly ischemia and reperfusion (I/R) injury in major liver using aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as marker of I/R injury.

Detailed Description

Liver resection is for many patients with primary or secondary hepatic malignancies the only curative treatment option. Often, the complete clearance of the hepatic tumor disease can be only achieved by extended liver resections. Clinical studies have demonstrated that intra-operative blood loss is associated reduced outcome after major liver resection. An effective strategy to reduce blood loss is the occlusion of the portal triad (Pringle manoeuvre). On the other hand, inflow occlusion results in ischemia- and reperfusion (I/R) injury. Randomized trials have shown that ischemic preconditioning (10 min clamping, 10 min reperfusion) and intermittent clamping (15 min clamping, 5 min reperfusion) result in reduction of the I/R injury. Another potential strategy to reduce I/R injury is the pharmacological protection. One promising drug is pentoxyfilline (PTF) which has vasodilative and hemorheologic effects. Furthermore, PTF suppresses the TNF release. These effects may be also protective in major liver resection under inflow occlusion (Pringle manoeuvre)and increase the liver regeneration. Therefore, we designed a randomised prospective trial to investigate the effects of PTF treatment in liver resection under inflow occlusion. The specific aims of the research project are:The investigators hypothecate that pentoxyfilline increases significantly the liver regeneration and reduces significantly ischemia and reperfusion (I/R) injury in liver using aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as marker of I/R injury.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
100
Inclusion Criteria
  • Age > 18 years
  • Major liver resection (hemihepatectomies and extended hemihepatectomies) for benign and malignant lesions
  • Macroscopic and microscopic normal liver parenchyma
  • No underlying liver disease
  • Normal preoperative liver tests (quick, bilirubin, AST, ALT)
  • Signed informed consent
Exclusion Criteria
  • Age < 18 years
  • Minor liver resections (less than hemihepatectomies) or wedge resections
  • Macroscopic and microscopic appearance of liver fibrosis or cirrhosis
  • Underlying liver disease such as viral hepatitis, cirrhosis, etc.
  • Pathological preoperative liver tests (quick, bilirubin, AST, ALT)
  • Intolerance to xanthine derivatives
  • History of myocardial or cerebrovascular insult
  • Total vascular exclusion during liver resection
  • Intra-operative detection of unresectable tumor disease
  • No signed informed consent

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
pentoxyfilline grouppentoxyfillinepentoxyfilline group
placebo groupPlaceboplacebo group
Primary Outcome Measures
NameTimeMethod
I. To determine the regeneration of the liver after liver resection with and without PTF treatmentpre- and up to day 8 after liver resection
Secondary Outcome Measures
NameTimeMethod
Il-6, TNF, procalcitonin for regeneration.AST & ALT peak for ischemic reperfusion injury. If PTF treatment has protective effects in steatotic/fibrotic liver.pre- and up to 8 days postoperatively

Trial Locations

Locations (1)

University Hospital Zurich, Department of Visceral and Transplantation Surgery

🇨🇭

Zurich, Zürich, Switzerland

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