The use of the so-called Pringle manoeuvre during the operative removal of a liver tumour increases the tumour's growth as well as the chance of the tumour recurring after the operation. This reduces the patient's survival chances after the operation. Therefore in her doctoral thesis, Te Velde strongly advises against the use of the standard manoeuvre in tumour operations.
During the Pringle manoeuvre the surgeon completely closes off the blood supply to the liver so as to limit the amount of blood loss during the liver operation. This closing off results in a reduced amount of oxygen in the liver. In response to this the body produces new capillaries which can transport oxygen-rich blood to the liver. It was already known that this blood vessel regeneration, angiogenesis, could promote tumour growth.
With the aid of molecular biology techniques, Te Velde demonstrated that the production of the proteins Hypoxia Inducible Factor-1alpha (HIF1a) and Vascular Endothelial Growth Factor (VEGF) increases as a result of the Pringle manoeuvre. These proteins are responsible for the regeneration of new blood vessels.
As well as the effect of the Pringle manoeuvre, Te Velde investigated how medicines that prevent blood vessel regeneration can be combined with other treatments to control tumours.
Medicines which combat blood vessel regeneration were found to hinder the healing of the damaged intestinal wall in mice. The poor healing of these types of wounds could result in patients not surviving operations to the large intestine. Therefore Te Velde advises against the use of these medicines in combination with an operation.
However, medicine use combined with chemotherapy was found to work well. After twelve days of double treatment, the tumours of mice with liver cancer had significantly shrunk. The effect of the combined treatment was even greater than the effect of both treatments separately.
For further information please contact Dr Lisette te Velde, (Department of Surgery, University Medical Centre Utrecht, now at the Diakonessen Hospital, Utrecht), tel. 31-0-6 22058749, e-mail: e.a.tevelde@chir.azu.nl. The doctoral thesis was defended on 20 June 2003. Dr Te Velde's supervisors were Prof. I.H.M. Borel Rinkes and Prof. E.E. Voest.
Image available at http://www.nwo.nl/news.