An unanticipated risk from isolated limb perfusion? - An article
in the September 1, 1996 issue of Cancer Research described a study
carried out at Groningen University Hospital in the Netherlands,
which raises the possibility of a risk of blood clots in patients
receiving isolated perfusion of the limb with chemotherapy
(usually melphalan) and tumor necrosis factor (TNF-alpha).
Melanoma, and other tumors such as osteosarcoma, often strike the
limbs, and isolated perfusion is regarded as an alternative or an
adjunct (by making the tumor smaller and killing metastatic
cancer cells) to limb amputation. One well-recognized risk of
the procedure is a shock-like state resembling sepsis, requiring
treatment with fluids and drugs to restore normal blood pressure.
These researchers pointed out an added potential risk. They
measured increase of a substance known as plasminogen activator
outside the perfused limb resulting from leakage of TNF-alpha.
This rise in serum plasminogen activator produced in response a
large secondary rise in PAI-1, a substance which antagonizes the
blood-clot suppressing action of plasminogen activator. These
elevated levels of PAI-1 were much more persistent, making the
patients potentially more liable to form small blood clots which
could travel around the body placing the patients at risk of
embolisms. (Zwaveling, Cancer Res 56:3948, 1996)
Editor's Comment: - As of yet there is no evidence that the
frequency of embolisms, always a risk anyway in any operation
involving intervention in the circulation, is actually increased
by this treatment. It is not possible to prevent leakage of TNF-alpha
(and of other drugs) from the perfused area, since the
blood circulation in the limb cannot be entirely cut off from the
rest of the body. The study, which has some support from other
research, does serve to emphasize the need to make every effort
to restrict leakage, and to flush out the perfused region after
treatment to minimize return of residual TNF-alpha into the total
circulation. Readiness to use anticoagulant therapy is also
essential.
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