annual report - O'Brien Institute

Overview
Bernard O’Brien Institute of Microsurgery
What is Microsurgery Research
Microsurgery literally means operating through a
microscope. In our field of Plastic and Reconstructive
Surgery we use the microscope to connect small blood
vessels (microsurgery) for the purpose of restoring
circulation to amputated parts (replantation), or to tissues
or parts that have been transferred from some other parts
of the body (transplantation) such as skin, muscle, bones,
joints, toes, etc.
This experimental research is widely applied to clinical
reconstructive microsurgery in trauma, cancer, burns and
congenital abnormalities. This spectrum of activity covers
all ages from infancy to the elderly and illustrates one of
the most important developments in modern surgery.
Currently we can join 0.5 mm diameter blood vessels
using stitches one half the thickness of a human hair but
there is still a risk that these vessels will clot off. When
the circulation to a tissue is reduced or ceases a condition
known as ischaemia, that tissue will atrophy or die occurs.
The most familiar example of this is an ischaemic heart
attack, but the same process occurs in strokes and
gangrene of the limbs.
At the Bernard O’Brien Institute of Microsurgery we are
involved in research to understand the normal process of
blood flow and factors which decrease it (ischaemia) or
enhance it (angiogenesis). This will lead to new ways of
reducing the effect of injury to tissues and to safer and
more effective techniques of replantation, tissue
transplants and even storage of tissue in tissue banks.
By a better understanding of the process of blood flow
and new blood vessel formation we will be able to help
wounds heal, especially chronic ulcers, and be able to
promote and manipulate the growth of tissues so that new
parts can be manufactured in the body. This process has
been termed “tissue engineering” and we have recently
used this technique in humans to grow new ears and noses.
Cancer growth and spread is dependent on new blood
vessels and by understanding how this process works we
can potentially inhibit new blood vessel formation. In
breast cancer and melanoma models in mice we have been
able to manipulate the cancer growth by using drugs
which have shown to be important in switching on and off
the angiogenic process.
Following trauma nerves as well as blood vessels are
commonly injured and microsurgery is used to repair them.
Nerves which function in a very similar way to electric
cables are composed of long fibres which are direct
extensions from the nerve cells housed in the spinal cord.
When a nerve is cut in the same way that tadpoles’ tails
regrow, so too the nerve will grow out again from its point
of injury. We are experimenting with ways to enhance the
outgrowth of nerves following injury, particularly using a
special growth factor “Leukaemia inhibitory Factor”.
The work undertaken at Bernard O’Brien Institute
Microsurgery is broadly based and links many surgical
disciplines and areas of applied science. Much
collaborative work is in progress with other research
institutes, both in Australia and overseas.
Plastic and Reconstructive Surgery Unit
The Plastic and Reconstructive Surgery Unit at St
Vincent’s continues to be a leader in its field with 1,483
patients having been admitted for treatment. The majority
of these patients required surgery and of these, 479 were
emergency patients with 429 requiring surgery from
injuries caused by accidents.
There were 31 replantation cases, the majority being
fingers but also including a whole arm. 77 vascularised
free tissue transfers were used for the reconstruction of
major deformities, 30 of which were for head and neck
cancer, 20 breast reconstructions and 17 for trauma. In
all, 53% of cases involved the hand or an upper limb,
31% general plastic surgery and the balance including
facial, head and neck and burns reconstruction.
The Research Fellows from the Bernard O’Brien Institute
of Microsurgery continue to be an integral part of our
surgical teams and play an important role in the many
difficult procedures that are undertaken by the Plastic
and Reconstructive Unit at St Vincent’s. We are indeed
indebted to the staff of the Plastic Surgery Unit at
St Vincent’s Hospital for their help throughout the year.
Professor Allan MacLeod
many ‘genetically engineered’ mice available
worldwide to answer crucial questions as to the
molecules involved in angiogenesis.
In the tissue culture laboratory we are currently
investigating how nitric oxide (NO) regulates
angiogenesis. We have recently established another
model of angiogenesis in our laboratory. Pieces of
vascular tissue are placed in a special gel in cell culture
plates, and new blood vessel growth is observed over a
2 week period. We are now about to test NO donors
and inhibitors to observe their effect on vessel growth.
In addition, we will test tissue from iNOS-/- mice to
see if lack of NO via a genetic alteration confers
different rates of vessel growth.
Haemangioma Research
We have begun examining the causes of
haemangiomas, which occur when blood vessels
spontaneously grow out of control. They are known
to contain high levels of inflammatory cells such
as mast cells. We have found that when these
haemangiomas are placed in culture and exposed
to FDA-approved. Lodoxamide, a mast cell stabiliser,
there is regression of blood vessel growth. Mirna
Boujaoude, PhD student, has recently joined our group
and is involved in these studies, together with surgical
fellows Drs. Tony Penington and Robert Donato.
Engineering new blood vessels
Another problem encountered by reconstructive
surgeons is a lack of healthy blood vessels for use in
repairing damaged tissues in trauma and cancer related
reconstruction. We are trying to create a ‘bank’ of
ready-to-use blood vessels that can be stored and taken
“off the shelf” when required for reconstructive
surgery. We have found that during storage blood
vessels lose their internal lining of cells, which are
essential for proper blood vessel function, particularly
to stop blood clotting within the blood vessel.
Therefore another tissue engineering project currently
underway is investigating ways to restore these internal
lining cells in stored blood vessels.
Rabbit Stent Model
Every year millions of Australians undergo heart
bypass surgery. This involves replacing the blood
vessels that supply the heart itself with new vessels
taken either from the leg or the arm. The short-term
success of this procedure is well documented however
10 years later 50% of these patients need to have the
MICROSURGERY
FOUNDATION
procedure repeated because the new vessels
themselves become narrowed and occlude. We have
developed a model in a rabbit where a polyester stent
is wrapped around an implanted vessel in the groin
and shown that the narrowing of the blood vessel
over time is reduced. Further studies are needed but
clinical implications are significant.
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