The homograft: organ or tissue?  

This was the first question to be confronted in research and clinical terms by the Vascular Surgery department at the University of Bologna. 
In the literature, the use of vascular homografts for prosthetic infections was accompanied by sparse attention being paid to the recipient's immune response, since vessels and tissue were considered to have low antigenicity. 
In fact, most authors in relating their clinical experiences did not respect any compatibility aspects between donor and recipient, whether with regard to the blood group (ABO compatibility) or to any possible antibodies pre-existing in the recipient's serum (cross matching). In reality, some clinical reviews reported late homograft complications to do with chronic rejection phenomena. 
In particular, the French school itself documented, in 25% of the cases treated, myointimal hyperplasia, tunica muscularis necrosis and adventitial inflammatory infiltration, typical vascular rejection aspects of parenchymatous organs and particularly of the kidneys (10). 
Indeed, it was documented that the cells of the vascular wall, just like endothelial cells but also smooth muscle cells and fibroblasts, express both blood group antigens (A,B,O) and the major histocompatibility antigens, the so-called human leukocyte or HLA antigens, capable of triggering rejection reactions (11). 
Research on rats revealed that an aorta transplant precipitates an immune response in the recipient that tends to attack the foreign cells (12, 13). 
Following the aortic graft, the receiving animal's immunocompetent system recognizes the foreign antigens as extraneous to its own genetic make-up, and responds to this stimulus by a series of immune reactions that involve macrophages, T-lymphocytes, B-lymphocytes and lymphokines. 
The early stages of the rejection are characterized by a first, cell-mediated immunological response (cytotoxic T-lymphocytes and macrophages), while later on, an antibody-mediated response prevails (B-lymphocytes), although both these phases are intimately linked to each other. 
The first consequences of the recipient's immunological response are an early disappearance of endothelial cells, strongly immunogenic and the first target of the direct cellular aggression (cytotoxic). Successively, the smooth muscle cells progressively disappear, mainly attacked with the antibody mechanism and resulting in a thinning of the tunica media. 
The last rejection phase is characterized by a myointimal proliferation, made up of recipient cells. From the functional point of view, in the broad-caliber vessels, the necrosis of the media, its thinning and replacement with fibrous tissue, predisposes the formation of an aneurysmatic dilatation. In the narrow-caliber vessels, on the contrary, the myointimal hyperplasia is responsible for a progressive reduction of vasal lumen. 
Experiments have shown that it is possible to modulate the immunological response by means of immunosuppressive drugs. In particular, the administration of low-dose cyclosporins combined with low molecular weight heparin protects the transplanted arterial wall from the rejection reaction through a reduction in muscle cell necrosis and inhibition of the myointimal hyperplasia (13, 14). 
In our own experience, post aortic transplantation immunological studies have demonstrated the presence of anti-HLA antibodies in the recipients' sera. Indeed, the use of immuno-enzymatic methods has allowed us to pinpoint the specificity of these antibodies, demonstrating that the transplant patient develops antibodies specifically against the donor's antigens (15). 
Such antibody production begins around the 2nd to 3rd post-transplantation month and progressively rises until the 12th month, in spite of cyclosporin administration (16). 
In conclusion, the arterial homografts are immunogenic and induce in the recipient a specific humoral and cellular immune response, responsible for the rejection phenomena. 
Experimental and clinical studies lead us to consider the transplantation of homologous arterial vessels such as a parenchymatous organ. 
This is why we are convinced that it is at least necessary to respect blood group compatibility and perform the grafting in the absence of preformed anti-HLA in the recipient's serum (a negative cross-match result). 

The supply - the donor 

There are two reference centers in Italy for the donation and transplantation of organs. The “A.I.R.T.” includes the Regions of Emilia-Romagna, Tuscany, Piedmont, Valle d'Aosta and Bolzano. 
The “NIT” covers the Regions of Lombardy, Venetia, Friuli, The Marches, Liguria and Trento. The Bologna Service refers to the A.I.R.T., which is supplied according to the demand (the waiting list) to provide the site where the explantation is possible in real time. 
The vascular segments drawn on are most often from the bifemoral or bisiliac tract and in this sense the withdrawable segment should be the abdominal aorta inclusive of the iliac bifurcation and the two femoral arteries. 
The multi-organ donor usually renders the two kidneys, liver, and the heart together with the lungs. This permits the subsequent transplantation on patients on the list for the relevant conditions. 
The problem of the vascular segment withdrawal should for these reasons take account of such demands and therefore it is not always available as an anatomic model. The most difficult segment to obtain integrally is the iliac bifurcation. 
This is why one often has to fall back on an impromptu preparation of which the most made use of is the remaking of the aortic bifurcation. 
The aortic arch is withdrawn and sutured to a segment of thoracic aorta. The whole piece is tilted distally and the aortic stump sutured, proximal to the arch, the arteria anonyma is made use of excluding the subclavian, and left common carotid (Fig. 1). 
This preparation thus reconstructs the iliac bifurcation with a possible extension for the two femorals to the two common carotids (Figg. 2, 3). 
At the same time, other segments for possible aorticorenal bypasses are withdrawn. Another technical problem is that of a possible aortoenteric fistula. The timing in the first instance provides for the repair of the duodenal breach with a resection and a termino-terminal intestinal anastomosis. 
This time the implanting of the graft takes place beforehand so as to avoid contact of the duodenal and biliary fluid with the homograft. 
The implanting of the homograft takes place with termino-terminal suturing onto the residual aortic stump having the adroitness to expose anteriorly the thoracic aorta segment where the previously tied arteriae intercostales are present. The continuous suturing is carried out with filum 4/o. 
The distal implantation is conditioned by the prior operation and therefore it can be an aorto-aortica anastonmosis, mono or bilateral femoral or bisiliac. 
It is always necessary to avoid the apposition of angiostats on the vascular segment and risking its fragmentation, opting instead for manual compression. 
The implantation effected, the preparation of a gastroenteric anastomosis is proceeded with, having the significance of not placing the duodenal anastomosis under tension. Frequently, and whenever possible, the graft is protected with an omentofixation. 
Another question linked to the parts supply, other than the assurance that there are no risk factors such as positivity to HIV or HCV or other infective states transmissible to the recipient, is the donor's age. 
A vascular segment in the grip of an arteriosclerotic degeneration is to be shunned. 
This means that the only probable donors are those in the age range 20 - 40 years, in whom the quality of the walls would have been carefully assessed. 

ACUTE REJECTION 
We have never come across this eventuality in our own experience, mainly due to respecting the ABO groups and the absence of specific antibodies in the recipient's serum against donor antigens (negative cross-match). 
Our first 10 aorta transplants saw the imposition of immunosuppressive therapy with cyclosporin that was administered directly in the blood. 
This did not produce any important complications but it was observed that the specific immune reaction only appeared after 3 months and so there is currently a control group without immunosuppressive therapy. 

CHRONIC REJECTION 
This event, indicated in the literature as at a variable distance of two years, has never been found in our patient group. The elements accepted as typical of chronic rejection are thrombosis of the graft, sudden lacerations, and dilatations. 
Such complications have never arisen in our own experience, which has a follow-up period of up to 50 months (average 20 months). Patients undergo periodic checks that involve an ultrasound and CAT scan at 6 months to 1 year, and a spiral CAT scan or angiography in cases of femoral aorta grafting or having had contemporaneous aorticorenal by-passes. The long-term patency is of the order of 100% with a total disappearance of symptoms. 

RESULTS 
Current experience with 30 treated cases allows some considerations to be made about this new vascular transplantation technique. 
At this stage, indications are mainly limited to prosthetic infections but it is surely predictable that these will soon be extended to other vascular traumas, infected or infectious aneurysms, patients with potential infections (diabetics) or having limited immune resources (dialysis and transplanted patients). 
It has also been shown that this therapy is currently burdened with a high mortality rate linked to the presence of the aortoenteric fistula, which in our experience represents some 56% of cases. The mortality rate in cases uncomplicated by a fistula is 15% in our casebook, only to 56% when there is an aortoenteric communication. 
Another factor gleaned from the literature is the type of germ present in the infection. 
This can be Staphylococcus aureus (43%), Escherichia coli (17%), Staphylococcus epidemidis (14%) and Pseudomonas (10%). 

CONCLUSION 
Undoubtedly, the transplantation of vascular segments, especially aortic grafts, is still weighed down by a high mortality rate, although it is always a question of patients having a serious general condition. 
As far as the grafting itself is concerned, we are of the view that it has to be a question of an organ transplant having all the immune problems that is certainly a theme for future research. 
The provision of segments is difficult and the future will see cryopreservation, though there are still some uncertainties over the means of effecting this, but this too is a topic of study and research.