Among the surgical sciences, paediatric cardiac surgery is one of the closest to the concept of reconstruction. Despite the common use of the verb ‘to recycle’ in the third millennium, this notion cannot always be applied to our field and a multitude of materials, patches and conduits have to be used, often leading to rejection, aneurysm formation, calcification and stenosis. Moreover, our population is very particular for the potential of growing inherent to the age of patients. For these reasons we are forced to use materials that can give the best results in short-term follow-up but that cannot remain effective in the longer term. The opportunity to use living materials, growing patches or valves, opens up exciting possibilities—opens up incredible possibilities for our patients. The extracellular matrix (ECM) is the naturally-occurring bioscaffold that surrounds cells in almost all tissues and organ structures. It is an acellular biomaterial that is gradually remodelled, leaving behind organized and healthy tissue. When implanted as a patch, the ECM acts as a scaffold into which the patient's cells migrate and integrate until it is gradually replaced. ECMs originating from various organs have been tested and good results reported. Among the types available, the CorMatrix™ patch (CorMatrix®, Alpharetta, Georgia, USA), which is derived from porcine small intestinal submucosa extracellular matrix (SIS-ECM), is one of the most promising options among those commercially available. In this issue of the Journal [1], Witt and colleagues report their experience in the use of the SIS-ECM CorMatrix patch in 37 paediatric patients. Their patient population was divided into four groups, depending on the implant location: septal defect patching, vascular patching, outflow tract patching or valve reconstruction. There were four deaths (10.8%) at a follow-up time of 411 ± 225 days (range 62–757 days), with no death attributed to the implanted SIS-ECM, even though, in one patient with coronary ostial stenosis after supravalvular aortic patch enlargement, the suspicion of a relationship is legitimate. The best results were reported in the septal closure group. Unfortunately, a septal closure can be accomplished perfectly with many other cheaper materials and the potential of SIS-ECM is probably greatly reduced in this situation. In adult patients, where the extent of the patch is bigger, SIS-ECM is probably justified and could provide better results in terms of the possibility of restoring suitable cardiac muscle. In pulmonary or aortic enlargement plasty, the growth potential of SIS-ECM is interesting. In Witt's experience [1], vascular patching accounted for more than 50% of SIS-ECM patch applications (26 locations), with just one re-operation for pulmonary artery residual stenosis. No aneurysm formation was reported when used for aortoplasty [1]. This promising experience confirms that of others. Indeed, Padalino implanted SIS-ECM patch on the abdominal aorta in 15 rats [2]. Graft re-population was demonstrated as early as 15 days after implantation, while it was almost completely remodelled 180 days after implantation. No significant graft aneurysmatic dilation or detachment was present. The new aortic wall presented with an intima incorporating an endothelial lining, a media with smooth muscle cells and an adventitia containing vessels and fibroblasts [2]. The same encouraging results were not obtained in the clinical experience by McCready, who reported seven episodes of patch aneurysm among 76 patients who had undergone patch angioplasty of the carotid artery following endoarterectomy [3]. The patch used in this latter study was another SIS-ECM product (Surgisis® by Cook Surgical, Bloomington, IN, USA) that was thinner than CorMatrix. However, aneurysmal dilation of the graft patch has been described when the CorMatrix was used in carotid patch angioplasty. As regards right ventricular outflow tract (RVOT) reconstruction, Witt reported on six patients with one re-operation. In three patients, a unicusp SIS-ECM valve was created but, unfortunately, one patient died from low cardiac output and the other two showed moderate-to-severe valve incompetence. School reported four unicusp valves implanted in pulmonary outflow tract reconstruction with three of them competent at an average follow-up of 9 months: too short to be of significance [4]. Quarti reported 26 cases treated with SIS-ECM patch reconstruction, nine of which were cusp extension valvular repairs: five aortic, two tricuspid, one mitral and one pulmonary valve. At a mean follow-up of 12.5 months no patients had undergone re-operation and no more than mild incompetence was evident [5]. A large variability of results is evident among all the reported experiences. An interesting experimental study by Tottey confirms that differences exist in the composition, structure and mechanical properties of SIS-ECM prepared from tissues harvested from animals of different ages. In their conclusion, SIS-ECMs harvested from pigs aged 12 weeks are suitable for withstanding substantial mechanical loading after in vivo implantation and remodelling into load-bearing or force-generating tissues, while animals aged >52 weeks will yield scaffolds that may persist longer after in vivo implantation [6]. The interactions between the CorMatrix patch and the surrounding tissues can also be affected by the implantation techniques, the suture materials and other factors, potentially explaining the extreme variability of the results. In our experience in Bologna, the SIS-ECM CorMatrix patch was used in 19 locations on 16 patients (septal patch in 6; pulmonary artery patch enlargement in 5; valve reconstruction in 5 [3 aortic, 1 mitral and 1 tricuspid]; Senning procedure as part of double switch operation in 2 and aortic arch reconstruction in 1). All patients are alive at a mean follow-up of 15 months. One patient underwent re-operation for recurrent incompetence 24 months after repair of a dysplastic aortic valve. The explanted patch appeared pliable and without any calcification. Our impression is that the SIS-ECM CorMatrix patch is very useful in pulmonary artery enlargement and valve cusp extension by reason of its pliability and thinness, whilst it is probably not necessary for septal closure. Since clinical studies so far have limited follow-up, it is not possible to confirm the ability of the patch to regenerate normal tissue in anatomical and functional terms, although this has been demonstrated in experimental studies. However, the absence of calcific degeneration is encouraging and sufficiently important to recommend its use. If the material proves capable of allowing for growth, previously unimagined possibilities will open up, forever solving all the problems related to the use of non-living materials.

Do not throw away anything from the pig.

GARGIULO, GAETANO DOMENICO
2013

Abstract

Among the surgical sciences, paediatric cardiac surgery is one of the closest to the concept of reconstruction. Despite the common use of the verb ‘to recycle’ in the third millennium, this notion cannot always be applied to our field and a multitude of materials, patches and conduits have to be used, often leading to rejection, aneurysm formation, calcification and stenosis. Moreover, our population is very particular for the potential of growing inherent to the age of patients. For these reasons we are forced to use materials that can give the best results in short-term follow-up but that cannot remain effective in the longer term. The opportunity to use living materials, growing patches or valves, opens up exciting possibilities—opens up incredible possibilities for our patients. The extracellular matrix (ECM) is the naturally-occurring bioscaffold that surrounds cells in almost all tissues and organ structures. It is an acellular biomaterial that is gradually remodelled, leaving behind organized and healthy tissue. When implanted as a patch, the ECM acts as a scaffold into which the patient's cells migrate and integrate until it is gradually replaced. ECMs originating from various organs have been tested and good results reported. Among the types available, the CorMatrix™ patch (CorMatrix®, Alpharetta, Georgia, USA), which is derived from porcine small intestinal submucosa extracellular matrix (SIS-ECM), is one of the most promising options among those commercially available. In this issue of the Journal [1], Witt and colleagues report their experience in the use of the SIS-ECM CorMatrix patch in 37 paediatric patients. Their patient population was divided into four groups, depending on the implant location: septal defect patching, vascular patching, outflow tract patching or valve reconstruction. There were four deaths (10.8%) at a follow-up time of 411 ± 225 days (range 62–757 days), with no death attributed to the implanted SIS-ECM, even though, in one patient with coronary ostial stenosis after supravalvular aortic patch enlargement, the suspicion of a relationship is legitimate. The best results were reported in the septal closure group. Unfortunately, a septal closure can be accomplished perfectly with many other cheaper materials and the potential of SIS-ECM is probably greatly reduced in this situation. In adult patients, where the extent of the patch is bigger, SIS-ECM is probably justified and could provide better results in terms of the possibility of restoring suitable cardiac muscle. In pulmonary or aortic enlargement plasty, the growth potential of SIS-ECM is interesting. In Witt's experience [1], vascular patching accounted for more than 50% of SIS-ECM patch applications (26 locations), with just one re-operation for pulmonary artery residual stenosis. No aneurysm formation was reported when used for aortoplasty [1]. This promising experience confirms that of others. Indeed, Padalino implanted SIS-ECM patch on the abdominal aorta in 15 rats [2]. Graft re-population was demonstrated as early as 15 days after implantation, while it was almost completely remodelled 180 days after implantation. No significant graft aneurysmatic dilation or detachment was present. The new aortic wall presented with an intima incorporating an endothelial lining, a media with smooth muscle cells and an adventitia containing vessels and fibroblasts [2]. The same encouraging results were not obtained in the clinical experience by McCready, who reported seven episodes of patch aneurysm among 76 patients who had undergone patch angioplasty of the carotid artery following endoarterectomy [3]. The patch used in this latter study was another SIS-ECM product (Surgisis® by Cook Surgical, Bloomington, IN, USA) that was thinner than CorMatrix. However, aneurysmal dilation of the graft patch has been described when the CorMatrix was used in carotid patch angioplasty. As regards right ventricular outflow tract (RVOT) reconstruction, Witt reported on six patients with one re-operation. In three patients, a unicusp SIS-ECM valve was created but, unfortunately, one patient died from low cardiac output and the other two showed moderate-to-severe valve incompetence. School reported four unicusp valves implanted in pulmonary outflow tract reconstruction with three of them competent at an average follow-up of 9 months: too short to be of significance [4]. Quarti reported 26 cases treated with SIS-ECM patch reconstruction, nine of which were cusp extension valvular repairs: five aortic, two tricuspid, one mitral and one pulmonary valve. At a mean follow-up of 12.5 months no patients had undergone re-operation and no more than mild incompetence was evident [5]. A large variability of results is evident among all the reported experiences. An interesting experimental study by Tottey confirms that differences exist in the composition, structure and mechanical properties of SIS-ECM prepared from tissues harvested from animals of different ages. In their conclusion, SIS-ECMs harvested from pigs aged 12 weeks are suitable for withstanding substantial mechanical loading after in vivo implantation and remodelling into load-bearing or force-generating tissues, while animals aged >52 weeks will yield scaffolds that may persist longer after in vivo implantation [6]. The interactions between the CorMatrix patch and the surrounding tissues can also be affected by the implantation techniques, the suture materials and other factors, potentially explaining the extreme variability of the results. In our experience in Bologna, the SIS-ECM CorMatrix patch was used in 19 locations on 16 patients (septal patch in 6; pulmonary artery patch enlargement in 5; valve reconstruction in 5 [3 aortic, 1 mitral and 1 tricuspid]; Senning procedure as part of double switch operation in 2 and aortic arch reconstruction in 1). All patients are alive at a mean follow-up of 15 months. One patient underwent re-operation for recurrent incompetence 24 months after repair of a dysplastic aortic valve. The explanted patch appeared pliable and without any calcification. Our impression is that the SIS-ECM CorMatrix patch is very useful in pulmonary artery enlargement and valve cusp extension by reason of its pliability and thinness, whilst it is probably not necessary for septal closure. Since clinical studies so far have limited follow-up, it is not possible to confirm the ability of the patch to regenerate normal tissue in anatomical and functional terms, although this has been demonstrated in experimental studies. However, the absence of calcific degeneration is encouraging and sufficiently important to recommend its use. If the material proves capable of allowing for growth, previously unimagined possibilities will open up, forever solving all the problems related to the use of non-living materials.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/396464
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