Wspolczesna Onkol 2012; 16 (6): 546–550 DOI: 10.5114/wo.2012.32488 Original paper AAiimm ooff tthhee ssttuuddyy::The aim of the study The use of prefabrication technique was to develop standards for the pre- fabrication of free microvascular flaps in in microvascular reconstructive surgery an animal model, followed by their application in clinical practice, and quan- titative/qualitative microscopic assess- ment of the extent of development of a new microvascular network. MMaatteerriiaall aanndd mmeetthhooddss:: The study was Łukasz Krakowczyk, Adam Maciejewski, Cezary Szymczyk, Janusz Wierzgoń, carried out in 10 experimental pigs. As the first stage, a total of 20 prefabricated Ryszard Szumniak, Piotr Jędrzejewski, Maciej Grajek, Mirosław Dobrut, flaps were created using polytetrafluo- Rafał Ulczok, Stanisław Półtorak roethylene (PTFE) as a support materi- al, placed horizontally over an isolated Department of Oncological and Reconstructive Surgery, Center of Oncology – and distally closed vascular pedicle ba - Maria Sklodowska-Curie Institute of Oncology, Branch Gliwice, Poland sed on superficial abdominal vessels. After completing the animal model study, one patient was selected for the grafting of the prefabricated free flap. RReessuullttss::All 20 free flaps prefabricated in Introduction the animal model were analyzed micro- scopically, exhibiting connective tissue Oncologic reconstructive and microvascular surgery involves a range of com- rich in fibroblasts and small blood ves- plex and often multi-stage techniques aimed at restoring the structure of soft sels in the porous areas across the tissues, bones, blood vessels and nerves previously removed along with the entire thickness of the PTFE element. cancerous tumour. The aim of reconstructive surgical procedures is to achieve CCoonncclluussiioonnss::Flap prefabrication is a new anatomical, topographical, functional and aesthetic effects which approximate and fast developing reconstruction tech- as closely as possible normal physiological conditions. Microsurgery has already nique. The usefulness of prefabrication defined and investigated the suitability of several hundred free tissue flaps (har- techniques and their status in recon- vested from distant sites of the body) which can be routinely used for elective structive surgery still needs to be inves- tigated experimentally and clinically. The reconstructive surgery [1, 2]. In 1964, Nakayama was the first to use a tissue method based on prefabricated free graft based on vascular microanastomoses, which triggered a rapid develop- flaps is the first step towards anatomical ment of microvascular reconstructive surgery [3]. bioengineering that will make it possible Despite multiple benefits of using conventional microvascular flaps, there to replace missing organs with their is as yet no perfect flap with individually modifiable characteristics that would anatomically perfect equivalents. ensure optimum functional and visual effects. Great hopes are currently being pinned on the prefabrication of microvascular flaps, since the technique allows KKeeyy wwoorrddss:: prefabrication techniques, reconstructive surgery, free flaps. extremely precise planning and construction of a complex which closely mir- rors missing tissues that have previously been resected [4]. The term pre- fabricationwas coined in 1982 by Shen et al.who described the technique of free flap formation based on a specially prepared vascular pedicle implant- ed under the selected skin flap fragment [5]. Flap prefabrication refers to the precise customized construction and remod- elling of the flap in the donor site. The technique involves the preparation of exactly defined amounts of different flap tissues, followed by flap customization to match the specific needs of the defect to be corrected. A combination of conventional plastic surgery techniques and tissue engineering procedures make prefabrication one of the most promising areas of plastic surgery. The suitability of these techniques and their status in reconstructive surgery still need verification in experimental and clinical investigations [6]. Flap prefab- rication techniques require extreme precision, as each inaccuracy, slight as it may be, carries the risk of partial or complete necrosis of the flap, secondary separation of its components or infection. Consequently, introduction of these techniques into clinical practice, just like any modifications of existing methods, must be preceded by experimental studies in animal models in com- pliance with international laws in place. The studies must provide unequiv- ocal documented evidence for the efficacy and safety of microsurgical reconstruction techniques under investigation [7, 8]. Aim of the study The aim of the study was to develop standards for the prefabrication of free microvascular flaps in an animal model, followed by their application in clinical practice, and quantitative/qualitative microscopic assessment of the extent of development of a new microvascular network. 554477 The use of prefabrication technique in microvascular reconstructive surgery desired skin flap muscle deep vascular pedicle pedicle with fascia or small cuff muscle dissected out vascular pedicle placed on top of tissue expander expansion started 1 week and continued for 8 weeks goretex tubing or silicon sheed around proximal pedicle to facilitate later flap harvest tissue expander fully expanded at 8 weeks neovascularization od skin and capsule around tissue expander prefabricated flap raised with tissue expander of capsule goretex around proximal pedicle facilitates flap dissection FFiigg.. 11.. Prefabrication technique 554488 współczesna onkologia/contemporary oncology Material and methods for any other reconstructive surgery methods following com- plete surgical resection of the nose. A prefabricated vascu- Prior to the application of prefabrication techniques in the larized flap was created on the patient’s left thigh, on the Department of Oncologic and Reconstructive Surgery of the descending branch of the deep circumflex femoral artery. Oncology Centre, IMSC Institute in Gliwice, an experimen- A total of five PTFE elements implanted in the subcutaneous tal study was conducted in an animal model. The study was tissue of the left thigh were used as a support material. After carried out in 10 experimental pigs. As the first stage, a total eight weeks a prefabricated free flap was prepared and then of 20 prefabricated flaps were created using polytetrafluo- transferred to the recipient site (Fig. 2). roethylene (PTFE) as a support material, placed horizontal- ly over an isolated and distally closed vascular pedicle based Results on superficial abdominal vessels. Before commencing the sur- gical procedure each of the animals was anaesthesized with According to the method proposed by Steinhart, Walton and sodium thiopental. All the animals also received prophylac- Brown, and Cane [9], the microvascular network overgrows tic antibiotic therapy for 24 hours. In view of the activities the perforated alloplast and naturally creates a vascularized involved in the process of flap prefabrication, the experiment support element. Following the integration of the alloplast with was scheduled to take place in three stages. An 8-week inter- the vascular network the vascularized graft in the form of val between stages 1 and 2 was sufficient for the process of a prefabricated microvascular flap can be used as a customized angiogenesis, formation of the vascular network and ade- free flap. All 20 free flaps prefabricated in the animal model quate vascularization of prefabricate components. Anoth- were analyzed microscopically, exhibiting connective tissue rich er stage (stage 3) was conducted a week after the comple- in fibroblasts and small blood vessels in the porous areas across tion of stage 2 in order to harvest tissue samples for the entire thickness of the PTFE element. Numerous foreign- macroscopic and histological analysis. The prefabrication tech- body giant cells were observed in the immediate vicinity of the nique is presented in detail in Fig. 1. The operating materi- support material, forming occasional granulomas. Also, there al, consisting of 20 prefabricated flaps, was fixed in 10% were areas with abundant infiltrations from lymphoid cells, neu- buffered formalin. Slices were taken and processed in the trophils granulocytes and eosinophil granulocytes. None of the tissue processor, following which they were embedded in preparations under analysis revealed the presence of fibrous paraffin. 4 µm slices were stained with hematoxylin-eosin capsule around the board or collagen fibres in the open spaces. and then assessed under the light microscope. The final outcome of the surgical procedure, as well as func- After completing the animal model study, one patient was tional and aesthetic effects of using a prefabricated free flap selected for the grafting of the prefabricated free flap. The in a patient who has had complete surgical resection of the patient, suffering from cancer of the nose, was not eligible nose, is presented in Fig. 3. FFiigg.. 22..Experimental data on animal model. 554499 The use of prefabrication technique in microvascular reconstructive surgery Discussion Reconstructive surgery is increasingly search- ing for new methods that would allow precise and customized design and fabrication of tissue complexes to achieve optimum postoperative effect and, at the same time, ensure reasonably limited functional and aesthetic defects in the donor sites. Even though conventional recon- structive microsurgery techniques are success- fully used for correcting the majority of postre- sective defects within the head and neck area, there are currently no standards applicable to the reconstruction of the nose and other structures of the middle section of the face, the trachea and other large three-dimensional skin areas, while the final effects of reconstruction procedures are usually unsatisfactory. Most reports published worldwide on problems associated with the prefabrication of artificial microvascular complexes describe experiences with using double-component pedicled flaps prefabricated on small laboratory animals (rats, rabbits) [8, 10, 11]. They have proven beyond doubt that the process of neovascularization carries the possibility of designing simple connections between blood vessels and tissues. The procedure has already been used several times in humans for the reconstruction of defects located in the head and neck region. Moreover, isolated case FFiigg.. 33.. Aesthetic and functional effect after use of prefabrication free flap. Flap reports seem to corroborate the claim that allo- prefabrication starts with introduction of a vascular pedicle (descending branch plastic materials implanted into the developing of the deep femoral artery) to a desired donor tissue that on its own does not vascular network can be successfully employed possess an axial blood supply. After a period of neovascularization of at least 8 weeks, this donor tissue can be transferred to the recipient defect based on in reconstructive surgery as microvascular sup- the newly acquired axial vasculature port elements. Reconstruction of the complex structures of the nose, involving nasal bones, cartilage and soft tissues, continues to present some of the most unique challenges to the reconstructive surgeon [1, 12]. There are as yet no algorithms or standards for nasal reconstruction. Reconstructive surgery of the nose usually involves complex multi- 555500 współczesna onkologia/contemporary oncology stage procedures with prelaminated radial flaps that are com- 4. Atabey A, McCarthy E, Manson P, Vander Kolk CA. Prefabrication bined with non-vascularized grafts of ear or rib cartilage, and of combined composite (chimeric) flaps in rats. Ann Plast Surg 2000; 45: 581-7. additionally covered with rotational frontal flaps. The com- 5. Walton R, Brown R, Zhang L. Creation of a vascularized alloplastic plexes are, however, very difficult to obtain and the technique unit for composite reconstruction. Plast Surg Forum 1987; 56: 32. requires a high degree of precision. The total duration of all 6. Staudenmaier R, Hoang TN, Kleinsasser N, Schurr C, Frölich K, Wen- surgical procedures often exceeds 4 years, while the final func- zel MM, Aigner J. Prefabrication of large fasciocutaneous flaps using tional and visual effect is largely unpredictable. Therefore, an isolated arterialised vein as implanted vascular pedicle. J Reconstr Microsurg 2004; 20: 555-64. attempts are constantly being made to find solutions allow- 7. Baudet J, Pelissier P, Casoli V. 1984-1994: Ten years of skin flaps. Pre- ing faster, simpler and better nasal reconstruction. Theoret- fabricated flaps. Ann Chir Plast Esthet 1995; 40: 597-605. ically, if a framework for the nasal root, columella and alae 8. Abbase EA, Shenaq SM, Spira M, el-Falaky MH. Prefabricated flaps: exper- could be precisely modelled out of an artificial material, then imental and clinical review. Plast Reconstr Surg 1995; 96: 1218-25. transformed into a vascularized structure additionally covered 9. Khouri RK, Upton J, Shaw WW. Principles of flap prefabrication. Clin Plast Surg 1992; 19: 763-71. with an inner surface restoring nasal ducts, transposed to the 10. Pribaz JJ, Maitz PK, Fine NA. Flap prefabrication using the “vascu- defect site and covered with a frontal flap, the reconstruction lar crane” principle: an experimental study and clinical application. procedure would be reduced to just two stages and would Br J Plast Surg 1994; 47: 250-6. yield a very good and predictable final effect [13–15]. 11. Can Z, Apaydin I, Erçöçen AR, Demirseren ME, Sabuncuo?lu B. Pre- fabrication of a high-density porous polyethylene implant using Flap prefabrication is a new and fast developing recon- a vascular induction technique. Ann Plast Surg 1998; 41: 264-9. struction technique. The usefulness of prefabrication tech- 12. Ozdemir R, Kocer U, Tiftikcioglu YO, Karaaslan O, Kankaya Y, Cuz- niques and their status in reconstructive surgery still needs dan S, Baydar DE. Axial pattern composite prefabrication of high- to be investigated experimentally and clinically. Flap pre- density porous polyethylene: experimental and clinical research. Plast fabrication techniques call for extreme precision because even Reconstr Surg. 2005; 115: 183-96. 13. Guo L, Pribaz JJ. Clinical flap prefabrication. Plast Reconstr Surg 2009; the slightest inaccuracy carries the risk of partial or complete 124: 340-50. necrosis of the flap, secondary separation of its components or infection. Introduction of these techniques into clinical prac- tice, just like any modifications of existing methods, must Adres do korespondencji be preceded by experimental studies in animal models in com- dr n. med. ŁŁuukkaasszz KKrraakkoowwcczzyykk pliance with international laws. The studies must provide indis- Department of Oncological and Reconstructive Surgery putable evidence for the efficacy and safety of microsurgi- Center of Oncology – Maria Sklodowska-Curie cal reconstruction techniques under investigation [9, 16]. Institute of Oncology, Branch Gliwice Good effects obtained to date by the Reconstructive and Wybrzeże Armii Krajowej 15 Microvascular Surgery Team at the Oncology Institute in Gli- 44-101 Gliwice, Poland tel. +48 32 278 84 17 wice (three-year symptom-free survival rate of 85% in a group fax +48 32 278 84 17 of over 300 patients suffering from locally advanced cancer e-mail: [email protected] of the oral cavity and throat) validate and legitimize the exten- sion of the arsenal of available reconstruction surgery tech- SSuubbmmiitttteedd:: 11.12.2011 niques with prefabricated flaps in order to improve the func- AAcccceepptteedd:: 18.04.2012 tional and aesthetic outcome, and expand the qualification criteria for these therapeutic options. The method based on prefabricated free flaps is the first step towards anatomical bioengineering that will make it possible to replace missing organs with their anatomically perfect equivalents [17]. Although a considerable body of experimental research and broadly understood cooperation between medical centres are still necessary, it seems quite likely that tissue bioengineering will one day make routine use of the vascular foundations of prefabrication techniques. The authors declare no conflict of interest. References 1. Shen TY. Vascular implantation into skin flaps:experimental study and clinical application:a preliminary report. Plast Reconstr Surg 1981; 68: 404-10. 2. Erol OO. The transformation of a free skin graft into a vascularized pedicled flap. Plast Reconstr Surg 1976; 58: 470-7. 3. Tan BK, Chen HC, He TM, Song IC. Flap prefabrication – the bridge between conventional flaps and tissue-engineered flaps. Ann Acad Med Singapore 2004; 33: 662-6.