CLINICAL CASES
Daniel Ciapiński
1, B–C, Iwona Niedzielska
1, D–F, Andrzej Witowski
2, BA Suggestion as to Guided Regeneration
of Bone Defects After Cystectomy
– Case Report
Propozycja sterowanej regeneracji dużych ubytków pocystektomijnych
– opis przypadku
1 Department of Cranio-Maxillo-Facial and Oral Surgery, Medical University of Silesia, Katowice, Poland 2 Clinic of Anesthesiology and Intensive Care, Medical University of Silesia, Katowice, Poland
A – research concept and design; B – collection and/or assembly of data; C – data analysis and interpretation; D – writing the article; E – critical revision of the article; F – final approval of article
Abstract
The methods used to treat small cysts are well-established and undisputable. Nowadays, the process of bone regen-eration for future implants and prosthetic treatment is supplemented by inserting bone-replacement materials into such defects. A problem arises in the case of large cysts, where bone-replacement materials cannot be used to secure proper bone regeneration. After operations on large mandible cysts, the patients are often compelled to use an obdurate for a period of about 2 years to heal the site or decompress the cyst. This makes the treating process very strenuous and long for patients. On the other hand, an excellent alternative seems to be the use of autogenic materials causing no significant mutilation or severe complications. Currently, the best in the regeneration of bone is considered to be autogenously materials that have not only osteoconductive properties, but also osteoinductive and osteogenic. However, it is important to note that obtaining this material was the least burdensome for the patient and it was possible to collect a large amount of tissue. Based on the case presented in this paper, we suggest a tibiae bone as a donor place and platelet rich fibrin as a membrane covering the material and support rapid heal-ing (Dent. Med. Probl. 2014, 51, 2, 252–258).
Key words: guided bone regeneration, bone defect, autogenic bone graft, platelet-rich fibrin.
Streszczenie
Metody stosowane w leczeniu małych torbieli są ugruntowane i niepodważalne. Obecnie proces regeneracji kości pod przyszłe leczenie implantologiczne oraz protetyczne polega na uzupełnieniu defektów kostnych materiałami kościozastępczymi. Pojawia się problem w przypadku dużych torbieli i dużych ubytków kości, ponieważ materia-ły kościozastępcze w tych przypadkach nie mogą być zastosowane. Po zabiegach chirurgicznych usunięcia dużej torbieli żuchwy pacjenci są często zmuszani do korzystania z obturatora przez około 2 lata w celu zmniejszenia i dekompresji torbieli. To powoduje, iż leczenie staje się długie i męczące dla pacjentów. Doskonałą alternatywą wydaje się jednak zastosowanie materiałów autogennych, które nie powodują znacznego okaleczenia oraz licz-nych komplikacji. Obecnie za najlepsze w regeneracji kostnej uważa się materiały autogenne, które mają nie tylko właściwości osteokondukcyjne, lecz także osteoindukcyjne i osteogenne. Ważne jest jednak, aby pozyskanie tego materiału było jak najmniej obciążające dla pacjenta oraz możliwe było pobranie dużej ilości tkanek. Opierając się na przypadku opisanym w pracy, autorzy proponują kość piszczelową jako miejsce dawcze oraz fibrynę bogato-płytkową jako membranę pokrywającą przeszczepiony materiał i wspomagający jego szybkie wgajanie (Dent. Med.
Probl. 2014, 51, 2, 252–258).
Słowa kluczowe: fibryna bogatopłytkowa, sterowana regeneracja kości, autogenny przeszczep kości, ubytek
kostny.
Dent. Med. Probl. 2014, 51, 2, 252–258
Odontogenic cysts are usually treated by sur-gical methods [1]. To avoid neoplastic metaplasia of the cyst lining epithelium (some authors report that this occurs in 17% of the cases), most odonto-genic cysts are treated by one-stage procedure [1]. In the past, large cysts were most often treated by two-stage methods as suggested by Drozdowski (modified Partsch I) due to the high risk of patho-logical fractures. Stage 1 consists of cutting a hole into the cyst cavity through the layers between the mouth and the cyst lumen. The hole is preserved by means of an obturator until the time a radical procedure can be performed. Stage 2, i.e. enucle-ation of the cyst, is performed when the cyst be-comes small enough to remove it safely for ad-jacent anatomical structures and teeth. Disad-vantages of this method are long duration of the treatment, necessity to perform two operations, discomfort connected with the necessity to use an obturator or to observe special regulations of oral hygiene, and possible neoplastic transformation of the cyst lining [2].
One-stage (Partsch I) treatment consists of enucleating the cyst sac with its contents and clos-ing the postoperative wound [1]. The bone cavity becomes filled with clot that will undergo gradual organization and regeneration resulting finally in fibrous or bone tissue. Apart from the morphology of the defects, one of the most commonly reported local factors restricting the regeneration processes is their size. So-called critical size defects (CSDs) will not be filled with good bone tissue. Studies on human patients have shown that CSD values range most often from 5 mm to 7 mm. If the defects are greater, the plasma will extravasate, causing the re-traction and isolation of the fibrin marginal layer from its walls. As a result, mesenchymal cells will fail to penetrate properly the defect, and the blood clot will be replaced by connective tissue. This may lead to the development of scar tissue [3]. System-ic factors also have a great impact on bone heal-ing, as well as bone loss itself, its shape, the volume of the spatial arrangement. Therefore, the surgical treatment of cysts larger than 7 mm will require special attention, aside from the enucleation of the lesion, so as to stimulate correct bone reconstruc-tion, in terms of volume and quality, in the defect site, that will facilitate in the future application of prostheses, conventional or implantological, after the bone has regenerated.
Methods of treatment used in order to fill in-traosseous defects with good bone tissue are com-monly called guided bone regeneration (GBR). A combined therapeutic approach, consisting of filling the defect with augmentation material, cov-ering it with a barrier membrane and closing the wound is considered by the majority of authors as
the best way of treating intraosseous defects [4]. Alloplastic bone-replacement materials, xenogen-ic or allogenxenogen-ic materials and autogenxenogen-ic bone grafts are currently being used to fill bone defects [5, 6]. Among a wide variety of reconstructive materi-als used in medicine, the patient’s own tissue (au-togenic material) in the form of bone chips or blocks, harvested and grafted at the same time, is definitely the best [7]. Such a material activates three important mechanisms: osteogenesis, i.e. creating bone tissue as a result of transferring pro-genitor cells which undergo differentiation into osteoblasts, osteoinduction, i.e. stimulating mes-enchymal cells through bone morphogenetic pro-teins (BMPs) to differentiate into osteoblasts, and osteoconduction, i.e. creating a skeleton to enable bone tissue growth. The bone can be harvested in-traorally or exin-traorally. Inside a mouth, the bone is usually harvested from retromolar regions in the mandible, mentum, maxillary tuber or edentulous maxilla, but the volume of such bone is limited. If larger defects must be filled, the bone is harvest-ed from remote places, most often from the iliac ala, rib, parietal bone or shank bone. In the case of cancellous bone grafts, the greatest volumes are obtained from the iliac crest and proximal tibial metaphysis [6]. Platelet-rich fibrin (PRF) is used to isolate the autogenic graft that has been placed to fill the defect after a cystectomy from the muco-periosteal flap, and for its regenerative and healing properties. Platelet-rich fibrin is a product of pe-ripheral blood centrifugation, and it contains plas-matic growth factors like platelet-derived growth factor (PDGF), insulin growth factor (IGF), trans-forming growth factor β (TGF-β), vascular endo-thelial growth factor (VEGF), epidermal growth factor (EGF), hepatocyte growth factor (HGF) and cytokinins. The autogenic nature of the materi-al eliminates the danger of a cross infection de-veloping. Although immunogenic, the material shows strong tissue-forming potential. Dense fi-brin network of PRF together with PDGF content inhibit the growth of keratocytes into the postop-erative wound, and make favourable conditions for reconstructing physiological structures [8,9]. Ease of preparation and manipulation combined with low costs make PRF a reasonable alternative for artificial resorbable and nonresorbable bar-rier membranes. There are reports on using PRF in periodontology and implantology, both as clots immediately after centrifugation and as ready membranes.
A total of 23 cystectomies of large cysts, using tibial bone chips and platelet-rich fibrin, were per-formed in Department and Hospital of Maxillofa-cial and Oral Surgery, Katowice, between 2010 and 2012. Healing of the donor or recipient sites was
correct and bone reconstruction normal in most of the patients. One of the cases is presented below to show some details of the procedure.
Case Report
A 33-year-old woman B.K. (case record no.10/654C) was referred by her family doctor to Outpatient Clinic of Maxillofacial and Oral Sur-gery, Silesian Medical University, Katowice, on 18 August 2010 because of tissue deformation in the region corresponding to molar teeth 46 and 47 which she had observed a few weeks before. She used medical drugs (Propranolol 10 mg 3 × 1 tabl. daily, Amertil 10 mg 1 × 1 tabl. daily and Buder-hin 1 × 1 one dose to each nostril) due to systemic diseases (arterial hypertension, cardioneurosis, al-lergy to pollen from trees, grasses and corn). Her history revealed nephrotic syndrome in childhood and radical operation on her right middle ear for
cholesteatoma in 2005. Intraoral examination re-vealed ectatic mandibular body around 47–48 and necrotic pulp with 25, 27. A pantomography re-vealed a follicular cyst in tooth 48 and an impact-ed tooth 47 (Fig. 1, 2). Upon adequate preparation, including sanation of the mouth, the patient was admitted to Hospital of Maxillofacial Surgery in Katowice on 27 September 2010. Cystectomy was performed together with the removal of the im-pacted teeth in a standard way. A hole was planned across the compact bone with the diameter suf-ficient to allow enucleation of the entire cyst sac (Fig. 4). Donor site bone (Fig. 3, 5) was harvest-ed upon making an incision on the skin and sub-cutaneous tissue 2 cm below and medially from the right tibial tubercle, removing the compact bone with a trephine and curetting the cancellous
Fig. 1. Pantomographic x-ray picture of the patient
before operation
Ryc. 1. Zdjęcie RTG pantomograficzne pacjentki przed
zabiegiem chirurgicznym
Fig. 2. Pantomographic x-ray picture of the patient
before operation: close-up
Ryc. 2. Zdjęcie RTG pantomograficzne pacjentki przed
zabiegiem chirurgicznym – zbliżenie
Fig. 3. Radiograph of shanks before operation Ryc. 3. Zdjęcie RTG podudzi przed zabiegiem
opera-cyjnym
Fig. 4. Operation – mandibular bone defect upon
removal of the cyst together with impacted teeth
Ryc. 4. Zabieg chirurgiczny – ubytek kostny żuchwy po
bone chips. The chips (5 cm3) were inserted into
the mandibular defect (Fig. 6, 8) and covered with PRF membranes (Fig. 7, 9). PRF membranes were prepared through centrifugation of peripheral vein fresh blood (48 mL). The wounds in the mouth and lower limb (Fig. 10) were treated surgically.
The patient received antibiotic prophylaxis af-ter the operation: Taromentin 3 × 625 mg p.o. for 6 days in the hospital and 8 days upon discharge, Metronidazol 3 × 500 mg p.o. for 6 days, Trilac 3 × 1 caps. as protection. A follow-up pantomogra-phy (Fig. 11) and radiograpantomogra-phy of the shank (Fig. 12) were performed. On day 2 and day 5 her body tem-perature rose to 37.6°C in the afternoon. The su-tures were removed after 14 days. The length of
Fig. 5. Operation – surgical approach to the donor site
i.e.right proximal tibial metaphysic
Ryc. 5. Zabieg chirurgiczny – dostęp operacyjny do
miejsca dawczego (nasady bliższej kości piszczelowej prawej)
Fig. 6. Operation – cancellous bone harvested from
the right tibia
Ryc. 6. Zabieg chirurgiczny – pobrana kość gąbczasta
z kości piszczelowej prawej
Fig. 7. Operation – platelet-rich fibrin (PRF)
Ryc. 7. Zabieg chirurgiczny – fibryna bogatopłytkowa
(PRF)
Fig. 8. Operation – using a cancellous bone graft to
augment the bone defect
Ryc. 8. Zabieg chirurgiczny – augmentacja ubytku
kostnego przeszczepem kości gąbczastej
Fig. 9. Operation – using a cancellous bone graft and
platelet-rich fibrin (PRF) to fill the bone defect
Ryc. 9. Zabieg chirurgiczny – wypełnienie ubytku
kostnego przeszczepem kości gąbczastej i fibryną boga-topłytkową PRF
her hospital stay was 8 days. The patient was dis-charged on 4 October 2010. During the postoper-ative period she reported skin hypesthesia in her right lower lip and in the region of right shank tibial tubercle. She was given vit. B1 forte 3 × 1 tabl. daily. A pantomography was performed af-ter 2 months (Fig. 13) and afaf-ter 6 months (Fig. 14) showing correct bone regeneration of the right mandibular angle. Lower lip dysesthesia disap-peared after 6 months, but she received biostimu-lating laser therapy for a slight skin hypesthesia in her right shank (3 × 5 cm) which still persisted.
Discussion
As bone tissue has limited regenerative abili-ties, large mandibular defects, if no augmentation materials are used, take a long time to heal and of-ten without full success [10]. Therefore, it is nec-essary to fill them with materials which have the ability to activate all basic mechanisms that lead
Fig. 10. Operation – donor site after operation Ryc. 10. Zabieg chirurgiczny – miejsce dawcze po
za-biegu
Fig. 11. Follow-up pantomographic x-ray picture
2 days after operation
Ryc. 11. Zdjęcie RTG pantomograficzne kontrolne
2 dni po zabiegu chirurgicznym
Fig. 12. Follow-up radiograph of the shank 2 days after
operation
Ryc. 12. Zdjęcie RTG podudzi kontrolne 2 dni po
za-biegu chirurgicznym
Fig. 13. Follow-up pantomographic x-ray picture
2 months after operation
Ryc. 13. Zdjęcie RTG pantomograficzne kontrolne
2 miesiące po zabiegu chirurgicznym
Fig. 14. Follow-up pantomographic x-ray picture
6 months after operation
Ryc. 14. Zdjęcie RTG pantomograficzne kontrolne
to bone reconstruction: osteoconduction, osteoin-duction and osteogenesis. There are many reports in the literature on materials and methods used for this purpose [3–7, 10].
Cancellous bone, harvested from the proxi-mal tibia, and platelet-rich fibrin (PRF), obtained as a result of venous blood centrifugation, were in sufficient volumes to fill a large defect after the re-moval of the cyst together with the two impacted molars. Using autogenic grafts is the best method to stimulate the reconstruction of bone tissue [11– 14]. An autogenic bone graft not only fulfils a sup-porting function but it stimulates reconstructive processes on the recipient site due to its mother cells, osteoblasts and quite a number of morpho-genetic proteins.
Apart from its supporting function, a bone graft plays a role as biological stimulator of osteo-genesis. Each graft behaves in a similar way: it is gradually resorbed to finally replace the recipient’s own tissue.
Host’s cells cause resorption of the dead bone tissue, thus leading to the release of factors in-ducing osteogenesis. A new bone tissue is creat-ed on the graft-resorbcreat-ed surfaces. Gradually, the graft will be completely replaced. The process of bone graft reconstruction takes a long time, some-times many months or even years [5]. In the case of large bone defects, special attention should be given to the proper choice of a donor site, as a suf-ficient volume of bone tissue has great significance for the treatment.
Iliac ala and proximal tibial metaphysis seem to be the cancellous bone donor sites of choice for filling large defects after cystectomies. Other do-nor sites will give definitely smaller bone grafts. Engelstad et al. [acc. 15] compared the volumes of compressed cancellous bone harvested by means of conventional surgical methods from three do-nor sites in fresh cadavers. The greatest volumes were obtained from proximal tibia (11.3 mL) as compared with posterior iliac crest (10.1 mL) or anterior iliac crest (7.0 mL).
Many authors report that autogenic bone har-vesting from the proximal tibial metaphysis is ac-companied by definitely less complications as com-pared with the iliac ala. O’Keeffe et al. [14] noted that the rate of complications after graft harvest-ing from the proximal tibial metaphysis was 1.3%. Much higher rate of complications is connected with harvesting from the iliac ala. Dimitriou et
al. [15] report that the rate of complications, infec-tions, hematomas, fractures, hypertrophied scars) in their group was over 19% with graft harvest-ing from the iliac bone as compared with 6% with grafts from long bones.
Geideman et al. [16] observed only one com-plication in one patient (postoperative hematoma) among a group of 155 patients in whom a cancellous bone graft was harvested from the proximal tibia.
Bone graft harvesting from the iliac crest is of-ten followed by persisof-tent chronic donor site pain. Sacco et al. [17] report that only 1% of their study patients in whom a bone graft was harvested from the iliac ala did not complain of donor site pain on discharge. Their further observations were that only 17% of patients did not complain of pain af-ter 6 weeks and 43% of patients did not complain of pain after 3 months.
On the other hand, donor site pain persisted in 41% of patients after 6 months, in 33% of patients after 1 year and in 31% of patients after 2 years [17]. Owoola et al. [18] compared the bone donor sites: proximal tibial metaphysis and iliac crest, based on intraoperative evaluation (amount of the blood loss, volume of the harvested graft, time need-ed for graft harvesting) and six-month follow-up. Graft harvesting from the iliac crest took a much longer time and involved a greater intraoperative loss of blood and postoperative pain [18].
Platelet-rich fibrin (PRF), described for the first time in 2001 by dr. Joseph Choukroun et al. of Nice, is currently widely used in oral surgery and maxillofacial surgery. In Dohan Choukroun et al. [19–23] published a series of their studies de-scribing PRF and its potential clinical applications. When placed on the surfaces of autogenic bone chips and inserted into a defect after cystecto-my, PRF membranes not only function as a bar-rier separating the graft from the mucoperiosteal flap but also stimulate correct the healing of the postoperative wound as they contain a number of growth factors that are gradually released.
PRF harvesting technique is relatively simple and does not require any clotting factors, bovine thrombin, calcium chloride or gelating factors. PRF is solely a product of blood centrifugation.
Based on our first experience we believe that using an autogenic cancellous bone, harvested from the tibial tubercle, together with PRF mem-branes obtained from patient’s venous blood upon centrifugation, is a very good solution.
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Address for correspondence:
Daniel Ciapiński
Department of Cranio-Maxillo-Facial and Oral Surgery Medical University of Silesia
Francuska 20/24 40-027 Katowice Poland
E-mail: daniel.ciapinski@gmail.com Conflict of interest: None declared Received: 20.03.2014
Revised: 30.03.2014 Accepted: 14.05.2014
Praca wpłynęła do Redakcji: 20.03.2014 r. Po recenzji: 30.03.2014 r.