- Email: [email protected]
The use of buccal fat pad in surgical treatment of ‘Krokodil’ drug-related osteonecrosis of maxilla
Journal of Cranio-Maxillo-Facial Surgery 46 (2018) 831e836
Contents lists available at ScienceDirect
Journal of Cranio-Maxillo-Facial Surgery journal homepage: www.jcmfs.com
The use of buccal fat pad in surgical treatment of ‘Krokodil’ drug-related osteonecrosis of maxilla Koryun Hakobyan a, *, Yuri Poghosyan b, Aram Kasyan a a b
Department of Maxillofacial Surgery, Kanaker-Zeytun Medical Centre, (Head: Aram Kasyan, MD), 7 Nersisyan Str, Yerevan, 0014, Armenia Chair of Postgraduate Maxillofacial Surgery, Yerevan State Medical University, (Head: Prof. Yuri Poghosyan DSc), 2 Koryun Str, Yerevan, 0025, Armenia
a r t i c l e i n f o
a b s t r a c t
Article history: Paper received 25 October 2017 Accepted 13 March 2018 Available online 20 March 2018
‘Krokodil’ is the street name of a new synthetic drug mixture. It is a light brown liquid that is used intravenously without previous purification. Osteonecrosis of the jaw (ONJ) is a common complication among Krokodil users. Krokodil drug-related ONJ presents as alveolar process exposure in the oral cavity. Surgery is the main method for treatment of Krokodil drug-related ONJ patients. In a study by Poghosyan et al., no cases of recurrence were seen after surgery on the maxilla, but 38% of cases (8/21) developed an oroantral communication after surgical treatment for maxillary osteonecrosis (Poghosyan et al., 2014). The aim of this study is to report on the results of buccal fat pad use in closure of maxillary sinus floor defects after partial maxillary resection in Krokodil drug-related ONJ patients. Six male patients with Krokodil drug-related distal maxillary osteonecrosis were included in this retrospective study. All patients underwent surgical treatment, which included surgical removal of necrotic bone, and closure of formed maxillary sinus floor defects with buccal fat pad and local mucoperiosteal flaps. In all patients the postoperative period was uneventful. After suture removal small areas of buccal fad pad exposure were found in all patients, which epithelialized successfully over the following month. During the postoperative follow-up period (8e12 months) no signs of recurrence were found. © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
Keywords: Krokodil drug Jaw osteonecrosis Oroantral communication Buccal fat pad
1. Introduction Krokodil is the street name of a new synthetic drug mixture. It is a light-brown liquid that is used intravenously without previous purification. The drug component of Krokodil is desomorphine, which is an opiate. The mixture also includes dihydromorphine3,6-dideoxy and morphinan-4,5-epoxy-3-ol (Alves et al., 2015). The drug abusers synthesize Krokodil themselves. They use cheap and widely available substances, which are easily obtained, for example from drug-stores. Codeine-containing analgesics (Sedalgin, Pentalgin etc.), iodine, soda, red phosphorus (from matches), hydrochloric acid, and gasoline are among the substances used in the process, so during intravenous use many side products enter the bloodstream.
* Corresponding author. 7 Baghyan Str, Apt 3, Yerevan, 0056, Armenia. E-mail address: [email protected] (K. Hakobyan).
Osteonecrosis of the jaw (ONJ) is a common complication in Krokodil users. Low levels of serum C-terminal telopeptide (CTX) are found in these patients (Hakobyan et al., 2017), indicating decreased bone turnover, which is the result of Krokodil use (Hakobyan et al., 2017). Thus, Krokodil has an anti-resorptive effect on bone tissue (Hakobyan et al., 2017), which means that ONJ in Krokodil abusers is a new type of medication-related osteonecrosis of the jaw (MRONJ) (Hakobyan et al., 2017). Krokodil drug-related ONJ presents as alveolar process bone exposure in the oral cavity. The exposed bone is a pale yellow-grey color, and is usually covered with greyish plaque. Empty dental sockets filled with purulent discharge are also found in such patients. The surrounding mucosa is pale pink in color and rarely hyperemic. Clinically intact teeth are often seen in the necrotic jawbones. Intraoral and extraoral fistulas in the affected area are common symptoms of the disease. In up to 92.3% of cases jaw osteonecrosis develops after tooth extraction, either by the dentist or the patient himself (Hakobyan, 2013). The patients experience bone exposure either immediately
https://doi.org/10.1016/j.jcms.2018.03.007 1010-5182/© 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
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K. Hakobyan et al. / Journal of Cranio-Maxillo-Facial Surgery 46 (2018) 831e836
after the tooth removal or up to 12 months later (Hakobyan, 2013). Among other risk factors for jawbone osteonecrosis development in Krokodil users are poor-quality removable and fixed dentures, failed endodontic treatment, marginal or apical periodontitis, acute or chronic trauma of the oral cavity mucosa, bone trauma, anatomical features of the jaws (exostoses, palatal torus), and poor oral hygiene (Hakobyan, 2013). Radiographic signs of jaw osteonecrosis in Krokodil-addicted patients depend on the terms of drug-use withdrawal and the stage of disease onset (Poghosyan et al., 2013). In the early stages of the disease radiographic examination can be uninformative as nonspecific signs are often revealed: osteosclerosis, destruction, and empty dental alveoli without demarcation of osteonecrotic zone (Poghosyan et al., 2013). Surgery is the main method for the treatment of Krokodil drugrelated ONJ (Poghosyan et al., 2014). Low rates of recurrence are found in patients with drug withdrawal (minimum 1 month prior to surgery) and following jaw resection for a minimum of 0.5 cm into healthy tissue (Poghosyan et al., 2014). According to Poghosyan et al. (2014), no cases of recurrence were seen after surgery on the maxilla. However, in 38% (8/21) of cases, oroantral communication developed after surgical treatment for maxillary osteonecrosis (Poghosyan et al., 2014). Formation of oroantral communication was not a sign of osteonecrosis recurrence, because in these patients no exposed bone, purulent discharge, or inflammatory signs were found. In all cases the main cause of oro-antral communication formation was failure of intraoral sutures in the first 3e6 postoperative days (Poghosyan et al., 2014). In 1977 Egyedi was the first to describe the use of buccal fat pad (BFP) as a flap in oral surgery (Egyedi, 1977). Initially it was used for closing oronasal and oroantral communications (Egyedi, 1977). The buccal fat pad has a body from which four processes extend. It has rich vascularity from the facial artery, transverse facial artery, and branches of the internal maxillary artery. BFP is now used for closure of oral cavity defects of different size and origin. The main advantages of using BFP are its rich blood supply, elasticity, absence of restriction by age, safety, and spontaneous epithelialization. Fat -Guasch et al., 2010). These fattissue also contains stem cells (Farre derived stem cells promote angiogenesis (Mirancille et al., 2004). The aim of this study is to report the results of buccal fat pad use in closure of maxillary sinus floor defects after partial maxillary resection in Krokodil drug-related ONJ patients. 2. Materials and methods Six male patients with Krokodil drug-related distal maxillary osteonecrosis were included in this retrospective study. All cases were analyzed regarding complaints, age, period of Krokodil use, Krokodil withdrawal period, number of lesions, and surgery outcome. All patients underwent cone beam computed tomography (CBCT) prior to surgery. 2.1. Surgery In all patients surgery was performed a minimum of 1 month after drug cessation. Surgery in all cases included removal of necrotic bone and closure of formed maxillary sinus floor defects with BFP and local mucoperiosteal flaps. 2.1.1. Necrotic bone removal In all patients necrotic bone exposure was achieved through midcrestal incision with releasing incisions in both sides. Mucoperiosteal flaps were elevated, exposing underlying bone tissue (Fig. 2c).
After necrotic bone exposure, if: - clinically formed sequestrum was found, this was removed and bone debridement was continued about 0.5 cm in all directions. - a clear demarcation line was found between vital and non-vital bone, resection of necrotic bone was performed and debridement was continued about 0.5 cm in all directions. - no demarcation line or sequestrum formation was found, resection of necrotic bone was performed until the appearance of areas of bleeding. The height of interdental septa and vestibular bone adjacent to teeth in necrectomy zones was reduced by one-third to prevent their exposure in the postoperative period. All bone margins were rounded with burs. Pathologically thickened sinus mucosa was removed only from the sinus floor, because removal of mucosa from the sinus walls would expose underlying bone and could lead to new osteonecrotic zones (Figs. 1c and 2d). 2.1.2. Sinus floor defect closure with buccal fat pad A small incision was made over the periosteum in the posterolateral region of the maxilla. After blunt dissection, buccal fat pad was relocated into the wound (Figs. 1d and 2e, and f). Then, buccal fat pad was placed over the defect and fixed to vestibular and palatal soft tissues using transmucosal sutures (Fig. 1e). Vestibular mucoperiosteal flap was mobilized using horizontal incisions over the periosteum in its basis. Horizontal mattress sutures were used to close the mucosa and a secondary running continuous suture was placed over the horizontal mattress sutures (Fig. 1f). 2.2. Postoperative period Besides postoperative antiseptic wound care, conservative treatment was also performed, which included clindamycin, metronidazole, oral cavity rinses with antiseptics, and nasal vasoconstrictors. Sutures were removed on the 10th day. Patients were considered as recovered if local signs of inflammation (intra- and extraoral suppuration, -issue abscesses, and inflammatory masses) and exposed bone were absent (Figs. 1g and 2g). 2.3. Statistical analysis Data are expressed as means ± SEM. IBM SPSS Statistics 20 was used for statistical analysis. 3. Results All patients were HCV positive. Mean age of patients was 42.7 ± 2.4 (range 36e52) years. Mean periods of Krokodil use and Krokodil withdrawal were 13 ± 1.8 (range 6e18) months and 9 ± 4 (range 1e24) months respectively. All patients had complaints related to intraoral bone exposure (Figs. 1a and 2a), purulent discharge from the affected area and from the nose, and pain in the midface. In all patients stage-3 osteonecrosis (according to the American Association of Oral and Maxillofacial Surgeons (AAOMS)) was found in the distal maxilla. Unilateral exposure of the maxillary alveolar process was found in five patients (Fig. 1a). Total involvement of the maxillary alveolar process was found in one patient (Fig. 2c). The exposed area was about 2e8 cm in length. The exposed bone was a pale yellow-grey color and was covered with greyish plaque. Granulation tissue growth was found in the maxillary sinus. The surrounding mucosa was pale pink in color. Defects in the vestibular mucosa over the
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Fig. 1. Patient A: a) unilateral exposure of maxillary alveolar process; b) opacification of right maxillary, ethmoidal, and frontal sinuses on cone beam computed tomogram; c) maxillary sinus floor defect formed after necrectomy; d) exposed buccal fat pad; e) buccal fat pad fixed over the sinus floor defect; f) intraoral wound view on first postoperative day; g) 2-month postoperative intraoral view.
exposed bone was found in full height in all patients (Figs. 1a and 2a). The trigger for osteonecrosis development was tooth removal 8 ± 1.6 (range 3e12) months before examination.
On CBCT total or partial opacification of the maxillary sinus was found on the affected side. Clear demarcation of the necrotic zone was found on the tomograms of five patients, while in one patient no signs of demarcation were found.
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Fig. 2. Patient B: a) bilateral exposure of maxillary alveolar process; b) bilateral opacification of maxillary sinuses on cone beam computed tomogram; c) whole maxillary alveolar process and palatal bone found to be necrotic; d) combined bilateral maxillary sinus floor and nasal floor defects; e,f) bilateral exposure of buccal fat pads; g) 2-month postoperative intraoral view.
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During surgery, clinically formed sequestrums were found in two patients; a clear demarcation line between vital and non-vital bone was found in three patients; in one patient no demarcation line or sequestrum formation was found. Isolated maxillary sinus floor total defects were formed after necrectomy in four patients (Fig. 1c). In one patient, maxillary sinus floor total defect was combined with a partial defect of the nasal floor (about 6 cm 4.5 cm in size). In another patient, bilateral maxillary sinus floor total defect was combined with total defect of the nasal floor (Fig. 2d). In one patient the formed defect was closed by bilateral use of BFP, whilst unilateral use of BFP was applied in five patients. In all cases, it was not possible to achieve tension-free BFP closure with local mucoperiosteal flaps due to primary defects of the vestibular and palatal mucosa. In all patients the postoperative period was uneventful. After suture removal, small areas (about 3e5 mm in diameter) of buccal fad pad exposure were found in all patients, which epithelialized successfully over the following month. The postoperative follow-up period was 8e12 months, during which all patients were free of symptoms: no signs of recurrence or of oroantral communication were found (Figs. 1g and 2g). 4. Discussion Maxillary sinusitis is a common complication in patients with upper-jaw osteonecrosis of different origin. In BRONJ patients maxillary sinusitis is found in 43.6% of patients (Mast et al., 2012). Krokodil drug-related ONJ has been found to affect the maxilla in 48% (19/40) of patients (Poghosyan et al., 2014). The rate of maxillary sinusitis in Krokodil abusers with upper jaw osteonecrosis was 50% (Poghosyan et al., 2012). The main clinical findings in these patients were: oroantral fistulas; purulent discharge from the nose; opacification of the maxillary sinus on radiographic examination (Figs. 1b and 2b) (Poghosyan et al., 2012). Involvement of the maxillary sinus implicates stage-3 osteonecrosis (according to AAOMS). Surgical management of stage-3 Krokodil drug-related ONJ includes removal of necrotic bone and closure of the defect with soft tissues (Poghosyan et al., 2014). Maxillary sinus floor defect occurs after necrectomy of stage-3 distal maxilla osteonecrosis. There are several difficulties in achieving permanent closure of oroantral communications in Krokodil drug-related ONJ patients. In most cases it is impossible to achieve tension-free closure of maxillary sinus floor defects with local mucoperiosteal flaps due to the initial vertical defects of the vestibular and palatal gingiva. This is the main cause of wound dehiscence 3e6 days postoperatively, causing formation of oroantral communication in 38% of patients (Poghosyan et al., 2014). Infection is common in ONJ patients. It can jeopardize healing processes, promoting wound dehiscence. If the wound is closed using local mucoperiosteal flaps some surfaces of bone tissue are left uncovered by soft tissues. This condition increases the risk of ONJ recurrence. The size of maxillary sinus floor defects may vary. Total defects of the maxillary sinus floor are common in Krokodil abusers. In some cases, maxillary sinus floor defect is combined with partial nasal floor defect. Bilateral maxillary sinus floor defect combined with total nasal floor defect is not rare in ONJ patients (Fig. 2d). Buccal fat pad (BFP) is a reliable method for the closure of maxillary sinus floor defects in osteonecrosis patients. Over recent years there have been several reports of BFP use in MRONJ patients for the closure of maxillary sinus floor defects after distal maxillary resection. All authors reported good results (Berrone et al., 2015; Rotaru et al., 2015; Melville et al., 2016).
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The advantages of BFP can overcome the main problems associated with closure of oroantral communications in Krokodil drugrelated ONJ patients mentioned above. The use of BFP makes possible the closure of the defect with two layers (BFP and mucoperiosteal flaps). Almost all bone surfaces can be closed with BFP. Even if BFP exposure is seen after suture removal (in all our cases), spontaneous epithelialization occurs within about 1 month. Low rates of infection are found after BFP use, which makes the use of BFP a reliable method for infected areas (as found in ONJ patients). Stem cells found in fat tissue promote angiogenesis, decreasing ONJ recurrence rates. The size of BFP makes possible the closure of large defects. Combined bilateral maxillary sinus floor and nasal floor defects can be successfully closed with bilateral use of BFP. Finally, there are significant problems in the management of drug-addicted patients due to their social status. According to Hakobyan (2013): 11.1% of Krokodil users had no family (10 patients from 90); 78.9% had no job (71 patients from 90); 55.6% were exprisoners (50 patients from 90). The main reason these patients visit the doctor is for pain relief. It is difficult to keep track of them in the postoperative period. Most of the patients do not visit the doctor for postoperative checkups. The only way to contact them is with phone calls, but in many cases this is impossible. The patients might have no contact information; they may have been imprisoned, or even died. The most reliable patients are those who receive methadone treatment. 5. Conclusion Radical debridement of necrotic bone, partial sinusotomy and the transposition of buccal fat pad can be used as an effective and predictable method for the treatment of distal maxillary osteonecrosis due to Krokodil drug use. Funding There are no sources of support in the form of grants. Conflicts of interest There is no conflict of interest that has to be indicated by the authors. References Alves EA, Soares JX, Afonso CM, Grund JP, Agonia AS, Cravo SM, et al: The chemistry behind ‘krokodil’: street-like synthesis and product analysis. Forensic Sci Int 257: 76e82, 2015 Berrone M, Florindi FU, Carbone V, Aldiano C, Pentenero M: Stage 3 medicationrelated osteonecrosis of the posterior maxilla: surgical treatment using a pedicled buccal fat pad flap: case reports. J Oral Maxillofac Surg 73(11): 2082e2086, 2015 Egyedi P: Utilization of the buccal fat pad for closure of oro-antral and/or oro-nasal communications. J Maxillofac Surg 5: 241, 1977 -Guasch E, Martí-Page s C, Hern Farre andez-Alfaro F, Klein-Nulend J, Casals N: Buccal fat pad, an oral access source of human adipose stem cells with potential for osteochondral tissue engineering: an in vitro study. Tissue Eng Part C Methods 16: 1083, 2010 Hakobyan KA: Clinical picture, diagnosis and treatment of facial bones osteonecrosis at patients who use the drug ‘Krokodil’. Yerevan State Medical University, 2013 Dissertation Hakobyan KA, Poghosyan YM, Poghosyan AY: C-terminal telopeptide level in ‘Krokodil’ drug-related jaw osteonecrosis patients. New Armen Med J 11: 57e61, 2017 Melville JC, Tursun R, Shum JW, Young S, Hanna IA, Marx RE: A technique for the treatment of oral-antral fistulae resulting from medication-related osteonecrosis of the maxilla: the combined buccal fat pad flap and radical sinusotomy. Oral Surg Oral Med Oral Pathol Oral Radiol 122(3): 287e291, 2016 Mast G, Otto S, Mücke T, Schreyer C, Bissinger O, Kolk A, et al: Incidence of maxillary sinusitis and oro-antral fistulae in bisphosphonate-related osteonecrosis of the jaw. J Craniomaxillofac Surg 40(7): 568e571, 2012 A: ImproveMirancille A, Heeschen C, Senqenes C, Curat CA, Busse R, Bouloumie ment of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation 110: 349, 2004
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Poghosyan YM, Hakobyan KA, Gasparyan LL: Radiographic diagnosis of jaw osteonecrosis at patients who use the drug ‘Krokodil’. Issue Theor Clin Med 2(78): 44e47, 2013 Poghosyan YM, Hakobyan KA, Manukyan EV: Features of clinical course and treatment of chronic maxillary sinusitis caused by osteonecrosis of maxilla at drug addict patients who use the drug ‘Krokodil’ (desomorphine). Bull Stomatol Maxillofac Surg 2e3: 18e24, 2012
Poghosyan YM, Hakobyan KA, Poghosyan AY, Avetisyan EK: Surgical treatment of jaw osteonecrosis in ‘Krokodil’ drug addicted patients. J Cranio Maxillo Facial Surg 42: 1639e1643, 2014 Rotaru H, Kim M-K, Kim S-G, Park Y-W: Pedicled buccal fat pad flap as a reliable surgical strategy for the treatment of medication-related osteonecrosis of the jaw. J Oral Maxillofac Surg 73(3): 437e442, 2015
Contents lists available at ScienceDirect
Journal of Cranio-Maxillo-Facial Surgery journal homepage: www.jcmfs.com
The use of buccal fat pad in surgical treatment of ‘Krokodil’ drug-related osteonecrosis of maxilla Koryun Hakobyan a, *, Yuri Poghosyan b, Aram Kasyan a a b
Department of Maxillofacial Surgery, Kanaker-Zeytun Medical Centre, (Head: Aram Kasyan, MD), 7 Nersisyan Str, Yerevan, 0014, Armenia Chair of Postgraduate Maxillofacial Surgery, Yerevan State Medical University, (Head: Prof. Yuri Poghosyan DSc), 2 Koryun Str, Yerevan, 0025, Armenia
a r t i c l e i n f o
a b s t r a c t
Article history: Paper received 25 October 2017 Accepted 13 March 2018 Available online 20 March 2018
‘Krokodil’ is the street name of a new synthetic drug mixture. It is a light brown liquid that is used intravenously without previous purification. Osteonecrosis of the jaw (ONJ) is a common complication among Krokodil users. Krokodil drug-related ONJ presents as alveolar process exposure in the oral cavity. Surgery is the main method for treatment of Krokodil drug-related ONJ patients. In a study by Poghosyan et al., no cases of recurrence were seen after surgery on the maxilla, but 38% of cases (8/21) developed an oroantral communication after surgical treatment for maxillary osteonecrosis (Poghosyan et al., 2014). The aim of this study is to report on the results of buccal fat pad use in closure of maxillary sinus floor defects after partial maxillary resection in Krokodil drug-related ONJ patients. Six male patients with Krokodil drug-related distal maxillary osteonecrosis were included in this retrospective study. All patients underwent surgical treatment, which included surgical removal of necrotic bone, and closure of formed maxillary sinus floor defects with buccal fat pad and local mucoperiosteal flaps. In all patients the postoperative period was uneventful. After suture removal small areas of buccal fad pad exposure were found in all patients, which epithelialized successfully over the following month. During the postoperative follow-up period (8e12 months) no signs of recurrence were found. © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
Keywords: Krokodil drug Jaw osteonecrosis Oroantral communication Buccal fat pad
1. Introduction Krokodil is the street name of a new synthetic drug mixture. It is a light-brown liquid that is used intravenously without previous purification. The drug component of Krokodil is desomorphine, which is an opiate. The mixture also includes dihydromorphine3,6-dideoxy and morphinan-4,5-epoxy-3-ol (Alves et al., 2015). The drug abusers synthesize Krokodil themselves. They use cheap and widely available substances, which are easily obtained, for example from drug-stores. Codeine-containing analgesics (Sedalgin, Pentalgin etc.), iodine, soda, red phosphorus (from matches), hydrochloric acid, and gasoline are among the substances used in the process, so during intravenous use many side products enter the bloodstream.
* Corresponding author. 7 Baghyan Str, Apt 3, Yerevan, 0056, Armenia. E-mail address: [email protected] (K. Hakobyan).
Osteonecrosis of the jaw (ONJ) is a common complication in Krokodil users. Low levels of serum C-terminal telopeptide (CTX) are found in these patients (Hakobyan et al., 2017), indicating decreased bone turnover, which is the result of Krokodil use (Hakobyan et al., 2017). Thus, Krokodil has an anti-resorptive effect on bone tissue (Hakobyan et al., 2017), which means that ONJ in Krokodil abusers is a new type of medication-related osteonecrosis of the jaw (MRONJ) (Hakobyan et al., 2017). Krokodil drug-related ONJ presents as alveolar process bone exposure in the oral cavity. The exposed bone is a pale yellow-grey color, and is usually covered with greyish plaque. Empty dental sockets filled with purulent discharge are also found in such patients. The surrounding mucosa is pale pink in color and rarely hyperemic. Clinically intact teeth are often seen in the necrotic jawbones. Intraoral and extraoral fistulas in the affected area are common symptoms of the disease. In up to 92.3% of cases jaw osteonecrosis develops after tooth extraction, either by the dentist or the patient himself (Hakobyan, 2013). The patients experience bone exposure either immediately
https://doi.org/10.1016/j.jcms.2018.03.007 1010-5182/© 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
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K. Hakobyan et al. / Journal of Cranio-Maxillo-Facial Surgery 46 (2018) 831e836
after the tooth removal or up to 12 months later (Hakobyan, 2013). Among other risk factors for jawbone osteonecrosis development in Krokodil users are poor-quality removable and fixed dentures, failed endodontic treatment, marginal or apical periodontitis, acute or chronic trauma of the oral cavity mucosa, bone trauma, anatomical features of the jaws (exostoses, palatal torus), and poor oral hygiene (Hakobyan, 2013). Radiographic signs of jaw osteonecrosis in Krokodil-addicted patients depend on the terms of drug-use withdrawal and the stage of disease onset (Poghosyan et al., 2013). In the early stages of the disease radiographic examination can be uninformative as nonspecific signs are often revealed: osteosclerosis, destruction, and empty dental alveoli without demarcation of osteonecrotic zone (Poghosyan et al., 2013). Surgery is the main method for the treatment of Krokodil drugrelated ONJ (Poghosyan et al., 2014). Low rates of recurrence are found in patients with drug withdrawal (minimum 1 month prior to surgery) and following jaw resection for a minimum of 0.5 cm into healthy tissue (Poghosyan et al., 2014). According to Poghosyan et al. (2014), no cases of recurrence were seen after surgery on the maxilla. However, in 38% (8/21) of cases, oroantral communication developed after surgical treatment for maxillary osteonecrosis (Poghosyan et al., 2014). Formation of oroantral communication was not a sign of osteonecrosis recurrence, because in these patients no exposed bone, purulent discharge, or inflammatory signs were found. In all cases the main cause of oro-antral communication formation was failure of intraoral sutures in the first 3e6 postoperative days (Poghosyan et al., 2014). In 1977 Egyedi was the first to describe the use of buccal fat pad (BFP) as a flap in oral surgery (Egyedi, 1977). Initially it was used for closing oronasal and oroantral communications (Egyedi, 1977). The buccal fat pad has a body from which four processes extend. It has rich vascularity from the facial artery, transverse facial artery, and branches of the internal maxillary artery. BFP is now used for closure of oral cavity defects of different size and origin. The main advantages of using BFP are its rich blood supply, elasticity, absence of restriction by age, safety, and spontaneous epithelialization. Fat -Guasch et al., 2010). These fattissue also contains stem cells (Farre derived stem cells promote angiogenesis (Mirancille et al., 2004). The aim of this study is to report the results of buccal fat pad use in closure of maxillary sinus floor defects after partial maxillary resection in Krokodil drug-related ONJ patients. 2. Materials and methods Six male patients with Krokodil drug-related distal maxillary osteonecrosis were included in this retrospective study. All cases were analyzed regarding complaints, age, period of Krokodil use, Krokodil withdrawal period, number of lesions, and surgery outcome. All patients underwent cone beam computed tomography (CBCT) prior to surgery. 2.1. Surgery In all patients surgery was performed a minimum of 1 month after drug cessation. Surgery in all cases included removal of necrotic bone and closure of formed maxillary sinus floor defects with BFP and local mucoperiosteal flaps. 2.1.1. Necrotic bone removal In all patients necrotic bone exposure was achieved through midcrestal incision with releasing incisions in both sides. Mucoperiosteal flaps were elevated, exposing underlying bone tissue (Fig. 2c).
After necrotic bone exposure, if: - clinically formed sequestrum was found, this was removed and bone debridement was continued about 0.5 cm in all directions. - a clear demarcation line was found between vital and non-vital bone, resection of necrotic bone was performed and debridement was continued about 0.5 cm in all directions. - no demarcation line or sequestrum formation was found, resection of necrotic bone was performed until the appearance of areas of bleeding. The height of interdental septa and vestibular bone adjacent to teeth in necrectomy zones was reduced by one-third to prevent their exposure in the postoperative period. All bone margins were rounded with burs. Pathologically thickened sinus mucosa was removed only from the sinus floor, because removal of mucosa from the sinus walls would expose underlying bone and could lead to new osteonecrotic zones (Figs. 1c and 2d). 2.1.2. Sinus floor defect closure with buccal fat pad A small incision was made over the periosteum in the posterolateral region of the maxilla. After blunt dissection, buccal fat pad was relocated into the wound (Figs. 1d and 2e, and f). Then, buccal fat pad was placed over the defect and fixed to vestibular and palatal soft tissues using transmucosal sutures (Fig. 1e). Vestibular mucoperiosteal flap was mobilized using horizontal incisions over the periosteum in its basis. Horizontal mattress sutures were used to close the mucosa and a secondary running continuous suture was placed over the horizontal mattress sutures (Fig. 1f). 2.2. Postoperative period Besides postoperative antiseptic wound care, conservative treatment was also performed, which included clindamycin, metronidazole, oral cavity rinses with antiseptics, and nasal vasoconstrictors. Sutures were removed on the 10th day. Patients were considered as recovered if local signs of inflammation (intra- and extraoral suppuration, -issue abscesses, and inflammatory masses) and exposed bone were absent (Figs. 1g and 2g). 2.3. Statistical analysis Data are expressed as means ± SEM. IBM SPSS Statistics 20 was used for statistical analysis. 3. Results All patients were HCV positive. Mean age of patients was 42.7 ± 2.4 (range 36e52) years. Mean periods of Krokodil use and Krokodil withdrawal were 13 ± 1.8 (range 6e18) months and 9 ± 4 (range 1e24) months respectively. All patients had complaints related to intraoral bone exposure (Figs. 1a and 2a), purulent discharge from the affected area and from the nose, and pain in the midface. In all patients stage-3 osteonecrosis (according to the American Association of Oral and Maxillofacial Surgeons (AAOMS)) was found in the distal maxilla. Unilateral exposure of the maxillary alveolar process was found in five patients (Fig. 1a). Total involvement of the maxillary alveolar process was found in one patient (Fig. 2c). The exposed area was about 2e8 cm in length. The exposed bone was a pale yellow-grey color and was covered with greyish plaque. Granulation tissue growth was found in the maxillary sinus. The surrounding mucosa was pale pink in color. Defects in the vestibular mucosa over the
K. Hakobyan et al. / Journal of Cranio-Maxillo-Facial Surgery 46 (2018) 831e836
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Fig. 1. Patient A: a) unilateral exposure of maxillary alveolar process; b) opacification of right maxillary, ethmoidal, and frontal sinuses on cone beam computed tomogram; c) maxillary sinus floor defect formed after necrectomy; d) exposed buccal fat pad; e) buccal fat pad fixed over the sinus floor defect; f) intraoral wound view on first postoperative day; g) 2-month postoperative intraoral view.
exposed bone was found in full height in all patients (Figs. 1a and 2a). The trigger for osteonecrosis development was tooth removal 8 ± 1.6 (range 3e12) months before examination.
On CBCT total or partial opacification of the maxillary sinus was found on the affected side. Clear demarcation of the necrotic zone was found on the tomograms of five patients, while in one patient no signs of demarcation were found.
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Fig. 2. Patient B: a) bilateral exposure of maxillary alveolar process; b) bilateral opacification of maxillary sinuses on cone beam computed tomogram; c) whole maxillary alveolar process and palatal bone found to be necrotic; d) combined bilateral maxillary sinus floor and nasal floor defects; e,f) bilateral exposure of buccal fat pads; g) 2-month postoperative intraoral view.
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During surgery, clinically formed sequestrums were found in two patients; a clear demarcation line between vital and non-vital bone was found in three patients; in one patient no demarcation line or sequestrum formation was found. Isolated maxillary sinus floor total defects were formed after necrectomy in four patients (Fig. 1c). In one patient, maxillary sinus floor total defect was combined with a partial defect of the nasal floor (about 6 cm 4.5 cm in size). In another patient, bilateral maxillary sinus floor total defect was combined with total defect of the nasal floor (Fig. 2d). In one patient the formed defect was closed by bilateral use of BFP, whilst unilateral use of BFP was applied in five patients. In all cases, it was not possible to achieve tension-free BFP closure with local mucoperiosteal flaps due to primary defects of the vestibular and palatal mucosa. In all patients the postoperative period was uneventful. After suture removal, small areas (about 3e5 mm in diameter) of buccal fad pad exposure were found in all patients, which epithelialized successfully over the following month. The postoperative follow-up period was 8e12 months, during which all patients were free of symptoms: no signs of recurrence or of oroantral communication were found (Figs. 1g and 2g). 4. Discussion Maxillary sinusitis is a common complication in patients with upper-jaw osteonecrosis of different origin. In BRONJ patients maxillary sinusitis is found in 43.6% of patients (Mast et al., 2012). Krokodil drug-related ONJ has been found to affect the maxilla in 48% (19/40) of patients (Poghosyan et al., 2014). The rate of maxillary sinusitis in Krokodil abusers with upper jaw osteonecrosis was 50% (Poghosyan et al., 2012). The main clinical findings in these patients were: oroantral fistulas; purulent discharge from the nose; opacification of the maxillary sinus on radiographic examination (Figs. 1b and 2b) (Poghosyan et al., 2012). Involvement of the maxillary sinus implicates stage-3 osteonecrosis (according to AAOMS). Surgical management of stage-3 Krokodil drug-related ONJ includes removal of necrotic bone and closure of the defect with soft tissues (Poghosyan et al., 2014). Maxillary sinus floor defect occurs after necrectomy of stage-3 distal maxilla osteonecrosis. There are several difficulties in achieving permanent closure of oroantral communications in Krokodil drug-related ONJ patients. In most cases it is impossible to achieve tension-free closure of maxillary sinus floor defects with local mucoperiosteal flaps due to the initial vertical defects of the vestibular and palatal gingiva. This is the main cause of wound dehiscence 3e6 days postoperatively, causing formation of oroantral communication in 38% of patients (Poghosyan et al., 2014). Infection is common in ONJ patients. It can jeopardize healing processes, promoting wound dehiscence. If the wound is closed using local mucoperiosteal flaps some surfaces of bone tissue are left uncovered by soft tissues. This condition increases the risk of ONJ recurrence. The size of maxillary sinus floor defects may vary. Total defects of the maxillary sinus floor are common in Krokodil abusers. In some cases, maxillary sinus floor defect is combined with partial nasal floor defect. Bilateral maxillary sinus floor defect combined with total nasal floor defect is not rare in ONJ patients (Fig. 2d). Buccal fat pad (BFP) is a reliable method for the closure of maxillary sinus floor defects in osteonecrosis patients. Over recent years there have been several reports of BFP use in MRONJ patients for the closure of maxillary sinus floor defects after distal maxillary resection. All authors reported good results (Berrone et al., 2015; Rotaru et al., 2015; Melville et al., 2016).
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The advantages of BFP can overcome the main problems associated with closure of oroantral communications in Krokodil drugrelated ONJ patients mentioned above. The use of BFP makes possible the closure of the defect with two layers (BFP and mucoperiosteal flaps). Almost all bone surfaces can be closed with BFP. Even if BFP exposure is seen after suture removal (in all our cases), spontaneous epithelialization occurs within about 1 month. Low rates of infection are found after BFP use, which makes the use of BFP a reliable method for infected areas (as found in ONJ patients). Stem cells found in fat tissue promote angiogenesis, decreasing ONJ recurrence rates. The size of BFP makes possible the closure of large defects. Combined bilateral maxillary sinus floor and nasal floor defects can be successfully closed with bilateral use of BFP. Finally, there are significant problems in the management of drug-addicted patients due to their social status. According to Hakobyan (2013): 11.1% of Krokodil users had no family (10 patients from 90); 78.9% had no job (71 patients from 90); 55.6% were exprisoners (50 patients from 90). The main reason these patients visit the doctor is for pain relief. It is difficult to keep track of them in the postoperative period. Most of the patients do not visit the doctor for postoperative checkups. The only way to contact them is with phone calls, but in many cases this is impossible. The patients might have no contact information; they may have been imprisoned, or even died. The most reliable patients are those who receive methadone treatment. 5. Conclusion Radical debridement of necrotic bone, partial sinusotomy and the transposition of buccal fat pad can be used as an effective and predictable method for the treatment of distal maxillary osteonecrosis due to Krokodil drug use. Funding There are no sources of support in the form of grants. Conflicts of interest There is no conflict of interest that has to be indicated by the authors. References Alves EA, Soares JX, Afonso CM, Grund JP, Agonia AS, Cravo SM, et al: The chemistry behind ‘krokodil’: street-like synthesis and product analysis. Forensic Sci Int 257: 76e82, 2015 Berrone M, Florindi FU, Carbone V, Aldiano C, Pentenero M: Stage 3 medicationrelated osteonecrosis of the posterior maxilla: surgical treatment using a pedicled buccal fat pad flap: case reports. J Oral Maxillofac Surg 73(11): 2082e2086, 2015 Egyedi P: Utilization of the buccal fat pad for closure of oro-antral and/or oro-nasal communications. J Maxillofac Surg 5: 241, 1977 -Guasch E, Martí-Page s C, Hern Farre andez-Alfaro F, Klein-Nulend J, Casals N: Buccal fat pad, an oral access source of human adipose stem cells with potential for osteochondral tissue engineering: an in vitro study. Tissue Eng Part C Methods 16: 1083, 2010 Hakobyan KA: Clinical picture, diagnosis and treatment of facial bones osteonecrosis at patients who use the drug ‘Krokodil’. Yerevan State Medical University, 2013 Dissertation Hakobyan KA, Poghosyan YM, Poghosyan AY: C-terminal telopeptide level in ‘Krokodil’ drug-related jaw osteonecrosis patients. New Armen Med J 11: 57e61, 2017 Melville JC, Tursun R, Shum JW, Young S, Hanna IA, Marx RE: A technique for the treatment of oral-antral fistulae resulting from medication-related osteonecrosis of the maxilla: the combined buccal fat pad flap and radical sinusotomy. Oral Surg Oral Med Oral Pathol Oral Radiol 122(3): 287e291, 2016 Mast G, Otto S, Mücke T, Schreyer C, Bissinger O, Kolk A, et al: Incidence of maxillary sinusitis and oro-antral fistulae in bisphosphonate-related osteonecrosis of the jaw. J Craniomaxillofac Surg 40(7): 568e571, 2012 A: ImproveMirancille A, Heeschen C, Senqenes C, Curat CA, Busse R, Bouloumie ment of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation 110: 349, 2004
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Poghosyan YM, Hakobyan KA, Gasparyan LL: Radiographic diagnosis of jaw osteonecrosis at patients who use the drug ‘Krokodil’. Issue Theor Clin Med 2(78): 44e47, 2013 Poghosyan YM, Hakobyan KA, Manukyan EV: Features of clinical course and treatment of chronic maxillary sinusitis caused by osteonecrosis of maxilla at drug addict patients who use the drug ‘Krokodil’ (desomorphine). Bull Stomatol Maxillofac Surg 2e3: 18e24, 2012
Poghosyan YM, Hakobyan KA, Poghosyan AY, Avetisyan EK: Surgical treatment of jaw osteonecrosis in ‘Krokodil’ drug addicted patients. J Cranio Maxillo Facial Surg 42: 1639e1643, 2014 Rotaru H, Kim M-K, Kim S-G, Park Y-W: Pedicled buccal fat pad flap as a reliable surgical strategy for the treatment of medication-related osteonecrosis of the jaw. J Oral Maxillofac Surg 73(3): 437e442, 2015