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IMPLANT /VOLUME 0, NUMBER 0 2013 1

Use of N-Butyl Cyanoacrylate With Metacryloxisulfolane (Glubran 2) Surgical Glue for Flapless Closure of Oroantral Communication

Nikola Buric, DMD, MSD, PhD*

roantral communication (OAC) Aim: To present first experience Results: The extraction wounds is an abnormal connection of the use N-butyl cyanoacrylate with OACs were monitored until O between the maxillary sinus with metacryloxisulfolane (Glubran 23rd and 25th postinterventional and the oral cavity, and it is mostly 2) synthetic surgical glue, in the non- days, when epithelization of socket fi formed after the extraction of the rst surgical closure of oroantral com- ended successfully. On the pano- and second upper molar. The incidence munication (OAC). ramic image and Water’sview of the formation of OAC is one in 180 extractions of the upper first molar and 1 Material and methods: Two radiography, there were no radio- OAC in 280 extractions of the upper OACs, created after the exodontia of logical signs of maxillary sinus second molar.1 For many decades, the tooth 27 in 2 female patients, were pathoses. “gold standard” for the surgical repair of sealed and closed with Glubran 2 Conclusion: Glubran 2 can be OACs of a diameter greater than 4 mm surgical glue and monitored OACs, successfully applied in the closure of and alveolar depth less than 5 mm has until the epithelization of the sockets OAC from 3 to 5 mm in diameter. been though the use of a buccal muco- was ended successfully. Two months (Implant Dent 2013;0:1–6) periosteal advancement flap, according postclosure of OACs, the sealed OACs Key Words: maxillary sinus, oroan- 2 3 to Rehrmann, with 93% success. were evaluated on the panoramic tral communication, cyanoacrylate An OAC with the diameter of 3 to 4 image and Water’s view radiography. glue, Glubran 2 mm and the alveolar depth greater than 5 mm, without permanent sinus pathol- ogy or foreign bodies, could be closed with alloplastic or biological material, emergency tool to stop the bleeding on closure of OAC with synthetic surgical ensuring stable blood and thus closing the battlefield. The structural ability to glue, which has adhesive and haemo- the OAC. enhance the coagulation process and to static actions on the tissue, when applied. Cyanoacrylate glue was first syn- create a mechanical barrier at the site of Glubran 2 (GEM S.r.l., Viareggio, thesized in 1949 by Ardis and was first breakdown of tissue enabled glues, ad- Italy) is a new synthetic tissue adhesive used in in 1959 by Coover hesives, and sealants to be used suc- (in Europe), which is a result of the et al.4 During the Vietnam War in the cessfully in clinical practice in the mixture of 2 monomers: N-butyl-2- 1960s, cyanoacrylate glue was used on subsequent years. Medical reports on cyanoacrylate and metacryloxisulfo- wounded American soldiers, as an the use of cyanoacrylates as tenacious lane, produced in a “ready to use” car- adhesives have also shown their suc- tridge-applicator. It is manufactured for *Head of Oral Surgery, Assistant Director of Clinic of Stomatology, , Stomatology, University of Nis, cessful use in the closure of abdominal internal use, and in a moist environment Nis, Serbia. fistulas5 and gastrointestinal fistulas.6 (blood or water) and in contact with liv-

Reprint requests and correspondence to: Nikola Buric, Basedonthispremise,ratherthanon ing tissue, Glubran 2 polymerizes rap- DMD, MSD, PhD, Clinic of Stomatology, Oral and the constant clinical demands for idly to create a thin and elastic film of Maxillofacial Surgery, Dr Zorana Djindjica 52 a minimum invasive procedure in sur- high tensile resistance, thus enabling Boulevard, 18000 Nis, Serbia, Phone: +381184538655, Fax: +381184537919, E-mail: [email protected] gery, the closure of OAC with surgical firm adherence of tissues. It also has glues or sealants would be a worthwhile better properties than the previously ISSN 1056-6163/13/00000-001 Implant Dentistry biological and clinical goal. Thus, inter- available cyanoacrylate adhesives, in Volume 0  Number 0 Copyright © 2013 by Lippincott Williams & Wilkins est has emerged, in a simplified, time- terms of elasticity and polymerization DOI: 10.1097/ID.0b013e318287a975 saving, and reliable technique in the temperature, which occurs at 45°C,

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avoiding thermal damage to the surface and underlying tissues.7 To date, there has only been 1 report8 on the use of cyanoacrylate sur- gical glue (Glubran 2) in a surgical pro- cedure, combined with the buccal advancement flap in the closure of the oroantral fistula. We present our first experience of the use of Glubran 2 synthetic surgical glue, manufactured for internal use, in the nonsurgical closure of OACs, which occurred after the exodontia of the upper molar tooth, and provide an explanation of the procedure. CASE REPORTS Before the intervention, patients were provided with the description of the procedures and possible complica- tions. Patients were treated in accor- dance with the ethical principles of the Helsinki’s Declaration and the ethical principles of treating patients at our clinic. They were interviewed and Fig. 1. A, Intraoral appearance of OAC at the site of the extracted tooth 27; B, the coronal informed of the risks of the proposed view shows pathosis of the right maxillary sinus and the presence of mucocele in the left procedure, and they gave consent to maxillary sinus; C, panoramic radiography shows the extent of OAC (arrow). the procedure. Medical history data were taken to rule out the existence of maxillary sinus recorded on the ipsilat- decongestant and with a previous maxillary sinus disease or eral nostril; (3) curettage processing of clindamycin (Clindamycin-MIP; St. another paranasal . the extraction wound to provoke alveo- Ingbert, Germany; 600 mg every 12 A standard panoramic image was lar bleeding; (4) sealing the OAC with hours for at least 7 days) and until the taken before and 2 months after closure Glubran 2 surgical glue “drop-by-drop” end of the therapy; and (7) to avoid pro- of OAC, with the radiographic appara- Plus from the syringe of 1 mL, with extreme voking OAC failure by blowing the tus ORTHOPOS XG (SIRONA, patient’s nose, not to rinse the oral cavity Blenheim, Germany) with kilovolt in caution for the purpose of avoiding leak- age of the surgical glue into the oral cav- or endanger the closed OAC mechani- the range between 65 and 80 kV and cally by tooth brush, and to adhere to 16 mA. In addition, Water’s view radio- ity and the surrounding oral mucosa, with constant vacuum aspiration; (5) a soft diet 24 hours after the procedure. graph was used before the intervention The healing of extraction wounds was and 2 months postclosure of OAC. application of a sterile swab over the sealed OAC after the cessation of poly- clinically inspected until the cessation Metal probes with a diameter from 3 of epithelization of the alveolus, which to 5 mm were used for the measurement merization time for Glubran 2 surgical – was recorded. of the maximum diameter of the OAC. glue (60 90 seconds), with the patient The following procedures9 were holding the sterile swab in place over Case 1 performed before the sealing of OAC the next 15 to 20 minutes by biting; (6) An X-year-old white woman with with Glubran 2: (1) inspection of the the patient was instructed to take nasal an OAC formed in the left was extraction wound with subsequent irri- gation with a sterile physiological solu- tion to eliminate any residue in the form of a foreign body; (2) irrigation of the maxillary sinus through the OAC with 15 to 20 mL of a sterile physiological solution, (Clindamycin- MIP, 600 mg/2 mL solution; St. Ingbert, Germany), and corticosteroids (dexa- Fig. 2. A, Panoramic radiography shows the absence of pathoses at the site of the previously methasone, 1 mL of the 4-mg/mL solu- glued OAC; B, the coronal view of the left maxillary sinus shows the absence of any pathoses, tion; Galenika a.d., Belgrade), with the whereas significant pathoses are still present in the right untreated maxillary sinus. patency of the sinus ostium of the

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referred to our department. A history of complaints revealed that the patient had had an exodontic treatment of the max- illary left second molar with a large caries lesion, necrotic pulp, and periap- ical radiolucency the day before. The general health status of the patient and blood and urine analyses were not contributory. The extraoral examination revealed no , whereas an OAC was present in the region of the second left molar, after an intraoral examina- tion (Fig. 1, a). Before the interven- tion, the panoramic image and Water’s view radiograph showed the presence of the OAC and a slight opacification of the maxillary sinus (Fig. 1, b and c) in the form of a mucocele of the left maxillary sinus, suctioned by syringe through the OAC before closure with Glubran 2. Metal probes in the diameter of 5 mm were used for the measurement of the maximum diameter of the OAC. The OAC was sealed and closed with Glu- bran 2 in the described manner. After the postclosure day 7, the patient was regu- Fig. 3. A, Intraoral appearance of OAC (mirror images) at the site of the extracted tooth 27; B, larly examined 2 times per week for Water’s view radiography shows discreet left pathoses of the left maxillary sinus; C, panoramic removing the excess particles of Glubran radiography shows a nonvital second upper molar tooth before the exodontia. 2, which remained in the form of flakes on the socket wall. The OAC was com- pletely closed on the 23rd postinterven- tional day. Two months postclosure of OAC, the sealed OAC was evaluated on the panoramic image and Water’sview radiography to ascertain whether the performed procedure justified the ex- pected successful result (Fig. 2, a and b).

Case 2 A 44-year-old woman with an OAC in the left maxilla, previously treated in another dental institution, was referred to our department. The OAC formed within 48 hours before admission to our institution. The pa- tient’s medical and family history was unremarkable. On clinical examination, there was an OAC as a consequence of the exodontia of the second left upper molar (Fig. 3, a). Metal probes in the diameter of 3 mm were used for the measurement of the maximum diameter of the OAC. The patient was routinely diagnosed with the use of the panoramic ’ Fig. 4. A, Intraoral appearance of the OAC sealed with Glubran 2; B, shrinkage of the alveolar x-ray imaging technique and Water s socket after 7 days; C, almost normal healing of the extraction socket with the surface view radiograph, which showed the presence of Glubran 2 flakes (black arrow); D, successful epithelization of the extraction absence of maxillary sinus disease and wound with an OAC on the 25th postinterventional day (mirror images). the breakdown of bone septa in the

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simple and efficient technique, it has postoperative surgical morbidity, and the most frequent are pain, swelling, discomfort because of suture swelling, reduces the depth of the buccal vestibular sulcus, and possible hemorrhage from the incised periosteum. The minimal invasive procedure in surgery is more beneficial for the patients if it provides the same or better results than surgery. This was possible in the described cases Fig. 5. A, Panoramic radiography shows dense bone opacification at the site of the extracted with Glubran 2. The application of tooth 27 (arrow); B, Water’s view radiography shows the absence of maxillary sinus pathoses. cyanoacrylate glue in the closure of OACs is a painless, rapid, and easy technique, as there is no need for suture alveolus of the second left upper molar type I membrane for OAC closure removal. 14 (Fig. 3, b and c). According to the located on the lateral sinus wall, and This article also describes an excep- described protocol, the OAC was sealed the sandwich technique and guided tis- tional haemostatic and adhesive result in with Glubran 2 (Fig. 4, a). At the end of sue regeneration in the closure of the closure of OACs. This is not a sur- 15 epithelization, a few excess particles of OAC. The specific chemical structure prise because Glubran 2 has these prop- Glubran 2, which remained in the form of cyanoacrylates as synthetic com- erties, with the subsequent production of fl of akes, emerged in the mucosa over pounds, and used as surgical glues, en- an effective antiseptic barrier against the socket with the OAC. On 25th post- ables them to firmly bond living tissue germ colonization, commonly found in interventional day, the OAC was com- through the process of rapid polymeri- the oral cavity. Although it is packed in 16 pletely closed (Fig. 4, d). Two months zation in contact with water or blood. a special vial, we found that it was not postclosure of OAC, radiography was However, cyanoacrylate glue was not suitable for the closure of OAC as the performed to examine the postclosure FDA-approved for medical use, mainly vial may easily leak glue from the morbidity of the treated tissue. There because of the side effects such as skin alveolus into the surrounding tissue of fl were no radiological signs of in amma- irritation and the generation of heat the oral cavity. Hence, it is imperative to tory disease of the maxillary sinus or the above normal body temperature. Cya- use a syringe and aspirate the glue from alveolus and OAC treated with Glubran noacrylate glue, Histoacryl (B Braun, the vial and then apply the glue drop by 2 (Fig. 5, a and b). Melsungen, Germany), has been used drop, slowly closing the OAC, with the extensively in the endoscopic procedure constant aspiration of the leaking glue. for the last 20 years.17,18 In 1998, the The use of Glubran 2 in the closure of DISCUSSION FDA approved 2-octylcyanoacrylate OAC would probably be more practical To the best of the author’s knowl- (Dermabond; Ethicon, Inc., Somerville, if it were used in combination with edge, these are the first cases of a suc- NJ) for external application, and some a collagen material, to prevent the cessful closure of OAC with the single authors have reported favorable clinical leakage of glue out of the alveolar use of Glubran 2 surgical glue. There experiences regarding the sutureless socket, but this method has not been are numerous reports concerning the closure of very thin skin, such as eyelid the subject of this work. successful use of alloplast in the closure skin wounds.19 However, there are two questions of OAC. The latest reports9 showed Another surgical synthetic glue, ie, about Glubran 2 used in this article, promising results by using polyglycolic N-butyl-2-cyanoacrylate with metacry- which remain unanswered and raise acid/poly-L-lactic acid (90/10) (Ethi- loxisulfolane (Glubran 2; GEM S.r.l.), doubts. One is the biological fate of sorb) in the nonsurgical closure of has recently been approved for internal- Glubran 2 on the internal tissue. The OAC. Considering the surgical history endoscopic use in Europe. Cyanoacry- possible toxic reaction of the highly of OAC, there is a myriad of other suc- late glue has recently been used by vari- sensitive internal tissue, ie, sinus cessful reports of the use of alloplasts in ous specialists, such as orthopedic mucosa, remains a concern. To date, the closure of OAC. Al-Sibah and Al- surgeons,20 ophthalmologists,21 neurosur- experimental data has shown that Glu- Badri10 described their experience with geons,22 and urologists.23 Glubran 2 Sur- bran 2 is less harmful, when used for the soft polymethylmethacrylate in the clo- gical Glue is a class III medical-surgical embolization of the a-v fistula on the sure of the oroantral fistula. Goldman product (for internal and external surgi- carotid common artery and the jugular et al11 used gold foil in the closure of cal use), which completely fulfills the vein in sheep, because of the lower OAC, whereas Mitchell and Lamb12 requirements of the European Directive thermal effect, compared with Histo- described the immediate closure of on Medical Devices 93/42/EEC. acryl glue.24 Safe aerostatic effects on OAC with a collagen implant. Other Even though the conventional sur- the resected pulmonary parenchyma authors have described the use of fibrin gical closure of OAC with the buccal were presented in an experimental glue in the closure of OAC,13 collagen- advancement mucoperiosteal flap is an study on a pig’s resected pulmonary

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tissue. No differences were noted application. Other reports dealing with Dtsch Zahnartzl Wschr. 1936;39:1136– between air loss and the survival of the use of cyanoacrylate glue in peri- 1139. fi 3. Killey HC, Kay LW. An analysis of experimental pigs considering the con- odontal procedures for the xation and fi ventional technique and Glubran 2. The prevention of shrinkage of free gingival 250 cases of oro-antral stula treated by the buccal flap operation. Oral Surg Oral authors concluded that aerostatic ef- graft showed better results compared Med Oral Pathol. 1967;24:726–739. fects of Glubran 2 on pulmonary tissue with the control group, where the graft 4. Coover HW, Jr, Joyner FB, Shearer are biologically beneficial and the same was sutured to the recipient bed by NH Jr, et al. Chemistry and performance of as in the case of mechanical postresec- 5-0 silk sutures.28 In the modified Wid- cyanoacrylate adhesives. Soc Plast Eng J. tion suturing techniques.25 man flap surgery, Nectacryl (N-butyl 2- 1959;5:413–417. The second concern is the influence cyanoacrylate) serves as a more efficient 5. Seewald S, Groth S, Sriram PV, of Glubran 2 on bone tissue, ie, the tool for the sutureless closure of the flap et al. Endoscopic treatment of biliary leak- age with n-butyl-2 cyanoacrylate. Gastro- alveolar socket. Clinical results concern- than the conventional suture technique – 29 intest Endosc. 2002;56:916 919. ing the use of Glubran 2 to seal the with 3-0 silk sutures. However, 6. Lee YC, Na HG, Suh JH, et al. Three oroantral fistula (adjunctable material) in because of the short-term follow-up, cases of fistulae arising from gastrointesti- combination with the mucoperiosteal the full biological behavior of Glubran nal tract treated with endoscopic injection buccal flap and absorbable sutures 2couldnotbedefinitely concluded of histoacryl. Endoscopy. 2001;33:184– proved successful. In the postoperative because this material may inhibit forma- 186. follow-up period from 6 months to 3 tion of bone in the socket. 7. Leonardi M, Barbara C, Simonetti L, et al. Glubran 2: A new acrylic glue for years, authors did not observe any neuro-radiological endovascular use reaction or medical problems in relation CONCLUSIONS experimental study on animals. Interv Neu- 8 to the applied treatment. Other authors roradiol. 2002;8:245–250. have used Glubran 2 for the fixation of The described technique with sur- 8. Hajioannou J, Koudounarakis E, bone pieces used for the repair of the gical glue in closure of OACs was an Alexopoulos K, et al. Maxillary sinusitis of anterior cranial fossa bone defects in easy, an efficient, and a safe alternative dental orig due to oroantral fistula treated a 12-year-old boy with brain injury, to surgical closure of OACs. The use of by endoscopic sinus surgery and primary Glubran 2 in the nonsurgical closure of fistula closure. J Laryngol Otol. 2010;124: and the subsequent formation of brain – OAC was successful in the permanent 986 989. abscess caused by Streptococcus pyo- 9. Buric N, Jovanovic G, Krasic D, et al. genes. No complications were observed obturation of OACs. Moreover, Glu- The use of absorbable polyglactin/polydiox- in the postoperative course in relation to bran 2 showed the rapidity of the anone implant (EthisorbÒ) in non-surgical the use of Glubran 2 on the bone tissue in polymerization process and permanent closure of oro-antral communication. the proximity of severe infections.26 alveolar hemostasis in its application J Cranio-Maxillofac Surg. 2012;40:71–77. Experimental results on mongrel dogs during the closure of OACs ranging 10. Al-Sibah A, Al-Badri A. The use of fi from 3 to 5 mm. A complete epitheli- soft polymethylmethacrylate in closure of with arti cial, surgically created, stan- fi zation of alveolar sockets, and thus, oroantral stula. J Oral Maxillofac Surg. dardized dehiscence bone defects on 1982;40:165–166. the buccal side of the installed implants closure of OACs occurred on the 23rd 11. Goldman EH, Stratigos GT, Arthur showed that cyanoacrylate-combined and 25th postclosure day, respectively. AL. Treatment of oroantral fistula by gold calcium phosphate can serve as scaffold However, further studies with longer foil closure: Report of a case. J Oral Surg. and substitute for the barrier membrane clinical and radiological follow-ups (6 1969;27:875–877. and 12 months postclosure) would help 12. Mitchell R, Lamb J. Immediate clo- during a guided bone regeneration pro- fi cedure.27 As a possible inert material, to better show the place that Glubran 2 sure of oroantral stula with collagen im- cyanoacrylate surgical glue occupies in plants. A preliminary report. Br Dent J. Glubran 2 may be present for years to 1983;154:171–173. come. Therefore, more investigation is the treatment of OAC. 13. Gattinger B. Der verschluß von essential, because this material may mund-antrum-verbindungen mit dem lyo- inhibit the formation of bone regenera- DISCLOSURE philisierten fibrinklebesystem. Zahnartzl – tion in the alveolar socket. The author claims to have no Prax. 1984;35:8 10. 14. Becker J, Neukam FW, It has been observed that Glubran 2 financial interest, either directly or needs a longer time period to be removed Schliephake H. Restoration of lateral sinus indirectly, in the products or informa- wall using a collagen type I membrane for from the mucosa over the alveolar tion listed in the article. The author also guided tissue regeneration. Int J Oral Max- socket. The complete epithelization of claims that there were no sources of illofac Surg. 1992;21:243–246. the extraction wound in both patients funding for this study. 15. Ogunsalu C. 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