Resolution of a large periapical lesion in an immature maxillary lateral incisor with the aid of triple antibiotic paste

A healthy 21-year old male presented with pulpal necrosis, a large periapical lesion, incomplete root formation and an open apex on a maxillary right lateral incisor. Triple antibiotic paste was used to achieve antimicrobial control after traditional calcium hydroxide paste medicament failed to resolve the symptoms. Obturation was achieved using MTA and the conventional apexification technique. Excellent healing of the large periapical lesion was achieved without surgical intervention and the 4-year follow-up CBCT demonstrated complete bone fill of the lesion.

Apexification procedures are frequently performed on immature permanent teeth with incomplete root formation, open apices and necrotic pulp status with or without periapical lesions in order to induce a calcific barrier prior to root canal therapy. The elimination and control of infection in the root canal space is critical to the success of these procedures.
A healthy 21-year old male presented with pulpal necrosis, a large periapical lesion, incomplete root formation and an open apex on a maxillary right lateral incisor. Triple antibiotic paste was used to achieve antimicrobial control after traditional calcium hydroxide paste medicament failed to resolve the symptoms. Obturation was achieved using MTA and the conventional apexification technique. Excellent healing of the large periapical lesion was achieved without surgical intervention and the 4-year follow-up CBCT demonstrated complete bone fill of the lesion.
Clinicians should be aware that alternative antimicrobial medicaments, such as triple antibiotic paste, may be beneficial in situations where conventional medicaments prove unsuccessful. The use of triple antibiotic paste may result in sufficient healing of the periapical lesion to justify placement of an MTA apical barrier without the need for surgical intervention.
Apexification is a term referring to endodontic procedures performed to achieve apical closure of immature permanent teeth presenting with incomplete root development, open apices and pulpal necrosis. 1 Historically, apexification involved the placement of calcium hydroxide (CH) paste over multiple treatment appointments in order to create a calcific barrier in the apical area prior to the completion of root canal treatment. 2 Whilst this approach demonstrated clinical success, several disadvantages were reported with the technique, including: difficulty with patient follow-up, delayed treatment, risk of root fracture and unpredictability of the apical seal. 1 Additionally, placement of CH for extended periods has been demonstrated to weaken tooth structure. 3 In modern endodontics, calcium silicate cements such as mineral trioxide aggregate (MTA) are recommended as the preferred material for use in apexification procedures due to their excellent sealing properties, biocompatibility 4 and antimicrobial activity. 5 The use of calcium silicate cements has additionally led to the ability to complete apexification procedures in a single visit. 6 Whilst single-visit apexification approaches may be beneficial to both patients and practitioners in terms of decreased time and a reduced need for follow-up/patient compliance, great care must be taken to ensure that adequate disinfection of the root canal space is achieved prior to obturation. Triple antibiotic paste (TAP), first described by Sato et al. 7 , is an effective antimicrobial agent, consisting of a mixture of ciprofloxacin, metronidazole and minocycline and has been successfully used in regenerative endodontic procedures for permanent teeth demonstrating pulpal necrosis. 8  The tooth was anesthetized, isolated with a rubberdam and an emergency root canal treatment was performed for pain relief. Pus drainage was established through the canal and buccal soft tissue during copious irrigation with a saline solution. Digital pressure was applied to the buccal swelling to further express inflammatory exudates. Chlorhexidine (2% concentration) was chosen as the preferred irrigant, considering the absence of an apical stop and increased risk of sodium hypochlorite extrusion and injury. Calcium hydroxide paste (Calacept, Ultradent, South Jordan, USA) was placed as an intracanal medicament and the access cavity temporarily sealed with glass-ionomer cement, placed on clean dentine and enamel. (Fuji IX GP, GC Corporation, Tokyo, Japan).
The patient was referred for a small-volume cone-beam computed tomography (CBCT) scan. The scan revealed a periapical lesion with well-defined borders, ballooning appearance, radiolucent lumen, perforation of the cortical plate, size greater than 10mm in diameter and open apex of the right maxillary lateral incisor ( Figure 2). Differential diagnosis included either a large periapical granuloma or radicular cyst. The initial treatment plan included apexification, obturation of the canal and -if required at a later stagecystectomy or periapical surgery. The final diagnosis was to be confirmed by biopsy and histopathological evaluation.
At the subsequent follow-up visit, no swelling or drainage was clinically visible however the patient reported continued symptoms of discomfort. Following anaesthesia and rubber dam isolation, the canal was cleared of CH medicament and working length was determined by an apex locator (ProPex Pixi, Dentsply Sirona, Ballaigues, Switzerland) and confirmed with a radiograph. Negative pressure irrigation with 6% sodium hypochlorite (Chlor-Xtra, Vista Dental, Racine, USA) was performed using the Endovac irrigation system (Kerr Corp., California, USA) during instrumentation of the canal with a size #90 k-file. After instrumentation, 17 % ethylenediaminetetraacetic acid (EDTA, Vista Dental, Racine, USA) irrigation was used followed by a final rinse of NaOCl. When attempting to dry the canal with paper points, persistent clear fluid drainage was found.
A triple antibiotic paste (TAP), consisting of a mixture of metronidazole, ciprofloxacin and minocycline was mixed in a 1:1:1 ratio with propylene glycol as carrier and placed into the canal using a k-file and anticlockwise rotation. Precautions were taken to place the TAP beneath the level of the cemento-enamel junction to prevent subsequent tooth discoloration of the crown. The access cavity was temporarily sealed with glass-ionomer cement (Fuji IX GP, GC Corporation, Tokyo, Japan) placed on clean dentine and enamel.
The patient failed to return for follow-up visits in the subsequent months due to personal circumstances. Numerous attempts were made to contact the patient, motivating a return for follow-up and completion of the treatment. The patient finally returned after 2 years and 3 months. At this visit, the patient was asymptomatic and radiographic evaluation demonstrated sufficient healing of the periapical lesion around the maxillary right lateral incisor to justify placement of a Mineral Trioxide Aggregate (MTA) apical barrier ( Figure 3A).
The patient was not committed to attend regular follow up visits, but was finally convinced to return for a follow-up evaluation. Four years after the initiation of the treatment, the patient was asymptomatic and the follow-up CBCT ( Figure 4) showed bone fill around the right maxillary lateral incisor with complete healing of the buccal bone plate. The patient gave written consent for the use of the images and radiographs for publication.

DISCUSSION
When pulpal necrosis occurs in immature permanent teeth with open apices, treatment options may include either root-end closure via apexification or regenerative endodontic procedures. 1 Kim et al. 11 recommended that whilst either of the above-mentioned treatment approaches may be selected -teeth with near complete root formation (Stage 4 of Cvek's classification of root development, 10 Figure 5) -may be better suited for apexification using MTA-barrier techniques. Whilst regenerative endodontics has the potential to produce vital periodontal-like tissues in the root canal space and encourage continued root formation, the literature still lacks high-level evidence supporting this approach 12 with the majority of studies relying on case reports and case-series, and only a few randomized clinical trials with short-term follow-up. 11 Additionally, fewer appointments are required to complete apexification procedures as compared to regenerative endodontic procedures. In the present case, the tooth was classified as Stage 4 according to Cvek's classification of root development and following discussion and informed consent with the patient, MTA apexification was considered the treatment of choice.
Appropriate cleaning, shaping, disinfection and filling of the root canal system is essential to the success of all nonsurgical endodontic treatment. 13 Calcium hydroxide is commonly used as an intracanal medicament due to its bacteriostatic effects, due to the high pH value, and its ability to induce hard tissue formation. 3 Triple antibiotic paste has been demonstrated to effectively eliminate bacteria when used in a protocol termed lesion sterilisation and tissue repair therapy (LSTR). 7,14 When compared to CH, TAP has been reported to demonstrate superior antimicrobial activity. 15 For this reason, TAP may be selected as an alternative medicament in non-surgical endodontic cases where traditional CH paste fails to eliminate the symptoms. 16,17 The healing demonstrated in the present case following the application of TAP supports these findings.  Crown discolouration may occur following apexification procedures due to either the minocycline present in TAP 9 or the bismuth oxide found in MTA. 4 In order to avoid this complication, some authors have suggested the use of Biodentine (Septodont, St. Maur-des-Fossés, France) instead of MTA, as this material does not contain bismuth oxide. 18 Crown discolouration is however a known complication when selecting these materials and this risk should be well-communicated to the patient prior to treatment.

CASE REPORT 562 >
The diagnosis of large periapical lesions as radicular cysts on radiography alone remains a clinical challenge. 19 Cone-beam computed tomography (CBCT) scanning has been proposed as a non-invasive method for differentiating between radicular cysts or periapical granulomas by measuring ''grayscale value''. 20 Rosenberg et al. 19 however reported that CBCT imaging is not a reliable method for diagnosing radicular cysts.The present case supports this assertion. The lesion associated with the right maxillary lateral incisor in the present case displayed many of the criteria used for the diagnosis of radicular cysts, which have been described as: welldefined uniform borders, a ballooning appearance, uniformly radiolucent lumen, perforation of the cortical plate and a size greater than 20mm in diameter. 19 Extensive bone loss surrounding open apices presents an additional clinical challenge to accurately seal the apex without extrusion of medicaments and other dental materials. A variety of matrices, such as collagen plugs, have been proposed as preliminary barriers to prevent over-extrusion of materials during apexification procedures. In recent years, platelet-rich fibrin (PRF) has been used as biocompatible, economical alternative barrier material that can additionally promote angiogenesis and wound healing. 21 The use of barrier methods may however be technique sensitive. The healing of the periapical bone in the present case provided the clinician with an apical stop-therefore not necessitating the use of a preliminary apical barrier or the necessity of apical surgery with retrograde filling.

CONCLUSION
The present case demonstrates the successful nonsurgical endodontic treatment of a maxillary lateral incisor, classified as Cvek Stage 4 of root development, using TAP medicament and conventional MTA-barrier apexification.
Clinicians should be aware that alternative inter-appointment medicaments, such as TAP, may be beneficial in cases where conventional CH paste proves unsuccessful and that large periapical lesions of endodontic origin may heal sufficiently with non-surgical endodontic treatment alone and no surgical intervention.