Association between the Irrigation-Agitation Techniques and Periapical Healing of Large Periapical Lesions: A Randomized Controlled Trial

Association between the Irrigation-Agitation Techniques and Periapical Healing of Large Periapical Lesions: A Randomized Controlled Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association between the Irrigation-Agitation Techniques and Periapical Healing of Large Periapical Lesions: A Randomized Controlled Trial Mehmet Umutcan Doğan, Banu Arıcıoğlu, Taha Emre Köse, Ahter Şanal Çıkman, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4014149/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Jun, 2024 Read the published version in Clinical Oral Investigations → Version 1 posted 7 You are reading this latest preprint version Abstract Objectives The aim of this study was to evaluate the effects of manual dynamic activation (MDA), passive ultrasonic irrigation (PUI), and laser-activated irrigation (shock wave-enhanced emission photoacoustic streaming (SWEEPS)) on the periapical healing of large periapical lesions following nonsurgical root canal treatment. Materials and Methods A total of fifty-six systemically healthy patients with a mandibular single-rooted tooth with periapical lesions of endodontic origin and a periapical index score of 3 or higher were included in the study. Before the treatment procedures, lesion volumes were determined volumetrically using cone–beam computed tomography (CBCT). Patients were randomized into treatment (MDA, PUI, SWEEPS) and control groups (n = 14). Root canal treatment and irrigation procedures were performed by a calibrated postgraduate operator and completed at one visit. For routine follow-up, clinical and radiographic evaluations were performed by a blinded evaluator using periapical (PA) radiographs according to Molven's criteria at 3, 6, and 9 months. At 12 months, lesion volumes were quantified volumetrically using CBCT (ITK-SNAP). The data were statistically analyzed with the Wilcoxon test. The significance level was set at p < 0.05. Results In all groups, the mean lesion volume after treatment was significantly smaller than the mean volume before treatment (p = 0.001). Among the 56 teeth, 11 teeth were ‘totally healed’, and 39 teeth were ‘reduced’ on PA radiographs. No ‘enlargement’ was detected in any group. On CBCT, the lesion volume decreased in the following order: LAI-SWEEPS (86.9%) > PUI (85.4%) > MDA (80.4%) > control (74.5%), with no statistically significant difference (p > 0.05). Conclusions Despite the limitations of the present study, although a greater percentage of healing was observed in the LAI-SWEEPS and PUI groups, irrigation procedures had no statistically significant effect on the healing of periapical lesions with a single root canal at the 12-month follow-up. On the other hand, the outcome may change in multirooted teeth with curved and complex root canal systems. Clinical Relevance: In the short term and in single-canal teeth, advanced irrigation agitation methods such as laser and ultrasonic did not make a difference in healing other than manual irrigation agitation. Irrigation activation LAI SWEEPS PUI periapical healing CBCT Figures Figure 1 Figure 2 INTRODUCTION Microorganisms and their products play pivotal roles in the initiation, progression, and establishment of periradicular conditions [ 1 ]. The main aim of root canal treatment for teeth with necrotic, contaminated pulp is to treat the infection and prevent future infections. A significant portion of the root canal surface remains untouched during treatment with mechanical instrumentation alone[ 2 ]. Therefore, irrigation is crucial for thorough disinfection of the root canal system [ 3 , 4 ]. Manual dynamic activation (MDA) involves moving a fitted gutta percha master cone in amplitude strokes following canal preparation after canal preparation is completed. This pecking movement aims to increase the effectiveness of disinfection by allowing the solution to contact more surfaces [ 5 ]. Passive ultrasonic irrigation (PUI), one of the most widely used activation systems today, creates an acoustic flow by providing hydrodynamic activation and contributes to disinfection by increasing the cavitation effect with the bubbles it produces. When applying this technique, small-diameter tips should not touch the root canal walls and should be used close to the apical region of the canal[ 6 – 8 ]. In recent decades, laser-activated irrigation (LAI) has become popular for debris and smear layer removal and antibacterial efficacy. Shock wave-enhanced emission photoacoustic stream (SWEEPS) is the most recent technology of the Er:YAG laser model used to improve irrigation efficiency. The application of two consecutive laser pulses to the irrigation solution at a certain time ensures that the bubbles created by the first laser beam collapse more quickly and that the photoacoustic shock wave reaches the narrow, inaccessible parts of the root canal [ 9 , 10 ]. In the SWEEPS technique, it is sufficient to place only the laser tip in the pulp chamber, but in traditional laser activation, canal expansion is needed to reach the laser tip to the root apex. This advantage of the SWEEPS is that it allows minimally invasive endodontic preparation[ 11 ]. Yang et al. reported that SWEEPS could emit synchronized laser pulses. In this way, the movement of the irrigation fluid and the bubble collapse rate increase. As a result, the SWEEPS can clear both the main channel and irregularities[ 12 ]. Successful healing of apical periodontitis requires a reduction in the size of the radiolucent area and healing of the bone [ 13 ]. The evaluation of periapical pathologies and changes in their volumes with CBCT is more successful than that with 2D radiographs [ 14 ]. In the literature, there are numerous studies on the efficacy of irrigation activation methods for debris smear removal [ 15 – 17 ], calcium hydroxide removal [ 18 – 20 ] and sealer penetration in dentinal tubules [ 21 – 23 ] under in vitro conditions. Therefore, the aim of this study was to evaluate the healing rates of large periapical lesions after the use of different irrigation-agitation methods (MDA, PUI, LAI-SWEEPS) using CBCT scans for volumetric change analysis during a 1-year follow-up. The null hypothesis was that there was no significant difference in lesion healing between the groups. MATERIALS AND METHODS Local ethics committee approval was obtained from the Ethical Review Committee of the Research Foundation at the Medical Faculty of Recep Tayyip Erdogan University (No: 2023/35) and the study protocol was registered at ClinicalTrials.gov (NCT06204887). Sample size calculation The G Power 3.0.10 (University Kiel, Germany) program was used to calculate the effect size. The effect size was calculated based on chi-square analysis data between the control group and the laser group in the Verma, Yadav study[ 24 ]. An effect size of 0.51 Cohen d value was found to be sufficient for significance. With a type 1 error of 0.05, it was determined that at least 56 subjects were required for a total of 4 groups, 14 in each study group, with 95% power. Patient Recruitment and Randomization Patients were informed about the procedure, and written informed consent was obtained before the commencement of treatment. The study included mandibular single-rooted teeth that were diagnosed with asymptomatic apical periodontitis and had a periapical index (PAI) score of 3 or higher. A total of 97 patients were evaluated radiographically and clinically for conformity with the inclusion and exclusion criteria. Patients with systemic diseases (diabetes, hypertension, chronic liver disease, coagulation disorders), bone metabolism disease and/or patients using drugs that affect bone metabolism (such as steroids and bisphosphonates) were excluded from the study. Immunosuppressed patients, patients with a history of radiotherapy, pregnant patients, patients with teeth with a mobility of 2 or more (Miller’s mobility index), patients with teeth with a periodontal pocket depth of 5 mm or more, patients with generalized asymptomatic apical periodontitis, patients with teeth with internal and external resorption, and patients with teeth with vertical and horizontal root fractures were not included. After applying the eligibility criteria, 70 patients were randomly divided into four groups using software ( www.random.org ) by a blinded researcher who was not otherwise involved in the study according to a standardized procedure. The numbers were placed in dark envelopes and concealed. The envelopes were only opened when the irrigation solution was to be activated. The patients were informed about the study without specifying the group to which they were assigned. All procedures were performed by a single operator with five years of experience (U.D.). CBCT imaging (Planmeca Romexis, Helsinki, Finland) was requested for patients who met the study criteria before the procedure to obtain information about periapical lesion size, proximity to anatomical landmarks, and anatomical variations of the tooth. CBCT images were acquired with a field of view (FOV) of 5×5 cm using ENDO mode, an 85 µm voxel size, 6.3 mA, 90 kV, and 8.7 s. Clinical procedures A CONSORT flow diagram outlining the treatment methodology is presented in Fig. 1 . After the administration of local anesthesia and the placement of a rubber dam, the access cavity was opened with a sterile diamond round bur under water cooling. Each canal was rinsed with 2 mL of sodium hypochlorite and explored with a size 08 K-file (FKG Dentaire, La Chaux-de-Fonds, Switzerland). The working length was determined using an electronic apex locator, Root ZX mini (J. Morita Co., Tokyo, Japan), to be 0.5 mm shorter than a 0.0 reading. The length was confirmed radiographically. After that, progressively larger K-files were passively introduced into the canal until the operator felt the first one to bind at the WL and the next larger one not to reach that position[ 25 ]. The first instrument used to bind the canal was recorded for each canal. The crown-down technique was applied with ProTaper Next rotary files (Dentsply Maillefer, Ballaigues, Switzerland) using a torque-controlled endodontic motor (SybronEndo, Glendora, CA, USA) at 300 rpm/2-5.2 Ncm rotation mode according to the manufacturer's instructions. The final instrumentation file was set to 3 sizes larger than the first file used[ 26 ]. Between each instrument change, the root canal was irrigated with 5 mL of 2.5% NaOCl (Microvem AF, Istanbul, Turkey) for 1 min. After canal preparation was completed, the final irrigation procedure was carried out with the corresponding irrigation method in each group. Control Group: Conventional Syringe Irrigation A 30-gauge side-vented irrigation needle (Kerr Hawe Sa, Bioggio, Switzerland) was used. The needle was inserted into the canal 1 mm shorter than the working length, and the canal was irrigated with up-and-down movements of 1–2 mm amplitude using the same and constant average pressure. The irrigation protocol was performed with 6 ml of 17% EDTA followed by 6 ml of 2.5% NaOCl for 1 min. Between each cycle, 5 ml of distilled water was used to prevent chemical interactions. Group 1: Manual Dynamic Activation (MDA) After the root canal preparation was completed, the final irrigation was started, the main gutta percha cone was positioned 1 mm shorter than the working length, and a 2 mm coronal-apical movement was performed at a speed of 100 strokes/minute for 60 seconds. The irrigation protocol was performed with 6 ml of 17% EDTA followed by 6 ml of 2.5% NaOCl for 1 min. Between each cycle, 5 ml of distilled water was used to prevent chemical interactions. Group 2: Passive Ultrasonic Irrigation (PUI) In this group, a noncutting ultrasonic tip (IRRI S 21/25; VDW, Munich, Germany) coupled to an ultrasonic device (DTE S6 Led, Guilin Woodpecker Co., Guilin, Guangxi, China) (mode: E, setting: 6) was used according to the manufacturer's recommendations. The tip was positioned 2 mm short of the working length without contacting the walls. Continuous irrigation was performed using 2 ml of 17% EDTA followed by 2 ml of 2.5% NaOCl with activation 3 times for 20 seconds. To prevent chemical interactions between NaOCl and EDTA, 5 ml of distilled water was used between each irrigant. In total, 1 min of irrigation activation was carried out. Group 3: Laser-Activated Irrigation (SWEEPS) In this group, a 2940 nm Er:YAG laser device (Lightwalker, Fotona, Ljubljana, Slovenia) equipped with a handpiece (H14, Fotona) holding an 8.5 mm long and 600 µm diameter tapered fiber tip (SWEEPS 600, Fotona) was used for irrigation activation. The device was set to AutoSWEEPS mode with two ultrashort micropulses (25 µs) continuously varying at 0.3 W, 20 mJ, and 15 Hz. The air and water sprays were turned off. A 30-gauge side-perforated irrigation needle (Kerr Hawe Sa, Bioggio, Switzerland) was inserted 1 mm shorter than the working length, and the fiber tip was positioned in the center of the access cavity and fixed in this position. Then, 2 ml of 17% EDTA was activated 3 times for 20 s. The same procedure was repeated with 2 ml of 2.5% NaOCl solution by flushing distilled water between each irrigant as described before. After the final irrigation procedures, the root canals were dried with 25/.06 paper cones (DiaDent, Heungdeok-gu, Korea), and the cold lateral compaction obturation technique with a root canal sealer (Meta Biomed, Cheongju, Güney, Korea) was used to fill all the canals. Permanent restoration was performed directly with composite resin material (Palfique Estelite, Tokuyama Dental Co., Tokyo, Japan). Follow-up procedures For routine follow-up, 2D radiographs were taken at 3, 6, and 9 months, as well as via intraoral examinations. Radiographic healing in both 2D and 3D at baseline and at a follow-up of 1 year was assessed by a calibrated evaluator who was blinded to the allocation group. The teeth were assessed for reported symptoms, sensitivity to palpation and percussion, mobility and probing depth. The presence of failure (intraoral swelling or sinus tract) was recorded. Healing evaluation: lesion area and volume calculation Twelve months after the root canal treatment, new CBCT images were taken with the same device (Planmeca Promax 3D Classic device (Planmeca Romexis, Helsinki, Finland)) and the same parameters (85 µm voxel size, 6.3 mA, 90 kV, 8.7 with FOV area 5x5 cm). 3D lesion volume calculation was performed using ITK SNAP (free software under the GNU General Public License developed by the National Institutes of Health, the US National Institute of Biomedical Imaging and Bioenergy needs, the US National Library of Medicine, the Universities of Pennsylvania and North Carolina, and an independent group of developers) by an oral maxillofacial radiologist with 12 + years of experience ( Fig. 2 ). The preoperative and 1-year postoperative CBCT images of the patients were measured following the same steps in the ITK-SNAP program. We used the same techniques used by Schloss et al[ 27 ]. First, the captured CBCT images were exported in DICOM file format from the Planmeca Romexis software. The exported images were then opened with ITK-SNAP software. Using the highest resolution allowed by the captured CBCT images (0.09 mm), the slice thickness and slice interval were set to 0.09 mm. The ITK-SNAP program includes a semiautomatic segmentation feature, which was utilized. In this feature, automated spherical fillers, or bubbles, as referred to in the program, were placed according to the grayscale of the lesion. Repeated runs were performed until the entire area of the lesion was filled, with the bubbles placed in the lesion area. After the internal area of the lesion was completely filled, the images were evaluated from axial, sagittal, and coronal sections to correct any possible overfilling or underfilling situations due to artifacts from canal filling materials using a manual marker. The volume of the painted area obtained was calculated in mm 3 using the program's feature. The evaluation of the tomography images obtained before and after treatment was conducted at one-month intervals. The images were provided to the evaluators in a randomized manner. The volume data were compared with the preoperative CBCT measurements for each patient. The volume changes were measured, and the long-term outcomes of the procedures were compared. Statistical analysis Analyses were carried out in the IBM SPSS 25 program. As the first step of the statistical analysis, the normality of the data was checked with the Shapiro–Wilk test. When normality was ensured, the Wilcoxon signed rank test was applied to examine the difference between the means of two dependent groups. ANOVA was used to examine the difference between the means of three or more independent groups. In cases where the data were not normally distributed, the Kruskal‒Wallis test was performed. The post hoc Bonferroni correction was used to determine the group or groups that were significantly different. Pearson’s chi-square test was applied to examine the relationships between study groups and sex. The Kruskal‒Wallis test was applied to examine the differences between the average ages of the participants in the study groups. Spearman correlations were used to control for the relationships between age and lesion volume measurements obtained at different times and from different study groups. To compare lesion volume measurements according to study group at different measurement times, ANOVA and the Kruskal‒Wallis test were applied. Bonferroni correction were performed to compare the groups. Wilcoxon signed rank tests were used to compare lesion volume measurements according to different measurement times in the study groups. For comparisons of lesion volume measurements at different measurement times in the study groups, assumptions were checked, and Wilcoxon signed-rank tests were used. Analyses were performed with the IBM SPSS 25 (SPSS Inc., Chicago, IL) program. The Pearson chi-square test was used to examine the relationships between study groups and sex. The Spearman correlation test was used to assess the relationships between lesion volume measurements obtained at different times and study group and age. RESULTS The number of patients lost to follow-up and assessed at the end of 12 months is shown in the CONSORT flow diagram. All patients had no signs/symptoms when assessed clinically during follow-up. A total of 56 people were included in the study; 22 (39.3%) were women, and 34 (60.7%) were men. The average age of the patients in all groups was homogeneous and similar (p > 0.05) (34.5 years) (Table 1 ). Table 1 Demonstration of participants according to age and sex n % p Gender Female 22 39.3 Male 34 60.7 n Minimum Maximum Mean Standard deviation Median Age 56 18 64 37.768 13.919 34.5 0.529 For the volume evaluation between groups, no significant differences were detected in the preoperative measurements. The mean lesion volume at pretreatment was significantly greater than the mean lesion volume at posttreatment in all groups. (p < 0.05) The categorical outcomes of healing regarding the volume changes according to group are presented in Table 2 . Among the 56 teeth, 11 (20%) were ‘totally healed’, and 39 (67%) were ‘reduced’, while 6 (11%) were ‘unchanged’ in terms of periapical lesions. No ‘enlargement’ was detected in any group. Table 2 Lesion volume changes after treatment Groups (n = 4) Totally healed Reduced Unchanged Enlarged Total MDA 3 9 2 0 14 PUI 1 13 0 0 14 SWEEPS 4 9 1 0 14 Control 3 8 3 0 14 Total 11 39 6 0 56 For the volume evaluation between groups, no significant differences were detected in the preop measurements (p > 0.05), whereas there were significant differences between the postop values in all groups (p < 0.005). There was a statistically significant difference between pretreatment and posttreatment lesion volume measurements in all groups (p < 0.05) (Table 3 ). Table 3 Lesion volume measurements before and after treatment Groups Time Mean Standard Deviation Rank Mean Test Statistic p MDA Preop. 193.936 29.441 8.00 -3.233 0.001* Postop. 41.727 66.473 1.00 PUI Preop. 158.343 40.275 7.50 -3.296 0.001* Postop. 22.813 15.93 0.00 SWEEPS Preop. 168.371 37.904 7.50 -3.296 0.001* Postop. 23.173 45.055 0.00 Control Preop. 172.2 41.707 7.50 -3.296 0.001* Postop. 49.646 76.794 0.00 * p < 0.05 When healing was categorized according to the reduction of the lesion (%) according to group, the SWEEPS and PIPS groups had the highest percentages (87% SWEEPS, 85% PUI), and the control group had the lowest percentage (75%). In the MDA group, the reduction in lesion size was 80%. However, there was no significant difference between the groups (p > 0.05) (Table 4 ). Table 4 Comparison of lesion volume change percentages between groups Groups Mean Standard Deviation Rank Mean Test Statistic p Dimensional Change (%) MDA 80.429 28.294 29.25 2.855** 0.414 PUI 85.429 8.635 23.00 SWEEPS 86.929 23.332 33.29 Control 74.571 36.515 28.46 *p < 0.05 and **Kruskal‒Wallis test DISCUSSION There are several studies in the literature comparing debris removal [ 16 , 17 ], antimicrobial [ 28 – 30 ] and effective activation efficiency of activation methods [ 31 – 33 ]. However, the effect of activation methods on the healing of large apical lesions has not yet been reported. This study was conducted to analyze the effectiveness of activation methods for healing teeth with large periapical lesions based on volumetric measurements using CBCT imaging. CBCT is an accurate 3D imaging technique and one of the best diagnostic tools for assessing regenerated tissue[ 34 – 37 ]. A strong correlation has been demonstrated between CBCT-based predictions and histologic evidence, suggesting that CBCT is an effective noninvasive diagnostic tool for periapical lesions [ 18 , 19 , 38 – 41 ]. In this study, the preoperative and postoperative volumes of periapical lesions were measured, and the 1-year outcomes were compared. The study's treatment procedure was standardized as much as possible. Standardizing anatomic differences such as root canal curvatures in multirooted teeth and difficulty achieving healthy working lengths and evaluation are more difficult than in single-rooted teeth and may cause errors. Therefore, in this study, teeth with straight and single root canals were used. The follow-up period for teeth with apical periodontitis varies among studies. The 1-year[ 41 ] follow-up period was chosen for most studies [ 42 , 43 ]. In parallel, Çalışkan et al. [ 44 ] reported that the healing of a tooth with a large cyst-like lesion and a wide apex occurred within the first year. Considering the studies, the follow-up period was determined to be 1 year in this study. According to the volumetric changes, a total of 50 teeth were completely healed or reduced in size, for a success rate of 89.2%. Fourteen of them (28%) were in the PUI group, 13 in the SWEEPS group (26%), 12 in the MDA group (24%)11 and 11 in the control group (22%). The ‘unchanged’ lesions were mostly observed in the control group (conventional syringe). No increase in lesion volume was observed in any group. The decreases were as follows: SWEEPS (86.9%) > PUI (85.4%) > MDA (80.4%) > conventional syringe (74.5%). Although the success rates in the PUI and LAI-SWEEPS groups were greater than those in the MDA and control groups, which was indicative of better healing, the difference was not statistically significant. According to the comparisons, we failed to reject the null hypothesis. In view of these findings, irrigation with or without aeration was crucial for the healing of periapical lesions. However, irrigation–augmentation techniques did not improve the healing of periapical lesions in single and straight-rooted teeth. Due to the lack of clinical studies examining the effect of activation methods on the healing of apical periodontitis, the effectiveness of activation methods was compared with that of in vitro studies. In a study comparing the ER:YAG (2940 nm) laser and PUI methods, there was no significant difference in debris removal efficiency between the two groups [ 16 ]. Another study revealed no significant difference between an ER:YAG (2940 nm) laser and the PUI method in terms of debris removal efficiency [ 45 ]. In a study investigating the antimicrobial efficacy of these two methods, no significant difference was found between laser activation and PUI methods [ 28 ]. These results are consistent with the statistical data from the Er:YAG (2940 nm) laser and PUI groups in this study. Zhu X et al. [ 46 ] examined the effects of Er:YAG laser and conventional syringe irrigation on smear layer removal and antibacterial effects and reported no significant difference between the two methods. In another study, the smear removal efficiencies of Er:YAG (2940 nm) lasers and conventional syringes were compared in vitro . No significant difference was found between the laser and conventional syringe groups [ 47 ]. In a systematic review, Caputa et al. [ 48 ] concluded that ultrasonic activation was not superior to conventional syringing for periapical tissue healing. The differences between these results may be attributed to several reasons, including statistical power analysis and sample size, enhanced activation not resulting in statistically significantly superior healing, and variations in irrigation protocols used in the studies. In contrast to the results of the present study, in a study comparing the debris removal efficiency of LAI-SWEEPS and conventional syringes, the LAI-SWEEPS method was found to be superior [ 49 ]. In an in vitro study investigating the removal of smear layers and debris from the curved mesiobuccal canals of mandibular teeth, the LAI-SWEEPS and PUI methods were found to be superior to the conventional methods [ 50 ]. The exclusion of curved canals in this study may have caused a limitation in demonstrating the superiority of LAI-SWEEPS and PUI technology over the other methods. The current study was a prospective, randomized controlled trial with an optimal sample size. The follow-up period of the study was 1 year, which may have limited our ability to obtain definitive evidence of lesion changes in the long term. In addition, in multirooted teeth with curved and complex root canal anatomy, irrigation techniques may provide significant clinical benefits and improve outcomes. Another limitation concerns the 100% reliability of the cbct. Although cbct has high reliability, the margin of error can reach 18% [ 51 , 52 ]. In one study, evaluations of the size of periapical lesions were made with volume data of 20% or more [ 53 ]. cbct evaluation in combination with histologic evidence may be a better diagnostic way to determine the true nature of the healing process in tissues. However, it is unethical to procure postoperative healed tissue from patients to compare the histologic findings with those of CBCT scans [ 18 , 38 ]. Further research with larger sample sizes would be beneficial for analyzing the efficacy of iffiction agitation techniques on the morphology of multirooted and curved root canals. CONCLUSION Irrigation with or without agitation was crucial for the healing of periapical lesions. However, irrigation–agitation techniques did not improve the healing of periapical lesions in single and straight-rooted teeth. Although the LAI-SWEEPS and PUI irrigation activation methods resulted in a greater rate of apical periodontitis healing, there was no significant difference compared to that in the other groups at the 1-year follow-up. Further studies could be beneficial for analyzing the efficacy of irrigation-agitation techniques in multirooted teeth with curved and complex root canal morphologies. Long-term randomized clinical trials with large sample sizes are necessary to allow more reliable comparisons between results. DECLARATIONS Author Contribution: All authors reviewed the manuscript Mehmet Umutcan Doğan: Writing, Investigation, Original draft preparation. Banu Arıcıoğlu: Supervision, Methodology, Review & Editing. Taha Emre Köse: Methodology, Conceptualization, Data curation Merve Çoban Öksüzer: Review & Editing, Investigation, Original draft preparation. Ahter Şanal Çıkman: Supervision, Methodology, Review & Editing. Funding : No funding was obtained for this study. Data availability: The data used to support the findings of this study are available from the corresponding author upon reasonable request. Declarations: Local ethics committee approval was obtained from the Ethical Review Committee of the Research Foundation at the Medical Faculty of Recep Tayyip Erdogan University (No: 2023/35). Patients were informed about the procedure, and written informed consent was obtained before the commencement of treatment. Competing interests: The authors declare no competing interests. REFERENCES Ricucci, D. and J.F.J.J.o.e. Siqueira Jr, Biofilms and apical periodontitis: study of prevalence and association with clinical and histopathologic findings. 2010. 36 (8): p. 1277-1288. Peters, O.A., K. Schönenberger, and A. Laib, Effects of four Ni-Ti preparation techniques on root canal geometry assessed by micro computed tomography. Int Endod J, 2001. 34 (3): p. 221-30. 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Helvacioglu-Yigit, Effectiveness of Various Final Irrigation Techniques on Sealer Penetration in Curved Roots: A Confocal Laser Scanning Microscopy Study. BioMed Research International, 2020. 2020 : p. 8060489. Verma, A., et al., A randomized controlled trial of endodontic treatment using ultrasonic irrigation and laser activated irrigation to evaluate healing in chronic apical periodontitis. J Clin Exp Dent, 2020. 12 (9): p. e821-e829. Campello, A.F., et al., Determination of the Initial Apical Canal Diameter by the First File to Bind or Cone-beam Computed Tomographic Measurements Using Micro-computed Tomography as the Gold Standard: An Ex Vivo Study in Human Cadavers. J Endod, 2019. 45 (5): p. 619-622. Weine, F.S., Endodontic Therapy . 1989: Mosby, St. Louis. 277-369. Schloss, T., et al., A Comparison of 2- and 3-dimensional Healing Assessment after Endodontic Surgery Using Cone-beam Computed Tomographic Volumes or Periapical Radiographs. J Endod, 2017. 43 (7): p. 1072-1079. Cheng, X., et al., Bactericidal effect of Er: YAG laser-activated sodium hypochlorite irrigation against biofilms of Enterococcus faecalis isolate from canal of root-filled teeth with periapical lesions. 2017. 35 (7): p. 386-392. Miranda, R., et al., Ex vivo antimicrobial efficacy of the E ndo V ac® system plus photodynamic therapy associated with calcium hydroxide against intracanal E nterococcus faecalis. 2013. 46 (6): p. 499-505. Neuhaus, K.W., et al., Antibacterial Efficacy of a New Sonic Irrigation Device for Root Canal Disinfection. J Endod, 2016. 42 (12): p. 1799-1803. de Gregorio, C., et al., Efficacy of Different Irrigation and Activation Systems on the Penetration of Sodium Hypochlorite into Simulated Lateral Canals and up to Working Length: An In Vitro Study. Journal of Endodontics, 2010. 36 (7): p. 1216-1221. Iandolo, A., et al., Traditional and Recent Root Canal Irrigation Methods and Their Effectiveness: A Review. Clinics and Practice, 2023. 13 (5): p. 1059-1072. Nivedhitha, S., Comparing The Effectiveness Of Various Irrigant Activation Techniques With Conventional Needle Irrigation-A Systematic Review. Int J Dentistry Oral Sci, 2021. 8 (05): p. 2626-2631. Kaya, S., et al., Measuring bone density in healing periapical lesions by using cone beam computed tomography: a clinical investigation. J Endod, 2012. 38 (1): p. 28-31. Schulze, D., et al., Radiation exposure during midfacial imaging using 4- and 16-slice computed tomography, cone beam computed tomography systems and conventional radiography. Dentomaxillofacial Radiology, 2014. 33 (2): p. 83-86. Kumar, M., et al., Cone beam computed tomography - know its secrets. J Int Oral Health, 2015. 7 (2): p. 64-8. Patel, S., et al., Cone beam computed tomography in Endodontics - a review. Int Endod J, 2015. 48 (1): p. 3-15. Kanagasingam, S., et al., Diagnostic accuracy of periapical radiography and cone beam computed tomography in detecting apical periodontitis using histopathological findings as a reference standard. Int Endod J, 2017. 50 (5): p. 417-426. de Paula-Silva, F.W., et al., Accuracy of periapical radiography and cone-beam computed tomography scans in diagnosing apical periodontitis using histopathological findings as a gold standard. J Endod, 2009. 35 (7): p. 1009-12. Simon, J.H., et al., Differential diagnosis of large periapical lesions using cone-beam computed tomography measurements and biopsy. J Endod, 2006. 32 (9): p. 833-7. Orstavik, D., Time-course and risk analyses of the development and healing of chronic apical periodontitis in man. Int Endod J, 1996. 29 (3): p. 150-5. Waltimo, T., et al., Clinical efficacy of treatment procedures in endodontic infection control and one year follow-up of periapical healing. 2005. 31 (12): p. 863-866. Dorasani, G., K. Madhusudhana, and S.K.J.J.o.C.D. Chinni, Clinical and radiographic evaluation of single-visit and multi-visit endodontic treatment of teeth with periapical pathology: An in vivo study. 2013. 16 (6): p. 484. Çalışkan, M.J.I.e.j., Prognosis of large cyst‐like periapical lesions following nonsurgical root canal treatment: a clinical review. 2004. 37 (6): p. 408-416. Deleu, E., M.A. Meire, and R.J.J.L.i.m.s. De Moor, Efficacy of laser-based irrigant activation methods in removing debris from simulated root canal irregularities. 2015. 30 (2): p. 831-835. Zhu, X., et al., Comparison of the antibacterial effect and smear layer removal using photon-initiated photoacoustic streaming aided irrigation versus a conventional irrigation in single-rooted canals: an in vitro study. 2013. 31 (8): p. 371-377. Turkel, E., et al., Comparison of three final irrigation activation techniques: effects on canal cleanness, smear layer removal, and dentinal tubule penetration of two root canal sealers. 2017. 35 (12): p. 672-681. Căpută, P.E., et al., Ultrasonic irrigant activation during root canal treatment: a systematic review. 2019. 45 (1): p. 31-44. e13. Rödig, T., et al., Effect of preparation size on the removal of accumulated hard-tissue debris from the mesial root canal system of mandibular molars using SWEEPS technology. 2023: p. 1-10. Vatanpour, M., et al., Comparison of three irrigation methods: SWEEPS, ultrasonic, and traditional irrigation, in smear layer and debris removal abilities in the root canal, beyond the fractured instrument. 2022. 37 : p. 102707. Chang, P., et al., A comparison of the thresholding strategies of micro-CT for periodontal bone loss: a pilot study. 2013. 42 (2): p. 66925194. Kamburoğlu, K., et al., Accuracy of chemically created periapical lesion measurements using limited cone beam computed tomography. 2010. 39 (2): p. 95-99. Liang, Y.-H., et al., Radiographic healing after a root canal treatment performed in single-rooted teeth with and without ultrasonic activation of the irrigant: a randomized controlled trial. 2013. 39 (10): p. 1218-1225. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 15 Jun, 2024 Read the published version in Clinical Oral Investigations → Version 1 posted Editorial decision: Revision requested 06 May, 2024 Reviews received at journal 01 May, 2024 Reviewers agreed at journal 17 Mar, 2024 Reviewers invited by journal 11 Mar, 2024 Editor assigned by journal 08 Mar, 2024 Submission checks completed at journal 08 Mar, 2024 First submitted to journal 04 Mar, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4014149","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":278473066,"identity":"584c4988-33f8-41a4-add8-d2550397ba59","order_by":0,"name":"Mehmet Umutcan Doğan","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Mehmet","middleName":"Umutcan","lastName":"Doğan","suffix":""},{"id":278473067,"identity":"3bc37432-e7ef-48e3-824e-ae3d3583dfb7","order_by":1,"name":"Banu Arıcıoğlu","email":"","orcid":"","institution":"Istanbul Medeniyet University","correspondingAuthor":false,"prefix":"","firstName":"Banu","middleName":"","lastName":"Arıcıoğlu","suffix":""},{"id":278473068,"identity":"1ebc5a15-87e8-4cba-acbd-e0521f06870e","order_by":2,"name":"Taha Emre Köse","email":"","orcid":"","institution":"Recep Tayyip Erdoğan University","correspondingAuthor":false,"prefix":"","firstName":"Taha","middleName":"Emre","lastName":"Köse","suffix":""},{"id":278473069,"identity":"6d59070e-b3c9-48ef-95a2-d80c06298545","order_by":3,"name":"Ahter Şanal Çıkman","email":"","orcid":"","institution":"Recep Tayyip Erdoğan University","correspondingAuthor":false,"prefix":"","firstName":"Ahter","middleName":"Şanal","lastName":"Çıkman","suffix":""},{"id":278473070,"identity":"45275059-c99c-49ed-b8e2-5e3050472152","order_by":4,"name":"Merve Çoban Öksüzer","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9ElEQVRIiWNgGAWjYBCDBCBO//ChAkgxMzcQreUZ44wzIC2MRGthfMbM2QZiE9Ci2977TOJDjU0e/+zmtMeM82qj+duBWn5UbMOpxezMcTPJGcfSiiXuHEs3Ltx2PHfGYcYGxp4zt3FruZHGbMzbcDix4UZOgvTMbcdyG4BamBnb8Gi5/4zZ+C9Qy/wb+R+keeccy51PUMsNNsbHjEAtG24kpEnzNtTkbiCo5Uwa48MeoF8MbyQkG844diB3I1DLQbx+OX6M4cAPYIjJ3UhIfPChpi533vnDBx/8qMCtBR0cBpMHiFYPBHWkKB4Fo2AUjIIRAgC1gGRP+mu29QAAAABJRU5ErkJggg==","orcid":"","institution":"Recep Tayyip Erdoğan University","correspondingAuthor":true,"prefix":"","firstName":"Merve","middleName":"Çoban","lastName":"Öksüzer","suffix":""}],"badges":[],"createdAt":"2024-03-04 19:15:37","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4014149/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4014149/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00784-024-05758-4","type":"published","date":"2024-06-15T14:57:31+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":52549152,"identity":"99107fd3-ee9a-4c26-aa68-1fa9e3f317c2","added_by":"auto","created_at":"2024-03-12 20:02:22","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":423033,"visible":true,"origin":"","legend":"\u003cp\u003eConsolidated Standards of Reporting Trials (CONSORT) flow diagram for patients included in this study.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4014149/v1/832f1c2c762c6e3d862b63f7.png"},{"id":52549151,"identity":"2fefebfa-2f49-4dc5-afa1-cb84cef7092e","added_by":"auto","created_at":"2024-03-12 20:02:22","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":408775,"visible":true,"origin":"","legend":"\u003cp\u003eStaining of the patient's lesion in the ITK SNAP program and obtaining a 3D image\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-4014149/v1/daef917555b829bae06a3670.png"},{"id":58822447,"identity":"83e72757-c3d8-432f-9884-6af513358e32","added_by":"auto","created_at":"2024-06-21 16:43:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1451110,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4014149/v1/89022f38-92ab-44b5-93e6-6a696a6b6dc5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association between the Irrigation-Agitation Techniques and Periapical Healing of Large Periapical Lesions: A Randomized Controlled Trial","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eMicroorganisms and their products play pivotal roles in the initiation, progression, and establishment of periradicular conditions [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The main aim of root canal treatment for teeth with necrotic, contaminated pulp is to treat the infection and prevent future infections. A significant portion of the root canal surface remains untouched during treatment with mechanical instrumentation alone[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Therefore, irrigation is crucial for thorough disinfection of the root canal system [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eManual dynamic activation (MDA) involves moving a fitted gutta percha master cone in amplitude strokes following canal preparation after canal preparation is completed. This pecking movement aims to increase the effectiveness of disinfection by allowing the solution to contact more surfaces [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Passive ultrasonic irrigation (PUI), one of the most widely used activation systems today, creates an acoustic flow by providing hydrodynamic activation and contributes to disinfection by increasing the cavitation effect with the bubbles it produces. When applying this technique, small-diameter tips should not touch the root canal walls and should be used close to the apical region of the canal[\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In recent decades, laser-activated irrigation (LAI) has become popular for debris and smear layer removal and antibacterial efficacy. Shock wave-enhanced emission photoacoustic stream (SWEEPS) is the most recent technology of the Er:YAG laser model used to improve irrigation efficiency. The application of two consecutive laser pulses to the irrigation solution at a certain time ensures that the bubbles created by the first laser beam collapse more quickly and that the photoacoustic shock wave reaches the narrow, inaccessible parts of the root canal [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In the SWEEPS technique, it is sufficient to place only the laser tip in the pulp chamber, but in traditional laser activation, canal expansion is needed to reach the laser tip to the root apex. This advantage of the SWEEPS is that it allows minimally invasive endodontic preparation[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Yang et al. reported that SWEEPS could emit synchronized laser pulses. In this way, the movement of the irrigation fluid and the bubble collapse rate increase. As a result, the SWEEPS can clear both the main channel and irregularities[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSuccessful healing of apical periodontitis requires a reduction in the size of the radiolucent area and healing of the bone [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The evaluation of periapical pathologies and changes in their volumes with CBCT is more successful than that with 2D radiographs [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the literature, there are numerous studies on the efficacy of irrigation activation methods for debris smear removal [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], calcium hydroxide removal [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] and sealer penetration in dentinal tubules [\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] under \u003cem\u003ein vitro\u003c/em\u003e conditions. Therefore, the aim of this study was to evaluate the healing rates of large periapical lesions after the use of different irrigation-agitation methods (MDA, PUI, LAI-SWEEPS) using CBCT scans for volumetric change analysis during a 1-year follow-up. The null hypothesis was that there was no significant difference in lesion healing between the groups.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003e Local ethics committee approval was obtained from the Ethical Review Committee of the Research Foundation at the Medical Faculty of Recep Tayyip Erdogan University (No: 2023/35) and the study protocol was registered at ClinicalTrials.gov (NCT06204887).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSample size calculation\u003c/h2\u003e \u003cp\u003e \u003cb\u003eThe\u003c/b\u003e G Power 3.0.10 (University Kiel, Germany) program was used to calculate the effect size. The effect size was calculated based on chi-square analysis data between the control group and the laser group in the Verma, Yadav study[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. An effect size of 0.51 Cohen d value was found to be sufficient for significance. With a type 1 error of 0.05, it was determined that at least 56 subjects were required for a total of 4 groups, 14 in each study group, with 95% power.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePatient Recruitment and Randomization\u003c/h2\u003e \u003cp\u003ePatients were informed about the procedure, and written informed consent was obtained before the commencement of treatment. The study included mandibular single-rooted teeth that were diagnosed with asymptomatic apical periodontitis and had a periapical index (PAI) score of 3 or higher. A total of 97 patients were evaluated radiographically and clinically for conformity with the inclusion and exclusion criteria. Patients with systemic diseases (diabetes, hypertension, chronic liver disease, coagulation disorders), bone metabolism disease and/or patients using drugs that affect bone metabolism (such as steroids and bisphosphonates) were excluded from the study. Immunosuppressed patients, patients with a history of radiotherapy, pregnant patients, patients with teeth with a mobility of 2 or more (Miller\u0026rsquo;s mobility index), patients with teeth with a periodontal pocket depth of 5 mm or more, patients with generalized asymptomatic apical periodontitis, patients with teeth with internal and external resorption, and patients with teeth with vertical and horizontal root fractures were not included.\u003c/p\u003e \u003cp\u003eAfter applying the eligibility criteria, 70 patients were randomly divided into four groups using software (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e\u003ca href=\"http://www.random.org\" target=\"_blank\"\u003ewww.random.org\u003c/a\u003e\u003c/span\u003e\u003cspan address=\"http://www.random.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) by a blinded researcher who was not otherwise involved in the study according to a standardized procedure. The numbers were placed in dark envelopes and concealed. The envelopes were only opened when the irrigation solution was to be activated. The patients were informed about the study without specifying the group to which they were assigned. All procedures were performed by a single operator with five years of experience (U.D.).\u003c/p\u003e \u003cp\u003eCBCT imaging (Planmeca Romexis, Helsinki, Finland) was requested for patients who met the study criteria before the procedure to obtain information about periapical lesion size, proximity to anatomical landmarks, and anatomical variations of the tooth. CBCT images were acquired with a field of view (FOV) of 5\u0026times;5 cm using ENDO mode, an 85 \u0026micro;m voxel size, 6.3 mA, 90 kV, and 8.7 s.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eClinical procedures\u003c/h2\u003e \u003cp\u003eA CONSORT flow diagram outlining the treatment methodology is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. After the administration of local anesthesia and the placement of a rubber dam, the access cavity was opened with a sterile diamond round bur under water cooling. Each canal was rinsed with 2 mL of sodium hypochlorite and explored with a size 08 K-file (FKG Dentaire, La Chaux-de-Fonds, Switzerland). The working length was determined using an electronic apex locator, Root ZX mini (J. Morita Co., Tokyo, Japan), to be 0.5 mm shorter than a 0.0 reading. The length was confirmed radiographically. After that, progressively larger K-files were passively introduced into the canal until the operator felt the first one to bind at the WL and the next larger one not to reach that position[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The first instrument used to bind the canal was recorded for each canal. The crown-down technique was applied with ProTaper Next rotary files (Dentsply Maillefer, Ballaigues, Switzerland) using a torque-controlled endodontic motor (SybronEndo, Glendora, CA, USA) at 300 rpm/2-5.2 Ncm rotation mode according to the manufacturer's instructions. The final instrumentation file was set to 3 sizes larger than the first file used[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Between each instrument change, the root canal was irrigated with 5 mL of 2.5% NaOCl (Microvem AF, Istanbul, Turkey) for 1 min. After canal preparation was completed, the final irrigation procedure was carried out with the corresponding irrigation method in each group.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eControl Group: Conventional Syringe Irrigation\u003c/h2\u003e \u003cp\u003eA 30-gauge side-vented irrigation needle (Kerr Hawe Sa, Bioggio, Switzerland) was used. The needle was inserted into the canal 1 mm shorter than the working length, and the canal was irrigated with up-and-down movements of 1\u0026ndash;2 mm amplitude using the same and constant average pressure. The irrigation protocol was performed with 6 ml of 17% EDTA followed by 6 ml of 2.5% NaOCl for 1 min. Between each cycle, 5 ml of distilled water was used to prevent chemical interactions.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eGroup 1: Manual Dynamic Activation (MDA)\u003c/h2\u003e \u003cp\u003eAfter the root canal preparation was completed, the final irrigation was started, the main gutta percha cone was positioned 1 mm shorter than the working length, and a 2 mm coronal-apical movement was performed at a speed of 100 strokes/minute for 60 seconds. The irrigation protocol was performed with 6 ml of 17% EDTA followed by 6 ml of 2.5% NaOCl for 1 min. Between each cycle, 5 ml of distilled water was used to prevent chemical interactions.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eGroup 2: Passive Ultrasonic Irrigation (PUI)\u003c/h2\u003e \u003cp\u003e In this group, a noncutting ultrasonic tip (IRRI S 21/25; VDW, Munich, Germany) coupled to an ultrasonic device (DTE S6 Led, Guilin Woodpecker Co., Guilin, Guangxi, China) (mode: E, setting: 6) was used according to the manufacturer's recommendations.\u003c/p\u003e \u003cp\u003eThe tip was positioned 2 mm short of the working length without contacting the walls. Continuous irrigation was performed using 2 ml of 17% EDTA followed by 2 ml of 2.5% NaOCl with activation 3 times for 20 seconds. To prevent chemical interactions between NaOCl and EDTA, 5 ml of distilled water was used between each irrigant. In total, 1 min of irrigation activation was carried out.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eGroup 3: Laser-Activated Irrigation (SWEEPS)\u003c/h2\u003e \u003cp\u003eIn this group, a 2940 nm Er:YAG laser device (Lightwalker, Fotona, Ljubljana, Slovenia) equipped with a handpiece (H14, Fotona) holding an 8.5 mm long and 600 \u0026micro;m diameter tapered fiber tip (SWEEPS 600, Fotona) was used for irrigation activation. The device was set to AutoSWEEPS mode with two ultrashort micropulses (25 \u0026micro;s) continuously varying at 0.3 W, 20 mJ, and 15 Hz. The air and water sprays were turned off.\u003c/p\u003e \u003cp\u003eA 30-gauge side-perforated irrigation needle (Kerr Hawe Sa, Bioggio, Switzerland) was inserted 1 mm shorter than the working length, and the fiber tip was positioned in the center of the access cavity and fixed in this position. Then, 2 ml of 17% EDTA was activated 3 times for 20 s. The same procedure was repeated with 2 ml of 2.5% NaOCl solution by flushing distilled water between each irrigant as described before.\u003c/p\u003e \u003cp\u003eAfter the final irrigation procedures, the root canals were dried with 25/.06 paper cones (DiaDent, Heungdeok-gu, Korea), and the cold lateral compaction obturation technique with a root canal sealer (Meta Biomed, Cheongju, G\u0026uuml;ney, Korea) was used to fill all the canals. Permanent restoration was performed directly with composite resin material (Palfique Estelite, Tokuyama Dental Co., Tokyo, Japan).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eFollow-up procedures\u003c/h2\u003e \u003cp\u003eFor routine follow-up, 2D radiographs were taken at 3, 6, and 9 months, as well as via intraoral examinations. Radiographic healing in both 2D and 3D at baseline and at a follow-up of 1 year was assessed by a calibrated evaluator who was blinded to the allocation group. The teeth were assessed for reported symptoms, sensitivity to palpation and percussion, mobility and probing depth. The presence of failure (intraoral swelling or sinus tract) was recorded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eHealing evaluation: lesion area and volume calculation\u003c/h2\u003e \u003cp\u003eTwelve months after the root canal treatment, new CBCT images were taken with the same device (Planmeca Promax 3D Classic device (Planmeca Romexis, Helsinki, Finland)) and the same parameters (85 \u0026micro;m voxel size, 6.3 mA, 90 kV, 8.7 with FOV area 5x5 cm).\u003c/p\u003e \u003cp\u003e3D lesion volume calculation was performed using ITK SNAP (free software under the GNU General Public License developed by the National Institutes of Health, the US National Institute of Biomedical Imaging and Bioenergy needs, the US National Library of Medicine, the Universities of Pennsylvania and North Carolina, and an independent group of developers) by an oral maxillofacial radiologist with 12\u0026thinsp;+\u0026thinsp;years of experience \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe preoperative and 1-year postoperative CBCT images of the patients were measured following the same steps in the ITK-SNAP program. We used the same techniques used by Schloss et al[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. First, the captured CBCT images were exported in DICOM file format from the Planmeca Romexis software. The exported images were then opened with ITK-SNAP software. Using the highest resolution allowed by the captured CBCT images (0.09 mm), the slice thickness and slice interval were set to 0.09 mm. The ITK-SNAP program includes a semiautomatic segmentation feature, which was utilized. In this feature, automated spherical fillers, or bubbles, as referred to in the program, were placed according to the grayscale of the lesion. Repeated runs were performed until the entire area of the lesion was filled, with the bubbles placed in the lesion area. After the internal area of the lesion was completely filled, the images were evaluated from axial, sagittal, and coronal sections to correct any possible overfilling or underfilling situations due to artifacts from canal filling materials using a manual marker. The volume of the painted area obtained was calculated in mm\u003csup\u003e3\u003c/sup\u003e using the program's feature. The evaluation of the tomography images obtained before and after treatment was conducted at one-month intervals. The images were provided to the evaluators in a randomized manner.\u003c/p\u003e \u003cp\u003eThe volume data were compared with the preoperative CBCT measurements for each patient. The volume changes were measured, and the long-term outcomes of the procedures were compared.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAnalyses were carried out in the IBM SPSS 25 program. As the first step of the statistical analysis, the normality of the data was checked with the Shapiro\u0026ndash;Wilk test. When normality was ensured, the Wilcoxon signed rank test was applied to examine the difference between the means of two dependent groups. ANOVA was used to examine the difference between the means of three or more independent groups. In cases where the data were not normally distributed, the Kruskal‒Wallis test was performed. The post hoc Bonferroni correction was used to determine the group or groups that were significantly different.\u003c/p\u003e \u003cp\u003ePearson\u0026rsquo;s chi-square test was applied to examine the relationships between study groups and sex. The Kruskal‒Wallis test was applied to examine the differences between the average ages of the participants in the study groups. Spearman correlations were used to control for the relationships between age and lesion volume measurements obtained at different times and from different study groups. To compare lesion volume measurements according to study group at different measurement times, ANOVA and the Kruskal‒Wallis test were applied. Bonferroni correction were performed to compare the groups. Wilcoxon signed rank tests were used to compare lesion volume measurements according to different measurement times in the study groups.\u003c/p\u003e \u003cp\u003eFor comparisons of lesion volume measurements at different measurement times in the study groups, assumptions were checked, and Wilcoxon signed-rank tests were used. Analyses were performed with the IBM SPSS 25 (SPSS Inc., Chicago, IL) program. The Pearson chi-square test was used to examine the relationships between study groups and sex. The Spearman correlation test was used to assess the relationships between lesion volume measurements obtained at different times and study group and age.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThe number of patients lost to follow-up and assessed at the end of 12 months is shown in the CONSORT flow diagram. All patients had no signs/symptoms when assessed clinically during follow-up.\u003c/p\u003e\n\u003cp\u003eA total of 56 people were included in the study; 22 (39.3%) were women, and 34 (60.7%) were men. The average age of the patients in all groups was homogeneous and similar (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (34.5 years) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eDemonstration of participants according to age and sex\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth colspan=\"3\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth colspan=\"3\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003en\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e%\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"3\" rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e22\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e39.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e34\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e60.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eMinimum\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eMaximum\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eStandard deviation\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eMedian\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e56\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e64\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e37.768\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e13.919\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.529\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eFor the volume evaluation between groups, no significant differences were detected in the preoperative measurements. The mean lesion volume at pretreatment was significantly greater than the mean lesion volume at posttreatment in all groups. (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05)\u003c/p\u003e\n\u003cp\u003eThe categorical outcomes of healing regarding the volume changes according to group are presented in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. Among the 56 teeth, 11 (20%) were \u0026lsquo;totally healed\u0026rsquo;, and 39 (67%) were \u0026lsquo;reduced\u0026rsquo;, while 6 (11%) were \u0026lsquo;unchanged\u0026rsquo; in terms of periapical lesions. No \u0026lsquo;enlargement\u0026rsquo; was detected in any group.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eLesion volume changes after treatment\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGroups\u003c/p\u003e\n\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTotally healed\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eReduced\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eUnchanged\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eEnlarged\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTotal\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMDA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePUI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSWEEPS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eControl\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e56\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eFor the volume evaluation between groups, no significant differences were detected in the preop measurements (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), whereas there were significant differences between the postop values in all groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.005).\u003c/p\u003e\n\u003cp\u003eThere was a statistically significant difference between pretreatment and posttreatment lesion volume measurements in all groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eLesion volume measurements before and after treatment\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGroups\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTime\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eMean\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eStandard Deviation\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eRank Mean\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTest Statistic\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ep\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eMDA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePreop.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e193.936\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29.441\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-3.233\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.001*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePostop.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e41.727\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e66.473\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003ePUI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePreop.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e158.343\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40.275\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-3.296\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.001*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePostop.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.813\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15.93\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSWEEPS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePreop.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e168.371\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37.904\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-3.296\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.001*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePostop.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.173\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45.055\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eControl\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePreop.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e172.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e41.707\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-3.296\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.001*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePostop.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49.646\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e76.794\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"7\"\u003e\u003cstrong\u003e*\u003c/strong\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003eWhen healing was categorized according to the reduction of the lesion (%) according to group, the SWEEPS and PIPS groups had the highest percentages (87% SWEEPS, 85% PUI), and the control group had the lowest percentage (75%). In the MDA group, the reduction in lesion size was 80%. However, there was no significant difference between the groups (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eComparison of lesion volume change percentages between groups\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eGroups\u003c/p\u003e\n\u003c/th\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eMean\u003c/p\u003e\n\u003c/th\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eStandard Deviation\u003c/p\u003e\n\u003c/th\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eRank Mean\u003c/p\u003e\n\u003c/th\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eTest Statistic\u003c/p\u003e\n\u003c/th\u003e\n\u003cth style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003ep\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 140px;\" rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eDimensional Change\u003c/p\u003e\n\u003cp\u003e(%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eMDA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e80.429\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e28.294\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e29.25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e2.855**\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e0.414\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003ePUI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e85.429\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e8.635\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e23.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eSWEEPS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e86.929\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e23.332\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e33.29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003eControl\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e74.571\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e36.515\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n\u003cp\u003e28.46\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr style=\"height: 13px;\"\u003e\n\u003ctd style=\"height: 13px;\" colspan=\"7\"\u003e*p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 and **Kruskal‒Wallis test\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThere are several studies in the literature comparing debris removal [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], antimicrobial [\u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] and effective activation efficiency of activation methods [\u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. However, the effect of activation methods on the healing of large apical lesions has not yet been reported. This study was conducted to analyze the effectiveness of activation methods for healing teeth with large periapical lesions based on volumetric measurements using CBCT imaging.\u003c/p\u003e \u003cp\u003eCBCT is an accurate 3D imaging technique and one of the best diagnostic tools for assessing regenerated tissue[\u003cspan additionalcitationids=\"CR35 CR36\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. A strong correlation has been demonstrated between CBCT-based predictions and histologic evidence, suggesting that CBCT is an effective noninvasive diagnostic tool for periapical lesions [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan additionalcitationids=\"CR39 CR40\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. In this study, the preoperative and postoperative volumes of periapical lesions were measured, and the 1-year outcomes were compared.\u003c/p\u003e \u003cp\u003eThe study's treatment procedure was standardized as much as possible. Standardizing anatomic differences such as root canal curvatures in multirooted teeth and difficulty achieving healthy working lengths and evaluation are more difficult than in single-rooted teeth and may cause errors. Therefore, in this study, teeth with straight and single root canals were used.\u003c/p\u003e \u003cp\u003eThe follow-up period for teeth with apical periodontitis varies among studies. The 1-year[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e] follow-up period was chosen for most studies [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. In parallel, \u0026Ccedil;alışkan et al. [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e] reported that the healing of a tooth with a large cyst-like lesion and a wide apex occurred within the first year. Considering the studies, the follow-up period was determined to be 1 year in this study.\u003c/p\u003e \u003cp\u003eAccording to the volumetric changes, a total of 50 teeth were completely healed or reduced in size, for a success rate of 89.2%. Fourteen of them (28%) were in the PUI group, 13 in the SWEEPS group (26%), 12 in the MDA group (24%)11 and 11 in the control group (22%). The \u0026lsquo;unchanged\u0026rsquo; lesions were mostly observed in the control group (conventional syringe). No increase in lesion volume was observed in any group. The decreases were as follows: SWEEPS (86.9%)\u0026thinsp;\u0026gt;\u0026thinsp;PUI (85.4%)\u0026thinsp;\u0026gt;\u0026thinsp;MDA (80.4%)\u0026thinsp;\u0026gt;\u0026thinsp;conventional syringe (74.5%). Although the success rates in the PUI and LAI-SWEEPS groups were greater than those in the MDA and control groups, which was indicative of better healing, the difference was not statistically significant. According to the comparisons, we failed to reject the null hypothesis. In view of these findings, irrigation with or without aeration was crucial for the healing of periapical lesions. However, irrigation\u0026ndash;augmentation techniques did not improve the healing of periapical lesions in single and straight-rooted teeth.\u003c/p\u003e \u003cp\u003eDue to the lack of clinical studies examining the effect of activation methods on the healing of apical periodontitis, the effectiveness of activation methods was compared with that of \u003cem\u003ein vitro\u003c/em\u003e studies. In a study comparing the ER:YAG (2940 nm) laser and PUI methods, there was no significant difference in debris removal efficiency between the two groups [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Another study revealed no significant difference between an ER:YAG (2940 nm) laser and the PUI method in terms of debris removal efficiency [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. In a study investigating the antimicrobial efficacy of these two methods, no significant difference was found between laser activation and PUI methods [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. These results are consistent with the statistical data from the Er:YAG (2940 nm) laser and PUI groups in this study.\u003c/p\u003e \u003cp\u003eZhu X et al. [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e] examined the effects of Er:YAG laser and conventional syringe irrigation on smear layer removal and antibacterial effects and reported no significant difference between the two methods. In another study, the smear removal efficiencies of Er:YAG (2940 nm) lasers and conventional syringes were compared \u003cem\u003ein vitro\u003c/em\u003e. No significant difference was found between the laser and conventional syringe groups [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn a systematic review, Caputa et al. [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e] concluded that ultrasonic activation was not superior to conventional syringing for periapical tissue healing. The differences between these results may be attributed to several reasons, including statistical power analysis and sample size, enhanced activation not resulting in statistically significantly superior healing, and variations in irrigation protocols used in the studies.\u003c/p\u003e \u003cp\u003eIn contrast to the results of the present study, in a study comparing the debris removal efficiency of LAI-SWEEPS and conventional syringes, the LAI-SWEEPS method was found to be superior [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. In an \u003cem\u003ein vitro\u003c/em\u003e study investigating the removal of smear layers and debris from the curved mesiobuccal canals of mandibular teeth, the LAI-SWEEPS and PUI methods were found to be superior to the conventional methods [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. The exclusion of curved canals in this study may have caused a limitation in demonstrating the superiority of LAI-SWEEPS and PUI technology over the other methods.\u003c/p\u003e \u003cp\u003eThe current study was a prospective, randomized controlled trial with an optimal sample size. The follow-up period of the study was 1 year, which may have limited our ability to obtain definitive evidence of lesion changes in the long term. In addition, in multirooted teeth with curved and complex root canal anatomy, irrigation techniques may provide significant clinical benefits and improve outcomes.\u003c/p\u003e \u003cp\u003eAnother limitation concerns the 100% reliability of the cbct. Although cbct has high reliability, the margin of error can reach 18% [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e, \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. In one study, evaluations of the size of periapical lesions were made with volume data of 20% or more [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. cbct evaluation in combination with histologic evidence may be a better diagnostic way to determine the true nature of the healing process in tissues. However, it is unethical to procure postoperative healed tissue from patients to compare the histologic findings with those of CBCT scans [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Further research with larger sample sizes would be beneficial for analyzing the efficacy of iffiction agitation techniques on the morphology of multirooted and curved root canals.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eIrrigation with or without agitation was crucial for the healing of periapical lesions. However, irrigation\u0026ndash;agitation techniques did not improve the healing of periapical lesions in single and straight-rooted teeth. Although the LAI-SWEEPS and PUI irrigation activation methods resulted in a greater rate of apical periodontitis healing, there was no significant difference compared to that in the other groups at the 1-year follow-up.\u003c/p\u003e \u003cp\u003eFurther studies could be beneficial for analyzing the efficacy of irrigation-agitation techniques in multirooted teeth with curved and complex root canal morphologies. Long-term randomized clinical trials with large sample sizes are necessary to allow more reliable comparisons between results.\u003c/p\u003e"},{"header":"DECLARATIONS","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contribution:\u0026nbsp;\u003c/strong\u003eAll authors reviewed the manuscript\u003c/p\u003e\n\u003cp\u003eMehmet Umutcan Doğan: Writing, Investigation, Original draft preparation.\u003c/p\u003e\n\u003cp\u003eBanu Arıcıoğlu: Supervision, Methodology, Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003eTaha Emre K\u0026ouml;se: Methodology, Conceptualization, Data curation\u003c/p\u003e\n\u003cp\u003eMerve \u0026Ccedil;oban \u0026Ouml;ks\u0026uuml;zer: Review \u0026amp; Editing, Investigation, Original draft preparation.\u003c/p\u003e\n\u003cp\u003eAhter Şanal \u0026Ccedil;ıkman: Supervision, Methodology, Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: No funding was obtained for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u003c/strong\u003e The data used to support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations:\u003c/strong\u003e Local ethics committee approval was obtained from the Ethical Review Committee of the Research Foundation at the Medical Faculty of Recep Tayyip Erdogan University (No: 2023/35). Patients were informed about the procedure, and written informed consent was obtained before the commencement of treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors declare no competing interests.\u003c/p\u003e"},{"header":"REFERENCES","content":"\u003col\u003e\n\u003cli\u003eRicucci, D. and J.F.J.J.o.e. Siqueira Jr, \u003cem\u003eBiofilms and apical periodontitis: study of prevalence and association with clinical and histopathologic findings.\u003c/em\u003e 2010. \u003cstrong\u003e36\u003c/strong\u003e(8): p. 1277-1288.\u003c/li\u003e\n\u003cli\u003ePeters, O.A., K. Sch\u0026ouml;nenberger, and A. 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De Moor, \u003cem\u003eEfficacy of laser-based irrigant activation methods in removing debris from simulated root canal irregularities.\u003c/em\u003e 2015. \u003cstrong\u003e30\u003c/strong\u003e(2): p. 831-835.\u003c/li\u003e\n\u003cli\u003eZhu, X., et al., \u003cem\u003eComparison of the antibacterial effect and smear layer removal using photon-initiated photoacoustic streaming aided irrigation versus a conventional irrigation in single-rooted canals: an in vitro study.\u003c/em\u003e 2013. \u003cstrong\u003e31\u003c/strong\u003e(8): p. 371-377.\u003c/li\u003e\n\u003cli\u003eTurkel, E., et al., \u003cem\u003eComparison of three final irrigation activation techniques: effects on canal cleanness, smear layer removal, and dentinal tubule penetration of two root canal sealers.\u003c/em\u003e 2017. \u003cstrong\u003e35\u003c/strong\u003e(12): p. 672-681.\u003c/li\u003e\n\u003cli\u003eCăpută, P.E., et al., \u003cem\u003eUltrasonic irrigant activation during root canal treatment: a systematic review.\u003c/em\u003e 2019. \u003cstrong\u003e45\u003c/strong\u003e(1): p. 31-44. e13.\u003c/li\u003e\n\u003cli\u003eR\u0026ouml;dig, T., et al., \u003cem\u003eEffect of preparation size on the removal of accumulated hard-tissue debris from the mesial root canal system of mandibular molars using SWEEPS technology.\u003c/em\u003e 2023: p. 1-10.\u003c/li\u003e\n\u003cli\u003eVatanpour, M., et al., \u003cem\u003eComparison of three irrigation methods: SWEEPS, ultrasonic, and traditional irrigation, in smear layer and debris removal abilities in the root canal, beyond the fractured instrument.\u003c/em\u003e 2022. \u003cstrong\u003e37\u003c/strong\u003e: p. 102707.\u003c/li\u003e\n\u003cli\u003eChang, P., et al., \u003cem\u003eA comparison of the thresholding strategies of micro-CT for periodontal bone loss: a pilot study.\u003c/em\u003e 2013. \u003cstrong\u003e42\u003c/strong\u003e(2): p. 66925194.\u003c/li\u003e\n\u003cli\u003eKamburoğlu, K., et al., \u003cem\u003eAccuracy of chemically created periapical lesion measurements using limited cone beam computed tomography.\u003c/em\u003e 2010. \u003cstrong\u003e39\u003c/strong\u003e(2): p. 95-99.\u003c/li\u003e\n\u003cli\u003eLiang, Y.-H., et al., \u003cem\u003eRadiographic healing after a root canal treatment performed in single-rooted teeth with and without ultrasonic activation of the irrigant: a randomized controlled trial.\u003c/em\u003e 2013. \u003cstrong\u003e39\u003c/strong\u003e(10): p. 1218-1225.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"clinical-oral-investigations","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cloi","sideBox":"Learn more about [Clinical Oral Investigations](http://link.springer.com/journal/784)","snPcode":"784","submissionUrl":"https://submission.nature.com/new-submission/784/3","title":"Clinical Oral Investigations","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Irrigation activation, LAI, SWEEPS, PUI, periapical healing, CBCT","lastPublishedDoi":"10.21203/rs.3.rs-4014149/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4014149/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eThe aim of this study was to evaluate the effects of manual dynamic activation (MDA), passive ultrasonic irrigation (PUI), and laser-activated irrigation (shock wave-enhanced emission photoacoustic streaming (SWEEPS)) on the periapical healing of large periapical lesions following nonsurgical root canal treatment.\u003c/p\u003e\u003ch2\u003eMaterials and Methods\u003c/h2\u003e \u003cp\u003eA total of fifty-six systemically healthy patients with a mandibular single-rooted tooth with periapical lesions of endodontic origin and a periapical index score of 3 or higher were included in the study. Before the treatment procedures, lesion volumes were determined volumetrically using cone\u0026ndash;beam computed tomography (CBCT). Patients were randomized into treatment (MDA, PUI, SWEEPS) and control groups (n\u0026thinsp;=\u0026thinsp;14). Root canal treatment and irrigation procedures were performed by a calibrated postgraduate operator and completed at one visit. For routine follow-up, clinical and radiographic evaluations were performed by a blinded evaluator using periapical (PA) radiographs according to Molven's criteria at 3, 6, and 9 months. At 12 months, lesion volumes were quantified volumetrically using CBCT (ITK-SNAP). The data were statistically analyzed with the Wilcoxon test. The significance level was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn all groups, the mean lesion volume after treatment was significantly smaller than the mean volume before treatment (p\u0026thinsp;=\u0026thinsp;0.001). Among the 56 teeth, 11 teeth were \u0026lsquo;totally healed\u0026rsquo;, and 39 teeth were \u0026lsquo;reduced\u0026rsquo; on PA radiographs. No \u0026lsquo;enlargement\u0026rsquo; was detected in any group. On CBCT, the lesion volume decreased in the following order: LAI-SWEEPS (86.9%)\u0026thinsp;\u0026gt;\u0026thinsp;PUI (85.4%)\u0026thinsp;\u0026gt;\u0026thinsp;MDA (80.4%)\u0026thinsp;\u0026gt;\u0026thinsp;control (74.5%), with no statistically significant difference (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eDespite the limitations of the present study, although a greater percentage of healing was observed in the LAI-SWEEPS and PUI groups, irrigation procedures had no statistically significant effect on the healing of periapical lesions with a single root canal at the 12-month follow-up. On the other hand, the outcome may change in multirooted teeth with curved and complex root canal systems.\u003c/p\u003e\u003ch2\u003eClinical Relevance:\u003c/h2\u003e \u003cp\u003eIn the short term and in single-canal teeth, advanced irrigation agitation methods such as laser and ultrasonic did not make a difference in healing other than manual irrigation agitation.\u003c/p\u003e","manuscriptTitle":"Association between the Irrigation-Agitation Techniques and Periapical Healing of Large Periapical Lesions: A Randomized Controlled Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-12 20:02:17","doi":"10.21203/rs.3.rs-4014149/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-05-06T21:58:47+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-01T16:46:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"b7b328fd-60bb-423f-a580-499745e036e1","date":"2024-03-17T23:44:35+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-03-11T21:46:15+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-03-08T05:20:02+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-03-08T05:20:01+00:00","index":"","fulltext":""},{"type":"submitted","content":"Clinical Oral Investigations","date":"2024-03-04T17:47:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"clinical-oral-investigations","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cloi","sideBox":"Learn more about [Clinical Oral Investigations](http://link.springer.com/journal/784)","snPcode":"784","submissionUrl":"https://submission.nature.com/new-submission/784/3","title":"Clinical Oral Investigations","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"04139b06-43ea-440d-99a6-23face3c4b94","owner":[],"postedDate":"March 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-06-21T14:57:32+00:00","versionOfRecord":{"articleIdentity":"rs-4014149","link":"https://doi.org/10.1007/s00784-024-05758-4","journal":{"identity":"clinical-oral-investigations","isVorOnly":false,"title":"Clinical Oral Investigations"},"publishedOn":"2024-06-15 14:57:31","publishedOnDateReadable":"June 15th, 2024"},"versionCreatedAt":"2024-03-12 20:02:17","video":"","vorDoi":"10.1007/s00784-024-05758-4","vorDoiUrl":"https://doi.org/10.1007/s00784-024-05758-4","workflowStages":[]},"version":"v1","identity":"rs-4014149","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4014149","identity":"rs-4014149","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}