Dentistry, Faculty of
DSpace
UBCV
Awn, Sarah Mustafa
Master of Science - MSc
University of British Columbia
Objectives: Endodontic microsurgery (EMS) is a treatment modality indicated when conventional endodontic treatment and nonsurgical retreatment fail to eradicate periapical pathology or when a biopsy is required. Certain factors are associated with the prognosis of EMS and the outcome predictors. This study aimed to (i) assess the level of EMS success; (ii) examine the association between the two radiographic methods (CBCT and PA) used and the EMS outcome; and (iii) investigate the associations between each prognostic factor and the success of the EMS outcomes obtained based on information gained from the periapical radiographs (PA) and cone beam computed tomography (CBCT) scans. Methods: Fifty-one patients (78 teeth) who received EMS at the University of British Columbia (UBC) between 2010-2021 were included. Clinical and radiographic examinations assessed the long-term treatment outcome and its potential determinants. Different prognostic factors were collected retrospectively and prospectively. Two calibrated Endodontists assessed the radiographic healing outcomes (success, failure, and survival) using PA and CBCT indices. The analyzed prognostic factors were age, gender, tooth location, tooth type, medical condition(s), quality of the coronal restoration, preoperative pulpal diagnosis, preoperative periapical diagnosis, presence of preoperative clinical symptoms, quality of RCT, untreated anatomy, maxillary sinus perforation, retro-filling material, biopsy, grafting, and sequence of the treatment. Univariate, bivariate, and logistic regression analyses were used to determine the prognostic factors affecting the EMS outcomes. Results: The survival rate was 91.02%. The success rate was 80.8% using CBCT and 83.3% using PA when cases with vertical root fracture (VRF) were included; and 82.9% using CBCT, and 85.5% using PA when VRF cases were excluded. The inter-examiner agreement was almost perfect using CBCT, and moderate agreement using PA (P<0.001). Conclusions: EMS outcome was predictable, with a high success rate based on the two radiographic methods. The success rate appeared slightly lower when CBCT was used to evaluate the outcome. Owing to the fact that CBCT has higher sensitivity and specificity to assess a three-dimensional object than PA. The preoperative periapical diagnosis significantly predicted the EMS outcome. Grafting was noted as an effect modifier. Age and biopsy had confounded results; therefore, further investigation is recommended.
OUTCOME ANALYSIS OF ENDODONTIC MICROSURGERY IN UBC’S GRADUATE ENDODONTICS PROGRAM by Sarah Mustafa Awn BDS, Batterjee Medical College for science and technology, 2014 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Craniofacial Science) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) May 2023 Ó Sarah Mustafa Awn, 2023 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the thesis entitled: Outcome analysis of Endodontic Microsurgery in UBC’s Graduate Endodontic program submitted by Sarah Mustafa Awn in partial fulfilment of the requirements for the degree of Master of Science in Craniofacial Science Examining Committee: Dr. Ya Shen, Professor, Department of Oral Biological & Medical Sciences, UBC. Supervisor Dr. Markus Haapasalo, Professor, Department of Oral Biological & Medical Sciences, UBC. Supervisory Committee Member Dr. Ahmed Hieawy, Associate Professor, Department of Oral Biological & Medical Sciences, UBC. Supervisory Committee Member Dr. Edwin H.K.Yen, Professor, Department of Oral Biological & Medical Sciences, UBC. Additional Examiner iii Abstract Objectives: Endodontic microsurgery (EMS) is a treatment modality indicated when conventional endodontic treatment and nonsurgical retreatment fail to eradicate periapical pathology or when a biopsy is required. Certain factors are associated with the prognosis of EMS and the outcome predictors. This study aimed to (i) assess the level of EMS success; (ii) examine the association between the two radiographic methods (CBCT and PA) used and the EMS outcome; and (iii) investigate the associations between each prognostic factor and the success of the EMS outcomes obtained based on information gained from the periapical radiographs (PA) and cone beam computed tomography (CBCT) scans. Methods: Fifty-one patients (78 teeth) who received EMS at the University of British Columbia (UBC) between 2010-2021 were included. Clinical and radiographic examinations assessed the long-term treatment outcome and its potential determinants. Different prognostic factors were collected retrospectively and prospectively. Two calibrated Endodontists assessed the radiographic healing outcomes (success, failure, and survival) using PA and CBCT indices. The analyzed prognostic factors were age, gender, tooth location, tooth type, medical condition(s), quality of the coronal restoration, preoperative pulpal diagnosis, preoperative periapical diagnosis, presence of preoperative clinical symptoms, quality of RCT, untreated anatomy, maxillary sinus perforation, retro-filling material, biopsy, grafting, and sequence of the treatment. Univariate, bivariate, and logistic regression analyses were used to determine the prognostic factors affecting the EMS outcomes. iv Results: The survival rate was 91.02%. The success rate was 80.8% using CBCT and 83.3% using PA when cases with vertical root fracture (VRF) were included; and 82.9% using CBCT, and 85.5% using PA when VRF cases were excluded. The inter-examiner agreement was almost perfect using CBCT, and moderate agreement using PA (P<0.001). Conclusions: EMS outcome was predictable, with a high success rate based on the two radiographic methods. The success rate appeared slightly lower when CBCT was used to evaluate the outcome. Owing to the fact that CBCT has higher sensitivity and specificity to assess a three-dimensional object than PA. The preoperative periapical diagnosis significantly predicted the EMS outcome. Grafting was noted as an effect modifier. Age and biopsy had confounded results; therefore, further investigation is recommended. v Lay Summary Endodontic microsurgery (EMS) is an essential surgical treatment modality indicated when conventional endodontic treatment and nonsurgical retreatment fail to eradicate periapical pathology. This surgical intervention aids in direct access to the apical portion of a root and adherent soft tissues, removal of periapical pathosis and biopsy when possible. As the expected outcome for EMS is predictable, this treatment modality should be considered for saving the natural tooth when feasible. Therefore, this study aimed to analyze and correlate the impact of the selected prognostic factors on the EMS outcome during a specified period (2010-2021) at UBC's Grad Endo clinic; to analyze and compare the EMS outcome based on the periapical (PA) and cone-beam computed tomography (CBCT) radiographs. Based on both radiographic methods, PA radiographs and CBCT scans concluded that the biopsy result, the preoperative periapical diagnosis, and the bone graft could significantly impact the EMS's success. vi Preface The present study was approved by the University of British Columbia’s Clinical Research Ethics Board (Certificate H12-02430). This thesis was completed by Dr. Sarah Mustafa Awn, as per the requirements of a Master of Science in Craniofacial Science with a Diploma in Endodontics. Dr. Awn was responsible for the research's ethical application, data collection, analysis, and thesis writing. Dr. Awn prepared the research questions and study design with the assistance of her supervisor, Dr. Ya Shen. Dr. Awn performed the statistical analysis, interpretation of the collected data and the results with consultation and revision provided by Dr. Abdulelah Sindi. The thesis composition was carried out entirely by Dr. Awn, with editing by Dr. Ahmed Hieawy and under the supervision of Dr. Ya Shen. The committee members, Dr. Ahmed Hieawy and Dr. Markus Haapasalo contributed by reviewing the thesis. The relative contribution to this research project by Dr. Awn was 85%. vii Table of Contents Abstract ......................................................................................................................................... iii Lay Summary ................................................................................................................................ v Preface ........................................................................................................................................... vi Table of Contents ........................................................................................................................ vii List of Tables ................................................................................................................................. x List of Figures ............................................................................................................................... xi List of Abbreviations .................................................................................................................. xii Acknowledgments ...................................................................................................................... xiii Dedication .................................................................................................................................... xv Chapter 1: Introduction ............................................................................................................... 1 1.1 Etiology of apical periodontitis ............................................................................................. 1 1.2 Outcomes of primary root canal treatments .......................................................................... 2 1.3 The objective of root canal treatments .................................................................................. 3 1.4 Root canal infections ............................................................................................................. 3 1.5 Microorganisms in root canal infections ............................................................................... 4 1.5.1 Enterococcus faecalis ...................................................................................................... 5 1.5.2 Contributing factors to root canal failure ........................................................................ 5 1.6 Retreatment outcomes ........................................................................................................... 7 1.7 Saving the natural tooth vs implant replacement ................................................................... 7 viii 1.8 Endodontic microsurgery (EMS) .......................................................................................... 8 1.8.1 Indications and rationale for endodontic microsurgery .................................................. 9 1.9 Traditional root-end surgery (TRS) vs Modern endodontic microsurgery (EMS) .............. 10 1.9.1 Magnification ................................................................................................................ 10 1.9.2 Osteotomy ..................................................................................................................... 10 1.9.3 Root-end resections ....................................................................................................... 11 1.9.4 Root-end (Retro) preparations ...................................................................................... 11 1.9.5 Root-end (Retro) fillings ............................................................................................... 12 1.10 Endodontic microsurgery outcomes .................................................................................. 12 1.11 Follow-up .......................................................................................................................... 13 Chapter 2: Hypotheses and objectives ...................................................................................... 15 2.1 Rationale .............................................................................................................................. 15 2.2 Specific aim(s) ..................................................................................................................... 16 2. 3 Study hypothesis ................................................................................................................. 16 2.4 Study objectives .................................................................................................................. 17 Chapter 3: Materials and methods ............................................................................................ 18 3.1 Study design ........................................................................................................................ 18 3.2 Sample selection .................................................................................................................. 18 3.3 Inclusion and exclusion criteria: .......................................................................................... 20 3.4 Data collection ..................................................................................................................... 21 ix 3.5 Treatment planning and surgical procedures ....................................................................... 24 3.6 Outcome assessment ............................................................................................................ 25 3.6.1 Clinical assessment ....................................................................................................... 25 3.6.2 Radiographic assessment I (PA) ................................................................................... 25 3.6.3 Radiographic assessment II (CBCT) ............................................................................ 27 3.6.4 Radiographic assessment examples .............................................................................. 28 3.7 Examiners, examination process, and final assessment. ..................................................... 31 3.9 Statistical analysis ............................................................................................................... 33 Chapter 4: Results ....................................................................................................................... 35 4.2 Descriptive retrospective analysis for endodontically treated teeth .................................... 36 4.3 Descriptive prospective analysis for endodontically treated teeth based on CBCT and PA indices. ....................................................................................................................................... 38 Chapter 5: Discussion ................................................................................................................. 53 5.1 Study significance ............................................................................................................... 53 5.2 Major findings ..................................................................................................................... 53 5.3 Limitations ...................................................................................................................... 63 5.4 Future directions ............................................................................................................. 64 Chapter 6: Conclusions .............................................................................................................. 65 Bibliography ................................................................................................................................ 66 x List of Tables Table 1. Periapical service codes, meaning, and number of cases found. .................................... 19 Table 2. Illustrates the inclusion and exclusion criteria ................................................................ 20 Table 3. CBCT scoring system based on Chen et al. indices (86). ............................................... 27 Table 4. The definition of “success,” “failure,” and “survival” for outcomes. ............................. 32 Table 5. Descriptive data according to the tooth’s location and type. .......................................... 36 Table 6. Descriptive data of the prognostic factors. ..................................................................... 37 Table 7. Descriptive data for the sequence of the treatment. ........................................................ 38 Table 8. Treatment outcomes based on CBCT and PA indices I. ................................................. 39 Table 9. Treatment outcomes were based on CBCT and PA indices II. ...................................... 39 Table 10. Description of the radiographic findings after follow-up. ............................................ 40 Table 11. The association between the two radiographic methods and EMS outcomes I. ........... 41 Table 12. The association between the two radiographic methods and EMS outcomes II. ........ 42 Table 13. Association between the prognostic factors and radiographic outcomes using CBCT scans. ............................................................................................................................................. 44 Table 14. Association between the prognostic factors and radiographic outcome using PA radiographs. ................................................................................................................................... 48 Table 15. Results of the healing assessment for each examiner based on the CBCT indices. ..... 50 Table 16. Results of the healing assessment for each examiner based on the PA index. ............. 51 Table 17. : Inter-examiner agreement. .......................................................................................... 51 xi List of Figures Figure 1. Flow chart of patient sampling. ..................................................................................... 21 Figure 2. An example of the PowerPoint slides for the PA (2D) radiographic assessments. ....... 26 Figure 3. Illustrations of Molven et al. PA index for the healing assessment (83). ..................... 26 Figure 4. An example of the PowerPoint slides for the CBCT (3D) radiographic assessment. ... 27 Figure 5. Illustrations of Chen et al. CBCT indices for EMS healing assessment using CBCT. . 28 Figure 6. Radiographs (a-d) for a case with complete healing and a score of 6. .......................... 29 Figure 7. Radiographs (a-d) for a case with incomplete healing and a score of 5. ....................... 29 Figure 8. Radiographs (a-d) for a case with incomplete healing and a score of 4. ....................... 30 Figure 9. Radiographs (a-d) for a case with uncertain healing and a score of 3. .......................... 30 Figure 10. Radiographs (a-d) for a case with unsatisfactory healing with a score of 2. ............... 30 Figure 11. Radiographs (a-d) for a case with unsatisfactory healing and a score of 1. ................ 31 Figure 12. Radiographs (a-d) for a case with unsatisfactory healing and a score of 0. ................ 31 Figure 13. Participants’ health status, including types of medical condition(s). .......................... 36 xii List of Abbreviations % Percentage 2D Two dimensional 3D Three dimensional A Apica area C Cortical plate CBCT Cone-beam computed tomography E. faecalis Enterococcus faecalis EMS Endodontic microsurgery GE Graduate Endodontics MTA Mineral trioxide aggregates n number of teeth P Significance PA Periapical radiograph PARL Periapical radiolucency R Resection plane SPSS Statistical Package for the Social Sciences TRS Tradional root-end resection UBC University of British Columbia UBC University of British Columbia VRF Vertical root fracture ZOE Zinc oxide eugenol xiii Acknowledgments I have to start by thanking my research supervisor, Dr. Ya Shen. As my research supervisor, Dr. Shen was always available to answer my questions. Dr. Shen, completing this study under your supervision has been an absolute privilege. I cannot thank you enough for all your encouragement and support and for sharing your vast expertise and knowledge with me. Thank you for being a great role model and an amazing mentor. Dr. Markus Haapasalo, having you as a committee member was a great honour. Thank you for your continued support and gentle feedback throughout this research. To Dr. Abdulelah Sindi, I would like to extend my deepest gratitude. Thank you for your support, guidance, enthusiasm, and patience throughout the development of this project. I would like to express my sincere gratitude to Dr. Ahmed Hieawy, who is known for his passion for helping his students. I appreciate your thoughtful guidance throughout this journey. Thank you for always keeping your door open for any questions at any time. Dr. Mahmoud Ektefaie, thank you for making Friday our favourite day of the week, a day where we get challenged clinically and theoretically and learn the most from all aspects of dentistry. A day that we look forward to from the beginning of the week. xiv I am eternally grateful to my director, Dr. Jeffery Coil, for allowing me to join the UBC Graduate Endodontics family. I admire your humanity, your sense of humour, and how you always push and encourage us to work toward our dreams. Thank you for teaching us how to be human before becoming an endodontist. I would also like to further express my thanks to all my clinical instructors for their continued support and feedback, helping me to become a better clinician throughout the program. Last but not least, I would like to thank our CDAs, Shauna, Lois, and Francisco, for their continued daily support throughout the years. My co-residents, thank you for being a part of this journey. xv Dedication To my mom and dad, Najah and Mustafa, who have gone above and beyond in every chapter of my life. Who have embraced and supported my decisions to pursue my plans. Who believed in me throughout my career with unconditional love. Also, who taught me how to deal with people and flip pages to the next chapter and move on. To my small family in Vancouver, my siblings who lived with me throughout this journey, Walaa and Abdullah. Walaa, my little sister and best friend, always stood by me during my ups and downs with unconditional love and support. To my little brother, Abdullah, thank you for your continuous support throughout my journey. Thank you for always being there supporting your family. To my superheroes, my elder siblings, Neveen and Taha. Neveen, you are always our idol. Thank you for being not only our elder sister but also our second mother. Thank you for backing up our decisions. Thank you for always being generous with love and support. Taha, my elder brother, you know how much I love you. Thank you for believing in me. Thank you for your thoughtful advice and support over a long distance. To my Canadian mother, Viki, I do not have enough words to thank you for always being there during my ups and downs. Thank you for being constantly on my side and for being a mother figure for me in Canada. xvi To Dr. Ainaa Alsharif, my soulmate who can instantly know what I’m going through without saying a word. Thank you for your unconditional friendship and love. Thank you for always being there when I needed you. To Dr. Abduelah Sindi, my brother, I have no words to express my gratitude. Thank you for being a role model and for your guidance, timely support, and all the hours you have spent working on this project with me, explaining every aspect of Endodontics along the way. Dr. Mohsen Daghustani and Dr. Raif Marqoshi, you are the ones who taught me the essential information and skills that I needed to start my career and encouraged me to pursue my career in this specialty. Dr. Mohsen Daghustani, you were the very first Endodontic instructor I have ever met. You taught us with love, care and enthusiasm. With all the difficulties and complications in Endododnics, you made it sound easy and understandable. Without you, I wouldn't have been who I am today. To every member of my family and my overseas friends who joined me and supported me on my journey, even over great distances, with tremendous love and support. As promised, I will make you all endlessly proud since you believed in me. I’m so grateful for all the unconditional love and support I had throughout my journey. Family and friends, I would not have been as strong without you. My dreams are coming true, one after the other, and this is just the beginning of a bright future ahead. 1 Chapter 1: Introduction 1.1 Etiology of apical periodontitis Apical periodontitis is defined as a host-induced inflammation with rapid periapical tissue destruction that is secondary to a bacterial infection in the root canal system (1). Rickert and Dixon stated that the hollow tube theory is the reason behind the inflammation that occurs in pulpal and periapical spaces (2). This theory is defined as an empty space in the living organism that tends to be filled with tissue fluids in a short period of time. This definition was based on an observational animal experiment, where hollow tubes of platinum and steel hypodermic needles were inserted in connective tissues, and the tissues were examined macroscopically after specific periods of time. A large halo of irritation was seen around the inserted tubes but not in the middle, and the tubes were tolerated without irritation. Severe inflammation was observed at the ends of the tubes, and they concluded that circulatory elements seeped into the tubes, then stagnated, broke down, and released toxins causing inflammation. This was the start of the "Hollow Tube Theory" (2). The association between microorganisms and the etiology of periapical infection has been investigated for several decades. In a classic study that was done on germ-free rats, it wasn determined that bacterial presence is the main reason for apical periodontitis (3). Kakehashi et al. was the first to mention that apical periodontitis is caused by microorganisms and their by-products (3). Furthermore, Torneck concluded that when a root canal system has been thoroughly cleaned and adequately disinfected, even if the system was underfilled, no tissue reaction was seen. This would likely result in a normal capacity for healing of the surrounding 2 periapical tissue. He disproved the hollow tube theory (4). later on, Torneck has remarked that the prognosis for repair and healing capacity is least favourable in the presence of microorganisms. He also confirmed Kakehashi’s conclusion which stated that bacteria and their by-products influence the healing of apical tissues (5). Several studies proved that, bacteria were found to be responsible for the periapical destruction (3, 6). Also, it has been found that the number and combination of certain bacterial strains have an influence on the presence and the size of the periapical destruction (periapical lesion) and the exacerbation of clinical symptoms (4). Thereafter, it was proven that cleaned and shaped root canals must be completely filled, not only to prevent bacterial colonization and the accumulation of tissue fluids, but also to prevent the survival and multiplication of bacteria remaining even after a thorough sterilization procedure with the root canal therapy (5). 1.2 Outcomes of primary root canal treatments Root canal treatment outcomes have a high success rate. The success rate for treatments without periapical radiolucency ranges from 92% to 94%, and with periapical radiolucency it ranges from 74% to 81% (7, 8). Obviously, from the previous outcome studies the success rate never reaches 100%. Even when optimal chemo-mechanical cleaning and shaping of the system is followed, there will be some regions of the system that cannot be disinfected (9). These regions are inaccessible due to the complex anatomy of the root canals, and microbial biofilms are harbored in these inaccessible regions. Therefore, the inability to eliminate those hidden biofilms can lead to an endodontic failure (10). In other words, endodontic failures may occur as a consequence of bacterial persistence in the root canal system due to different etiological factors (1), such as: inadequate aseptic control, poor access cavity design, untreated canals, inadequate instrumentation, 3 inadequate debridement and leaking temporary or permanent restorations(11), a complex root canal morphology (12, 13), and the possibility of endodontic complications (14). 1.3 The objective of root canal treatments The main objective of a root canal treatment is to eliminate or heal apical periodontitis (15). This can be achieved by reducing the microbial load in the system using chemo-mechanical disinfection (16). Complete bacterial elimination and sterilization of the root canal system is almost impossible duo to the diversity of the bacterial species and the complexity of the system (12, 13). Thus, this can lead to a secondary infection (17). 1.4 Root canal infections As discussed earlier, bacteria are the main reason behind root canal infections (3); therefore, the main goal of a root canal treatment is to remove all microorganism from the infected system. Different environmental factors have an influence on the microorganisms present inside the root canal system, such as: amount and type of nutrients, bacterial interaction, and level of oxygen tension (18). In the early stage of the primary infection, facultative bacteria are dominant. With time, when the level of oxygen inside the system is reduced due to the depletion of pulp tissue, the obligate anaerobic bacteria start to grow. Then, the anerobic bacteria and their by-products colonize the root canal system, and anaerobes become dominant (19, 20). As the apical part of root canals are the most favourable region for bacteria to hide in and colonize, the bacteria can survive due to the inability to access these regions during endodontic treatments. As such, the endodontic treatment fails (1, 6) due to steadfast microorganisms (17); this is known as a 4 persistent infection. If bacteria is introduced during the root canal treatment steps or leakage through the restoration, this can lead to a secondary infection (21). 1.5 Microorganisms in root canal infections Studies show that there are a greater number of species in primary root canal infections (22) when compared with secondary infections (23). Primary root canal infections have an equal mix of Gram-negative and Gram-positive bacteria and mostly obligate anaerobes. A primary infection consists of Gram-negative anaerobic rods, Gram-positive anaerobic cocci, Gram-positive anaerobic and facultative rods, Lactobacillus species, and Gram-positive facultative Streptococcus species (24). The process of the progression of the primary root canal infection from facultative to anerobic species is called the “microbial succession”. This process has been observed to occur when there is a reduction in oxygen inside the system (20). In other words, during the root canal treatment, the system gets exposed to oxygen and this exposure aids in eliminating obligate anaerobic bacteria. Conversely, in the presence of oxygen, the facultative bacteria may switch to fermentation. These bacteria include non-mutans Streptococci, Enterococci, Lactobacilli, and other facultative Gram-positive bacteria, which are found in the secondary infection (25). Moreover, Porphyromonas gingivalis, P. endodontalis, Fusobacterium nucleatum, and Prevotella are gram-negative bacteria which appeared to be associated with persistent infection (26). When these bacteria resist root canal treatment, the treatment becomes more challenging (25); therefore, endodontic treatment failure occurs due to persistent microorganisms (17). 5 1.5.1 Enterococcus faecalis Enterococcus faecalis (E. faecalis) has been found to be associated with failed endodontic treatments or recurrent infections (25, 27, 28). It has also been concluded that E. faecalis is found to be nine times more likely to be associated with failed endodontic treatments than bacteria in primary infections (23). Also, studies show that E. faecalis makes the endodontic treatment more challenging, as it has been shown to have resistance to intracanal medicaments (29-31) and can survive by itself as a monoculture or as a major component of the flora (19, 32). Moreover, these bacterial cells can survive after the endodontic treatment, as they have the ability to invade the dentinal tubules even after the endodontic treatment, and re-infect and re-colonize the root canal system (30, 31, 33). 1.5.2 Contributing factors to root canal failure After having explained above that bacteria are the cause of primary infections, in this section we will discuss the cause of secondary infections. There are six biological factors that contribute to the failure of root canal treatments (34): 1. Persistence of intraradicular infection in the complex apical root canal system that has not been eliminated. Due to the complexity of the system and the inability to properly clean the areas where the accessory canals branch or their anastomoses (34). 6 2. Extraradicular infection, generally in the form of periapical actinomycosis. The most common gram-positive species isolated from the extraradicular area in humans are Actinomyces israelii (34), and Pseudopropionibacterium propionicum (35). In addition, Tannerella Forsythia is a gram-negative bacteria found as a key species in extraradicular infections (26). 3. Extruded root canal fillings or other exogenous materials that cause foreign body reactions. Delayed healing of the periapical area might occur due to extruded gutta-percha (36), endodontic sealer (37, 38), and calcium hydroxide Ca(OH)2 (34). 4. Accumulation of cholesterol crystals that irritate periapical tissues. Crystals are believed to be formed from cholesterol released by disintegrating erythrocytes, lymphocytes, and circulating plasma lipids. The major source of this cholesterol results from the disintegrating cells in long-standing lesions. 5. True cystic lesions. True cystic lesions are self-sustaining and independent of the absence or presence of irritants from the root canal (39). 6. Scar tissue healing of the lesion. Moreover, scar tissue healing of a lesion (40-43), which looks like unresolved periapical radiolucency, may be misdiagnosed as a radiographic sign of failed endodontic treatment. 7 1.6 Retreatment outcomes Non-surgical root canal retreatment is always the line of treatment if the tooth is deemed to be savable. Sundqvist et al. reported that the overall success rate for a non-surgical root canal treatment among cases with persistent periapical lesions is 75% (11). Another study reported different success rates for cases with and without periapical lesion and it was 78% and 97%, respectively (8). Therefore, for cases of asymptomatic persistent periapical radiolucencies, clinicians should consider the necessity of removing the extraradicular factors through apical surgery (44). 1.7 Saving the natural tooth vs implant replacement Endodontic treatment is always the first line of therapy when a tooth is deemed restorable. Whereas, when a tooth is not savable, then extraction and an implant should be considered. Each treatment modality has different purposes; endodontic treatment aims to prevent or heal apical periodontitis, whereas implants aim to replace a missing tooth (45). Generally, two eras of extractions have been reported. The first era occurred when focal infection theory suggested that any tooth with an endodontic problem must be extracted to avoid transmission of infection to other parts of the body (46). The second era started in the second millennium where it has been suggested that having an implant as a replacement of the natural tooth is an option (47). Several studies reported that the survival of an endodontically treated tooth is comparable to that of implant success, with significant postoperative complications associated with the implant placement (48-50). 8 In view of the fact that when non-surgical root canal treatments fail, a variety of different treatment options will be valid, such as non-surgical root canal retreatment or surgery which is associated with bone preservation/regeneration at the surgical site (45). On the other hand, dental implants have a physiological annual level of bone loss at the implant-bone interface which is generally expected to be 0.2 mm (51, 52). Therefore, when an implant fails, extraction will be the next treatment option, along with a significant amount of bone loss in the area associated with this failure (45). Other drawbacks associated with an implant placement, besides the annual bone loss, are lack of proprioception and esthetics when placed in the anterior regions. There was also the discovery of a significant amount of malpractice claims associated with implant placements (45). Therefore, saving the natural tooth—through endodontic retreatment and/or endodontic microsurgery (EMS)—is a better treatment option, which gives the patient an opportunity to save their natural teeth in a healthy state before considering extraction and implant replacement.(45) It is mistaken to think that extracting a restorable tooth and replacing it with an implant is better than performing an endodontic treatment (45). 1.8 Endodontic microsurgery (EMS) Endodontic microsurgery is a precise surgical procedure with an operating microscope for small and complex systems. This procedure allows the surgeon to evaluate the periapical changes and biopsy the pathological lesions accurately (53). 9 1.8.1 Indications and rationale for endodontic microsurgery I. According to Gutmann & Harrison (44) • Resorptive tissue removal. • Removal of complex anatomy such as: apical delta or accessory canals. • Removal of procedural error such as perforations, separated instruments, ledges, blockages, zips. • Apical seal assessment. • Apical seal creation. • Access to diseased tissue located lingually or palatally to the tooth. • When the root canal system is inaccessible such as: blocked canals with post and core. • Correction of fenestrated root apices within a healthy bone housing. • Removal of periapical pathosis and biopsy, when possible. II. According to the European Society of Endodontology (54) • When the canals are obstructed radiographically with/or a clinical symptoms. • When there are extruded materials associated with radiographic findings and/or clinical symptoms. • When the nonsurgical treatment fails, and the nonsurgical retreatment would not achieve a better result. • When there is perforation associated with radiographic findings and/or clinical symptoms and impossible to repair internally. 10 The surgical procedure was first described by removing the roughened root end and associated periodontal tissues, and smoothening, burnishing, and filing the root end using a bur (55). Then, the introduction of the modern endodontic surgery era began in the 19th century by using the operatory dental microscope, micro-instruments, ultrasonic tips, and biocompatible retro-filling materials which resulted in favorable long-term outcomes (53, 56). Therefore, the different between the traditional root-end surgery (TRS) and the modern endodontic microsurgery (EMS) will be discussed. 1.9 Traditional root-end surgery (TRS) vs Modern endodontic microsurgery (EMS) 1.9.1 Magnification Traditionally, limited or no magnification was used (53). However, in modern EMS the use of proper magnification and illumination helped with the following: i) identifying and managing the small and important anatomical details, ii) root integrity can be examined with great precision, iii) precise removal of granulation tissues, iv) the bone and root tip can be easily distinguished, v) the osteotomy size can be smaller, vi) operator’s stress is significantly reduced, and vii) digital documentation of procedures can be used for educational purposes (56-58). 1.9.2 Osteotomy Traditionally, the osteotomy size was approximately 8 to 10 mm (53). However, in modern EMS the osteotomy size is significantly smaller, around 3 to 4 mm in diameter, when compared with the traditional method (57, 58). The size of the osteotomy should be just larger than an ultrasonic tip of 3 mm in length, to allow the ultrasonic tip to vibrate freely within the bone cavity (53). Furthermore, the size of the osteotomy should be as small as possible, but as large as necessary 11 to accomplish the clinical objective. Also, the smaller the osteotomy size, the faster the healing, the better outcome (59). 1.9.3 Root-end resections Traditionally, a steep bevel angle of 45° to 60° using a rotary bur (44, 60-62) and large surgical instruments were recommended. Beveling was only justified for the convenience of the surgeon (63, 64). In modern EMS, the most appropriate angle for a root-end resection is perpendicular, with a bevel of 0° to 10° to the long axis of the tooth. It has been concluded that as the angle of the bevel increases, the apical leakage will increase (65). Also, it is recommended to resection at least 3 mm, as this is most likely to include the majority of the apical ramifications and lateral canals (63) which result in a better outcome. 1.9.4 Root-end (Retro) preparations Traditionally, retro-preparations were done using a bur, which was seldom inside the canal (53). More modern techniques now use ultrasonic tips, which are always inside the root canal system and produce parallel walls, deeper preparation, and cleaner walls (66). The advantages of using ultrasonic retro-preparation are that it gives superior operator control and decreases the risk of perforation by increasing the ability to stay centered in the canal when using ultrasonic retro-tips compared with a micro-handpiece (53). The most recent developments involve zirconium coated and diamond coated tips. Diamonds adhere to the surface of the tips resulting in a slightly larger diameter, whereas zirconium nitride is processed into the metal making the tip narrower. The diamond coated tips are more effective in removing gutta-percha (53), thus, resulting in better outcomes. 12 1.9.5 Root-end (Retro) fillings Traditionally, products containing amalgam and zinc oxide (ZOE) (e.g. SuperEBA and IRM) were used as root-end filling materials (67-70). More modern material is being used such as calcium silicate materials, which is commercially refered to as mineral trioxide aggregates (MTA). It was first made commercially available in 1999 as a ProRoot MTA (Dentsply Sirona, Charlotte, NC, USA)(71). MTA is biocompatible, prevents microleakage, and has the ability to regenerate original tissues when it comes into contact with vital tissues around the periapical area (72). Therefore, MTA has gained popularity among endodontists (72-75), resulting in better outcomes. 1.10 Endodontic microsurgery outcomes Surgery is more convenient and precise with the aid of magnification and illumination, as this is a valid approach to invest in maintaining natural teeth with a high success rate. The probability of success for EMS (94%) proved significantly greater than the probability of success for TRS (59%). This demonstrates the evolution of the modern EMS , such as the involvement of bone cutting burs (vs. standard size surgical burs), smaller osteotomy size, less bevelled angles, root-end preparation with ultrasonic tips, direction of preparation, root-end filling material, and higher power magnification. Lastly, Kim et al. found a higher success rate in cases that were not periodontally involved (95.2% vs. 77.5%) (76). Generally, it is important to study prognosis and treatment outcomes in order to select the right cases for performing periapical surgery. The differences in outcome reports are due to considering different factors such as the tooth location, number of roots, sample size, case 13 selection criteria, initial root canal treatment or retreatment, treatment providers, root end material used, pre-and post-operative restoration, study design and availability of data, recall rate, interpretation of radiographs, follow-up period, the unit of evaluation, and outcome assessment criteria (77, 78). Moreover, a prospective observational cohort study assessing 4-8-year outcomes concluded that 91% of teeth were asymptomatic, and 74% were healed (78). Moreover, 84% were healed and 94% stayed functional when the follow-up was 4-10 years (77). A systematic review and meta-analysis concluded that the probability of endodontic microsurgery success is significantly higher than for the TRS. This review indicated 94% apical periodontitis healing after EMS. This proves what can be achieved when the modern technique is followed, including proper magnification (microscopy) and illumination, root end preparation with ultrasonic tips, and MTA as a retro-filling material. Based on the results from this meta-analysis, it has been recommended that the use of TRS should not be considered anymore (79). In summary, the expected outcome for apical surgery is good. Therefore, before considering tooth extraction and replacement, apical surgery should be attempted when feasible. 1.11 Follow-up Studies show that a 1-year follow-up overestimates the long-term outcome (80). Also, it has been reported that there is a chance for the disease to re-occur in 5-25% of the healed cases within the 4-year follow-up window after treatment (81, 82). Therefore, it has been suggested (60) that an extension from a 1-year to a 4-year follow-up for some cases with uncertain healing is required based on Molven et al.’s (83) radiographic healing indices. 14 For instance, a study showed that some of the cases with uncertain healing at the 1-year follow-up changed at the long-term follow-up, to complete or incomplete healing. Also, some of those with unsatisfactory healing at the short-term follow-up presented as failed cases at the long-term follow-up (80). Another study has recommended that further treatment should be considered when the healing is still uncertain at the 4-year follow-up (60). Therefore, the standard recommendation for all endodontic treatments is a minimum follow-up time of 1-year to measure the endodontic treatment outcome; based on that, additional follow-ups could be required for an accurate outcome assessment (84). 15 Chapter 2: Hypotheses and objectives 2.1 Rationale Bacteria are the main reason for apical periodontitis (3). Which by itself represent the host-induced inflammation with rapid periapical tissue destruction (1). Therefore, root canal treatment aims to eliminate or heal this condition (15). Complete bacterial elimination is impossible for different reasons (12, 13), which can result in a secondary infection (17). Therefore, further treatment will be indicated, such as endodontic microsurgery (46). Modern endodontic microsurgery has promising outcomes compared to traditional root-end surgery (77). There are differences in the treatment outcomes based on the prognostic factors that have been studied and on the radiographic assessment tool that has been used. To the best of our knowledge, none of the previous studies have investigated the association between each prognostic factor and the success of EMS using the periapical radiographs (PA) and cone beam computed tomography (CBCT) scans independently. 16 2.2 Specific aim(s) I. To assess the outcome of EMS performed in the Graduate Endodontics (GE) program at UBC during the years 2010-2021. II. To examine the association between the two radiographic methods (CBCT and PA) used and the EMS outcome. III. To investigate the associations between each prognostic factor and the success of the EMS outcomes obtained based on information gained from the periapical radiographs (PA) and cone beam computed tomography (CBCT) scans. 2. 3 Study hypothesis H1. The EMS outcome in the UBC's GE program is successful. H2. The outcome obtained using cone-beam computed tomography (CBCT) scans has higher sensitivity and specificity when compared to periapical (PA) radiographs. H3. The prognostic factors are associated with the outcome of endodontic microsurgery using CBCT scans. H4. The prognostic factors are associated with the outcome of endodontic microsurgery using the PA radiographs. 17 2.4 Study objectives To assess the aforementioned hypotheses, the study objectives were as follows: Objective 1: To identify all patients treated with endodontic microsurgery (EMS) during a specified period (2010-2021) at UBC’s Graduate Endodontic clinic and to review their medical and dental histories. Objective 2: To retrospectively assess the outcome of surgical endodontic treatments performed at UBC’s Graduate Endodontic clinic. Objective 3: To compare the sensitivity and specificity of the cone-beam computed tomography (CBCT) scans with the periapical (PA) radiographs in relation to the EMS outcome. Objective 4: To assess the correlations between the prognostic factors and the EMS outcomes and compare the EMS outcomes using cone-beam computed tomography (CBCT) scans. Objective 5: To assess the correlations between the prognostic factors and the EMS outcomes and compare the EMS outcomes using periapical (PA) radiographs. 18 Chapter 3: Materials and methods 3.1 Study design This was a retropective cohort study. The population of this study included all patients referred to the Graduated Endodontic (GE) clinic (Faculty of Dentistry, The University of British Columbia, Vancouver, Canada) for an endodontic microsurgery between September 2010 and April 2021. The study protocol was approved by the Clinical Research Ethics Board of the University of British Columbia (H21-01250). 3.2 Sample selection Sample selection was conducted through three steps: First, eligible patients’ file records are extracted. UBC’s Faculty of Dentistry uses an electronic platform called Axium (Exan, Portland, Oregon), where all patient’s records for each tooth (e.g., treatment, conditions, notes, etc.) are saved onto the digital platform. All patients who had an EMS in the GE clinic were identified from the general pool of patients in the Axium software. This was done by using a keyword search of 32 different treatment codes that had potentially been used as a billing code in the patients’ charts. Among them, 16 codes were for EMS and the other 16 were for the retro-filling material used. The objective of this step was to collect all charts that included one or more of those codes. This resulted in a total of 296 file records, as seen in (Table 1). 19 Table 1. Periapical service codes, meaning, and number of cases found. Code Meaning Found cases Maxillary Anterior 34111 1 root 84 34311 1 root retreat 6 34112 2 roots 2 Maxillary Bicuspid 34121 1 root 29 34321 1 root retreat 1 34122 2 roots 18 Maxillary Molar 34131 1 root 33 34132 2 roots 34 34133 3 roots 7 Mandibular Anterior 34141 1 root 25 34341 1 root retreat 4 34142 2 or more roots 3 Mandibular Bicuspid 34151 1 root 9 34152 2 roots 1 34153 3 or more roots 0 Mandibular Molar 34161 1 root 20 34162 2 roots 17 34163 3 roots 2 34363 3 roots retreat 1 34164 3 or more roots 0 20 Second, after a unique code was given to each file record (identifiable only by the principal investigator), the 296 file records were individually assessed based on inclusion and exclusion criteria (see Section 3.3). Only 104 files met the inclusion criteria, as seen in (Figure 1). Most of the excluded file records were due to a lack of pre-operative CBCT. Third, patients were contacted to make clinical and radiographical follow-up appointments. There was a high number of non-responses due to several reasons, including patients who had a sign of VRF, changed their phone number or did not answer the phone; the tooth of interest was extracted; they passed away; or they were not interested in attending the follow-up visit. This resulted in a total of 51 patients with 78 teeth. Thus, the response rate in this study was 71%. 3.3 Inclusion and exclusion criteria: The specific inclusion and exclusion criteria for patients in this study are shown in Table 2, and patients’ sampling is explained in Figure 1. Table 2. Illustrates the inclusion and exclusion criteria Inclusion Criteria Exclusion Criteria • Pre-operative CBCT. • All genders • All ages. • All types of teeth • Follow-ups from 1 year up until 11 years • Prior to the EMS: o Signs of apical periodontitis o No mobility o No periodontal disease • Incomplete data (e.g., no pre-operative CBCT). • Tooth had been extracted for restorative reasons (e.g., denture) • Cases with signs of vertical root fracture (VRF). 21 Figure 1. Flow chart of patient sampling. 3.4 Data collection The data for this study were collected in four steps: • First, retrospective data was collected from the patient’s file, which included: o Patient age. o Patient gender. o Tooth location. o Tooth type 22 o Medical condition(s) (e.g., healthy, diabetes mellitus, hypertension, cholesterol, cancer, osteoporosis, lung disease, depression, thyroid disease, or liver disease) o Preoperative pulpal diagnosis (necrotic, irreversible pulpitis, or previously treated). o Preoperative periapical diagnosis (symptomatic apical periodontitis, asymptomatic apical periodontitis, or chronic apical abscess). o Preoperative clinical symptoms (yes or no) o Quality of the coronal restoration (good or poor). o Quality of RCT prior to surgery (adequate or inadequate) o Untreated anatomy (yes or no) o Type of retro-filling material used (ProRoot MTA or root repair material [RRM] putty). o Maxillary sinus perforation (yes or no). o Grafting (Yes/No) o The result of the biopsy, if any (radicular cyst, non-cystic lesion, or no biopsy) o Treatment sequence (e.g., initial RCT + EMS, retreatment + EMS, initial RCT, re-RCT + EMS, EMS only). o Number of months between treatment and follow-up. • Second, retrospective radiographic assessments were conducted, involving: i) The post-operative PA radiograph (representing the 2D assessment) - The quality of the root canal treatment (RCT) before the surgery was assessed according to Tornstad et al. and separated as follows: adequate (when all root canals are obturated within 2 mm of the radiographic apex, with no voids) or inadequate 23 (when the obturation is short/overextended more than 2 mm of the radiographic apex, missing a canal, and poor density)(85). - The quality of the coronal restoration before the EMS was assessed according to Tornstad et al. and separated as follows: good (when the permanent restoration looks intact on the radiograph) or poor (when the permanent restoration has an open margin, overhang, or recurrent decay on the radiograph)(85). - PA: lesion presence/absence and application of the Molven et al. index (83), which is explained below (section 3.6.2). ii) The pre-operative CBCT radiograph (representing the 3D assessment) - CBCT: lesion size and application of the Chen et al. indices (86), which is explained below (section 3.6.3). • Third, prospective data collection was performed for the clinical assessment during follow-up visits, which included palpation, percussion, biting, and periodontal probing. • Fourth, prospective radiographic assessments were conducted, including: o 1) follow-up PA radiographs. o 2) follow-up CBCT radiographs. The third and fourth steps (prospective steps) were done via inviting the patients to come for a follow-up appointment, which had to be at least 1 year after they received the treatment. During the follow-up, UBC’s GE clinic protocol was followed. For optimal evaluation and to control for 24 bias during the PA radiographic follow-up (at the fourth step), two PA radiographs were taken to find the best replica of the exact angle of the post-operative one (on the day of the surgery). All patients had to sign both a UBC consent of care form and a form consenting to participate in this project before the assessment took place. 3.5 Treatment planning and surgical procedures This section provides a description of the standard clinical and radiographic examinations that are done for all cases that required EMS at UBC’s GE clinic, including the cases in this study. It is important to clarify exactly what was done to the patients before we conducted our study. The examination was done by the GE resident before each surgery, using two different angled PA radiographs and a limited field CBCT scan using a 4 cm X 4 cm Veraviewepocs 3D (J Morita, Osaka, Japan). During the consult appointment, different treatment options were proposed to the patients, including either surgical or non-surgical endodontic treatments. The most appropriate intervention for the patients was an EMS, which was recommended by the GE resident and faculty at that visit. All surgical procedures were performed by GE residents using a surgical operating microscope under endodontic faculty supervision. The EMS protocol involved a full-thickness flap reflection, osteotomy to expose the root apices, removal of the peri-radicular pathosis, and biopsy if possible. This was followed by a root-end resection using a high-speed surgical fissure bur with minimal or no bevel, then root-end preparation (retro-preparation) was conducted using ultrasonic instruments. As for the material used during root-end filling (retro-filling), white Pro Root MTA (Dentsply Sirona, Charlotte, NC, USA) or BioCeramic (BC) RRM-Fast Set Putty (Brasseler, Savanna, GA, USA) were used. In cases where a bone graft was 25 indicated/recommended by the supervising faculty, a combination of a freeze-dried allograft (Alloss; ACE surgical supplies, Brockton, MA, USA) bone material with/without a resorbable collagen membrane (conFORM; ACE surgical supplies) was used. The flap margins were then re-approximated, and, intra-operative PA radiographs were taken. Then flap margins were sutured. Post-operative instructions were given pre- and post-operative to the patient, and a follow-up appointment was always booked within two weeks or sooner if the patient had any concerns. 3.6 Outcome assessment The outcome assessment was completed during the follow-up visits based on the clinical and radiographic examination (using both PA and CBCT). 3.6.1 Clinical assessment From the third data collection step, which is the prospective data collection for the clinical assessment during the follow-up visits, information obtained included palpation, percussion, biting, and periodontal probing, followed by the tooth being classified into symptomatic or asymptomatic apical periodontitis. 3.6.2 Radiographic assessment I (PA) All radiographs were exported and organized per patient, per tooth, and per date and incorporated into two PowerPoint presentations, one for the PA radiographs and one for the CBCT radiographs. These slides were assessed by two different examiners, as will be discussed below (section 3.7). The PA presentation slides showed the PA radiographs for all cases. In 26 addition, each PowerPoint slide contained the patient’s unique code, tooth number, and the year the radiographs were taken, as well as the post-operative and follow-up radiographs at almost the same angle. The presentation slides were supplied by the periapical (PA) index for the radiographic healing assessment based on Molven et al. (83), an example is shown in Figure 2. This PA index involves studying the 2D outcome after endodontic surgery and classifying the outcomes into four categories: complete, incomplete, uncertain, and unsatisfactory healing(83), as shown in Figure 3. The index was provided on an additional slide to be used as a reference for the examiner. Both examiners were asked to open the slides (using Microsoft PowerPoint for Mac, version 16.68) on two 27-inch iMac screens (Apple, Cupertino, CA, USA) with fixed brightness to standardize the viewing conditions. Figure 2. An example of the PowerPoint slides for the PA (2D) radiographic assessments. Figure 3. Illustrations of Molven et al. PA index for the healing assessment (83). 27 3.6.3 Radiographic assessment II (CBCT) The CBCT presentation showed the CBCT slides for all ca. Thethe same protocol was followed as for the PA presentation slides (see section 3.6.2). An example is shown in Figure 4. As for the CBCT, three quantitative indices based on Chen et al. were used: the apical (A) index, resection plane (R) index, and cortical plate (C) index. Each index received a score of 0, 1, or 2, as shown in Figure 5. The scores from the three indices are summed to give a final score per tooth (from 0 to 6). In the case of multiple roots, the root with the lowest score was used to evaluate the outcome. Chen et al. have also divided the final score of the healing outcome into four categories: complete (6), incomplete (5 or 4), uncertain (3), and unsatisfactory (2, 1, or 0). These categories were classified again into two subcategories: favourable (complete and incomplete healing) and unfavourable (uncertain and unsatisfactory) (86), as shown in Table 3. The indices slide was also provided as a reference for the examiners. Figure 4. An example of the PowerPoint slides for the CBCT (3D) radiographic assessment. Table 3. CBCT scoring system based on Chen et al. indices (86). CBCT score Four categories classification Two categories classification 6 Complete healing Favourable 4-5 Incomplete healing 3 0-2 Uncertain Unsatisfactory Unfavorable 28 Figure 5. Illustrations of Chen et al. CBCT indices for EMS healing assessment using CBCT. 3.6.4 Radiographic assessment examples In this section, six different cases will be presented. These cases are examples for each score given (6-0) using the healing assessment indices after the endodontic surgery using CBCT (3D radiographs). The first example (Figure 6) shows a case with complete healing and a score of 6. It shows preoperative and follow-up PA and CBCT radiographs of a complete healing case. Figure 7 shows an example of a case with incomplete healing and a score of 5; the preoperative and follow-up PA and CBCT radiographs indicate a case of incomplete healing. Figure 8 is another example of a case with incomplete healing but with a score of 4. Figure 9 shows an example of a case with uncertain healing and a score of 3. Finally, Figures 10, 11, and 12 show examples of cases with unsatisfactory healing with a score of 2, 1, and 0, respectively. 29 Figure 6. Radiographs (a-d) for a case with complete healing and a score of 6. The images show an anterior maxillary tooth where non-surgical root canal treatment was completed without success. (a) The preoperative PA radiograph shows a previously treated root canal tooth with a periapical radiolucency (PARL). (b) A pre-surgical CBCT image that was taken after the non-surgical root canal retreatment, which shows the extent of the PARL. (c) A PA radiograph was taken at the follow-up, at three years, which shows complete healing at the surgical site. (d) A follow-up CBCT image showing complete healing at all three indices. Each plane received a score of 2. A: Apical, C: Cortical plate, R: Resection plane. Figure 7. Radiographs (a-d) for a case with incomplete healing and a score of 5. The images show a maxillary molar tooth where non-surgical root canal retreatment was completed without success due to a separated instrument in the mesiobuccal root. (a) A preoperative PA radiograph shows a previously treated root canal tooth with a PARL. (b) A pre-surgical CBCT image that was taken after the non-surgical root canal retreatment shows the presence of the PARL associated with both mesiobuccal and palatal roots. (c) A PA radiograph was taken at the follow-up at 1 year and 4 months, showing complete healing when it was compared to the immediate post-op radiograph. (d) A follow-up CBCT image showed complete healing at both the A and C indices, with a score of 2 in both, while the R index received a score of 1 due to incomplete healing (the PARL around the palatal root has significantly improved compared with the preoperative CBCT image). A: Apical, C: Cortical plate, R: Resection plane. 30 Figure 8. Radiographs (a-d) for a case with incomplete healing and a score of 4. The images show a maxillary molar tooth where non-surgical root canal retreatment was completed without success. (a) A preoperative PA radiograph shows a previously treated root canal tooth with a PARL. (b) A pre-surgical CBCT image taken after the non-surgical root canal retreatment, which shows the presence of the PARL associated with distobuccal and palatal roots. (c) A PA radiograph was taken at the follow-up at 5 years and 2 months, showing complete healing at the surgical site compared to the pre-op radiograph. (d) A follow-up CBCT image showing incomplete healing at the palatal root receiving a score of 1 for both the A and R indices and a score of 2 for the C index. A: Apical, C: Cortical plate, R: Resection plane. Note: when multiple roots were involved, the root with the lowest score was used to evaluate the outcome. Figure 9. Radiographs (a-d) for a case with uncertain healing and a score of 3. The images show a maxillary molar tooth where non-surgical root canal retreatment was completed without success. (a) A preoperative PA radiograph showing a previously treated root canal tooth with a PARL. (b) A pre-surgical CBCT image that was taken before the non-surgical root canal retreatment, which shows the presence of the PARL associated with the mesiobuccal, untreated canal, over-extendedded root canal filling. (c) A PA radiograph was taken at the follow-up at 1 year, showing incomplete healing at the surgical site compared to the pre-op radiograph. (d) A follow-up CBCT image showing unsatisfactory healing receiving a score of 1 for the A index, a score of 0 for the C index and a score of 2 for the R index. A: Apical, C: Cortical plate, R: Resection plane. Figure 10. Radiographs (a-d) for a case with unsatisfactory healing with a score of 2. The images show a maxillary premolar tooth where non-surgical root canal treatment was completed without success. (a, b) Pre-surgical PA and CBCT radiographs showing a previously treated root canal tooth with a PARL. (c ) A PA radiograph taken at the follow-up at 3 years shows incomplete healing at the surgical site when compared to the immediate post-op radiograph. (d) A follow-up CBCT radiograph showed unsatisfactory healing, receiving a 31 score of 1 for both the A and C indices and a score of 0 for the R index. A: Apical, C: Cortical plate, R: Resection plane. Figure 11. Radiographs (a-d) for a case with unsatisfactory healing and a score of 1. The images show a maxillary molar tooth where non-surgical root canal treatment was completed without success. (a, b) preoperative PA and CBCT radiographs showing a previously re-treated root canal tooth with a PARL associated with multiple roots. (c ) The PA radiograph taken at the 7-year follow-up shows incomplete healing at the surgical site when compared to the immediate post-op radiograph. (d) A follow-up CBCT radiograph showed improvement in the lesion size, with a score of 1 for the A index but a score of 0 for both the C and R indices. A: Apical, C: Cortical plate, R: Resection plane. Figure 12. Radiographs (a-d) for a case with unsatisfactory healing and a score of 0. The images show a maxillary premolar tooth where non-surgical root canal treatment was completed without success. (a) A preoperative PA radiograph showing a previously treated root canal tooth with a PARL. (b) A pre-surgical CBCT radiograph that was taken after the non-surgical root canal treatment, which shows the extent of the PARL. (c) The PA radiograph taken at the follow-up at 1 year and 2 months shows uncertain healing at the surgical site when compared to the immidiate post-op radiograph. (d) A CBCT radiograph taken at the follow-up showed unsatisfactory healing, where there was no bone re-establishment of any of the three indices receiving a score of 0 for each. A: Apical, C: Cortical plate, R: Resection plane. 3.7 Examiners, examination process, and final assessment. Two calibrated external endodontists (both are Endodontists with at least five years of experience) were independently involved in the assessment of the PA and CBCT radiographs. The calibration was done before any assessment by the examiners. The calibration involved explaining the indices used for the examination for the radiographic healing assessment using the 32 PA and the CBCT indices to ensure consistency of examination results. Each examiner received a copy of the PA and CBCT slides. Each examiner was also asked to score each tooth on the same slides. Then, the scores went entered as data into an Excel spreadsheet. In case of disagreements on any of the PA or CBCT radiographs, both examiners were invited for an open discussion and re-evaluation of those cases until consensus was achieved. The final examination results were entered into the data sheet and labelled as combined PA, combined A, combined C, combined R, and combined CBCT scores. Each tooth then received a final assessment of “success,” “failure,” or “survival,” according to the combined PA and CBCT radiograph outcomes (83): • The outcome was a “success” when the tooth presented without any clinical symptoms and had a favourable radiographic outcome. • The outcome was a “failure” when the tooth presented with clinical symptoms and/or an unfavourable radiographic outcome. • The outcome was “survival” when the tooth presented without clinical symptoms and with favourable or unfavourable radiographic outcomes, as explained in Table 4. Table 4. The definition of “success,” “failure,” and “survival” for outcomes. Clinical signs & symptoms Yes No Survival will be the cells in red colour. CBCT 0,1,2,3 Failure Failure CBCT 4, 5, 6 Failure Success PA complete, incomplete Failure Success PA is uncertain, unsatisfactory Failure Failure 33 3.8 Inter-examiner agreement Weighted kappa analysis was performed to evaluate the inter-radiographic agreement between the PA and the CBCT using the four radiographic healing indices and the two radiographic outcome categories, see section 4.3. The inter-examiner agreements were calculated for the three CBCT indices independently, for tcombinedined CBCT scores (0-6), and for the combined PA indices (complete, incomplete, uncertain, and unsatisfactory), see section 4.6. The CBCT had “almost perfect” inter-examiner agreement amongst all planes (K=0.915; p<0.001) and when the radiographic outcome was dichotomized into favourable and unfavourable radiographic outcomes (K=0.816; p<0.001). In contrast, the 2D analysis showed a moderate inter-examiner agreement amongst the four healing categories (K=0.55; p<0.001). 3.9 Statistical analysis Data were analyzed using SPSS version 27 (IBM, Armonk, New York). All statistical tests were performed as two-tailed tests, and the significance level was set at p<0.05. The descriptive statistics included generating the mean, standard deviation, count, and percentage. The chi-square and Fisher’s exact test were used mainly for his project based on the available data. Moreover, logistic regression, multiple logistic regression, and weighted kappa test were used to assess the relationship between variables; no multiple testing correction was applied during testing. Additional details about each are described below: • Chi-square test: The chi-square test was used to assess the association between the bivariable analysis of the prognostic factors and the outcomes, based on the CBCT and PA criteria, when the chi-square assumptions were valid. 34 • Fisher’s exact test: The Fisher’s exact test was used when the assumptions (expected counts in any of the frequency cells being greater than 5) of the chi-square test were not met after assessing the association between the bivariable analysis of the prognostic factors and the outcomes based on CBCT and PA criteria. • Logistic regression: Logistic regression was used to assess the association of the continuous prognostic factors (age) with the outcomes based on the CBCT and PA outcome (categorical with two levels) as the dependent variables. • Multiple logistic regression with backward elimination method was used to assess the association between all the prognostic factors and outcomes based on PA and CBCT outcomes (categorical with two levels) as dependent variables. • Weighted Kappa test: Inter-examiner agreement for PA and CBCT outcomes were assessed using the weighted Kappa test. Also, the association between the PA outcome and CBCT outcomes as 2D and 3D radiographic assessments. 35 Chapter 4: Results The collected and analyzed data regarding all patient’s prognostic factors, along with the healing outcome assessments (based on both PA and CBCT radiographs), are divided into the following six parts: patient demographic data (51 patients), see section 4.1; descriptive retrospective analysis for the endodontically treated teeth (78 teeth), see section 4.2; descriptive prospective analysis for the endodontically treated teeth (78 teeth) based on CBCT and PA criteria, showing the association between them, see section 4.3; inferential analysis of the association between prognostic factors and radiographic outcome using CBCT, see section 4.4; inferential analysis of the association between prognostic factors and PA radiograph outcome, see section 4.5; and the inter-examiner agreement between the PA and the CBCT radiographs, see section 4.6. 4.1 Patient demographic data This part involved a description analysis at the patient level. A total of 51 patients were involved, with a mean age of 60.73 years ± 16.28 years. Among the patients, 43.14% were male, and 56.86% were female. Of those patients, 66.67% were healthy, while the remaining unhealthy patients had one of nine common medical condition(s). Among the unhealthy patients, 19.61% had hypertension, 9.80% had diabetes mellitus, 5.88% had lung disease, 3.92% had high cholesterol, 3.92% had osteoporosis, 3.92% had thyroid disease, 1.96% had liver disease, 1.96% had depression, and 1.96% had cancer. It should be noted that a patient can have multiple health conditions, which explains the sum of more than 100%, as shown in Figure 13. 36 Figure 13. Participants’ health status, including types of medical condition(s). *Note: some patients might have multiple diseases at the same time, which explains why the total sum is greater than 100%. (n=51). 4.2 Descriptive retrospective analysis for endodontically treated teeth This section involvess a description analysis at the tooth level (Table 5), at the patient level (Table 6), and the sequence of the treatment (Table 7). Table 5. Descriptive data according to the tooth’s location and type. Prognostic factors n=78 % Tooth location Maxillary 52 66.67% Mandibular 26 33.33% Tooth type Anterior 32 41.03% Premolar 17 21.79% Molar 29 37.18% 66.67%1.96%19.61%3.92% 9.80% 3.92% 5.88% 1.96% 3.92% 1.96%0.00%20.00%40.00%60.00%80.00%100.00%Healthy cancer Hypertension cholesterol DiabetesmellitusOsteoporosis Lung disease Depression ThyroiddiseaseLiver diseaseYes No 37 Table 6. Descriptive data of the prognostic factors. Prognostic factors n=78 % Preoperative pulpal diagnosis Necrotic 3 3.85% Irreversible pulpitis 1 1.28% Previously treated 74 94.87% Preoperative periapical diagnosis Symptomatic Apical periodontitis 33 42.31% Asymptomatic Apical periodontitis 29 37.18% Chronic apical abscess 16 20.51% Preoperative clinical symptoms Yes 49 62.82% No 29 37.18% Quality of the coronal restoration Good 30 38.46% Poor 48 61.54% Quality of RCT prior surgery Adequate 67 85.90% Inadequate 11 14.10% Untreated anatomy Yes 7 8.97% No 71 91.03% Maxillary sinus perforation Yes 5 6.41% No 73 93.59% Grafting Yes 15 19.23% No 63 80.77% Biopsy Radicular cyst 4 5.13% Non-cystic lesion 38 48.72% NA 36 46.15% 38 Table 7. Descriptive data for the sequence of the treatment. Treatment sequence n=78 % RCT & EMS 18 23.08% Re-RCT & EMS 23 29.49% RCT, ReRCT & EMS 2 2.56% EMS only 35 44.87% RCT: root canal treatment, EMS: endodontic microsurgery, Re-RCT: root canal retreatment. EMS only: previously endodontically treated tooth with persistent infection. 4.3 Descriptive prospective analysis for endodontically treated teeth based on CBCT and PA indices. A total of 78 teeth (51 patients) were involved in the follow-ups, with a median follow-up time of 29.5 months. Treatment outcomes based on CBCT (when the VRF cases were included) were 80.8% success, and 19.2% failure, whereas based on the PA indices was 83.3% success and 16.7% failure, and the survival was the same in both groups, as shown in Tables 8. Whereas, when the cases with VRF were excluded, there were no significant changes in treatment outcome, as shown in Table 8 and Table 9. The success rate was higher in the PA compared with the CBCT by 3.3%. This finding agrees with a previously published study (87, 88). Moreover, not all failed cases had clinical signs and symptoms; nor all patients with clinical signs and symptoms had radiographic signs of failure. 39 Table 8. Treatment outcomes based on CBCT and PA indices I. Based on CBCT criteria Based on PA criteria n=78 % n=78 % Success 63 80.8 65 83.3 Failure 15 19.2 13 16.7 Survival 71 91.02 71 91.02 *(including VRF cases) Table 9. Treatment outcomes were based on CBCT and PA indices II. Based on CBCT criteria Based on PA criteria n=76 % n=76 % Success 63 82.9 65 85.5 Failure 13 17.1 11 14.5 *(excluding VRF cases) Additionally, descriptions of the radiographic (CBCT and PA) findings (combined results of Examiners 1 and 2) after follow-up showed that in both groups and the highest percentage was for an agreement was for the favourable treatment outcome in both groups, as shown in Table 10. It is worth mentioning that our investigation showed that the bony healing improved at the follow-up visits, even in failed cases; this finding was consistent with a previously published study (87). The complete, incomplete, and uncertain cases were easier to evaluate and interpret when compared with cases that showed unsatisfactory healing; particularly with a total score of 1 (two teeth), 2 (three teeth) or 3 (two teeth) using the CBCT indices, as there were few cases for each total score. 40 In other instances, the bony healing was unlikely to improve further, and these cases presented a total score of 0. It should be noted that none of the patients with a total score of 6, 5, 3, 2 or 1 had any clinical symptoms. Whereas five cases presented with clinical signs of failure at the follow-up, three of those five cases had a total score of 4 and two patients had a total score of 0 (5/78 cases, two unfavourable and three favourable outcomes presented with clinical symptoms of failure). Also, it was noted that 80% of the teeth showing incomplete healing on the CBCT were mistaken for complete healing on the PA. Table 10. Description of the radiographic findings after follow-up. (combined results of Examiners 1 and 2) CBCT indices n (%) A index 0 7 (8.97) 1 14 (17.95) 2 57 (73.07) C index 0 9 (11.54) 1 10 (12.82) 2 59 (75.64) R index 0 9 (11.54) 1 10 (12.82) 2 59 (75.64) CBCT score (0-6) 0 5 (6.41) 1 2 (2.56) 2 3 (3.85) 3 2 (2.56) 4 6 (7.69) 5 14 (17.95) 6 46 (58.97) CBCT outcome Favourable (4-6) 66 (84.62) Not favourable (0-3) 12 (15.38) PA index n (%) PA Complete healing 55 (70.51) Incomplete healing 14 (17.95) Uncertain healing 6 (7.69) Unsatisfactory healing 3 (5.85) PA outcome Favourable (complete & incomplete) 69 (88.46) Unfavorable (uncertain & unsatisfactory) 9 (10.54) A: Apical, C: Cortical plate, R: Resection plane, CBCT: cone-beam computed tomography, PA: periapical. 41 The association between the PA and CBCT radiographic classification of the EMS outcomes when the outcome is categorized into four categories of healing (complete, incomplete, uncertain, and unsatisfactory) showed that the highest agreement is in the favourable group, and more specifically when it was complete healing, and the least was for the uncertain healing which belongs to the unfavourable group, as shown in Table 11. When conducting weighted Kappa tests for this comparison, we found a Kappa value of 0.354 (p<0.001). Furthermore, the association between the PA and CBCT radiograph classifications of the EMS outcomes when the outcome is categorized into two favourability categories (favourable and unfavourable) and the same results were shown but categorized differently, as shown in Table 12. When conducting the weighted Kappa test for this comparison, we found a Kappa value of 0.397 (p<0.001). Table 11. The association between the two radiographic methods and EMS outcomes I. (the outcome is categorized into four healing categories) 3D favourable radiographic outcome 3D unfavourable radiographic outcome Total Complete healing Incomplete healing Uncertain healing Unsatisfactory healing 2D favourable radiographic outcome Complete healing 39 16 0 0 55 Incomplete healing 5 2 2 5 14 2D unfavourable radiographic outcome Uncertain healing 2 1 0 3 6 Unsatisfactory healing 0 1 0 2 3 Total 46 20 2 10 78 Kappa value=0.354, p<0.001. Kappa values: <0, no agreement; 0–0.2, slight agreement; 0.21–0.40, fair agreement; 0.41– 0.60, moderate agreement; 0.61–0.80, substantial agreement; 0.81–1, almost perfect agreement. 42 Table 12. The association between the two radiographic methods and EMS outcomes II. (the outcome is categorized into two favourability categories) 3D radiographic outcome Total Favourable Not favourable 2D radiographic outcome Favourable 62 7 69 Not favourable 4 5 9 Total 66 12 78 Kappa value=0.397, p<0.001. Kappa values: <0, no agreement; 0–0.2, slight agreement; 0.21–0.40, fair agreement; 0.41– 0.60, moderate agreement; 0.61–0.80, substantial agreement; 0.81–1, almost perfect agreement. 4.4 Inferential analysis of the association between prognostic factors and radiographic outcome using CBCT The association between the prognostic factors and the CBCT outcomes was determined using two statistical methods. Bivariable analysis of the association between the prognostic factors and CBCT outcomes (with and without VRF) was conducted. For the categorical prognostic factors, Fisher’s exact tests (and chi-square test when applicable) were used, as shown in Table 13. For the continuous prognostic factors, logistic regressions were used. There was no significant association between the radiographic outcomes using CBCT and age (p=0.943). Also, when VRF cases were not included, there was no significant association between CBCT outcomes and age (p=0.553). A multiple logistic regression test was performed using a backward elimination method to assess the effects of age, gender, tooth location, tooth type, medical condition(s), preoperative pulpal diagnosis, preoperative periapical diagnosis, presence of preoperative clinical symptoms, quality of coronal restoration (good, poor), quality of RCT prior to surgery, untreated anatomy, retro-filling material used, maxillary sinus perforation, grafting, biopsy, and sequence of the treatment to predict if the failure of EMS outcome was based on CBCT criteria. The final logistic regression model included only the preoperative periapical diagnosis and grafting and was statistically significant (X2(3)=12.29, p=0.006). 43 The model explained 23.3% of the EMS failure outcomes based on CBCT indices and correctly classified 80.8% of cases. Participants with asymptomatic apical periodontitis are 5.63 times more likely (p=0.044) to exhibit failed EMS outcomes based on CBCT indices than participants with symptomatic apical periodontitis. Participants with chronic apical abscesses are 13.23 times more likely (p=0.005) to exhibit failed EMS outcomes based on CBCT indices than participants with symptomatic apical periodontitis. Grafting was not significant in the model, but it was included as it acts as an effect modifier for the model. This was repeated, excluding the VRF cases. A multiple logistic regression test was once again performed using a backward elimination method to assess the effects of age, gender, tooth location, tooth type, medical condition(s), preoperative pulpal diagnosis, preoperative periapical diagnosis, presence of preoperative clinical symptoms, quality of coronal restoration (good, poor), quality of RCT prior to surgery, untreated anatomy, retro-filling material used, maxillary sinus perforation, grafting, biopsy, and sequence of the treatment to predict if the EMS failure was based on CBCT indices without VRF cases. The final logistic regression model included only the preoperative periapical diagnosis and grafting and was statistically significant (X2(3)=17.494, p<0.001). The model explained 34.3% of the EMS failure based on CBCT indices without VRF cases and correctly classified 82.9% of cases. Participants with asymptomatic apical periodontitis are 11.81 times more likely (p=0.027) to exhibit failed EMS outcomes based on CBCT indices than participants with symptomatic apical periodontitis. Participants with chronic apical abscesses are 22.5 times more likely (p=0.009) to exhibit failed EMS outcomes based on CBCT criteria than participants with symptomatic apical periodontitis. Grafting was not significant, but it was included as it acts as an effect modifier for the model. 44 Table 13. Association between the prognostic factors and radiographic outcomes using CBCT scans. Prognostic factor CBCT outcome CBCT outcome (without VRF) Success Failure p-value Success Failure p-value n % n % n % n % Gender Male 22 70.97% 9 29.03% 0.074* 22 73.33% 8 26.67% 0.074* Female 41 87.23% 6 12.77% 41 89.13% 5 10.87% Tooth location Maxillary 42 80.77% 10 19.23% 1* 42 82.35% 9 17.65% 1 Mandibular 21 80.77% 5 19.23% 21 84.00% 4 16.00% Tooth type Anterior 26 81.25% 6 18.75% 0.871 26 83.87% 5 16.13% 0.737 Premolar 13 76.47% 4 23.53% 13 76.47% 4 23.53% Molar 24 82.76% 5 17.24% 24 85.71% 4 14.29% Medical condition(s) Healthy Yes 45 83.33% 9 16.67% 0.389* 45 83.33% 9 16.67% 1 No 18 75.00% 6 25.00% 18 81.82% 4 18.18% Preoperative pulpal diagnosis Necrotic 3 100.00% 0 0.00% 1 3 100.00% 0 0.00% 1 Irreversible pulpitis 1 100.00% 0 0.00% 1 100.00% 0 0.00% Previously treated 59 79.73% 15 20.27% 59 81.94% 13 18.06% Preoperative periapical diagnosis Symptomatic Apical periodontitis 31 93.94% 2 6.06% 0.017 31 96.88% 1 3.13% 0.01 Asymptomatic Apical periodontitis 22 75.86% 7 24.14% 22 75.86% 7 24.14% Chronic apical abscess 10 62.50% 6 37.50% 10 66.67% 5 33.33% Preoperative clinical symptoms Yes 40 81.63% 9 18.37% 0.801* 40 85.11% 7 14.89% 0.515* No 23 79.31% 6 20.69% 23 79.31% 6 20.69% Quality of coronal restoration Good crown 24 80.00% 6 20.00% 0.892* 24 80.00% 6 20.00% 0.588* Poor crown 39 81.25% 9 18.75% 39 84.78% 7 15.22% 45 Prognostic factor CBCT outcome CBCT outcome (without VRF) Success Failure p-value Success Failure p-value n % n % n % n % Quality of RCT prior to surgery Adequate 55 82.09% 12 17.91% 0.434 55 84.62% 10 15.38% 0.388 Inadequate 8 72.73% 3 27.27% 8 72.73% 3 27.27% Untreated anatomy Yes 4 57.14% 3 42.86% 0.125 4 57.14% 3 42.86% 0.092 No 59 83.10% 12 16.90% 59 85.51% 10 14.49% Retro-filling material ProRoot MTA 12 85.71% 2 14.29% 1 12 85.71% 2 14.29% 1 BC RRM Putty 51 79.69% 13 20.31% 51 82.26% 11 17.74% Maxillary sinus perforation Yes 4 80.00% 1 20.00% 1 4 80.00% 1 20.00% 1 No 59 80.82% 14 19.18% 59 83.10% 12 16.90% Grafting Yes 14 93.33% 1 6.67% 0.278 14 100.00% 0 0.00% 0.11 No 49 77.78% 14 22.22% 49 79.03% 13 20.97% Biopsy Radicular cyst 2 50.00% 2 50.00% 0.036 2 50.00% 2 50.00% 0.052 Non-cystic lesion 28 73.68% 10 26.32% 28 77.78% 8 22.22% NA 33 91.67% 3 8.33% 33 91.67% 3 8.33% Treatment sequence RCT + Apico 15 83.33% 3 16.67% 0.263 15 88.24% 2 11.76% 0.308 ReRCT + Apico 21 91.30% 2 8.70% 21 91.30% 2 8.70% RCT, ReRCT + Apico 2 100.00% 0 0.00% 2 100.00% 0 0.00% Apico only 25 71.43% 10 28.57% 25 73.53% 9 26.47% * Chi-square 46 4.5 Inferential analysis of the association between prognostic factors and radiographic outcome using PA. The association between the prognostic factors and radiographic outcomes using PA was determined using two statistical methods. Bivariable analysis of the association between the prognostic factors and radiographic outcome using PA (with and without VRF) was performed. For the categorical prognostic factors, Fisher’s exact tests (and chi-square test when applicable) were used, as shown in Table 14. For the continuous prognostic factors, logistic regressions were used. There was a significant association between the radiographic outcome using PA and age (p=0.043, Nagelkerke R Square=0.092); Furthermore, when VRF cases were not included, there was still a significant association between PA outcomes and age (p=0.009, Nagelkerke R Square=0.181). A multiple logistic regression test was performed using a backward elimination method to assess the effects of age, gender, tooth location, tooth type, medical condition(s), preoperative pulpal diagnosis, preoperative periapical diagnosis, presence of preoperative clinical symptoms, quality of coronal restoration (good, poor), quality of RCT prior to surgery, untreated anatomy, retro-filling material used, maxillary sinus perforation, grafting, biopsy, and sequence of the treatment to predict if the EMS failure was based on PA index. The final logistic regression model only included age and was statistically significant (X2(1)=4.365, p=0.037). The model explained 9.2% of the failed EMS outcomes based on the PA index and correctly classified 83.3% of cases. Each unit increased age decreased the likelihood of a failed EMS outcome by 1.041 times. 47 This was once again repeated, excluding the VRF cases. An additional multiple logistic regression test was performed using a backward elimination method to assess the effects of age, gender, tooth location, tooth type, medical condition(s), preoperative pulpal diagnosis, preoperative periapical diagnosis, presence of preoperative clinical symptoms, quality of coronal restoration (good, poor), quality of RCT prior to surgery, untreated anatomy, retro-filling material used, maxillary sinus perforation, grafting, biopsy, and sequence of the treatment to predict if the EMS failure was based on PA index without VRF cases. The final logistic regression model only included age, a was statistically significant (X2(1)=8.179, p=0.004). The model explained 18.1% of the failed EMS outcomes based on the PA index without VRF cases and correctly classified 85.5% of cases. Each unit increase in age decreased the likelihood of failure of the EMS by 1.064 times. 4.6 The inter-examiner agreement between the PA and CBCT radiographs A description of the examiners’ diagnosis based on CBCT and PA radiographs is shown in Table 15. The inter-examiner agreement between the CBCT and the PA radiograph analysis was performed using weighted kappa analysis. This analysis was done based on the CBCT and PA radiographic healing indices. The CBCT scores were 0-6, whereas the PA scores were one of four categories (complete, incomplete, uncertain, or unsatisfactory). The reliability and the internal consistency of the scoring system between the two examiners were tested using the weighted kappa, see Tables 15-17. 48 Table 14. Association between the prognostic factors and radiographic outcome using PA radiographs. PA outcome PA outcome (without VRF) Prognostic factor Success Failure p-value Success Failure p-value n % n % n % n % Gender Male 24 77.42% 7 22.58% 0.255* 24 80.00% 6 20.00% 0.269* Female 41 87.23% 6 12.77% 41 89.13% 5 10.87% Tooth location Maxillary 43 82.69% 9 17.31% 1 43 84.31% 8 15.69% 1 Mandibular 22 84.62% 4 15.38% 22 88.00% 3 12.00% Tooth type Anterior 26 81.25% 6 18.75% 0.926 26 83.87% 5 16.13% 1 Premolar 15 88.24% 2 11.76% 15 88.24% 2 11.76% Molar 24 82.76% 5 17.24% 24 85.71% 4 14.29% Medical condition(s) Healthy Yes 45 83.33% 9 16.67% 1 45 83.33% 9 16.67% 0.494 No 20 83.33% 4 16.67% 20 90.91% 2 9.09% Preoperative pulpal diagnosis Necrotic 3 100.00% 0 0.00% 1 3 100.00% 0 0.00% 1 Irreversible pulpitis 1 100.00% 0 0.00% 1 100.00% 0 0.00% Previously treated 61 82.43% 13 17.57% 61 84.72% 11 15.28% Preoperative periapical diagnosis Symptomatic Apical periodontitis Asymptomatic Apica periodontitis Chronic apical abscess 29 87.88% 4 12.12% 0.233 29 90.63% 3 9.38% 0.301 25 86.21% 4 13.79% 25 86.21% 4 13.79% 11 68.75% 5 31.25% 11 73.33% 4 26.67% Preoperative clinical symptoms Yes 40 81.63% 9 18.37% 0.757 40 85.11% 7 14.89% 1 No 25 86.21% 4 13.79% 25 86.21% 4 13.79% Quality of the coronal restoration Good 24 80.00% 6 20.00% 0.532* 24 80.00% 6 20.00% 0.269* Poor 41 85.42% 7 14.58% 41 89.13% 5 10.87% 49 * Chi-square test PA outcome PA outcome (without VRF) Prognostic factor Success Failure p-value Success Failure p-value n % n % n % n % Quality of RCT prior to surgery Adequate 55 82.09% 12 17.91% 0.679 55 84.62% 10 15.38% 1 Inadequate 10 90.91% 1 9.09% 10 90.91% 1 9.09% Untreated anatomy Yes 5 71.43% 2 28.57% 0.33 5 71.43% 2 28.57% 0.266 No 60 84.51% 11 15.49% 60 86.96% 9 13.04% Retro-filling material ProRoot MTA 12 85.71% 2 14.29% 1 12 85.71% 2 14.29% 1 BC RRM Putty 53 82.81% 11 17.19% 53 85.48% 9 14.52% Maxillary sinus perforation Yes 4 80.00% 1 20.00% 1 4 80.00% 1 20.00% 0.553 No 61 83.56% 12 16.44% 61 85.92% 10 14.08% Grafting Yes 13 86.67% 2 13.33% 1 13 92.86% 1 7.14% 0.678 No 52 82.54% 11 17.46% 52 83.87% 10 16.13% Biopsy Radicular cyst 2 50.00% 2 50.00% 0.016 2 50.00% 2 50.00% 0.031 Non-cystic lesion 29 76.32% 9 23.68% 29 80.56% 7 19.44% NA 34 94.44% 2 5.56% 34 94.44% 2 5.56% Treatment sequence RCT + Apico 14 77.78% 4 22.22% 0.821 14 82.35% 3 17.65% 1 ReRCT + Apico 20 86.96% 3 13.04% 20 86.96% 3 13.04% RCT, ReRCT + Apico 2 100.00% 0 0.00% 2 100.00% 0 0.00% Apico only 29 82.86% 6 17.14% 29 85.29% 5 14.71% 50 Table 15. Results of the healing assessment for each examiner based on the CBCT indices. CBCT: Cone-beam computed tomography. Examiner 1 Examiner 2 Combined Index n=78 (%) n=78 (%) n=78 (%) CBCT indices A Apical area 0 7 (8.97) 7 (8.97) 7 (8.97) 1 16 (20.51) 13 (16.67) 14 (17.95) 2 55 (70.51) 58 (74.36) 58 (74.36) C Cortical plate 0 7 (8.97) 9 (11.54) 9 (11.54) 1 12 (15.38) 8 (10.26) 10 (12.82) 2 59 (75.64) 61 (78.21) 59 (75.64) R Resection plane 0 10 (12.82) 11 (14.1) 9 (11.54) 1 13 (16.67) 9 (11.54) 10 (12.82) 2 55 (70.51) 58 (74.36) 59 (75.64) CBCT score (0-6) 0 5 (6.41) 5 (6.41) 5 (6.41) 1 2 (2.56) 3 (3.85) 2 (2.56) 2 3 (3.85) 3 (3.85) 3 (3.85) 3 3 (3.85) 1 (1.28) 2 (2.56) 4 9 (11.54) 5 (6.41) 6 (7.69) 5 10 (12.82) 14 (17.95) 14 (17.95) 6 46 (58.97) 47 (60.26) 46 (58.97) CBCT outcome Favourable (4-6) 64 (82.05) 66 (84.62) 66 (84.62) Not favourable (0-3) 14 (17.95) 12 (15.38) 12 (15.38) 51 Table 16. Results of the healing assessment for each examiner based on the PA index. Examiner 1 Examiner 2 Combined Index n=78 (%) n=78 (%) n=78 (%) PA index PA Complete healing 51 (65.38) 61 (78.21) 55 (70.51) Incomplete healing 19 (24.36) 11 (14.1) 14 (17.95) Uncertain healing 5 (6.41) 5 (6.41) 6 (7.69) Unsatisfactory healing 3 (3.85) 1 (1.28) 3 (5.85) PA outcome Favourable (complete, incomplete) 70 (89.74) 72 (92.30) 69 (88.46) Not favourable (uncertain, unsatisfactory) 8 (10.25) 6 (7.69) 9 (11.54) PA: Periapical radiograph. Table 17. : Inter-examiner agreement. Index K p-value Agreement (%) 3D: CBCT A 0.886 <0.001 92.40% C 0.905 <0.001 94.87% R 0.919 <0.001 94.87% CBCT score: Scoring system (0 – 6 scores) 0.915 <0.001 94.89% 2D: PA PA healing categories (complete, incomplete, uncertain, unsatisfactory) 0.55 <0.001 76.92% A: Apical; C: Cortical plate; R: Resection plane; K: Weighted Kappa. Kappa values: <0, no agreement; 0–0.2, slight agreement; 0.21–0.40, fair agreement; 0.41– 0.60, moderate agreement; 0.61–0.80, substantial agreement; 0.81–1, almost perfect agreement. 52 4.7 Summary of results The survival rate of the EMS was 91.02%. The success rate for EMS was 80.8% using CBCT radiographs and 83.3% using PA radiographs. Whereas, the failure rate was 19.2% using CBCT radiographs and 16.7% using PA radiographs. Based on CBCT criteria, the preoperative periapical diagnosis was the only significant predictor for EMS outcomes when the data was analyzed using bivariable and multivariable analysis. Participants with asymptomatic apical periodontitis are 5.63 times more likely to exhibit EMS failure based on CBCT criteria than participants with symptomatic apical periodontitis. Participants with chronic apical abscesses are 13.23 times more likely to show EMS failure outcomes based on CBCT criteria than participants with symptomatic apical periodontitis. Grafting was found to be an effect modifier in the multivariable analysis but was not significant. Based on both CBCT and PA criteria, the results of a biopsy were found to be a significant predictor of the outcome when the bivariable analysis was used; however, the results of a biopsy were not significant when the multivariable analysis was conducted in both radiographic methods. In fact, based on PA criteria, the multivariable analysis found that the age of the patient was the only significant prognostic factor, as each unit increase in the age decreased the likelihood of an EMS failure outcome by 1.041 times (based on PA criteria). The high success and survival rates support the idea that EMS is a good treatment approach that helps save natural teeth. 53 Chapter 5: Discussion 5.1 Study significance This outcome study design has both retrospective and prospective components to it. As the treatments were performed before initiating this study, the framework was set before starting the follow-up or outcome analyses to evaluate the outcomes of EMS performed by UBC graduate endodontic residents, investigating the outcome using two radiographic methods, and analyzing the correlation of the prognostic factors with the outcome. Several endodontic literature sources have investigated the correlation of different prognostic factors with EMS outcomes using CBCT scans (86, 87, 89) or PA radiographs (83, 90-92). To the best of our knowledge, this is the first outcome study designed to independently investigate and correlate the influence of each prognostic factor on the EMS outcome using the CBCT scans and PA radiographs. Evidence from this outcome study will aid graduate endodontic residents, clinicians and patients in discussing different treatment options, comparing and correlating the EMS outcome to the prognostic factors. This leaves the patient with sufficient information to choose the treatment option they want. 5.2 Major findings First hypothesis The first hypothesis (H1) suggested that the EMS outcome in UBC's graduate endodontics program is successful. This hypothesis has yet to be tested on this specific population. The outcome was successful when the tooth presented without clinical symptoms and had a favourable radiographic outcome (83). As the EMS outcomes were evaluated using two radiographic methods, the success rate in this study was 80.8% based on the CBCT scans; our 54 result was slightly lower than previously published findings, which ranged from 86%-94% (87, 88, 92). This slight difference was because of the different radiographic assessment methods used. In contrast, our study's success rate based on the PA was 83.3%; this rate was also comparable with previously published studies with an outcome ranging from 74%-86% (77, 87). Therefore, our findings are within the accepted range already reported implying the validity of the methodology we used in the outcome assessment for this study. Moreover, the cause of failures in this study, whether from VRF or persistent infection that required further intervention (e.g. resurgery, root amputation, or extraction), has not been investigated, due to the small sample size. When analyzing the treatment outcome, it is crucial to examine the cause of failure and compare the findings with similar clinical studies. For that reason the outcome was analyzed twice—with and without the VRF cases, which were involved in the survival, not the success rate. The success rate when the VRF cases were included was almost 81% using CBCT and 83% using PA; when the VRF cases were excluded, the success rate was nearly 83% using CBCT and 85% using PA, our findings were not significantly different compared to a similar outcome study (87). In other outcome studies, when analyzing the success rate, it was not mentioned whether the VRF cases were included or excluded from their outcome analysis (93, 94). Out of the fifteen (19.2%) failed cases in this study, two presented with signs of VRF, eight presented with no clinical symptoms, and five presented with clinical symptoms of failure. 55 The EMS protocol was followed at UBC’s GE clinic, and the treatment outcome in this study was similar to previously reported data (87, 95), thus supporting the idea that EMS is a predictable treatment with high success and survival rates. Second hypothesis The second hypothesis (H2) was that the CBCT scans have higher sensitivity and specificity when compared to the PA. Based on our results, the success rate was 3.3% lower using CBCT scans as opposed to PA radiographs; this finding was consistent with a previously published study (96). Also, the failure rate was 2.5% higher using CBCT scans rather than PA radiographs. Therefore, this hypothesis can be accepted. Also, previously published studies had inconsistent outcomes between the PA and CBCT, which ranged between 25% and 40.5% (96, 97). The inconsistencies in the results of the previously published data may come from the different CBCT criteria and categorizations. Some studies categorized their interpretation of the healing outcome as healed, non-healed, healing, and functional, based on “The American Association of Endodontics Glossary of Terms, 2016”. Others followed Molven’s categorization for their interpretation of the healing outcome to success, failure, and survival (83). Therefore, in this study, the interpretation of the healing outcome was categorized as success, failure, and survival (83) to be consistent with recently published data (87). It has been shown that CBCT is more precise than any 2-dimensional radiographs and has more reliable and accurate results at follow-up appointments (98). When the accuracy in identifying the periapical lesion was tested, the ability to detect the lesions on the CBCT was significantly 56 higher than on the PA radiographs (99). For decades, healing assessments based on PA radiographs have been used (61). Recent investigations showed that healing assessments based on the PA index might not be valid to evaluate a 3-dimensional element (96). At the same time, CBCT has higher sensitivity for detecting and analyzing the periapical area when compared to PA radiographs, even when the periapical radiolucency is as small as 1-2 mm (99-101). Also, it has been shown that CBCT is an essential tool for clinical assessment and treatment planning (96). Although our finding confirmed that the CBCT has higher sensitivity and specificity when compared to the PA, this finding was similar to a previously reported result, where the cases were followed up for only three years (87); unlike our study, we followed up with patients for up to 11 years. Therefore, our study's extended recall period may boost our results' validity. Third and fourth hypotheses The third and fourth hypotheses (H3 & H4) were that the prognostic factors are associated with the outcome of endodontic microsurgery using CBCT and/or PA radiographs. The prognostics factors included in this study were: age, gender, medical condition(s), tooth location, tooth type, preoperative pulpal diagnosis, preoperative periapical diagnosis, presence of preoperative clinical symptoms, quality of coronal restoration, quality of RCT prior to surgery, untreated anatomy, retro-filling material used, maxillary sinus perforation, grafting, biopsy, and sequence of the treatment. 57 The selected outcome predictors in this study were investigated twice, with and without cases diagnosed with VRF—to control for bias, as these cases are unrelated to the surgical treatment. Even though VRF cases were excluded when diagnosed or when there was a sign of VRF from the beginning, it could be invisible during the treatment, induced by the treatment, or could occur due to occlusal forces/parafunctional habits. Although studies showed that such a confounding factor would lower the survival rate following an endodontic treatment (93, 94), previously published similar outcome studies found no apparent distinction between including or excluding VRF cases from the success rate evaluation (90, 97). In this study, only two cases with VRF were discovered during follow-ups; this low number might not significantly affect the predictions based on this factor. The discussion of the third and fourth hypotheses will be categorized into three parts: I. Factors which have not been investigated before and did not have a significant impact on the treatment outcomes in this study: These factors are the medical condition(s), untreated anatomy, maxillary sinus perforation, preoperative pulpal diagnosis and preoperative periapical diagnosis. Medical condition(s), untreated anatomy—none of the medical conditions were found to be associated with the outcomes of EMS. Previous studies did not test these prognostic factors, but there could be a potential between these factors and the treatment outcome that was not significant in this study. Hence, a larger sample size is required to investigate these prognostic factors further and possibly correlate them to the EMS outcome in future studies. As for the untreated anatomy—found in seven teeth (8.9%); of 58 these seven teeth, three cases (42.8%) had a radiographic failure outcome using the CBCT. This could contribute to the persistence of the endodontic infection in those teeth. Maxillary sinus perforation was found in five cases (6.4%), a procedural error that occurred during the endodontic surgery. Of those five cases, only one had a failed radiographic outcome on both radiographic methods. As for the preoperative pulpal diagnosis—seventy-four of the cases (95%) were diagnosed as previously treated, only fifteen teeth (20%) had a failed radiographic using the CBCT; three teeth had necrotic pulp, and one tooth was diagnosed as an irreversible pulpitis, preoperatively. It is worth mentioning that the necrotic and irreversible pulpitis categories had no failed cases based on the CBCT. Similar findings were concluded when the analysis was done using the PA. The overall result for the preoperative pulpal diagnosis was non-significant when the bivariable and multivariable statistical analyses were conducted. Interestingly, the preoperative periapical diagnosis was the only significant predictor for EMS outcomes when the data was analyzed using bivariable and multivariable analysis. The most negligible percentage of failure was in cases diagnosed with symptomatic apical periodontitis, around 6%, followed by asymptomatic apical periodontitis and then chronic apical abscess, around 24% and 37%, respectively. Since the previous five prognostic factors have not been investigated before, whether the results were significant or non-significant, further investigation is recommended with a larger sample size to confirm the validity and the influence of these predictors on the EMS outcome. II. Prognostic factor(s) that resulted in a non-significant correlation to the EMS outcome based on our findings in this study and were consistent with previously published reports. 59 These factors are the age, gender, tooth type, preoperative clinical symptoms, treatment sequence, retro-filling material used, the biopsy result and grafing. Age, gender, tooth type, and location—of the 78 cases included in this study, 60.3% were female and 39.7% male, the same gender distribution as previously published data (78, 92, 102). The participants’ age in this study ranged from 29 to 85, with a mean age of 60.73 years ± 16.28 years, unlike in other studies where the age was grouped as ≤ 45 or ≥ 45 (78, 92). The maxilla was the most frequently operated on (66.7%), then the mandible (33.3%); this was similar to a previous investigation (102). The most commonly operated on teeth were the anterior (41%) teeth, molars (37.2%), and then the premolars (21.8%). Based on our results, there was no significant association between these prognostic factors and the treatment outcome. Although these results are consistent with previously published data (78, 92, 102), it is worth noting that maxillary molars have been shown to have better healing outcomes when compared to mandibular teeth (92). Our results indicated no significant difference. Preoperative clinical symptoms—62.8% of cases presented with preoperative clinical symptoms and 37.2% did not. Our results agreed with previously published data, which reported no significant correlation between preoperative clinical signs/symptoms and EMS outcome, although they had a larger sample size (78, 97). Thus indicating that this prognostic factor does not influence the treatment outcome. 60 Moreover, in terms of the treatment sequence, most of the patients (44.9%) had only EMS as the first treatment of choice, 30% of cases had non-surgical root canal retreatment (Re-RCT) followed by EMS, 23.1% of the patients had non-surgical root canal treatment (RCT) followed by EMS, and only 2% of patients went through all treatment modalities (RCT, Re-RCT, followed by EMS). This study found that the treatment sequence had no significant impact on the EMS outcome; this finding is in agreement with a previously published study (87). The retro-filling material used—in this study, only two retrofilling materials were used, ProRoot MTA (17.9%) or RRM putty (82.1%). The outcome was not affected by the retro-filling materials used; this finding is in agreement with previously published data (87, 97). The biopsy result report—out of the 78 teeth, the biopsy results were not applicable for 36 teeth. Most cases had a non-cystic lesion (48.7%) on their biopsy report, and only 5.1% had cystic lesions. The biopsy result had asignificant impact on the treatment outcome using both radiographic methods when the bivariable analysis was conducted; whereas, no significant effect on the treatment outcome was noted when the multivariable analysis was used. Based on the incosistencey of the results when different testing methods were used, suggested this factor is confounded and should be considered for further investigation in future studies with larger sample size. Therefore, based on our findings the biopsy results can not be considered as a significant prognostic factor. The biopsy result has been found to have no significant impact on the treatment outcome, 61 when the association between the cystic and non-cystic lesion have been previously invistigated (102). Moreover, our results showed that more more non-cystic lesions on the biopsy results than the radicular cyst, this finding is consistinent with what has been previously published (103). Moreover, the grafting techniques and materials should have been investigated more thoroughly, which can be considered a limitation of this project. Grafting has been proposed as an adjunct during EMS to enhance hard tissue healing at the surgical site, known as guided tissue regeneration (GTR) (104). GTR procedures can be done using bone graft material only, resorbable collagen membrane by itself, or a combination of both. Our results showed that grafting was found to be an effect modifier. This is consistent, to some extent, with what was found in previously published data; their results showed that grafting did not significantly impact the treatment outcome, but it did improve bone regeneration at the cortical plate based on the CBCT criteria (87). Therefore, a significant association was absent between the selected prognostic factors in this study and the EMS outcome using the CBCT and the PA indices separately. 62 III. Prognostic factor(s) that resulted in a non-significant correlation to the EMS outcome based on our findings in this study but are inconsistent with previously published reports: The two prognostic factors further discussed here are the quality of the coronal restoration and the quality of RCT prior to surgery. Based on our results, of the 78 teeth, 85.9% had adequate coronal restoration. Previous studies have found that there was significant periapical healing associated with an adequate coronal restoration (91, 105). Also, many studies concluded that there is a proportional correlation between the quality of the root canal treatment at the time of the surgery and the quality of the coronal restoration at the follow-up (85, 97, 105). It has been reported that inadequate root canal treatment has a greater chance of EMS failure (97), while another study noted that inadequate root canal treatment could be managed during the EMS by performing deeper retro-preparation (87). It has also been reported that when the quality of the coronal restoration was good, the chance of the periapical area having complete healing was three times more likely than when the coronal restoration was poor or absent (91). The current results showed that 85.9% of the cases had adequate RCT before the surgery and 14.1% were inadequate; also 38.5% of the cases had a good crown and 61.5% had a poor crown. Moreover, these two factors had no significant correlation with the EMS outcome. This inconsistency could be related to the methods used in evaluating the radiographic outcome, as one of the studies used PA radiographs to assess the healing of a three-dimensional object, or due to the different treatment approach that was followed. 63 Since most of the prognostic factors were not significantly associated with the EMS outcome. This could be related to the small sample size and/or the limitation associated with the retrospective study. Therefore, the prognostic factors were determined based on the available information on the patient’s charts. Accordingly, these two hypotheses can be partially accepted, since one of the prognostic factors was found to have a significant impact on the EMS outcome; two prognostic factors had inconsistent results when different statistical analysis tests were conducted, which means that these prognostic factors are worth further investigation with a larger sample size to confirm their impact on the EMS outcome. 5.3 Limitations There were a number of limitations in this study. One issue was the retrospective approach to collect all patients’ information from the electronic dental chart platform, where some local factors would have been beneficial to include, and we could not collect or identify all EMS cases on the electronic platform. Another issue was the small sample size. However, the number of included teeth was comparable to similar studies (87, 106). In this study a low sample size occurred because of the exclusion of many cases due to a lack of pre-operative CBCT radiographs, which are essential to assess the healing outcome based on indices set out by Chen et al. (86). And finally, there was inconsistency in the follow-up time and the low recall rate among residents. 64 5.4 Future directions Future prospective research with a larger sample size and consistent interval follow-up will provide better control of the prognostic variables. Including more than one group with/without GTR to compare and prove the clinical significance of grafting on the healing outcome. Additionally, pre- and post-EMS CBCT is recommended to investigate the quality of the hard tissue healing at the surgical site. Some prognostic factors that could influence the treatment outcome were investigated for the first time and needed further investigation with a larger sample size (e.g. medical condition(s) and untreated anatomy). In addition, annual follow-ups are required to analyze the healing process closely. 65 Chapter 6: Conclusions Within the limitations of the present study: I. The outcome of endodontic microsurgery performed by the Graduate Endodontic residents at the University of British Columbia was predictable, with a follow-up of 1 to 11 years, and had a high success rate. Overall all success was 80.8%, and survival was 91.02%. II. The success rate based on CBCT was slightly lower than PA, as it has higher sensitivity and specificity to evaluate a three-dimensional object than PA. Therefore, the success rate based on CBCT was lower than PA. III. 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Thesis/Dissertation
eng
Craniofacial Science
Vancouver : University of British Columbia Library
Attribution-NonCommercial-NoDerivatives 4.0 International
Graduate
Shen, Ya
Outcome analysis of endodontic microsurgery in UBC’s graduate endodontics program
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