**3. Results**

Out of 40 patients, 32 (80%) patients were below 30 years of age while only 8 (20%) patients were above the age of 30 years. The gender distribution showed that 88 (58.7%) of the patients were male and 62 (41.3%) were female. Most of the patients, 26 (65.0%), were nonsmokers. The size of the preoperative periapical lesion was arbitrarily categorized into 6 mm or less and more than 6 mm for this study. The results showed that half of the patients had a periapical lesion size of 6 mm or less, while another half had more than 6 mm. Preoperative pain was present in 22 patients (55.01%) (Table 1).

**Table 1.** Descriptive Statistics for Demographics.


There was a statistically significant association between periapical healing and age (*p*-value = 0.025), smoking (*p*-value = 0.029) and the size of periapical lesion (*p*-value < 0.001). After periapical surgery, healing was observed in 29 patients, in which 26 (81.3%) patients were below the age of 30 years while only 3 (37.5%) patients were above 30 years of age on one year follow-up. Similarly, 22 nonsmoking patients (84.6%) revealed periapical healing compared to 7 (50%) smoking patients. Although the success of healing was higher in males, at 78.6% (22/28), compared to females, at 58.3% (7/12), no statistically significant relationship was found between gender and healing (*p*-value = 0.254). Likewise, no significant association between the presence of preoperative pain and postoperative healing (*p*-value = 0.723) was observed (Table 2).


**Table 2.** Relationship of Periapical Healing with Age, Gender, Smoking, Preoperative pain, and Periapical lesion size on one year follow-up.

¥ Chi-squared test, ˆ Fisher's Exact Test.

#### **4. Discussion**

The current study was conducted to evaluate the effect of various preoperative factors such as age, gender, smoking, preoperative pain, and preoperative periapical lesion size on the outcome of surgical endodontic treatment. The results of the study showed a statistically significant relationship between periapical wound healing and age, smoking, and preoperative lesion size.

Surgical endodontic retreatment is employed in managing recurrent secondary periapical lesions as a consequence of primary root canal treatment failure [19]. Surgical endodontic retreatment involves re-root canal treatment with subsequent sectioning of the apical end of the root followed by retrograde obturation and establishment of the apical seal of the root canal system. This apical seal facilitates healing of the periapical tissues by preventing the ingress of microbial irritants into the periapical area and concomitant tissue reaction [3].

It has now become clinically evident that even if the surgical endodontic treatment has been conducted using the same procedure, patients respond differently with respect to periapical wound healing [3,4]. This difference in periapical wound healing may be due to the presence of various preoperative factors such as pain, swelling, sinus tract, smoking, and size of the periapical lesion. However, evidence to support the influence of these preoperative factors on the outcome of periapical surgery are conflicting. In addition, most of the clinical studies that exist in the literature are retrospective [8,20,21]. The novelty

of this study lies in following patients prospectively and opening an avenue for further research in this direction.

Age is considered a prognostic indicator of outcome for many surgical procedures [4]. In this study, 81.3% healing was achieved in patients below 30 years of age. This finding is in agreement with Kriesler et al. [22] They found a 95% success in patients between 21 to 40 years of age. Contrarily, Barone et al. [23] reported 84% success in periapical healing in patients above 45 years of age, compared to 68% in patients below 45 years of age. This study observed no significant relationship between healing and gender. Similarly, a large number of studies did not find gender as a prognostic factor for periapical surgery [18,24,25]. However, Peñarrocha-Diago et al. reported a higher success in males (60%) compared to females (40%) at 6 months [26].

The habit of smoking can influence the outcome of periapical surgery by several plausible biological mechanisms. First, smoking interferes with the function of lymphocytes, leukocytes, macrophages and increases the level of various proinflammatory mediators, such as TNF- α, IL-6, and C-reactive protein [27,28]. Second, smoking decreases the fibroblast migration to the periapical wound area and stimulates the function of osteoclastic cells, which encourage bone resorption [29]. Third, smoking causes morphological alteration in the microvasculature, which in turn disturbs the oxygen and nutrient supply to the periapical wound area [30]. In the current study, a positive trend of healing was observed in nonsmokers (84.6%). This finding conforms to Lopez et al. [8] and Kirkevang et al. [31], who found a statistically significant association between smoking and periapical healing. On the other hand, Rodriguez et al. [32] and Balto et al. [33] reported no significant difference in periapical periodontitis between smokers and nonsmokers.

The presence of preoperative pain and swelling or sinus tract may also govern the outcome of periapical surgery as indicated by many studies. Von Arc et al. [20] revealed that the presence of preoperative signs and symptoms discourages healing. They postulated that the healing potential of surgical wounds could be significantly affected by the stage of infection at the time of surgery, which is influenced by preoperative pain and signs. Similarly, Kreisler et al. [22] also claimed a lower success rate in patients with pretreatment pain. Contrastingly, the present study did not find any difference in the healing success rate in relation to the presence of preoperative pain, similarly to Song et al. [34] and Peñarrocha et al. [35]. The reason for there being no relation between the presence of preoperative pain and periapical healing after surgical endodontic treatment may be due to the fact that same treatment protocol was used for every patient and all treatment procedures were performed by the principal investigator.

Another important prognostic factor in periapical healing is the size of the lesion. In the present study, 100% successful healing was observed in patients with preoperative lesions of less than 6 mm, while 45% healing success was evident in patients with more than 6 mm of preoperative lesion size. A large number of studies have described the favorable prognosis after periapical surgery in patients with preoperative lesions of less than 5 mm in diameter [20,26,34]. Alternatively, Barone et al. [23] found an 80% success rate in periapical lesions of less than 10 mm in size at the time of surgery, compared to 53% success in periapical lesions of more than 10 mm in size.

Multiple systemic diseases are known to interfere with periapical healing, such as diabetes, hypertension, osteoporosis, or any uncontrolled systemic disease. Hyperglycemia increases the level of inflammatory markers and influences the various functions of the patient immune system [36]. Similarly, hypertension is associated with alterations in response and differentiation of bone cells at various levels [21]. Moreover, the drug bisphosphonate is commonly used for the treatment and prevention of osteoporosis and it is well-established that it reduces bone remodeling [37], therefore patients with these systemic diseases were excluded from this study, in addition to the patients with a preexisting medical condition such as pregnancy and lactating mothers. Further prospective studies are required to evaluate postoperative healing in relation to the presence of different chronic systemic diseases using microsurgical techniques.

The findings of the study must be seen in light of some limitations. First, periapical surgery was performed by the conventional approach rather than microsurgical. The microsurgical approach offers numerous benefits such as small osteotomy, easy identification of root apices, visualization of minor anatomical variations, and preservation of cortical bone and root length by nearly 90-degree root resection. Several studies have shown the superiority of microsurgical endodontic treatment in comparison to traditional root-end surgery [38,39]. Second, the healing was assessed on a digital periapical radiograph, using a cone indicator and reference marker to ensure constant distance and angle between X-ray cone and sensor on every shoot. Moreover, exposure time, tube current, and voltage were the same on recall images. However, the X-ray image obtained was still two-dimensional, with a high probability of missing details in the third dimension. Nowadays, cone beam computed tomography (CBCT) is considered a standard of care [40] and has great value in establishing the correct diagnosis and in evaluating periapical healing after surgical endodontic treatment. Third, periapical surgery was performed on single-rooted anterior teeth only, multirooted posterior teeth where surgical access to treatment is difficult and high chances of variation in root morphology were excluded. Lastly, the sample size of the study was small due to the constrained study time, therefore; the results should be interpreted cautiously and may not represent the large population.

There is also a dire need to design a questionnaire which can evaluate the healthrelated quality of patients' life after endodontic surgery, similar to The University of Washington Quality of Life Questionnaire (UW-QOL) for head-and-neck cancer patients [41]. Future studies are also desirable with the inclusion of a large sample size, multirooted teeth and various other treatment-related factors such as microsurgical technique, type of root-end filling, method of root-end resection and retrograde cavity preparation. Addition of tools such as fractal analysis used for the quantitative evaluation of bone trabeculation following periapical surgery will also help in the early detection of complex structural patterns in the trabecular bone [42].

#### **5. Conclusions**

Patient age, smoking status, and size of the preoperative lesion had a strong influence on periapical healing after surgical endodontic treatment. However, other perioperative (treatment-related) factors should also be taken into account to establish conclusive evidence.

**Author Contributions:** Conceptualization, M.A.A., N.M. and S.H.A.; methodology, M.A.A.; software, M.A.A.; validation, F.V., M.M., A.A. and M.F.B.; formal analysis, M.A.A.; investigation, M.A.A. and A.A.; resources, N.M. and S.H.A.; data curation, M.F.B.; writing—original draft preparation, M.A.A. and A.A.; writing—review and editing, M.A.A., F.V., M.M., A.A. and S.H.A.; visualization, N.M.; supervision, N.M., S.H.A. and M.F.B.; project administration, M.A.A. and A.A.; funding acquisition, M.A.A. All authors have read and agreed to the published version of the manuscript.

**Funding:** The authors are grateful to the Deanship of Scientific Research, King Saud University for supporting through Vice Deanship of Scientific Research Chairs, Engr. Abdullah Bugshan research chair for Dental and Oral Rehabilitation.

**Institutional Review Board Statement:** The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board, Dow University of Health Sciences (IRB-862/DUHS/Approval/2017/50) on 10 July 2017.

**Informed Consent Statement:** Informed consent was obtained from all subjects involved in the study.

**Data Availability Statement:** The data presented in this study are available on request from the corresponding author. The data are not publicly available due to ethical concerns.

**Conflicts of Interest:** The authors declare no conflict of interest.
