Australian Dental Journal
The official journal of the Australian Dental Association
Australian Dental Journal 2015; 60: 233–239 doi: 10.1111/adj.12326
Diagnostic value of panoramic radiography in predicting inferior alveolar nerve injury after mandibular third molar extraction: a meta-analysis W Liu,*# W Yin,†# R Zhang,‡ J Li,§ Y Zheng¶ *Department of Stomatology of Shanghai Xuhui Central Hospital, Shanghai, China. †Department of Prosthodontics of Yangpu Dental Clinic, Shanghai, China. ‡Department of Stomatology of the Fifth People’s Hospital, Shanghai, China. §Department of Stomatology of Shanghai Huadong Hospital affiliated to Fudan University, Shanghai, China. ¶Department of Stomatology, Special Consultation Clinic, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.
ABSTRACT Background: The aim of this study was to evaluate the predictive value of panoramic radiography on inferior alveolar nerve (IAN) injury after extraction of the mandibular third molar. Methods: Relevant studies up to 1 June 2014 that discussed the association of panoramic radiography signs and postmandibular third molar extraction IAN injury were systematically retrieved from the databases of PubMed, Embase, Springerlink, Web of Science and Cochrane library. The effect size of pooled sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR) and diagnostic odds ratio (DOR) with their 95% confidence intervals (CI) were statistically analysed with Meta-disc 1.4 software. Results: Nine articles were included in this meta-analysis. The pooled estimates of sensitivity and specificity were 0.56 (95% CI: 0.50–0.61) and 0.86 (95% CI: 0.84–0.87), respectively. The overall PLR was 3.46 (95% CI: 2.02–5.92) and overall NLR was 0.58 (95% CI: 0.45–0.73). The pooled estimate of DOR was 6.49 (95% CI: 2.92–14.44). The area under the summary receiver operating characteristic curve was 0.7143 0.0604. Conclusions: The meta-analysis indicated that interpretation of panoramic radiography based on darkening of the root had a high specificity in predicting IAN injury after mandibular third molar extraction. However, the ability of this panoramic radiography marker to detect true positive IAN injury was not satisfactory. Keywords: Inferior alveolar nerve injury, mandibular third molar extraction, meta-analysis, panoramic radiography, post-mandibular. Abbreviations and acronyms: DOR = diagnostic odds ratio; FN = false negative; FP = false positive; IAN = inferior alveolar nerve; NLR = negative likelihood ratio; PLR = positive likelihood ratio; QUADAS = Quality Assessment of Diagnostic Accuracy; Sen = sensitivity; Spe = specificity; SROC = summary receiver operating characteristic; TR = true negative; TP = true positive. (Accepted for publication 14 July 2014.)
INTRODUCTION Extraction of the mandibular third molar is one of the most common surgical procedures performed by oral and maxillofacial surgeons. There are complications associated with this procedure, mainly neurosensory deficit. Inferior alveolar nerve (IAN) injury, which can result in paraesthesia of the lower lip region and significantly affect patient quality of life, is an infrequent but serious nerve complication following the extraction of mandibular third molars.1–3 The reported incidence of IAN paraesthesia after mandibular third molar extraction ranges from 0.4% to 8.4%.4 #The first two authors contributed equally to this work. © 2015 Australian Dental Association
Usually, the injured IAN can recover spontaneously. The frequency of permanent dysfunction of IAN is less than 1%.5 Permanent IAN injury can lead to considerable morbidity and patient dissatisfaction. Multiple clinical studies have investigated the relationships between IAN injury and the status of the third molar, such as the depth of impaction, angulation, and the number and divergence of the roots. It has been proposed that the most important factor contributing to IAN injury may be the anatomic proximity of the IAN to the third molar root.6–8 Therefore, it is essential to evaluate the anatomic relationship between the IAN (in the mandibular canal) and the impacted third molar prior to mandibular third molar surgery. 233
W Liu et al. Currently, panoramic radiography is the most commonly used radiographic technique for this purpose. Researchers have identified several radiographic signs which might be significantly associated with IAN injury following third molar extraction. These include darkening of the root, deflected roots, narrowing of the root, interruption of the white line and diversion of the IAN canal.3,9 However, the predictive values of some signs are subject to much debate. Some researchers believe panoramic radiography cannot provide reliable images for predicting the risk of IAN injury after third molar surgery.5,10 Therefore, it is necessary to comprehensively evaluate the diagnostic value of panoramic radiography on IAN injury after extraction of the mandibular third molar. MATERIALS AND METHODS
form: first author’s name; year of publication; region where the research was conducted; sample size; age and gender of the subjects; TP, FP, TN and FN data; and the diagnosed time of mandibular third molar surgery. Any discrepancies were resolved by discussion or by referencing the original publishers. The quality of the articles was evaluated with a 14-item Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool.11 Each item was to be answered with a ‘Yes’, ‘No’ or ‘Not clear’. Given the quality of the literature was largely associated with methods and outcomes, a study lacking detail in these two areas may have resulted in a relatively lower score, even if it was a scientifically rigorous study. Therefore, we provided a brief description of the quality of the literature but did not report the evaluation scores.
Search strategy
Statistical analysis
We pre-established a search strategy and systematically retrieved relevant literature published up to 1 June 2014 from the PubMed, Embase, Web of Science, Cochrane library and Springerlink databases. The keywords used for all searches were ‘inferior alveolar nerve’ OR ‘inferior dental nerve’; AND ‘mandibular third molar’ OR ‘third molar extraction’ OR ‘third molar surgery’; AND ‘radiographic’ OR ‘panoramic radiography’ OR ‘orthopantomogram’ OR ‘pantomography’. In addition, a manual search of print documents and citations from identified articles and relevant review articles was performed for any additional studies.
Analyses in this study were conducted with Meta-disc 1.4 software.12 The effect size of adjusted sensitivity (Sen), specificity (Spe), positive likelihood ratios (PLR), negative likelihood ratios (NLR) and diagnostic odds ratio (DOR) with their 95% CI were pooled. The DOR, as a measurement of test performance, combines the strengths of sensitivity and specificity with the advantage of accuracy as a single indicator. The value of DOR ranges from 0 to infinity, with higher values indicating a better discriminatory test performance.13 A summary receiver operating characteristic (SROC) curve was constructed to quantitatively summarize the study results. The SROC curve, another measure of test performance, also combines the strengths of sensitivity and specificity. The area under the curve ranges from 0 to 1, with a value closer to 1 indicating higher diagnostic validity.14 Heterogeneity among studies was evaluated by chisquare test for pooling Sen, Spe, PLR and NLR data. The heterogeneity of pooling DOC was evaluated by
Inclusion and exclusion criteria Studies included in the present meta-analysis had to meet the following criteria: (1) the research was on the IAN injury diagnosed with panoramic radiographs; (2) the subject was a patient who underwent a surgical extraction of a mandibular third molar; (3) the detection standards were the clinical manifestations or follow-up data after third molar extraction surgery; (4) the true positive (TP), false positive (FP), true negative (TN) and false negative (FN) diagnosed based on darkening of the root (one type of radiographic sign) could be provided or calculated from the provided data. The exclusion criteria were: (1) articles that were not in English; (2) articles that were not original literature, e.g. reviews, letters or comments; (3) articles that were republished or literature that shared the same population data. Data extraction and quality evaluation Two investigators independently reviewed the articles and extracted the following data using a standardized 234
Fig. 1 Literature search and study selection. © 2015 Australian Dental Association
Panoramic radiography in predicting inferior alveolar nerve injury Cochran’s Q test.15 The I2 parameter was applied to evaluate the total heterogeneity of the study.16 P < 0.05 or I2 > 50% was considered to be heterogeneous.
strategies, we achieved 72, 164, 122, 127 and 11 articles from the databases of Embase, PubMed, Springer, Web of Science and Cochrane library, respectively. A total of 184 republications and 292 irrelevant articles were eliminated. We then reviewed the full texts of the remaining 20 articles. Another 11 articles were excluded for not meeting the required criteria. Ultimately, only nine articles met the inclusion criteria and were used for the metaanalysis. There were no additional articles obtained by the manual search.
RESULTS Literature retrieval A flow chart of the literature searched is shown in Fig. 1. In accordance with pre-established search
Table 1. Characteristics of the included studies Author
Year
Area
TP
FP
FN
TN
Patient, F/M
Third molars
Age
Rood Blaeser Bell Sedaghatfar Tantanapornkul Gomes Szalma Leung Kim
1990 2003 2004 2005 2007 2008 2010 2011 2012
UK USA UK USA Japan Brazil Hungary China Korea
8 26 12 17 19 3 27 6 55
38 56 11 55 43 50 22 44 62
13 14 23 7 8 6 14 3 49
701 154 254 344 72 201 337 125 73
552# 25# 219# 230, 138/92 120# 153, 113/40 400, 424/156 118, 73/45 239, 107/132
760 250* 300 423 142 260 400 178 239
NP 28.1a NP 24.0(5.2) 18–74 19.96(4.06)b 15–77 26.2(6.3) 15–61c
TP: true positive; FP: false positive; TN: true negative; FN: false negative; #: No sample size of the female and male numbers; *: 25 patients who have 2 mandibular third molars were evaluated by 5 surgeons independently, so there were 250 data; a: mean; b: mean(SD); c: range of age; NP: not provided.
Table 2. Quality assessment of the included articles QUADAS list item 1. Did the spectrum of patients represent the patients who will receive the test in practice? 2. Were selection criteria clearly described? 3. Is the reference standard likely to correctly classify the target condition? 4. Is the period between the reference standard and index test short enough to be reasonably sure that the target condition did not change between the 2 tests? 5. Did the entire sample or a random selection of the sample receive verification using a reference standard of diagnosis? 6. Did patients receive the same reference standard regardless of index test result? 7. Was the reference standard independent of the index test (i.e. index test did not form part of the reference standard)? 8. Was execution of the index test described in sufficient detail to permit replication of the test? 9. Was execution of the reference standard described in sufficient detail to permit its replication? 10. Were index test results interpreted without knowledge of results of the reference standard? 11. Were reference standard results interpreted without knowledge of results of the index test? 12. Were the same clinical data available when test results were interpreted as would be available when the test is used in practice? 13. Were uninterruptable/intermediate test results reported? 14. Were withdrawals from the study explained?
Rood
Bell
Blaeser
Sedaghatfar
Tantanapornkul
Gomes
Szalma
Leung
Kim
0
0
+
+
0
+
+
0
+
+ +
+ +
+ +
+ +
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QUADAS: Quality Assessment of Diagnostic Accuracy Studies; +: YES; © 2015 Australian Dental Association
0
: NO; 0: not clear. 235
W Liu et al.
(a)
(b)
Fig. 2 Sensitivity and specificity of each study of panoramic radiography on IAN injury after mandibular third molar extraction. The red circles represent the effect size for the sensitivity (A) and specificity (B) of panoramic radiography on IAN injury after mandibular third molar extraction. Size of the squares is proportional to the size of the cohorts. Error bars represent 95% CI. The diamond shape represents the pooled estimates within each analysis.
Study characteristics and quality assessment Characteristics of the included studies are shown in Table 1. The nine eligible articles,5,7,8,17–22 comprised 2056 patients for the extraction of 2952 mandibular third molars. Three studies were conducted in Europe (2 in the UK and 1 in the Hungary); 3 in Asia (1 each in China, Korea and Japan); 2 in the USA; and 1 in Brazil. Quality assessment of the included articles is shown in Table 2. All nine studies clearly described items 2–8 and 12–14 of the QUADAS list. Overall, the quality of the meta-analysis was moderate.
Meta-analysis of the diagnostic value of panoramic radiography The pooled estimates of sensitivity and specificity were 0.56 (95% CI: 0.50–0.61) and 0.86 (95% CI: 0.84–0.87) respectively for the ability of panoramic radiography, based on darkening of the root marker, to predict risk of IAN injury. Obvious heterogeneity for sensitivity (P = 0.0116 and I2 = 59.3%) and specificity (P < 0.0001 and I2 = 97.1%) was found (Fig. 2). The estimates of PLR and NLR are shown in Fig. 3. The overall PLR was 3.46 (95% CI: 2.02– 5.92), and significant heterogeneity was observed (P < 0.0001 and I2 = 93.0%). The overall NLR was 236
0.58 (95% CI: 0.45–0.73) with significant heterogeneity across the included studies (P = 0.0023 and I2 = 66.6%). The pooled estimate of DOR, presented in Fig. 4, was 6.49 (95% CI: 2.92–14.44) and significant heterogeneity (P < 0.0001 and I2 = 86.9%) was evident. The area under the SROC curve (AUC) for the marker of darkening of the root was 0.7143 0.0604 (Fig. 5). DISCUSSION IAN injury after mandibular third molar surgery is a well-recognized postoperative complication and may occur for a variety of reasons, including direct or indirect nerve compression, direct trauma from the surgical elevators or indirect trauma from root dislodgement or lack of bone protection, and postoperative IAN peripheral inflammation.4,19 Preoperative radiologic assessment of the characteristics of the mandibular third molar is essential to evaluate the topographic relationship between the mandibular canal and the impacted third molar, thus avoiding nerve injury. Panoramic radiography is most commonly used for this purpose.6–8 In the present study, we summarized the results of several diagnostic tests based on darkening of the root (one type of radiographic sign) indicated by panoramic radiogra© 2015 Australian Dental Association
Panoramic radiography in predicting inferior alveolar nerve injury
(a)
(b)
Fig. 3 Positive likelihood ratios and negative likelihood ratios of each study of panoramic radiography on IAN injury after mandibular third molar extraction. The red circles represent the effect size for the positive likelihood ratios sensitivity (A) and negative likelihood ratios (B) of panoramic radiography on IAN injury after mandibular third molar extraction. Size of the squares is proportional to the size of the cohorts. Error bars represent 95% CI. The diamond shape represents the pooled estimates within each analysis.
Fig. 4 Diagnostic odds ratio of each study of panoramic radiography on IAN injury during and after mandibular third molar extraction. The red circles represent the effect size for the diagnostic odds ratio of panoramic radiography on IAN injury after mandibular third molar extraction. Size of the squares is proportional to the size of the cohorts. Error bars represent 95% CI. The diamond shape represents the pooled estimates within each analysis.
phy. Our data showed that pooled sensitivity and specificity were 0.56 and 0.86, respectively. Clearly, sensitivity was relatively low although specificity was high. Sensitivity was less than 0.40 in three of the included studies. In addition, the overall PLR was 3.46, indicating that the ratio of the true positive in sick people correctly diagnosed as sick was only 3.46 fold to the ratio of the false positive in healthy people incorrectly identified as sick. Thus, the diagnostic © 2015 Australian Dental Association
ability of panoramic radiography based on darkening of the root is satisfactory but not ideal. Several studies have discussed the accuracy of panoramic radiography. As two-dimensional imaging, panoramic radiography has projection-geometric characteristics which may reduce accuracy. For example, it not only provides information on the position of the inferior alveolar canal in the vertical plane, but also has variable magnification. In panoramic radiography, lin237
W Liu et al.
Fig. 5 SROC curve of each study of panoramic radiography on IAN injury during and after mandibular third molar extraction.
gually positioned structures are projected upward, producing a sharp image layer (focal trough) of limited width.10,23,24 However, panoramic radiography is still the most common radiographic tool for third molar assessment in dental practice due to its lower cost, greater availability and low radiation exposure.25 In summary, the positive result of the present metaanalysis is consistent with published studies in which radiographic darkening of the third molar root is correlated with the occurrence of IAN injury after third molar surgery.7,19,20 Some limitations of this study should be noted. Firstly, there were only nine articles included in this meta-analysis. As the sample size was relatively small, there may be a potential risk for type II errors and therefore we caution against heavily weighting the negative findings. Secondly, there were obvious heterogeneities across studies included in this study which may have resulted from differences in population composition, quality of medical care and sample size. Thus, the results should be interpreted with caution. Finally, the present study included only published papers and some of the grey literature that might cause biases is excluded. Therefore, more high quality studies with large sample sizes should be undertaken to assess the generalization of our results. Panoramic radiography based on darkening of the root had a higher specificity in predicting IAN injury after mandibular third molar extraction. However, the positive result was not satisfactory as the accuracy was not significant. More high quality clinical data is required for further assessment of the value of radio238
graphic signs in predicting IAN injury post mandibular third molar surgery. REFERENCES 1. Bataineh AB. Sensory nerve impairment following mandibular third molar surgery. J Oral Maxillofac Surg 2001;59:1012– 1017. 2. Queral-Godoy E, Valmaseda-Castell on E, Berini-Aytes L, Gay-Escoda C. Incidence and evolution of inferior alveolar nerve lesions following lower third molar extraction. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;99:259–264. 3. Howe G, Poyton H. Prevention of damage to the inferior dental nerve during the extraction of mandibular third molars. Br Dent J 1960;109:353–363. 4. Jerjes W, Swinson B, Moles D, et al. Permanent sensory nerve impairment following third molar surgery: a prospective study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;102: e1–e7. 5. Gomes ACA, do Egito Vasconcelos BC, de Oliveira Silva ED, de Francßa Caldas A Jr, Neto ICP. Sensitivity and specificity of pantomography to predict inferior alveolar nerve damage during extraction of impacted lower third molars. J Oral Maxillofac Surg 2008;66:256–259. 6. Valmaseda-Castell on E, Berini-Aytes L, Gay-Escoda C. Inferior alveolar nerve damage after lower third molar surgical extraction: a prospective study of 1117 surgical extractions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;92:377–383. 7. Rood J, Nooraldeen Shehab B. The radiological prediction of inferior alveolar nerve injury during third molar surgery. Br J Oral Maxillofac Surg 1990;28:20–25. 8. Sedaghatfar M, August MA, Dodson TB. Panoramic radiographic findings as predictors of inferior alveolar nerve exposure following third molar extraction. J Oral Maxillofac Surg 2005;63:3–7. 9. Kipp DP, Goldstein BH, Weiss WW. Dysesthesia after mandibular third molar surgery: a retrospective study and analysis of 1377 surgical procedures. J Am Dent Assoc 1980;100:185–192. © 2015 Australian Dental Association
Panoramic radiography in predicting inferior alveolar nerve injury 10. Bell GW, Rodgers JM, Grime RJ, et al. The accuracy of dental panoramic tomographs in determining the root morphology of mandibular third molar teeth before surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:119– 125. 11. Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 2003;3:25. 12. Zamora J, Abraira V, Muriel A, Khan K, Coomarasamy A. Meta-DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol 2006;6:31. 13. Glas AS, Lijmer JG, Prins MH, Bonsel GJ, Bossuyt PM. The diagnostic odds ratio: a single indicator of test performance. J Clin Epidemiol 2003;56:1129–1135.
19. Leung YY, Cheung LK. Correlation of radiographic signs, inferior dental nerve exposure, and deficit in third molar surgery. J Oral Maxillofac Surg 2011;69:1873–1879. 20. Blaeser BF, August MA, Donoff RB, Kaban LB, Dodson TB. Panoramic radiographic risk factors for inferior alveolar nerve injury after third molar extraction. J Oral Maxillofac Surg 2003;61:417–421. 21. Szalma J, Lempel E, Jeges S, Szab o G, Olasz L. The prognostic value of panoramic radiography of inferior alveolar nerve damage after mandibular third molar removal: retrospective study of 400 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109:294–302.
14. Moses LE, Shapiro D, Littenberg B. Combining independent studies of a diagnostic test into a summary roc curve: dataanalytic approaches and some additional considerations. Stat Med 1993;12:1293–1316.
22. Kim J-W, Cha I-H, Kim S-J, Kim M-R. Which risk factors are associated with neurosensory deficits of inferior alveolar nerve after mandibular third molar extraction? J Oral Maxillofac Surg 2012;70:2508–2514. € 23. Flygare L, Ohman A. Preoperative imaging procedures for lower wisdom teeth removal. Clin Oral Investig 2008;12:291– 302.
15. Deeks JJ, Altman DG, Bradburn MJ. Statistical methods for examining heterogeneity and combining results from several studies in meta-analysis. In: Egger M, Davey Smith G, Altman DG, eds. Systematic Reviews in Health Care: Meta-analysis in Context. 2nd edn. London: BMJ Publishing Group, 2001:285– 312.
24. Scarfe W, Eraso F, Farman A. Characteristics of the orthopantomograph OP 100. Dentomaxillofac Radiol 1998;27:51–57. € 25. Ohman A, Kull L, Andersson J, Flygare L. Radiation doses in examination of lower third molars with computed tomography and conventional radiography. Dentomaxillofac Radiol 2008;37:445–452.
16. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557–560. 17. Bell G. Use of dental panoramic tomographs to predict the relation between mandibular third molar teeth and the inferior alveolar nerve: radiological and surgical findings, and clinical outcome. Br J Oral Maxillofac Surg 2004;42: 21–27. 18. Tantanapornkul W, Okouchi K, Fujiwara Y, et al. A comparative study of cone-beam computed tomography and conventional panoramic radiography in assessing the topographic relationship between the mandibular canal and impacted third molars. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:253–259.
© 2015 Australian Dental Association
Address for correspondence: Dr Yuanli Zheng Stomatology Special Consultation Clinic Ninth People’s Hospital Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Stomatology Shanghai 200011 China Email: [email protected]
239
The official journal of the Australian Dental Association
Australian Dental Journal 2015; 60: 233–239 doi: 10.1111/adj.12326
Diagnostic value of panoramic radiography in predicting inferior alveolar nerve injury after mandibular third molar extraction: a meta-analysis W Liu,*# W Yin,†# R Zhang,‡ J Li,§ Y Zheng¶ *Department of Stomatology of Shanghai Xuhui Central Hospital, Shanghai, China. †Department of Prosthodontics of Yangpu Dental Clinic, Shanghai, China. ‡Department of Stomatology of the Fifth People’s Hospital, Shanghai, China. §Department of Stomatology of Shanghai Huadong Hospital affiliated to Fudan University, Shanghai, China. ¶Department of Stomatology, Special Consultation Clinic, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.
ABSTRACT Background: The aim of this study was to evaluate the predictive value of panoramic radiography on inferior alveolar nerve (IAN) injury after extraction of the mandibular third molar. Methods: Relevant studies up to 1 June 2014 that discussed the association of panoramic radiography signs and postmandibular third molar extraction IAN injury were systematically retrieved from the databases of PubMed, Embase, Springerlink, Web of Science and Cochrane library. The effect size of pooled sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR) and diagnostic odds ratio (DOR) with their 95% confidence intervals (CI) were statistically analysed with Meta-disc 1.4 software. Results: Nine articles were included in this meta-analysis. The pooled estimates of sensitivity and specificity were 0.56 (95% CI: 0.50–0.61) and 0.86 (95% CI: 0.84–0.87), respectively. The overall PLR was 3.46 (95% CI: 2.02–5.92) and overall NLR was 0.58 (95% CI: 0.45–0.73). The pooled estimate of DOR was 6.49 (95% CI: 2.92–14.44). The area under the summary receiver operating characteristic curve was 0.7143 0.0604. Conclusions: The meta-analysis indicated that interpretation of panoramic radiography based on darkening of the root had a high specificity in predicting IAN injury after mandibular third molar extraction. However, the ability of this panoramic radiography marker to detect true positive IAN injury was not satisfactory. Keywords: Inferior alveolar nerve injury, mandibular third molar extraction, meta-analysis, panoramic radiography, post-mandibular. Abbreviations and acronyms: DOR = diagnostic odds ratio; FN = false negative; FP = false positive; IAN = inferior alveolar nerve; NLR = negative likelihood ratio; PLR = positive likelihood ratio; QUADAS = Quality Assessment of Diagnostic Accuracy; Sen = sensitivity; Spe = specificity; SROC = summary receiver operating characteristic; TR = true negative; TP = true positive. (Accepted for publication 14 July 2014.)
INTRODUCTION Extraction of the mandibular third molar is one of the most common surgical procedures performed by oral and maxillofacial surgeons. There are complications associated with this procedure, mainly neurosensory deficit. Inferior alveolar nerve (IAN) injury, which can result in paraesthesia of the lower lip region and significantly affect patient quality of life, is an infrequent but serious nerve complication following the extraction of mandibular third molars.1–3 The reported incidence of IAN paraesthesia after mandibular third molar extraction ranges from 0.4% to 8.4%.4 #The first two authors contributed equally to this work. © 2015 Australian Dental Association
Usually, the injured IAN can recover spontaneously. The frequency of permanent dysfunction of IAN is less than 1%.5 Permanent IAN injury can lead to considerable morbidity and patient dissatisfaction. Multiple clinical studies have investigated the relationships between IAN injury and the status of the third molar, such as the depth of impaction, angulation, and the number and divergence of the roots. It has been proposed that the most important factor contributing to IAN injury may be the anatomic proximity of the IAN to the third molar root.6–8 Therefore, it is essential to evaluate the anatomic relationship between the IAN (in the mandibular canal) and the impacted third molar prior to mandibular third molar surgery. 233
W Liu et al. Currently, panoramic radiography is the most commonly used radiographic technique for this purpose. Researchers have identified several radiographic signs which might be significantly associated with IAN injury following third molar extraction. These include darkening of the root, deflected roots, narrowing of the root, interruption of the white line and diversion of the IAN canal.3,9 However, the predictive values of some signs are subject to much debate. Some researchers believe panoramic radiography cannot provide reliable images for predicting the risk of IAN injury after third molar surgery.5,10 Therefore, it is necessary to comprehensively evaluate the diagnostic value of panoramic radiography on IAN injury after extraction of the mandibular third molar. MATERIALS AND METHODS
form: first author’s name; year of publication; region where the research was conducted; sample size; age and gender of the subjects; TP, FP, TN and FN data; and the diagnosed time of mandibular third molar surgery. Any discrepancies were resolved by discussion or by referencing the original publishers. The quality of the articles was evaluated with a 14-item Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool.11 Each item was to be answered with a ‘Yes’, ‘No’ or ‘Not clear’. Given the quality of the literature was largely associated with methods and outcomes, a study lacking detail in these two areas may have resulted in a relatively lower score, even if it was a scientifically rigorous study. Therefore, we provided a brief description of the quality of the literature but did not report the evaluation scores.
Search strategy
Statistical analysis
We pre-established a search strategy and systematically retrieved relevant literature published up to 1 June 2014 from the PubMed, Embase, Web of Science, Cochrane library and Springerlink databases. The keywords used for all searches were ‘inferior alveolar nerve’ OR ‘inferior dental nerve’; AND ‘mandibular third molar’ OR ‘third molar extraction’ OR ‘third molar surgery’; AND ‘radiographic’ OR ‘panoramic radiography’ OR ‘orthopantomogram’ OR ‘pantomography’. In addition, a manual search of print documents and citations from identified articles and relevant review articles was performed for any additional studies.
Analyses in this study were conducted with Meta-disc 1.4 software.12 The effect size of adjusted sensitivity (Sen), specificity (Spe), positive likelihood ratios (PLR), negative likelihood ratios (NLR) and diagnostic odds ratio (DOR) with their 95% CI were pooled. The DOR, as a measurement of test performance, combines the strengths of sensitivity and specificity with the advantage of accuracy as a single indicator. The value of DOR ranges from 0 to infinity, with higher values indicating a better discriminatory test performance.13 A summary receiver operating characteristic (SROC) curve was constructed to quantitatively summarize the study results. The SROC curve, another measure of test performance, also combines the strengths of sensitivity and specificity. The area under the curve ranges from 0 to 1, with a value closer to 1 indicating higher diagnostic validity.14 Heterogeneity among studies was evaluated by chisquare test for pooling Sen, Spe, PLR and NLR data. The heterogeneity of pooling DOC was evaluated by
Inclusion and exclusion criteria Studies included in the present meta-analysis had to meet the following criteria: (1) the research was on the IAN injury diagnosed with panoramic radiographs; (2) the subject was a patient who underwent a surgical extraction of a mandibular third molar; (3) the detection standards were the clinical manifestations or follow-up data after third molar extraction surgery; (4) the true positive (TP), false positive (FP), true negative (TN) and false negative (FN) diagnosed based on darkening of the root (one type of radiographic sign) could be provided or calculated from the provided data. The exclusion criteria were: (1) articles that were not in English; (2) articles that were not original literature, e.g. reviews, letters or comments; (3) articles that were republished or literature that shared the same population data. Data extraction and quality evaluation Two investigators independently reviewed the articles and extracted the following data using a standardized 234
Fig. 1 Literature search and study selection. © 2015 Australian Dental Association
Panoramic radiography in predicting inferior alveolar nerve injury Cochran’s Q test.15 The I2 parameter was applied to evaluate the total heterogeneity of the study.16 P < 0.05 or I2 > 50% was considered to be heterogeneous.
strategies, we achieved 72, 164, 122, 127 and 11 articles from the databases of Embase, PubMed, Springer, Web of Science and Cochrane library, respectively. A total of 184 republications and 292 irrelevant articles were eliminated. We then reviewed the full texts of the remaining 20 articles. Another 11 articles were excluded for not meeting the required criteria. Ultimately, only nine articles met the inclusion criteria and were used for the metaanalysis. There were no additional articles obtained by the manual search.
RESULTS Literature retrieval A flow chart of the literature searched is shown in Fig. 1. In accordance with pre-established search
Table 1. Characteristics of the included studies Author
Year
Area
TP
FP
FN
TN
Patient, F/M
Third molars
Age
Rood Blaeser Bell Sedaghatfar Tantanapornkul Gomes Szalma Leung Kim
1990 2003 2004 2005 2007 2008 2010 2011 2012
UK USA UK USA Japan Brazil Hungary China Korea
8 26 12 17 19 3 27 6 55
38 56 11 55 43 50 22 44 62
13 14 23 7 8 6 14 3 49
701 154 254 344 72 201 337 125 73
552# 25# 219# 230, 138/92 120# 153, 113/40 400, 424/156 118, 73/45 239, 107/132
760 250* 300 423 142 260 400 178 239
NP 28.1a NP 24.0(5.2) 18–74 19.96(4.06)b 15–77 26.2(6.3) 15–61c
TP: true positive; FP: false positive; TN: true negative; FN: false negative; #: No sample size of the female and male numbers; *: 25 patients who have 2 mandibular third molars were evaluated by 5 surgeons independently, so there were 250 data; a: mean; b: mean(SD); c: range of age; NP: not provided.
Table 2. Quality assessment of the included articles QUADAS list item 1. Did the spectrum of patients represent the patients who will receive the test in practice? 2. Were selection criteria clearly described? 3. Is the reference standard likely to correctly classify the target condition? 4. Is the period between the reference standard and index test short enough to be reasonably sure that the target condition did not change between the 2 tests? 5. Did the entire sample or a random selection of the sample receive verification using a reference standard of diagnosis? 6. Did patients receive the same reference standard regardless of index test result? 7. Was the reference standard independent of the index test (i.e. index test did not form part of the reference standard)? 8. Was execution of the index test described in sufficient detail to permit replication of the test? 9. Was execution of the reference standard described in sufficient detail to permit its replication? 10. Were index test results interpreted without knowledge of results of the reference standard? 11. Were reference standard results interpreted without knowledge of results of the index test? 12. Were the same clinical data available when test results were interpreted as would be available when the test is used in practice? 13. Were uninterruptable/intermediate test results reported? 14. Were withdrawals from the study explained?
Rood
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QUADAS: Quality Assessment of Diagnostic Accuracy Studies; +: YES; © 2015 Australian Dental Association
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: NO; 0: not clear. 235
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(a)
(b)
Fig. 2 Sensitivity and specificity of each study of panoramic radiography on IAN injury after mandibular third molar extraction. The red circles represent the effect size for the sensitivity (A) and specificity (B) of panoramic radiography on IAN injury after mandibular third molar extraction. Size of the squares is proportional to the size of the cohorts. Error bars represent 95% CI. The diamond shape represents the pooled estimates within each analysis.
Study characteristics and quality assessment Characteristics of the included studies are shown in Table 1. The nine eligible articles,5,7,8,17–22 comprised 2056 patients for the extraction of 2952 mandibular third molars. Three studies were conducted in Europe (2 in the UK and 1 in the Hungary); 3 in Asia (1 each in China, Korea and Japan); 2 in the USA; and 1 in Brazil. Quality assessment of the included articles is shown in Table 2. All nine studies clearly described items 2–8 and 12–14 of the QUADAS list. Overall, the quality of the meta-analysis was moderate.
Meta-analysis of the diagnostic value of panoramic radiography The pooled estimates of sensitivity and specificity were 0.56 (95% CI: 0.50–0.61) and 0.86 (95% CI: 0.84–0.87) respectively for the ability of panoramic radiography, based on darkening of the root marker, to predict risk of IAN injury. Obvious heterogeneity for sensitivity (P = 0.0116 and I2 = 59.3%) and specificity (P < 0.0001 and I2 = 97.1%) was found (Fig. 2). The estimates of PLR and NLR are shown in Fig. 3. The overall PLR was 3.46 (95% CI: 2.02– 5.92), and significant heterogeneity was observed (P < 0.0001 and I2 = 93.0%). The overall NLR was 236
0.58 (95% CI: 0.45–0.73) with significant heterogeneity across the included studies (P = 0.0023 and I2 = 66.6%). The pooled estimate of DOR, presented in Fig. 4, was 6.49 (95% CI: 2.92–14.44) and significant heterogeneity (P < 0.0001 and I2 = 86.9%) was evident. The area under the SROC curve (AUC) for the marker of darkening of the root was 0.7143 0.0604 (Fig. 5). DISCUSSION IAN injury after mandibular third molar surgery is a well-recognized postoperative complication and may occur for a variety of reasons, including direct or indirect nerve compression, direct trauma from the surgical elevators or indirect trauma from root dislodgement or lack of bone protection, and postoperative IAN peripheral inflammation.4,19 Preoperative radiologic assessment of the characteristics of the mandibular third molar is essential to evaluate the topographic relationship between the mandibular canal and the impacted third molar, thus avoiding nerve injury. Panoramic radiography is most commonly used for this purpose.6–8 In the present study, we summarized the results of several diagnostic tests based on darkening of the root (one type of radiographic sign) indicated by panoramic radiogra© 2015 Australian Dental Association
Panoramic radiography in predicting inferior alveolar nerve injury
(a)
(b)
Fig. 3 Positive likelihood ratios and negative likelihood ratios of each study of panoramic radiography on IAN injury after mandibular third molar extraction. The red circles represent the effect size for the positive likelihood ratios sensitivity (A) and negative likelihood ratios (B) of panoramic radiography on IAN injury after mandibular third molar extraction. Size of the squares is proportional to the size of the cohorts. Error bars represent 95% CI. The diamond shape represents the pooled estimates within each analysis.
Fig. 4 Diagnostic odds ratio of each study of panoramic radiography on IAN injury during and after mandibular third molar extraction. The red circles represent the effect size for the diagnostic odds ratio of panoramic radiography on IAN injury after mandibular third molar extraction. Size of the squares is proportional to the size of the cohorts. Error bars represent 95% CI. The diamond shape represents the pooled estimates within each analysis.
phy. Our data showed that pooled sensitivity and specificity were 0.56 and 0.86, respectively. Clearly, sensitivity was relatively low although specificity was high. Sensitivity was less than 0.40 in three of the included studies. In addition, the overall PLR was 3.46, indicating that the ratio of the true positive in sick people correctly diagnosed as sick was only 3.46 fold to the ratio of the false positive in healthy people incorrectly identified as sick. Thus, the diagnostic © 2015 Australian Dental Association
ability of panoramic radiography based on darkening of the root is satisfactory but not ideal. Several studies have discussed the accuracy of panoramic radiography. As two-dimensional imaging, panoramic radiography has projection-geometric characteristics which may reduce accuracy. For example, it not only provides information on the position of the inferior alveolar canal in the vertical plane, but also has variable magnification. In panoramic radiography, lin237
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Fig. 5 SROC curve of each study of panoramic radiography on IAN injury during and after mandibular third molar extraction.
gually positioned structures are projected upward, producing a sharp image layer (focal trough) of limited width.10,23,24 However, panoramic radiography is still the most common radiographic tool for third molar assessment in dental practice due to its lower cost, greater availability and low radiation exposure.25 In summary, the positive result of the present metaanalysis is consistent with published studies in which radiographic darkening of the third molar root is correlated with the occurrence of IAN injury after third molar surgery.7,19,20 Some limitations of this study should be noted. Firstly, there were only nine articles included in this meta-analysis. As the sample size was relatively small, there may be a potential risk for type II errors and therefore we caution against heavily weighting the negative findings. Secondly, there were obvious heterogeneities across studies included in this study which may have resulted from differences in population composition, quality of medical care and sample size. Thus, the results should be interpreted with caution. Finally, the present study included only published papers and some of the grey literature that might cause biases is excluded. Therefore, more high quality studies with large sample sizes should be undertaken to assess the generalization of our results. Panoramic radiography based on darkening of the root had a higher specificity in predicting IAN injury after mandibular third molar extraction. However, the positive result was not satisfactory as the accuracy was not significant. More high quality clinical data is required for further assessment of the value of radio238
graphic signs in predicting IAN injury post mandibular third molar surgery. REFERENCES 1. Bataineh AB. Sensory nerve impairment following mandibular third molar surgery. J Oral Maxillofac Surg 2001;59:1012– 1017. 2. Queral-Godoy E, Valmaseda-Castell on E, Berini-Aytes L, Gay-Escoda C. Incidence and evolution of inferior alveolar nerve lesions following lower third molar extraction. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;99:259–264. 3. Howe G, Poyton H. Prevention of damage to the inferior dental nerve during the extraction of mandibular third molars. Br Dent J 1960;109:353–363. 4. Jerjes W, Swinson B, Moles D, et al. Permanent sensory nerve impairment following third molar surgery: a prospective study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;102: e1–e7. 5. Gomes ACA, do Egito Vasconcelos BC, de Oliveira Silva ED, de Francßa Caldas A Jr, Neto ICP. Sensitivity and specificity of pantomography to predict inferior alveolar nerve damage during extraction of impacted lower third molars. J Oral Maxillofac Surg 2008;66:256–259. 6. Valmaseda-Castell on E, Berini-Aytes L, Gay-Escoda C. Inferior alveolar nerve damage after lower third molar surgical extraction: a prospective study of 1117 surgical extractions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;92:377–383. 7. Rood J, Nooraldeen Shehab B. The radiological prediction of inferior alveolar nerve injury during third molar surgery. Br J Oral Maxillofac Surg 1990;28:20–25. 8. Sedaghatfar M, August MA, Dodson TB. Panoramic radiographic findings as predictors of inferior alveolar nerve exposure following third molar extraction. J Oral Maxillofac Surg 2005;63:3–7. 9. Kipp DP, Goldstein BH, Weiss WW. Dysesthesia after mandibular third molar surgery: a retrospective study and analysis of 1377 surgical procedures. J Am Dent Assoc 1980;100:185–192. © 2015 Australian Dental Association
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22. Kim J-W, Cha I-H, Kim S-J, Kim M-R. Which risk factors are associated with neurosensory deficits of inferior alveolar nerve after mandibular third molar extraction? J Oral Maxillofac Surg 2012;70:2508–2514. € 23. Flygare L, Ohman A. Preoperative imaging procedures for lower wisdom teeth removal. Clin Oral Investig 2008;12:291– 302.
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16. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557–560. 17. Bell G. Use of dental panoramic tomographs to predict the relation between mandibular third molar teeth and the inferior alveolar nerve: radiological and surgical findings, and clinical outcome. Br J Oral Maxillofac Surg 2004;42: 21–27. 18. Tantanapornkul W, Okouchi K, Fujiwara Y, et al. A comparative study of cone-beam computed tomography and conventional panoramic radiography in assessing the topographic relationship between the mandibular canal and impacted third molars. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:253–259.
© 2015 Australian Dental Association
Address for correspondence: Dr Yuanli Zheng Stomatology Special Consultation Clinic Ninth People’s Hospital Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Stomatology Shanghai 200011 China Email: [email protected]
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