Accepted Manuscript

Enucleation with or without adjuvant therapy versus marsupialization with or without

secondary enucleation in the treatment of keratocystic odontogenic tumors: a
systematic review and meta-analysis

Essam Ahmed Al-Moraissi, BDS, MSc, PhD, Assistant Professor, M. Anthony Pogrel,
DDS, MD, Edward Ellis, III, DDS, MS
PII: S1010-5182(16)30072-5
DOI: 10.1016/j.jcms.2016.05.020
Reference: YJCMS 2378

To appear in: Journal of Cranio-Maxillo-Facial Surgery

Received Date: 29 February 2016

Revised Date: 17 April 2016
Accepted Date: 24 May 2016

Please cite this article as: Al-Moraissi EA, Pogrel MA, Ellis III E, Enucleation with or without adjuvant
therapy versus marsupialization with or without secondary enucleation in the treatment of keratocystic
odontogenic tumors: a systematic review and meta-analysis, Journal of Cranio-Maxillofacial Surgery
(2016), doi: 10.1016/j.jcms.2016.05.020.

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 ACCEPTED MANUSCRIPT

Enucleation with or without adjuvant therapy versus marsupialization with or

without secondary enucleation in the treatment of keratocystic odontogenic tumors:
A systematic review and meta-analysis

Essam Ahmed Al-Moraissi, BDS, MSc, PhD1, M. Anthony Pogrel, DDS, MD2, Edward

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Ellis III3, DDS, MS

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1Assistant Professor, Department of Oral and Maxillofacial Surgery, Faculty of
Dentistry, Thamar University, Thamar, Yemen.

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2 Professor Department of Oral and Maxillofacial Surgery, University of California, San
Francisco, California
3Professor and Chair, Department of Oral and Maxillofacial Surgery, University of Texas

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Health Science Center, San Antonio, Texas
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Address correspondence and reprint requests to

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Dr Essam Ahmed Al-Moraissi

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Department of Oral and Maxillofacial Surgery, Faculty Dentistry, Thamar University,

Redaa Street, Thamar, Yemen;
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e-mail:dressamalmoraissi@gmail.com, dr_essamalmoraissi@yahoo.com
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 ACCEPTED MANUSCRIPT

Summary

The purpose of this study was to compare the recurrence rate (RR) of keratocystic

odontogenic tumors (KOTs) in patients who underwent enucleation with or without

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adjuvant therapy, to patients who underwent decompression with or without residual

cystectomy. An extensive search of major databases through PubMed, EMBASE, and

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Cochrane CENTRAL was conducted to identify all relevant articles published without

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date and language restrictions from inception to December 2015. Relevant articles were

selected based on the following specific inclusion criteria. A weighted RR and odds ratio

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(OR) using a random with 95% confidence interval (CI) were performed. Meta-
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regression analysis was conducted to further identify the influence of the duration of

follow-up periods on the overall OR. A total of 1182 KOT patients enrolled in 14 studies
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were included in this analysis. There was a significant advantage for the enucleation ±

adjuvant therapy group in preventing recurrence for patients with KOTs (OR, 0.541 mm;
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95% CI, 0.302 to 0.875 mm; p = 0.001). The overall pooled weighted RR for enucleation
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± adjuvant therapy and decompression ± secondary cystectomy were 18.2% and 27.1%,

respectively. The meta-regression analysis showed that duration of follow-up time did not
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significantly influence the OR of KOT recurrence (Q = 0.506, p = 0.646). In conclusion,

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initial cystectomy ± adjuvant therapy were associated with fewer recurrences than
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decompression ± secondary cystectomy.

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INTRODUCTION

The keratocystic odontogenic tumor (KOT), formerly known as the odontogenic

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keratocyst (OKC), is of odontogenic origin. Unlike odontogenic cysts, the KOT shows

locally aggressive behavior, has a high recurrence rate, and has a distinct and

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characteristic histologic appearance that caused the World Health Organization (WHO) in

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2005 to reclassify this lesion as a tumor instead of a cyst (Barnes et al., 2005; Kramer et

al.,1992; Brannon, 1976).

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Radiographically, displacement of impacted or erupted teeth, root resorption, root
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displacement, or extrusion of erupted teeth may be evident (Brannon, 1976). KOTs may
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occur in any part of the jaws; however, in common with ameloblastomas, calcifying

epithelial odontogenic tumors, and myxomas, it has a predilection for the posterior body
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of the mandible and ascending ramus. KOTs have a peak incidence in patients between
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the ages of 10 and 30 years and a slight male predominance (Myoung et al., 2001;

Maurette et al., 2006; Zhou et al., 2005). KOTs are of great interest among oral and
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maxillofacial surgeons because of their high recurrence rate. The current literature has

reported a recurrence rate of 0% to 50% (Johnson et al., 2013; Johnson et al., 2012). Like
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other odontogenic tumors, the KOT has a tendency to expand through bony walls and to
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invade deeper structures (Tolstunov et al., 2008).

Various treatment modalities have been used in the treatment of KOTs and can be

classified as aggressive or conservative approaches. Aggressive approaches could be

simple enucleation without adjuvant therapy or enucleation with adjuvant therapy, such

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as the application of Carnoy’s solution, cryotherapy, or peripheral ostectomy.

Conservative approaches include decompression with or without subsequent residual

cystectomy.

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The treatment of KOTs remains controversial, and there is no consensus as to whether an

aggressive treatment is superior to conservative treatment in reducing the recurrence rate

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for treatment of patients with KOTs. Therefore, the authors of the present study tested,

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through a meta-analysis, the null hypothesis that for management of patients with KOTs

there is no difference between these treatments The specific aim of this study was to

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compare the recurrence rate of KOTs in patients who underwent enucleation with or
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without adjuvant therapies to patients who underwent decompression with or without

residual cystectomy.
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MATERIALS AND METHODS

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To ensure a systematic approach and more reliable findings, this systematic review was

conducted in accordance with the Preferred Reporting Items for Systematic reviews and
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Meta-Analyses (PRISMA) statement for reporting systematic reviews (Liberati et al.,

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2009).
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Literature search strategy

An extensive electronic search without date or language was conducted from the

respective dates of inception to November 2015 using the following online databases,

with specific keywords according to PICOS criteria: PubMed, Ovid MEDLINE, and

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Cochrane CENTRAL. The electronic search and the PICO strategy are shown in Table 1.

The search combination of all keywords of PICOS component was (keratocystic

odontogenic tumor) OR odontogenic keratocyst) OR KOT) OR okc OR kot) AND

decompression) OR marsupialization) OR decompression followed by enucleation) OR

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compression followed by residual cystectomy) OR cystostomy) exteriorization) OR

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fenestration) OR pouch procedure) OR Partsch operation) OR marsupialization followed

by secondary cystectomy) AND enucleation) OR enucleation with adjuvant therapy) OR

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enucleation with curettage) OR enucleation plus Carnoy’s solution) OR enucleation with

cryotherapy) OR enucleation with peripheral ostectomy) AND recurrence) AND relapse)

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To avoid missing any articles, the references of each selected publication that yielded

from an electronic search were performed by Google Scholar and by hand.

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Study eligibility
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Inclusion criteria
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Inclusion criteria were adopted using the following PICOTS components. Population (P):

adult, young and elderly patients with nonsyndromic, parakeratinized odontogenic tumors
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(virgin or recurrent) that were diagnosed and confirmed histologically. Intervention (I):
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Marsupialization or decompression with or without secondary cystectomy and adjunctive

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therapy. Comparator (C): Enucleation with or without adjunctive therapy, such as

cryotherapy, peripheral ostectomy, or Carnoy’s solution. Outcome (O): Recurrence rate

of KOT for the two universally accepted treatments. Time (T): Adequate follow up

period (at least 1 year). Study Design (S): Prospective randomized controlled clinical

trials, controlled clinical studies either prospective or retrospective, retrospective reviews,

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and case series comparing enucleation with or without adjuvant therapy to decompression

with or without secondary cystectomy with regard to recurrence rate with an adequate

follow-up period

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Exclusion criteria

The following exclusion criteria were used: animal or in vitro studies; editorial letters;

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articles in which a total number of treated KOT was less than 10; articles that did not

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sufficiently specify a type of surgical method; articles that included patients with nevoid

basal cell carcinoma syndrome (NBCCS or Gorlin-Goltz syndrome), as there can be

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newly developed cysts in these patients, resulting in bias when estimating recurrence rate,
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except for studies that specified and accounted for patients with NBCCS separately

(Blanas et al., 2000;Antonoglou et al., 2014); studies that did not give an adequate
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follow-up period; and reviews articles.

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Data extraction process

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The screening process of articles and eligibility of retrieved articles were reviewed by

two independent reviewers. Any disagreement between the two reviewers was resolved
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by a third judge. The following data were extracted from the studies: authors, year of
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publication, study, male-to-female ratio, patient age (average), number of

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patients/lesions, location of lesion (maxilla or mandible), association with unerupted

tooth, surgical treatments, follow-up period, and recurrence rate.

Critical appraisal of individual studies

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Two authors (E.E and M.A) independently assessed the risk of bias for each study by

using the Newcastle–Ottawa Scale (Wells et al., 2013). Disagreements were resolved by

discussion or by involving the third author (E.A) to adjudicate. A study could receive a

maximum of one star for each numbered item within the selection and outcome

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categories. A maximum of two stars could be given for comparability. The greatest score

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that could be given to a study according to the Newcastle–Ottawa Scale was nine stars

(low risk of bias). Studies scoring six stars or more were considered to be of high quality.

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Summary measures and synthesis of results

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The recurrence rate of KOT were pooled and reported as recurrence event rate, risk ratio
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(RR) and odds ratio (OR) with corresponding 95% confidence intervals (95% CIs).

Significant heterogeneity among the studies included for this analysis was formally
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assessed by Cochran’s χ2 test and the I2 index, where a p value <0.1 by the χ2 test and I2
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value <0.25 indicate a low degree of heterogeneity; otherwise a fixed effects model with
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95% confidence intervals [CI] was to be performed. In the present study, because there

was variation of follow-up periods among the included studies, a random-effect model
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was used even when there was no significant heterogeneity (I2 < 50%) among the studies.

To assess the effect of the duration of follow-up periods within the included studies, a
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meta-regression analysis was performed. When there were 10 included studies, an Egger
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funnel plot was used for analysis of the publication bias. When the p value was >0.05,

there was no publication bias. The meta-analysis was conducted using a comprehensive

meta-analysis software package (Biostat Inc, Englewood, NJ) (Borenstein et al., 2009).

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RESULTS

Literature search

Search outcome

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Figure 1 depicts the process of evaluating articles for inclusion in the review and meta-

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analysis. The search strategy yielded a total of 840 articles from all databases and 7

additional articles identified thorough hand search. Of the 847 articles, 559 articles

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remained after removal of duplicates. A total of 205 articles were excluded after reading

the titles and abstracts, and the full text articles of the remaining 83 studies were

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reviewed independently by two authors for eligibility. At this stage of the analysis, 69
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studies were excluded because of they did not meet inclusion criteria. Finally, a total of
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14 studies (Maurette et al., 2006; Nakamura et al., 2002; Zhao et al., 2002;

Chirapathomsakul et al., 2006; Driemel et al., 2007; Kolokythas et al., 2007; Madras,
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2008; Boffano et al., 2010; Zecha et al., 2010; Güler et al., 2012; Selvi et al., 2012;
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Titinchi, 2012; Sánchez-Burgos et al., 2014; Kinard et al., 2015) met the inclusion criteria

and were processed for critical review.

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Characteristics of included studies

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The details of included studies are presented in Table 2.

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Risk of bias within included studies

No studies were given less than 6 stars. Eight studies received a total of 8 stars (Maurette

et al., 2006; Nakamura et al., 2002; Zhao et al., 2002; Chirapathomsakul et al., 2006;

Driemel et al., 2007; Kolokythas et al., 2007; Madras, 2008; Boffano et al., 2010;

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Sánchez-Burgos et al., 2014), five studies six stars (Madras, 2008; Güler et al., 2012;

Selvi et al., 2012; Titinchi., 2012, Kinard et al., 2015), and one study seven stars (Zecha

et al., 2010). The details of critical appraisal according to the Newcastle−Ottawa Scale

are presented in Table 3

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Results of variable outcomes

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Weighted recurrence rate

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A. Enucleation with or without adjuvant therapy (Carnoy’s solutions, liquid nitrogen

cryotherapy, and peripheral ostectomy)

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A total of 843 KOT patients were enrolled in 14 studies (Maurette et al., 2006; Nakamura

et al., 2002; Zhao et al., 2002; Chirapathomsakul et al., 2006; Driemel et al., 2007;
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Kolokythas et al., 2007; Madras, 2008; Boffano et al., 2010; Zecha et al., 2010; Güler et

al., 2012; Selvi et al., 2012; Titinchi., 2012; Sánchez-Burgos et al., 2014; Kinard et al.,
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2015) that evaluated recurrence rates after treatment using enucleation alone or with
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Carnoy’s solutions, cryotherapy, or peripheral ostectomy. The mean follow-up period

varied from 1 year to 25 years. There was significant heterogeneity among the studies (I2
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= 44.7%; p = 0.036). The weighted recurrence rate ranged from 14.3% to 22.2%. The
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overall pooled recurrence rate was 18.2% random (95% CI = 14.3%, 22.2%) (Fig. 2).
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B. Decompression/marsupialization with or without secondary cystectomy

Fourteen studies (Maurette et al., 2006; Nakamura et al., 2002; Zhao et al., 2002;

Chirapathomsakul et al., 2006; Driemel et al., 2007; Kolokythas et al., 2007; Madras,

2008; Boffano et al., 2010; Zecha et al., 2010; Güler et al., 2012; Selvi et al., 2012;

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Titinchi., 2012; Sánchez-Burgos et al., 2014; Kinard et al., 2015) with 154 KOT patients

used decompression (marsupialization) either alone or followed by secondary

cystectomy. There was significant heterogeneity among the studies (I2 = 27.7%; p =

0.157). The weighted recurrence rate ranged from 18% to 38.5%. The overall pooled

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recurrence rate was 27.1% (random: 95% CI = 18%, 38.5%) (Fig. 3).

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Odds ratio for recurrence rate

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A total of 997 KOT patients were enrolled in 15 studies (Maurette et al., 2006; Nakamura

et al., 2002; Zhao et al., 2002; Chirapathomsakul et al., 2006; Driemel et al., 2007;

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Kolokythas et al., 2007; Madras,2008; Boffano et al., 2010; Zecha et al., 2010; Güler et
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al., 2012; Selvi et al., 2012; Titinchi., 2012; Sánchez-Burgos et al., 2014; Kinard et al.,

2015) that compared enucleation ± adjuvant therapy (n = 843) to decompression ±

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secondary cystectomy (n =154). The mean follow-up period varied from 1 year to 25
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years. There was a significant advantage for the enucleation ± adjuvant therapy group in
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recurrence prevention (OR, 0.514; 95% CI, 0.302 to 0.875; p = 0.001 [random-effects

model]). There was no heterogeneity among studies (I2 = 0.761%; p = 0.438). The OR
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was 0.514, meaning that using enucleation ± adjuvant therapy in the treatment of KOTs

decreases the incidence of recurrences by 41.4% compared with using decompression ±

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secondary cystectomy (Fig. 4).

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Linear regression of follow-up periods (mean, months) on MH odds ratio

The association between duration of follow-up of included studies and recurrent KOTs

(odds ratio) was investigated using a linear meta-regression. The meta-regression analysis

showed that the duration of follow-up periods did not influence the recurrence rate of

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KOTs (Q = 0.506, p = 0.64643). The slope of the meta-regression line was a negative

value, indicating that with an increase of 1 month of follow-up time, the odds ratio would

decrease by 1 unit, meaning that there would be an increasing in KOT recurrence (Table

4 and Fig. 5)

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Publications bias

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The funnel plot did not show any noticeable asymmetry. Accordingly, the Egger test was

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not significant for bias (one-tailed p = 0.34, two-tailed p = 0.68), indicating an absence of

publication bias (Fig. 6)

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DISCUSSION
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To date, there is no consensus regarding the best treatment with the lowest recurrence
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rate for patients with KOT. The two most universally accepted treatment options for
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patients with KOT are either conservative methods using marsupialization (possibly

followed by residual cystectomy) or aggressive methods using enucleation alone

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(possibly followed by application or chemical cauterization, cryotherapy, or peripheral

ostectomy).
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The authors of this study hypothesized that there would be no difference between
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enucleation ± adjuvant therapy and decompression ± secondary cystectomy for patients

with nonsyndromic KOTs. The specific aims were 1) to compare RR between two

universally accepted treatments by using meta-analysis, and 2) to estimate the recurrence

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rate of KOTs after enucleation ± adjuvant therapy and decompression ± secondary

cystectomy for patients with nonsyndromic KOTs.

To the best of the authors’ knowledge, this is the first meta-analysis comparing these two

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treatments for the management of nonsyndromic KOTs. The predictor variable was the

treatment group, namely enucleation ± adjuvant therapy (Carnoy solution, cryotherapy,

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or peripheral ostectomy) versus decompression ± residual cystectomy.

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The main finding of this study was that there was a significant advantage to the

enucleation ± adjuvant therapy group in preventing recurrence for patients with KOTs

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(OR, 0.543; 95% CI, 0.364 to 0.809; p = 0.003 [random-effects model]). The OR was
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0.543, meaning that using enucleation ± adjuvant therapy in the treatment of KOTs

decreases the incidence of recurrences dby 35.3% compared with using decompression ±
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secondary cystectomy. This is in accorance with other literature (Maurette et al., 2008;
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Driemel et al., 2001; Kolokythas et al., 2007; Güler et al., 2012; Titinchi et al., 2012;
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Kaczmarzyk et al., 2012; Stoelinga.,2001) and in disagreement with others studies (Zhao

et al., 2002; Madras et al., 2008; Boffano et al., 2010., Stoelinga., 2010) The overall
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pooled weighted recurrence rate was 17.7% for the enucleation ± adjuvant therapy groups

and 26.5% for the decompression ± secondary cystectomy groups. This is inconsistent
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with previous literature (Boffano et al., 2010; Zecha., 2010; Titinchi., 2010; Wushou et
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al., 2014).

Part of the problem may lie in the relatively short follow-up time evident in some papers.

It is well known that KOTs can recur at any time and should be followed up for at least

15−20 years. It does appear that decompression or marsupialization (there are subtle

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differences between the two34) may cause rapid resolution of the lesion, but with this

treatment alone the recurrence rate is high and may approach 30% (Pogrel.,2015).

Decompression plus adjuvant therapy may lower this recurrence rate, but it is believed

that the main problem may be that as the lesion decreases in size and the cyst lining is

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carried forward, small remnants may be left behind, such that enucleation and further

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treatment of the residual cyst may not eliminate these small cell nests, which may be

distant from the residual cyst. In contrast, enucleation of the original lesion without

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decompression, with or without similar ancillary treatments, may be more effective in

treating microextensions of the lesion that normally do not penetrate more than 1 or 2

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mm. This may explain why enucleation appears to work better than decompression.
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There are several strengths to the present study. First, the pooling of data (meta-analysis)
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for included studies was thorough, using a weighted calculation of recurrence rate, that is,

it was more accurate in representation of the incidence of an event among populations

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exposed to an outcome. Second, patients with NBCCS were excluded from this analysis
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because those patients have new lesions constantly developing, so a recurrence in a

patient with NBCCS could be a new cyst (Johnson et al.,2013; Liberati et al.,2011).
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These factors should avoid the misleading findings and bias that have been present in
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some studies (Johnson.,2013; Blanas et al.,2000; Kaczmarzyk et al.,2012).

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How should the results of this study affect treatment of patients with KOTs? It seems

appropriate that, when possible, initial enucleation with or without adjuvant therapy

should be implemented. However, when doing so would jeopardize vital anatomic

structures (for instance, the inferior alveolar nerve) or potentially result in fracture of the

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jaw, decompression may be a better initial option. Thus, the recurrence rate is not the

only factor affecting the choice of treatment when confronted by a KOT.

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CONCLUSION

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In conclusion, initial cystectomy, with or without adjuvant therapy, is associated with the

least chance of recurrence. A prospective, randomized, blinded, multicenter study with a

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long follow-up period to compare various treatments for patients with KOTs in regard to

recurrence are strongly recommended.

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combined treatment of odontogenic keratocyst and mandibular defect with

marsupialization, enucleation, iliac crest bone graft, and dental implants. J Oral

Maxillofac Surg 66:1025, 2008.

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Wells G, Shea B, O'Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-

Ottawa Scale (NOS) for assessing the quality of non randomised studies in meta-

analyses. Ottawa, Ontario, Canada: Ottawa Hospital Research Institute; 2013. Available

at: www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed August 23, 2013.

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Wushou A, Zhao Y-J, Shao Z-M. Marsupialization is the optimal treatment approach for

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keratocystic odontogenic tumour. J Craniomaxillofac Surg 42(7):1540–4,2014.

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Zecha J a EM, Mendes RA, Lindeboom VB, van der Waal I. Recurrence rate of

keratocystic odontogenic tumor after conservative surgical treatment without adjunctive

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therapies─a 35-year single institution experience. Oral Oncol 46(10):740–2,2010.
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Zhao YF, Wei JX, Wang SP. Treatment of odontogenic keratocysts: a follow-up of 255
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Chinese patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 94(2):151-

156,2002.
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Zhou J, Jiao S, Chen X, Wang Y. [Treatment of recurrent odontogenic keratocyst with

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enucleation and cryosurgery: a retrospective study of 10 cases]. Shanghai Kou Qiang Yi

Xue 14(5):476-8,2005.
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Figure 1. Study screening process

Figure 2. Forest plot, enucleations ± adjuvant therapy, weighted recurrence rate.

Figure 3. Forest plot, decompression ± residual cystectomy, weighted recurrence rate.

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Figure 4. Forest plot, enucleation ± adjuvant therapy versus decompression ± residual

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cystectomy, odds ratio.

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Figure 5. Scatter plot of meta-regression of follow-up times (as a predictor) against the

odds ratio (recurrence rate).

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Figure 6. Funnel plot, publications bias within included studies.
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Table 1. Search strategy for the systematic review

ACCEPTED MANUSCRIPT
Problem Keratocystic odontogenic tumors OR kcot OR kot OR odontogenic keratocyst OR okc OR non-
syndromic keratocystics odontogenic tumuors .

Intervention Decompression OR marsupialization OR decompression followed by enucleation OR compression

followed by residual cystectomy OR cystostomy OR marsupialization followed by secondary
cystectomy OR exteriorization OR fenestration OR pouch procedure OR Partsch operation

Comparisons Simple enucleation OR enucleation with adjuvant therapy OR enucleation with curettage OR
enucleation plus carnoy s solution OR enucleation with cryotherapy OR enucleation with peripheral
ostectomy OR enucleation with liquid nitrogen cryotherapy OR enucleation with chemical
cauterization
Outcomes Recurrence OR relapse

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Study design Randomized controlled trials OR controlled clinical trials OR comparative studies OR case series
Search combination Populations AND intervention AND comparator AND outcome AND study design
Language No restriction
Electronic data MEDLINE/PubMed and Cochrane Central Register of Controlled Trials (CENTRAL)/EMBASE

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base
Focused question For patients with keratocystic odontogenic tumors, dose enucleation ± adjuvant therapy produce
fewer recurrent KOT when compared to decompression ± residual cystectomy ?

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MeSH, medical subject heading adjuvant.

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Table 2. Characteristics of studies included

Authors Study design Male/ Patient No. of Location Associated Surgical Follow- Recurrence rate

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age patients/ up period
female (average) of lesion (maxilla with treatments
No. Percentage
lesions or mandible) unerupted
ratio of
tooth or
pati

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not
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(Nakamura et al., 2002). Retrospective 13:10 11−70 23 Mandible NM Mars(5) 6.6 years 0 0%

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study years Mars +enuc.+curettage(23) 6 26.1%
. Enuc+Cur.(15) 3 20%
(Zhao et al., 2002) Retrospective 1.93:1 31.2 years 489 KOT in 162 173 cases Enuc.(163) 3-29 29 17.79%
Study 255 patients (33.13%) maxilla (35.38%) Enuc.+CS (29) years 2 6.70%

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327 were Mars.+Enuc.(11) 0 0%
(66.87%) associated Resection(52) 0 0%

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mandible with an
impacted
tooth. .
(Chirapathomsakul et al., Retrospective 1:1.2 36.9 years 67lesion in 21 lesions Not Mars (13) 1-14.6 1 16.7%
2006) study 51 patient (31.3%) recorded Enuc (30) years 2 13.3%

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Maxilla Enuc with CS (11) 1 20%
46 lesions Enuc, curettage (2) 2 100%
(68.7%) Marginal resection (1) 0 0%
Segmental resection (6)

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mandible 1 16%
7 20%
Total

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(Maurette et al., 2006) Retrospective 0.47:1 30 years 28 patients 12 maxilla and 13 -Decom. and curettage ( 20) 24.89 2 10%
study with 30 (16 patients, of 28 -Enuc.and curettage only(10) months
KOTs 53.3%) patients 0 20%
presented
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impacted
teeth
(Driemel et al., 2007) Retrospective 2:1 47 years 86 patient 18 maxilla and 76 Not record Cystectomy (46), Mars. (6) 5,5 years 6
study with 94 mandible (Abstract Cystectomy and curettage 4
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KOT only) (17) 3 11,7%

cystectomy and marginal
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ostectomy and resection

(25).
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(Kolokythas et al., 2007) Retrospective 0.83:1 54-year 22 patients 6 maxilla and 16 Not -Resection or follow- 0 0%
study range mandible recorded enuc with peripheral up of 1.5
(18−90) ostectomy (11) to 9 years
in group 9.09%
Decom.with or without 1 and 1.5 2
enuc (11) to
3 years in
group 2.
(Madras & Lapointe Case series NM 45-year 21 patients 6 maxilla NM Curettage (22) 1 to7 6 29%,
2008) range (27 KOTs) 21 mandible Mars. (3) years 0 0%
(10−80) Resection (2) 0 0%
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* (Boffano et al., 2010) Retrospective 2:1 43.34-year 241 patients 70 lesions Not Enuc + curettage (250) 36 28 11.2%
study range (7− with 261 (26.8%), maxilla recorded months
87) KOTs and Mars.(11)
191 KCOTs 3 36%
(73.2%)
mandibular (ratio,
1:2.7).
Zecha et al., 2010) Retrospective 43:25 12−79 68 patients Maxila(16) NM Enuc. (58) 65.1 12 20.7%
study (39.51) and KOCTs Mandible (52) Mars. (10) months, 4 40%

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(Güler et al., 2012) Retrospective 1.4:1 52 years 39 patients 10 maxilla 20 (46.5%) Enuc only (18) 40.45 No 0%
study with 43 (23.3%) and were months recu
KOTs 33 mandible associated Enuc with CS (10) rren 0%

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(76.7%) with the ce
impacted Mars. Followed by enuc.
third molar with CS (15) 0%

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(Selvi et al., 2012) Retrospective 14:8 51 years 22 5 maxilla NM Enuc with curettage (20) 37.8 2 5%
study 17 mandible Decom with Enuc (2) months
1 50%
(Titinchi & Nortje 2012) Retrospective 1:0.6 34.5 years 106 patients 36 (24.8%) 52.4% of Mars. (5) 19.8 .3 60%
study with 145 maxilla 109 KCOT Enuc. (47) months 13 27%

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KOT (75.2%) mandible were Enuc. +CS (8) 0 0%
15of 106 has associated Resection (1) 0 0%

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NBCCS with
impacted
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(Sánchez-Burgos et al., Retrospective NM 42 years 55 10(maxilla) 15 Enuc. (42) Average 9 25%
2014) study 45(mandible81%) Enuc.+CS (2) 5 years 2 100%

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Enuc+Apicectomy (8) 2 60&
Mars. (3) 1 0%

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Resection (2) 0 0%

Kinard et al., 2015 Retrospective 26:19 43.3 45 patient 53 (mandible) 30 Enuc. With or without 10 31.13%
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study with 66 13 (maxilla) adjuvant therapy (32)
KOTs Decom. With or without
secondary 13 38.23%
Cystectomy (34)
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Abbreviations: NM = not mentioned, Enuc.= enucleation, Mars = marsupialization, Decom.= decompression, KOT=keratocystics odontogenic tumor, NBCCS = nevoid basal cell
carcinoma syndrome, CS = Carnoy’s solution.
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Table 3. Critical appraisal of included studies

Authors Selections Comparability of cohorts on Outcomes

the basis of the design or Total no. of

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analysis* stars
Consecutive Representati Ascertainm Demonstration Control for Control for Assessm Follow-up Adequacy of
or obviously veness of ent of that outcome of NBCCS parakeratinize ent of was long follow up of
representativ exposed exposure interest was not d entity outcome enough for cohorts

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e series of cohort present at start outcomes
cases of study to occur#
(Nakamura et al., 2002). * * * No No * * * * 8 of 9
(Zhao et al., 2002) * * * No * * * * * 8 of 9

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(Chirapathomsakul et al., 2006) * * * No * * * * * 8 of 9
(Maurette et al., 2006) * * * No * * * * * 8 of 9
(Driemel et al., 2007) * * * No * * * * * 8 of 9
(Kolokythas et al., 2007) * * * No * * * * * 8 of 9

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(Madras and Lapointe, 2008) * * * No * * * No No 6 of 9

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(Boffano et al., 2010) * * * No * * * * * 8 of 9
Zecha et al., 2010) * * * No * * * * No 7 of 9
(Güler et al., 2012) * * * No * * * No No 6 of 9
(Selvi et al., 2012) * * * No * * * No No 6 of 9

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(Titinchi and Nortje, 2012) * * * No * * * No No 6 of 9
(Sánchez-Burgos et al., 2014) * * * No * * * * * 8 of 9
Kinard et al., 2015 * * * No * * * No No 6 of 9

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comparability.

# Three years of mean follow-up was chosen to be sufficient for the outcome recurrence to occur.
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*Comparability was divided into follow-up of nevoid basal cell carcinoma syndrome (NBCCS) and parakeratinized entity confirmation.
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Table 4. Meta regression of the follow up periods of included studies against log odds
ratio (recurrence rate)

Coefficient standard Lower Upper z Value p Value

errors limit limit
Slope −0.00595 0.0180 −0.02611 −0.01621 −0.45873 0.64643

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Intercept −0.44675 0.56831 −0.56062 0.66713 −0.78609 0.431
Tau-squared: 0.06403

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Q df p Value

Model 0.21043 1 0.646

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Residual 11,04962 11 0.439

Total 11,2600 12 0.506

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840 of records identified through 7 additional records identified

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Identification

electronic database through other source

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559 articles for screening after
duplicate removed
Screening

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205 articles excluded after
evaluation of title and abstract
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83 articles of full text assessed for

Eligibility

eligibility
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69 of records excluded due to

they did not meet inclusion
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Included

14 articles included in qualitative and

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quantitative synthesis (meta-analysis)

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Figure 1 : Selecting screening process

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