Clinical Oral Investigations

https://doi.org/10.1007/s00784-017-2315-8

ORIGINAL ARTICLE

Conservative surgical treatments for nonsyndromic odontogenic

keratocysts: a systematic review and meta-analysis
Mayara Santos de Castro 1 & Clenivaldo Alves Caixeta 2 & Marina Lara de Carli 2 & Noé Vital Ribeiro Júnior 2 &
Marta Miyazawa 2 & Alessandro Antônio Costa Pereira 1 & Felipe Fornias Sperandio 1 & João Adolfo Costa Hanemann 2

Received: 13 June 2017 / Accepted: 12 December 2017

# Springer-Verlag GmbH Germany, part of Springer Nature 2017

Abstract
Objectives This manuscript presents a systematic review of the clinicopathologic features and outcomes of conservative surgical
treatments for nonsyndromic odontogenic keratocysts (OKCs) and assesses the recurrence rates through a meta-analysis, in order
to indicate the best conservative approach.
Materials and methods PRISMA guidelines for systematic reviews were followed, and the protocol was registered
(PROSPERO/Nr.: CRD42017060964). An electronic search was conducted using the PubMed/MEDLINE, Science Direct,
Web of Science, Scopus, and The Cochrane Library databases, and relevant articles were selected based on specific inclusion
criteria. The PICOS criteria (Population: nonsyndromic patients of any age with OKC, with histopathological diagnosis and
minimum follow-up of 12 months; Intervention and Comparison: marsupialization or decompression with or without enucle-
ation, and enucleation alone; Outcome: recurrence rates; Study design: clinical trials, controlled trials, retrospective studies, and
case series containing at least 10 cases of OKC) were employed. A pooled odds ratio (OR) was computed through the Mantel-
Haenszel test (M-H) with 95% confidence intervals (CI).
Results One thousand nine hundred OKCs were analyzed; the age of the patients varied from 6 to 90 years (mean of 38.6 years); a
male to female ratio of 1.57:1 was observed; 74.5% of the lesions occurred in the mandible; 75.7% of OKCs were unilocular; the
association with impacted tooth was reported for 344 OKCs; and the mean follow-up was 60.1 months. One thousand three
hundred thirty-one OKCs were treated by conservative surgical treatments, and 261 cases (19.8%) presented recurrence.
Nonetheless, minor total recurrence rates were observed after decompression followed by enucleation (11.9%) and
marsupialization followed by enucleation (17.8%). In contrast, enucleation alone showed a total recurrence rate of 20.8%.
Conclusion The results suggest a significant superiority of success for OKC treatments that use decompression followed by
enucleation, instead of an initial enucleation (M-H, OR = 0.48; 95% CI = 0.22 to 1.08; P = 0.0163).
Clinical relevance No consensus exists concerning the best management for OKCs. More aggressive treatments (ostectomy,
resection, or use of adjunctive therapies like Carnoy’s solution and liquid nitrogen) can have many disadvantages and risks.
Therefore, it is necessary to identify the conservative approach for OKCs that results in a lower recurrence rate.

Keywords Odontogenic keratocyst . Marsupialization . Decompression . Enucleation . Recurrence . Meta-analysis

Introduction

The odontogenic keratocyst (OKC) is an entity of controver-

* Mayara Santos de Castro
maya.castro@outlook.com sial nature [1] originated from dental lamina remnants or basal
cells of the overlying epithelium [2]. Essentially, the OKC was
1
first described as a cystic lesion [3]. However, due to its po-
Department of Pathology and Parasitology, Institute of Biomedical
Sciences, Federal University of Alfenas, 700 Gabriel Monteiro da
tential Baggressive growth^ [4], high recurrence rates after
Silva Street, Alfenas, MG 37130001, Brazil treatment [5–8], and most importantly, mutations found in
2
Department of Clinic and Surgery, School of Dentistry, Federal
PTCH, CDKN2A, TP53, MCC, CADMI, and FHIT [9–12],
University of Alfenas, 700 Gabriel Monteiro da Silva Street, this lesion was reclassified in 2005 by the World Health
Alfenas, MG 37130001, Brazil Organization (WHO) as a benign neoplasm, being renamed

as keratocystic odontogenic tumor (KCOT) [13].
Interestingly, the WHO Classification of Head and Neck
Tumors was updated in 2017 and now puts KCOT back to
the Cyst category; WHO chooses to name it simply
odontogenic keratocyst (OKC) and highlights current gaps
regarding scientific evidences that could state this lesion as a
tumor [1].
Clinically, OKC may occur in any part of the jaws [6, 7, 14,
15]; however, it has predilection for the posterior body of the
mandible and ascending ramus [6, 7, 14, 15].
Radiographically, OKC presents as an unilocular or
multilocular radiolucency with uniform sclerotic borders [5,
7] and may be associated with unerupted tooth, more frequent-
ly an impacted third molar [15]. Bone expansion is poorly
observed due to its antero-posterior growth within the bone
marrow cavity [14]. In addition, resorption of the roots of
adjacent erupted teeth is also uncommon [14]. Large OKCs
may be associated with pain, edema, or drainage [16], and
multiple lesions are generally related to the nevoid basal cell
carcinoma syndrome (NBCCS) (Gorlin-Goltz syndrome)
[17].
The diagnosis of OKC is based on its histopathological
features, although the clinical, radiographic, and
transoperatory findings (such as a positive aspirative puncture
for yellowish white liquid content evidencing remains of
keratinocytes) are quite suggestive [18, 19]. Microscopically,
OKC exhibits a thin capsule of fibrous connective tissue, lack-
ing inflammatory infiltrate and covered by parakeratinized
stratified epithelium presenting few layers, superficial corru-
gation, and a basal layer with hyperchromatic cells in palisade
[20]; variable amounts of keratin can be visualized in the
cystic lumen [18–20].
Currently, no consensus exists concerning the best manage-
ment of OKC [21]. In this perspective, the surgical approaches
range from conservative to more aggressive treatments [22].
Conservative treatments consist of marsupialization, decom-
pression, and enucleation, while more aggressive approaches
are based on ostectomy, resection, or use of adjunctive thera-
pies like Carnoy’s solution and liquid nitrogen [23].
Marsupialization and decompression are distinct surgical tech-
niques indicated to reduce the size of extensive OKCs prior to
an intervention by enucleation, enabling the preservation of
important structures such as inferior alveolar nerve [24]. Both
methods allow a decrease of the intraluminal volume [18, 25],
and lining of many marsupialized or decompressed cysts ap-
pears more similar to oral mucosa than to OKC histologically
[1, 14]. In fact, complete remission of OKCs following
marsupialization or decompression has been reported, dis-
pensing a secondary enucleation [18, 22, 25, 26].
Briefly, marsupialization is described as the surgical re-
moval of a wall in the OKCs’ body followed by the suture
of the lesion’s boundaries to the adjacent mucosa [21, 27].
Consequently, a surgical window communicating the cyst
Clin Oral Invest
with the oral cavity is created, allowing regular irrigations
by the patient [27]. Distinctly, decompression involves the
attainment of an opening in the cystic cavity and use of a
drain, which allows the decrease of intracystic pressure and
consequent bone formation [18]. In contrast, enucleation con-
sists of complete removal of OKC from the bone cavity with-
out leaving any macroscopic remnants of the lesion [28].
However, enucleation alone has been associated with high
recurrence rates (range, 13.3 to 56%) [21, 26], mainly due to
the thin and friable capsule of OKC, which is easily
fragmented during the excision [20]. Moreover, the recurrence
of OKC may also be related to the following reasons: satellite
or daughter cysts left beyond the enucleated cyst, particularly
in multilocular lesions; epithelia islands or microcysts left be-
hind in the overlying mucosa adjacent to the cyst; and perma-
nence of the impacted tooth associated with the lesion [20, 29,
30].
In this way, this manuscript aims to present a systematic
review of the clinicopathologic features and outcomes of con-
servative surgical treatments of nonsyndromic OKCs, and
through a meta-analysis compare the recurrence rates of
OKCs from different studies addressing marsupialization
followed or not by enucleation, decompression followed or
not by enucleation, and enucleation alone.
Materials and methods
Systematic review and meta-analysis
The present study was performed and reported according to
PRISMA (Preferred Reporting Items for Systemic Reviews
and Meta-Analysis) guidelines [31]. The protocol was regis-
tered in the International Prospective Register of Systematic
Reviews (PROSPERO/Nr.: CRD42017060964).
Literature search
An extensive electronic search was conducted from December
1945 to October 2017 using the PubMed/MEDLINE, Science
Direct, Web of Science, Scopus, and The Cochrane Library
databases. The keywords selected according to Medical
Subject Heading (MeSH) terms and PICOS criteria
(Population, Intervention, Comparison, Outcome, and Study
design) were as follows: odontogenic keratocyst OR
keratocystic odontogenic tumor AND marsupialization OR
decompression OR enucleation, or else, marsupialization OR
decompression followed by enucleation.
Eligibility criteria
Articles were eligible under the following inclusion criteria
and PICOS criteria:
Clin Oral Invest
1. English language
2. Full-text available
3. Population: nonsyndromic patients of any age with OKC
(Bde novo^ or recurrent), with histopathological diagnosis
and minimum follow-up of 12 months
4. Intervention and comparison: marsupialization or decom-
pression with or without enucleation, and enucleation
alone
5. Outcome: recurrence rates of the conservative surgical
treatments cited above
6. Study design: clinical trials, controlled trials, retrospective
studies, and case series containing at least 10 cases of
OKC
The exclusion criteria adopted were as follows:
1. Articles published in any other language than English
2. Animal or in vitro studies
3. Duplicate publications (risk of bias)
4. Articles that included patients with NBCCS (risk of bias
due to the high recurrence rates of OKC reported for
these patients compared to nonsyndromic patients) [29,
32]
5. Articles without complete demographic information of
each patient and without histopathological diagnosis
6. Orthokeratinized OKCs (risk of bias because of lower
recurrence rates than parakeratinized OKCs) [26]
7. Aggressive treatments for OKC (ostectomy, resection
and adjunctive therapies)
8. Follow-up lower than 12 months
9. Studies evaluating less than 10 cases of OKC
10. Editorial letters, case reports, and review articles
Study selection
The retrieved records were screened by title and abstract, in
addition to review of the full-text publication of potentially
relevant studies. Two reviewers (MSC and CAC) performed
this eligibility assessment independently in an unblind stan-
dardized manner. The level of agreement between reviewers
was measured by kappa statistic for all steps of the screening
process. Values of kappa between 0.40 and 0.59 were consid-
ered to reflect fair agreement, between 0.60 and 0.74 to reflect
good agreement and 0.75 or more to reflect excellent agree-
ment [33]. Disagreements between reviewers were resolved
by consensus, and when necessary, a third reviewer was
consulted (MM).
Quality assessment
The quality of each eligible article was assessed using the
Methodological Index for Nonrandomized Studies
(MINORS) scoring system [34] and the Newcastle Ottawa
Quality Assessment Scale (NOS) (http://www.ohri.ca/
programs/clinicalepidemiology/oxford.htm). These scales
were used to allocate a maximum of nine points for quality
of selection, comparability, exposure, and outcome of
participant studies.
Data extraction process
Two independent reviewers (MSC and CAC) extracted the
following data from included articles: authors, year of publi-
cation, study design, number of patients and lesions, mean age
of patients, male to female ratio, location of OKC (mandible
or maxilla), association with impacted tooth, radiographic as-
pects (unilocular or multilocular), treatment, mean follow-up
(months), and recurrence. The level of agreement between
reviewers was calculated by kappa statistic, employing the
same parameters already mentioned in the Bstudy selection^
process [33]. Disagreements were resolved by discussion and
a third reviewer (MM) was invited to make an assessment if
the two reviewers (MSC and CAC) could not reach a
consensus.
T he co ns er vat i v e su rgic al tr e atm e nts o f O K C
(marsupialization followed or not by enucleation, decompres-
sion followed or not by enucleation, and enucleation alone)
were classified according to the nomenclature found in the
included studies. In addition, a review of the surgical tech-
nique described by the authors was performed in order to
verify the veracity of the nomenclature used by them.
Marsupialization and decompression are distinct surgical tech-
niques [27], although both have a similar treatment outcome;
therefore, these two approaches were not grouped in the same
group in our study, respecting the nomenclature and surgical
method used by the authors.
Statistical analysis
All data were analyzed statistically using the BioEstat 5.3
software [35]. First, the I2 test with 95% confidence interval
(CI) was used to establish if there was any statistical hetero-
geneity between the included studies. Basically, the value of I2
is given by the following formula, where x2 is the chi-squared
statistic and df is its degree of freedom [36]:
 2 
x −d f
I2 ¼  100%
x2
A rough guide to interpret the value of I2 is as follows: 0 to
40% = might not be important; 30 to 60% = may represent
moderate heterogeneity; 50 to 90% = may represent substan-
tial heterogeneity; 75 to 100% = considerable heterogeneity
[33]. Generally, one can choose between two models of meta-
analysis, the Bfixed^ and the Brandom effect^ models. If

I2 ≤ 25%, studies are regarded homogeneous and the fixed
effect model of meta-analysis can be used. On the other hand,
if I2 ≥ 75%, then heterogeneity is very high and one should use
a random effect model for meta-analysis [37].
In this way, identified homogeneity among our included
studies, in this meta-analysis, it was used the Mantel-
Haenszel test (fixed effect) with corresponding 95% CI. A
pooled odds ratio was computed for each comparison between
studies. In addition, parameter estimations of proportions with
95% CI were calculated to measure the clinical, radiographic,
therapeutic, and prognostic aspects of OKCs, and Z test was
used for comparisons between two proportions. Statistical sig-
nificance was set at alpha 5% (P < 0.05) for all meta-analysis
results.
Results
Literature search
The initial search from databases provided a total of 1889
potential articles (PubMed/MEDLINE = 703, Science
Direct = 528, Web of Science = 357, Scopus = 298, and The
Cochrane Library = 3). After removal of duplicates, 836
remained. Of these, 727 articles were discarded after their
corresponding titles and abstracts were reviewed and shown
not to meet the inclusion criteria. The full texts of the remain-
ing 109 articles were evaluated in more detail, excluding 80
studies that did not match the inclusion criteria as described. In
this way, a total of 29 articles (25 retrospective studies, 1
cohort study, and 3 case series) were identified for inclusion
in this systematic review (Fig. 1). The measured inter-
reviewer kappa values were 0.83 ± 0.03 (95% CI = 0.79 to
0.91) at the title and abstract level, 0.79 ± 0.09 (95% CI =
0.71 to 0.88) at the full text level, and 0.94 ± 0.04 (95% CI =
0.90 to 0.97) for the final screening, indicating an excellent
agreement between the reviewers throughout the steps of the
literature appraisal process.
Quality assessment
Assessing the quality of the included articles, the level of
agreement was very high among the two reviewers (MSC
and CAC) with a mean score of 7.5 using the NOS question-
naire and mean score of 8.0 using the MINORS tool, indicat-
ing a good quality of the articles and reducing the risk of bias.
Data synthesis
For the Bdata extraction^ process, the calculated inter-
reviewer kappa value was 0.91 ± 0.005 (95% CI = 0.86 to
0.95), reflecting an excellent agreement between the re-
viewers. A total of 1900 OKCs were reported in the included
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studies (Table 1). Of these, 1321 were treated by conservative
surgical treatments with adequate follow-up, while the other
579 OKCs were treated by more aggressive approaches and
were not included in our analysis. The age of patients varied
from 6 to 90 years with a mean of 38.6 years. In addition, a
male to female ratio of 1.57:1 was detected. The mandible was
the most common site of involvement; in fact, 1371 cases
(74.5%; 95% CI = 72.5 to 76.5%) occurred in this region,
mainly in the posterior body and ascending ramus. The asso-
ciation with an impacted tooth was reported in 344 OKCs.
Radiographic aspects were attributed to 1460 lesions, of
which 1105 cases (75.7%; 95% CI = 73.5 to 77.9%) were
unilocular, while 355 cases (24.3%; 95% CI = 22.1 to
26.5%) were multilocular.
Regarding the 1321 conservative surgical treatments eval-
uated, 99 cases (7.5%) consisted of marsupialization; 45 cases
(3.4%) were treated by marsupialization followed by enucle-
ation; 27 cases (2.0%) by decompression; 101 cases (7.7%) by
decompression followed by enucleation; and 1049 cases
(79.4%) by enucleation alone. Considering all these treat-
ments, 261 cases (19.8%; 95% CI = 17.6 to 21.9%) resulted
in recurrence. The mean follow-up was 60.1 months.
Comparisons between OKC recurrence rates
of different conservative surgical treatments
Minor total recurrence rates were observed for decompression
followed by enucleation (11.9%; 95% CI = 5.6 to 18.2%) and
marsupialization followed by enucleation (17.8%; 95% CI =
6.6 to 28.9%), suggesting that these are the best conservative
surgical treatments for OKC. On the other hand, enucleation
alone resulted in a total recurrence rate of 20.8% (95% CI =
18.3 to 23.2%), whereas decompression and marsupialization
alone showed recurrence rates of 18.5% (95% CI = 8.2 to
28.9%) and 18.2% (95% CI = 10.6 to 25.8%), respectively.
Decompression followed by enucleation versus enucleation
alone
Five studies (Brøndum and Jensen [38], Kolokythas et al.
[22], Selvi et al. [39], Berge et al. [30], and Cunha et al.
[20]) compared the recurrence rates of OKC after decompres-
sion followed by enucleation and enucleation alone. Moderate
heterogeneity was observed among these studies (x2 = 1.71;
P = 0.09; I2 = 41.5%). Of 57 cases treated by decompression
followed by enucleation, 9 resulted in recurrence (15.8%;
95% CI = 6.3 to 25.3%) and of 140 cases treated by enucle-
ation alone, 38 recurrences occurred (27.2%; 95% CI = 19.8 to
34.5%). The pooled odds ratio was 0.48 (95% CI = 0.22 to
1.08). Therefore, these results indicate a significant superiority
of success in treatments of OKC using decompression follow-
ed by enucleation instead of an initial enucleation (P =
0.0163) (Fig. 2a).
Clin Oral Invest
Fig. 1 Flow diagram outlining
the selection process for the
inclusion of studies in the
systematic review. Adapted from:
Moher D, Liberati A, Tetzlaff J,
Altman DG; PRISMA Group
(2009) Preferred reporting items
for systematic reviews and meta-
analyses: the PRISMA statement.
PLoS Med 6:e1000097. For more
information, visit www.prisma-
statement.org.
Marsupialization followed by enucleation versus enucleation
alone
Only two studies (Zhao et al. [5] and Naruse et al. [40]) com-
pared recurrence rates of OKC after marsupialization followed
by enucleation and enucleation alone. Heterogeneity was not
observed among these studies (x2 = 0.05; P = 0.82; I2 = 0%).
Here, 3 recurrences (14.2%; 95% CI = 3.7 to 24.9%) were
reported from 21 cases treated by marsupialization followed
by enucleation, and 38 recurrences (19.5%; 95% CI = 13.9 to
25.0%) from 195 cases treated by enucleation alone. In addi-
tion, the pooled odds ratio was 0.73 (95% CI = 0.22 to 2.42).
Hence, the results of this comparison favor the intervention in
cases of OKC by marsupialization followed by enucleation,
although they are statistically not significant (P = 0.3130)
(Fig. 2b).
Decompression versus enucleation alone
Two studies (Maurette et al. [18] and Kolokythas et al. [22])
compared recurrence rates of OKC after decompression and
enucleation alone. Heterogeneity was not found among these
studies (x2 = 0.01; P = 0.94, I2 = 0%). Of the 24 evaluated
cases treated only by decompression, 4 presented recurrence
(16.7%; 95% CI = 6.1 to 27.2%), and 2 recurrences were re-
ported from 18 cases treated by enucleation alone (11.2%;
95% CI = 2.7 to 19.5%). The pooled odds ratio was 1.30
(95% CI = 0.27 to 6.34). Thus, this comparison favor the in-
tervention in cases of OKC by enucleation alone; nonetheless,
statistically significant differences between the recurrence
rates of cases treated by decompression and by enucleation
alone were not observed (P = 0.3873) (Fig. 2c).
Marsupialization versus enucleation alone
Comparisons between recurrence rates of OKC after
marsupialization and enucleation alone were performed by
five studies (Chirapathomsakul et al. [26], Madras and
Lapointe [16], Boffano et al. [7], Zecha et al. [6], and
Sánchez-Burgos et al. [41]). There was no heterogeneity
among these studies (x2 = 0.81; P = 0.37; I2 = 0%). In this
comparison, 73 cases of OKC were treated only by
marsupialization, and of these, 17 recurred (23.3%; 95%
CI = 13.6 to 33.0%). Moreover, of the 349 cases treated by
enucleation, 51 presented recurrence (14.7%; 95% CI = 10.9
to 18.3%). The pooled odds ratio was 1.57 (95% CI = 0.69 to
3.58). Although the quantitative comparison of the recurrence
rates favored the cases treated by enucleation alone, a statisti-
cally significant difference between marsupialization and enu-
cleation alone was not found (P = 0.2703) (Fig. 2d).
Discussion
The systematic review and meta-analysis reported here com-
bined data of different studies in order to compare the OKC
recurrence rates of conservative surgical treatments with more
precision than it would be possible with a single study. In this
way, our results suggest that nonsyndromic OKCs have a con-
siderable recurrence rate, which may vary significantly de-
pending on the type of treatment applied [21, 23, 29]. When
considering all cases reviewed, the probability of recurrence
was 19.8%. This rate may increase to 35.4% when patients
with NBCCS are analyzed [29]. On the other hand, minor
recurrence rates are found in cases related to more aggressive
treatments [21], for instance 0% for cases treated by resection
Table 1 Summary of selected studies

Author(s) Year Study No. of patients/ Mean Male:female Location Association with Radiographic Treatment Follow- Recurrence
design lesions age ratio impacted tooth aspects up
(years) (months)

Voorsmit et al. 1981 Retrospective 103 patients/106 Range, 61:42 Maxilla (37) N/A Unilocular (71) Enucleation (52) (range, 7 cases
[65] study lesions 10–89 Mandible (69) “Scalloped 12–252)
margins” (5)
Multilocular (19)
“Multilobular” (9)
“Indistinct” (2)
Jensen et al. [66] 1988 Retrospective 12 31.7 10:2 Maxilla (5) N/A Unilocular (10) Enucleation (12) 41.5 4 cases
study (range, Mandible (7) Multilocular (2) (range,
11–57) 17–58)
Brøndum and 1991 Retrospective 44 45 (range, 22:22 N/A N/A Unilocular (26) Decompression + 108 (range, 0 cases
Jensen [38] study 9–87) Multilocular (18) enucleation 22–228) 8 cases
(12)
Enucleation (32)
Marker et al. [48] 1996 Retrospective 23 36.5 14:9 Maxilla (3) N/A Unilocular (7) Decompression + 156 2 cases
study (range, Mandible (20) Multilocular (16) enucleation
10–87) (23)
Stoelinga [43] 2001 Retrospective 80 patients/82 Range, 39:41 Maxilla (anterior and N/A Unilocular (40) Enucleation (33) Range, 6 cases
study lesions 10–89 premolar region = 7, “Scalloped 12–300
molar region and margins” (17)
ramus = 7) Multilocular (7)
Mandible (anterior “Multilobular”(18)
and premolar region = 6,
molar region = 15,
molar region and
ramus = 47)
Nakamura et al. 2002 Retrospective 22 patients/23 36.9 12:10 Mandible (23) N/A Unilocular (16) Marsupialization 79.2 0 cases
[25] study lesions (range, Multilocular (7) (5) 5 cases
13–70) Marsupialization
+ enucleation
(18)
Zhao et al. [5] 2002 Retrospective 484 patients/489 31.2 319:165 Maxilla (162) 173 cases Unilocular (396) Marsupialization 93.6 0 cases
study lesions (range, Mandible (327) Multilocular (81) + enucleation 29 cases
13–76) (11)
Enucleation (163)
August et al. [50] 2003 Cohort study 14 32 (range, 6:8 Maxilla (4) N/A Unilocular (5) Decompression + 33.6 0 cases
9–62) Mandible (10) Multilocular (9) enucleation (range,
(14) 18–52)
Pogrel and Jordan 2004 Case series 10 37.5 6:4 Maxilla (2) 10 cases N/A Marsupialization 33.6 0 cases
[52] (range, Mandible (8) (10)
11–64)
Morgan et al. [53] 2005 Retrospective 40 40.7 25:15 Maxilla (11) N/A N/A Enucleation (11) 63.7 6 cases
study (range, Mandible (29)
11–81)
Chirapathomsakul 2006 Retrospective 51 patients/67 36.9 23:28 Maxilla (21) 21 cases Unilocular (48) Marsupialization Range, 1 case
et al. [26] study lesions (range, Mandible (46) Multilocular (19) (6) 12–175.2 4 cases
9–65) Enucleation (17)
Maurette et al. 2006 Retrospective 28 patients/30 30 (range, 9:19 Maxilla (N/A) “13 of 28 patients” N/A Decompression 24.9 2 cases
[18] study lesions 13–69) Mandible (angle and (20) 2 cases
ramus = 16) Enucleation (10)
Kolokythas et al. 2007 Retrospective 22 10:12 Maxilla (anterior = 1, N/A N/A Decompression Range, 2 cases
[22] study posterior region = 5) (4) 18–108 1 case
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Table 1 (continued)

Author(s) Year Study No. of patients/ Mean Male:female Location Association with Radiographic Treatment Follow- Recurrence
design lesions age ratio impacted tooth aspects up
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(years) (months)

46.9 Mandible (posterior Decompression + 0 cases

(range, region = 16) enucleation (7)
18–90) Enucleation (8)
Madras and 2008 Case series 21 patients/27 45 (range, N/A Maxilla (posterior region = 6) N/A N/A Marsupialization Range, 0 cases
Lapointe [16] lesions 10–80) Mandible (anterior = 3, posterior (3) 12–84 6 cases
region = 18) Enucleation (22)
Boffano et al. [7] 2010 Retrospective 241 patients/261 43.3 163:78 Maxilla (anterior = 16, N/A Unilocular (218) Marsupialization 36 3 cases
study lesions (range, premolar region =18, molar Multilocular (43) (11) 28 cases
7–87) region = 36) Enucleation (250)
Mandible (anterior = 13,
premolar region =42,
molar region = 59, angle and
ramus = 77)
Brzozowski et al. 2010 Retrospective 37 43.3 21:16 Maxilla (7) N/A N/A Enucleation (32) 36 7 cases
[67] study (range, Mandible (30)
14–78)
Gosau et al. [68] 2010 Retrospective 34 patients/36 40.9 21:13 Maxilla (2) N/A N/A Enucleation (22) 67.4 11 cases
study lesions (range, Mandible (34)
6–74)
Pitak et al. [14] 2010 Retrospective 109 patients/120 40 (range, 71:38 Maxilla (anterior and 24 cases Unilocular (85) Enucleation (119) 86 28 cases
study lesions 11–79) premolar region = 9, molar Multilocular (35)
region and ramus = 9)
Mandible (anterior and premolar
region = 12, molar region and
ramus = 89)
Zecha et al. [6] 2010 Retrospective 68 39.5 43:25 Maxilla (anterior = 6, posterior N/A N/A Marsupialization 65.1 4 cases
study (range, region = 10) (10) 12 cases
12–79) Mandible (anterior = 3, posterior Enucleation (58)
region = 35, ramus = 14)
Kuroyanagi et al. 2011 Retrospective 32 40 (range, 16:16 Maxilla (4) N/A Unilocular (23) Enucleation (32) 33 4 cases
[69] study 15–72) Mandible (anterior = 1, molar Multilocular (9)
region = 19, ramus = 8)
Güler et al. [15] 2012 Retrospective 39 patients/ 43 40.6 23:16 Maxilla (anterior and premolar 20 cases Unilocular (31) Enucleation (17) 40.5 0 cases
study lesions (range, region = 8, molar region = 2) Multilocular (12)
15–87) Mandible (anterior and premolar
region = 6, molar region and
ramus = 27)
Selvi et al. [38] 2012 Retrospective 22 47.5 15:7 Maxilla (5) N/A N/A Decompression + 37.8 1 case
study (range, Mandible (17) enucleation (2) 2 cases
21–68) Enucleation (20)
Tabrizi et al. [70] 2012 Case series 13 22.4 8:5 Mandible (13) 3 cases N/A Marsupialization 60 0 cases
(range, (10) 0 cases
16–31) Marsupialization
+ enucleation
(3)
MacDonald et al. 2013 Retrospective 29 35.7 16:13 Maxilla (9) 5 cases Unilocular (18) Enucleation (25) 60 16 cases
[71] study Mandible (20) Multilocular (11)
Sánchez-Burgos 2014 Retrospective 55 42 31:24 Maxilla (10) 15 cases Unilocular (39) Marsupialization 60 9 cases
et al. [41] Study Mandible (45) Multilocular (16) (43) 1 case
Enucleation (2)
Berge et al. [30] 2016 92 48 59:33 N/A N/A 66 4 cases
Table 1 (continued)

Author(s) Year Study No. of patients/ Mean Male:female Location Association with Radiographic Treatment Follow- Recurrence
design lesions age ratio impacted tooth aspects up
(years) (months)

Retrospective Maxilla (anterior = 10, posterior Decompression + 23 cases

study region = 15) enucleation
Mandible (anterior = 7, posterior (22)
region = 60) Enucleation (70)
Cunha et al. [20] 2016 Retrospective 24 32.1 15:9 Maxilla (4) 18 cases Unilocular (11) Decompression + 60.5 3 cases
study (range, Mandible (20) Multilocular (13) enucleation 5 cases
8–80) (14)
Enucleation (10)
Awni and Conn 2017 Retrospective 14 36.7 N/A Maxilla (1) 12 cases Unilocular (8) Marsupialization 84 1 case
[54] study (range, Mandible (13) Multilocular (6) (1) 0 cases
15–68) Marsupialization 1 case
+ enucleation 1 case
(3)
Decompression
(3)
Decompression +
enucleation (7)
Naruse et al. [40] 2017 Retrospective 63 patients/ 65 41 (range, 37:26 Maxilla (18) 30 cases Unilocular (53) Marsupialization 16 (range, 3 cases
study lesions 10–87) Mandible (47) Multilocular (12) + enucleation 6–252) 9 cases
(10)
Enucleation (32)
Mean total Retrospective 1826 patients/ 38.6 1095:696 = 1.57:1 Maxilla (470) 344 cases Unilocular (1105) Marsupialization 60.1 18 cases
study (25) 1900 lesions (range, Mandible (1371) Multilocular(355) (99) 8 cases
Cohort study 6 to 90) Marsupialization 5 cases
(1) + enucleation 12 cases
Case series(3) (45) 218 cases
Decompression
(27)
Decompression +
enucleation
(101)
Enucleation
(1049)

N/A not available

Clin Oral Invest
Clin Oral Invest

Fig. 2 Meta-analysis results. (a) Decompression followed by enucleation versus enucleation alone; (b) Marsupialization followed by enucleation versus
enucleation alone; (c) Decompression versus enucleation alone; (d) Marsupialization versus enucleation alone

[5, 22, 41, 42], 7.8% for cases treated by enucleation and
Carnoy’s solution [43], and 11.5% for cases approached by
enucleation and liquid nitrogen [44].
Nevertheless, more aggressive treatments have many dis-
advantages that must be considered [45]. Although resection
offers the highest cure rate, it produces significant morbidity
such as the loss of the jaws continuity or facial disfigurement
[14, 46]. Moreover, Carnoy’s solution, a caustic tissue fixa-
tive, may cause irreversible neurotoxicity; toxicity to the ad-
jacent soft tissue, skin and dental follicles (especially in chil-
dren); irreversible damage to the superficial and devitalized
osseous margin; and no possibility of immediate bone grafting
[43, 45, 47]. Accordingly, the liquid nitrogen can produce
cellular necrosis in bone while maintaining the inorganic

osseous framework [44]. However, the potential lack of pre-
cision in this technique can injure hard and soft tissue (thermal
trauma) and lead to pathological fractures through the thin
inferior border of the mandible that was exposed to the freez-
ing agent [45]. For these reasons, we advocate the use of
conservative surgical treatments for OKC whenever possible
and this meta-analysis focused only on this modality of treat-
ment in order to identify the best conservative approach.
Thereby, considering all the conservative surgical treat-
ments evaluated, the best result was obtained with cases facing
decompression followed by enucleation, with a recurrence
rate of 11.9% (95% CI = 5.6 to 18.2%), and a significant su-
periority of success when compared to other conservative
treatments [20, 22, 30, 39, 48]. The performance of a decom-
pression followed by enucleation is advantageous in cases of
large cysts [29, 49], especially when there is significant hard
and soft tissue trauma associated with an initial enucleation
(such as injury to nerves or sinuses and fracture of the mandi-
ble), difficulty of surgical access, and requirement of tooth
eruption assistance; besides being a conservative surgical op-
tion for children, elderly and medically compromised patients
[45]. A previous decompression of the lesion may cause en-
largement of the cystic capsule facilitating the complete sur-
gical removal of the lesion [20, 29, 48, 50]. This technique
reduces the levels of IL-1α and cytokeratin-10 that are related
to cyst increase [51]. Moreover, Pogrel and Jordan [52] ob-
served that the epithelial lining of OKC after marsupialization/
decompression displayed similar characteristics of normal oral
epithelium, whereas August et al. [53] suggested a dediffer-
entiation process of the epithelium as a result of the exposure
of OKC’s lining epithelial to the oral environment. This epi-
thelial changing followed by concomitant changes in the bio-
logic behavior of the lesion may explain the observed lower
recurrence rates of OKCs treated by decompression followed
by enucleation [29, 30].
Currently, it is well documented that OKC can completely
regress following decompression [18, 22, 23]. In contrast,
neoplasms should not regress spontaneously; they have auton-
omy to grow even when the initiating stimulus is removed [1].
Accordingly, this was one of the main arguments used by
WHO to readdress OKC to the Cyst category, discontinuing
the use of the term KCOT [1]. In those cases where only
decompression without secondary enucleation is capable to
completely eradicate the lesion, a long follow-up is necessary
to ensure no recurrence [22, 45]. It seems appropriate to ob-
serve these patients with an annual panoramic radiograph for
about 10 years after complete eradication of the cyst [45]. In
our study, an 18.5% (95% CI = 8.2 to 28.9%) recurrence rate
of OKC was found in cases treated only by decompression,
with a mean follow-up of 54.5 months [18, 54].
Distinctly from the treatments of OKC using decompres-
sion followed by enucleation, enucleation alone showed a
high recurrence rate (20.8%; 95% CI = 18.3 to 23.2%) [5–8,
Clin Oral Invest
20, 26, 29, 53], which has been suggested to be a consequence
of technical difficulties around the complete removal of the
lesion due to the thin cystic epithelium or often the inaccessi-
ble location of the cyst [5, 55]. Therefore, the enucleation of
OKC as a single piece, not fragmented whatsoever, may ac-
tually be difficult to accomplish in most instances [6].
Accordingly, epithelial remnants and/or satellite or daughter
cysts (microcysts) left behind after the enucleation ostensibly
potentiates recurrence [56], mainly due to some possible his-
topathological and immunohistochemical findings of OKC,
such as the budding of the basal cell layer of the lining epi-
thelium; synthesis of IL-1α and IL-6 by keratinocytes; elevat-
ed prostaglandin levels; and a high Ki-67 index of the epithe-
lial cells [55, 57–60]. Interestingly, the Ki-67 index has been
reported to diminish proportionally with the grade of IL-1α
expression [51], suggesting the regulation of epithelial cell
proliferation in OKC by IL-1α, which is also known to stim-
ulate the production of PGE2 in OKC fibroblasts [6, 61]. In
addition, Ogata et al. [61] also demonstrated that IL-1α may
stimulate COX-2 expression in OKC through the NFkB cas-
cade. These facts again highlight the advantageous initial ap-
proach by decompression, since this technique decreases the
levels of IL-1α [51].
Regarding the clinicopathologic features related to recur-
rence rates, there were no statistically significant differences
between male and female patients or between lesions located
in the maxilla and in the mandible [8, 29]. On the other hand,
when comparing the recurrence rates of unilocular and
multilocular lesions, it can be seen that multilocular lesions
have significantly more probability to recur [5, 29]. Moreover,
higher recurrence rates of parakeratinized OKCs compared to
orthokeratinized OKCs have been reported [26, 62]. Another
interesting fact that has been related to OKC recurrence is the
preservation of the tooth associated with the lesion after treat-
ment [14, 20, 26]. Cunha et al. [20] reported a recurrence rate
of 66.7% for these patients who had their tooth associated with
the lesion preserved during surgery (P = 0.009).
Therefore, the results of this meta-analysis should be
interpreted with caution due to study limitations. For instance,
the information about the removal of tooth associated with the
lesion was rarely available in the included publications, and
thus a proper analysis of the influence of this factor on the
recurrence was not feasible. In addition, in the present study,
unilocular lesions were not evaluated separately from
multilocular lesions, since most of the authors did not discrim-
inate the recurrence rates of these two radiographic aspects.
Also, authors rarely mention the initial size of the lesions, and
the follow-up time is different among studies. Thus, all these
factors may influence the results obtained on OKC recurrence
rates, and we suggest that future studies better investigate the
real dimension of such influences.
In conclusion, nonsyndromic OKCs have a considerable
recurrence rate that may vary depending on the type of applied
Clin Oral Invest
treatment. In fact, the recurrence rates of patients treated by
decompression followed by enucleation are significantly low-
er than those of other conservative surgical treatments, mainly
when compared to enucleation alone (P = 0.0163), which has
higher rates of recurrence, probably related to the challenging
initial approach and excision of the lesion without any frag-
mentation. Therefore, due to the possible disadvantages relat-
ed to the more aggressive treatments for OKC, we recommend
the performance of a more conservative initial approach
whenever possible, being the best of them the decompression
followed by enucleation. It is suggested that the decompres-
sion time must be at least 9 months, in order that the process of
epithelial dedifferentiation may occur; however, an additional
time may be necessary for a larger decrease in OKC size and
subsequent enucleation [50, 63]. In addition, a long follow-up
is also recommended since recurrence may occur 10 or more
years after the first surgical treatment [64].
Acknowledgements The authors express sincere gratitude to
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
(CAPES) for financial support.
Funding The authors wish to thank Coordenação de Aperfeiçoamento de
Pessoal de Nível Superior (CAPES) for the financial support (Masters
Scholarship).
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
Ethical approval This article does not contain any studies with human
participants or animals performed by any of the authors.
Informed consent For this type of study, formal consent is not required.
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