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Limited Evidence Suggests Benefits of Single Visit Revascularization Endodontic Procedures - A Systematic Review

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Brazilian Dental Journal (2019) 30(6): 527-535

ISSN 0103-6440
http://dx.doi.org/10.1590/0103-6440201902670

Limited Evidence Suggests


1Adelaide Dental School,
The University of Adelaide,
Adelaide, Australia
Benefits of Single Visit 2School of Dentistry, The University

of Queensland, Brisbane, Australia


Revascularization Endodontic 3School of Dentistry, International

Medical University, Kuala


Procedures – A Systematic Review Lumpur, Malaysia

Correspondence: Prof. Giampiero


Rossi-Fedele, Adelaide Dental
Giampiero Rossi-Fedele1 , Bill Kahler2 , Nagendrababu Venkateshbabu3 School, AHMS 10th floor, George
Street C/O North Terrace, Adelaide,
SA 5005, Australia. Tel: +61-8-
8313-8139. e-mail: giampiero.
Revascularization endodontic procedures commonly require multiple treatment sessions. rossi-fedele@adelaide.edu.au
However, single visit procedures may be advantageous from the clinical and patient
management standpoints. The purpose of this review was to evaluate the outcomes of
single-visit revascularization endodontic procedures for the management of immature
permanent teeth with non-vital pulp. Two electronic databases (Scopus and PubMed)
were searched, from their inception to July 2018, for studies that assessed clinical and/
or radiographic and/or histologic outcomes of single-visit revascularization endodontic
procedures performed in immature permanent teeth with non-vital pulp. Case reports,
animal studies and clinical trials were included. The quality of case reports was appraised
by Joanna Briggs Institute Critical Appraisal Checklist for Case Reports. The quality of
randomized clinical trials was assessed by the revised Cochrane risk of bias tool for
randomized trials. The risk of bias for animal studies was assessed using SYRCLE’s risk
of bias tool. Tabulation followed by narrative synthesis was used to draw conclusions.
Seven studies satisfied the selection criteria. Five were classified as case reports, one as a
randomized clinical trial and one as animal study. The latter presented with a high risk of
bias, whilst the remaining showed a low risk. The evidence supporting the potential use
of single-visit revascularization endodontic procedures is scarce. Successful single-visit
revascularization endodontic procedures commonly include the use of high concentrations
of sodium hypochlorite and EDTA combined with the use of agitation systems. Further Key Words: endodontics,
clinical trials with long term follow up are needed to confirm the results of the current dental pulp, necrosis,
review. regeneration, root canal.

Introduction drawbacks in two visit REPs are the need for increased
Trauma or caries in immature permanent teeth can visits, placement of temporary restorative materials, patient
result in necrosis of the pulp and cessation of the root compliance and longer treatment time (10,11). Single-visit
development process, leaving thin and fragile root canal REPs would be particularly advantageous when general
walls (1). Subsequently, non-vital immature teeth are anaesthesia is required. Further issues related to the use
associated with a high risk of root fracture, because of of intracanal medicament in REP are discoloration of
their inability to sustain physiological mastication forces tooth (11,12), reduced fracture resistance of tooth (13),
and further trauma (1). The management of immature detrimental effect on apical papilla stem cells survival (14)
permanent teeth with a non-vital pulp is a demanding and their retrieval from root canal walls (15). To overcome
procedure for clinicians (2,3). Amongst the possible these issues, and to achieve a significant saving in time and
treatment alternatives, calcium hydroxide multi-visit cost for patients and dentists (16) single visit REPs could
apexification (4), apical barrier techniques using tricalcium- be an alternative method. In fact, apical barrier techniques
silicate based materials (5,6) and revascularization (17), and non-surgical root canal treatment (16), can be
endodontic procedures (REPs) (7) have been proposed. performed with a single-visit protocol. Thus, it is worth
Whilst calcium hydroxide multi-visit apexification and investigating if a single-visit approach for REPs is effective
apical barrier techniques are not associated with further and safe. To the knowledge of authors, no review has been
root maturation (8), REPs are associated with root length published to critically appraise the evidence on single
and wall thickness increased together with reduction in visit REPs and the topic has received limited attention in
apical diameter (8). The aim of this root maturation is to the literature. Hence, the aim of the current systematic
reduce the risk of tooth fracture. review was to evaluate the published outcomes of single
REPs published protocols commonly require the use of visit REPs for the management of immature permanent
an intermediate medicament following chemo-mechanical tooth with non-vital pulp. The research question for the
preparation, thus with a two-visit approach (7-9). The present systematic review was designed according to the
Braz Dent J 30(6) 2019

PEO (Population; Exposure of interest; Outcome) format: duration of follow up, clinical and/or radiographic/and or
“In studies managing non-vital immature permanent teeth histological outcomes. In addition, further data collected
(P) treated with a single-visit REPs (E), what are the clinical included, for clinical studies, the age and the gender of the
AND/OR radiographic AND/OR histological outcomes (O)?” subject(s), aetiology of the loss of vitality, tooth type and
sample size, whilst for animal studies the animal species,
Material and Methods tooth type and sample size. Authors of the included studies
Literature Search Process were contacted for clarification and/or requested to provide
Initially, PubMed was explored for screening of search further information as needed.
terms pertinent to the research question using sentinel
studies as a reference. The search strategy was developed Quality and Risk of Bias Assessment of Included
from the appropriately identified key words and index Studies
terms and applied in combination, by using Boolean Two independent reviewers (VN, GRF) appraised the
terms (OR/ AND), to the selected databases. Two reviewers quality of included studies. Disagreements between the
independently (VN, GRF) performed a literature search reviewers at the different stages of the review were
in PubMed and Scopus databases from inception to July resolved by discussion. The quality of included case reports
2018 by using search strategy ((((regenerative endodontic) was assessed by Joanna Briggs Institute Critical Appraisal
OR revascularization) OR revitalization)) AND ((immature Checklist for Case Reports which consist of eight yes/no/
permanent tooth) OR immature permanent teeth). The title unclear questions (18). The quality of randomized clinical
and the abstract of the published studies were evaluated trial was assessed by the revised Cochrane risk of bias tool
independently by two reviewers (VN, GRF) and, if not clear for randomized trials (RoB 2.0) (19). Finally, the risk of bias
enough, the full text of the article was read for accuracy for animal studies was assessed using SYRCLE’s risk of bias
of data gathering. After title and abstract screening, full tool for animal studies (20).
text evaluation of the relevant articles was performed to To summarize the overall quality of case reports and
G. Rossi-Fedele et al.

identify their eligibility against the selection criteria. The animal study, these were grouped into the following
additional search was undertaken from the reference lists categories 1. Low risk of bias (studies that met at least
of the included articles and previously published reviews, 75% of the quality criteria) 2. Moderate risk of bias (studies
using the same selection criteria. Any disagreements that met between 50% and 74% of the quality criteria)
between two reviewers was resolved by team discussion 3. High risk of bias (studies that met less than 49% of the
or with the third reviewer (BK). quality criteria).
The overall quality of the randomized clinical trial was
Selection Criteria assessed: A “low risk” of bias score was given to a study
Inclusion criteria for our review were: single visit REPs when all the key domains in the assessment of bias were
performed in immature permanent tooth with non-vital found to be of low risk. When one of the key domains in
pulp, with no exclusions based on study design. Reviews the bias assessment was found to have some concerns, a
and studies in the form of conference proceedings, letters scoring of “some concerns” was accorded. The assessment
or commentaries, and publications without abstracts were of at least one key domain of bias with a high risk in a
excluded. The search was limited to publications written study rendered it to be of “high risk” of bias.
in English.
Data Synthesis
Outcome of Interest Following tabulation narrative synthesis was used to
The outcome of the review was clinical and/or draw conclusions.
radiographic and/or histologic outcome of single visit
REPs performed in immature permanent teeth with non- Results
vital pulp. A total of 359 studies were identified from electronic
databases, 164 studies were removed as duplicates. Among
Data Extraction Process the 195 studies, seven satisfied the criteria. Five were
Two independent reviewers (VN, GRF) performed data classified as case reports (10,21-24), one as a randomized
extraction process. After piloting, the data extraction clinical trial (25) and one as an animal study (26). Main
form was produced and consisted of first author, year, characteristics of the included case reports, clinical trial and
country, study design, pulpal and periapical pre-treatment animal study were reported in Tables 1, 2 and 3 respectively.
diagnosis, pre-operative radiographic findings, intra- Case reports and the animal study included presented with
operative disinfection protocol, intracanal coronal barrier, favorable outcomes, whereas the randomized controlled
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Braz Dent J 30(6) 2019

trial reported a fifty-percent success rate. questions. A good quality case report contains a clear and
The authors of two studies were contacted, firstly detailed description of a clinical condition; disease or
for clarification of pulpal and periapical pre-treatment treatment being described. A clear and systematic history
diagnosis, pre-operative radiographic findings and following the timelines gives the reader a contextual
aetiology of the loss of vitality at the different stages of relation and the importance of the condition being
the study (25), and the second regarding some features of reported. Reports on an intervention should explain the
the study design (26), as this was not able to be determined procedure and provide vivid pre and post intervention
by the data provided in the identified studies. Of these clinical features with good quality pictures. Relevant and
authors, one provided some of the requested information important investigative and diagnostic tests are reported
(25), with the second not replying. Figure 1 shows the along with their interpretations (18). Any anticipated
summary of the details and results of the search process. or unexpected adverse events should be reported. Five
included case reports in current review satisfied all eight
Discussion questions, hence included case report was scored as high
The current review aims to obtain a narrative integration quality. The quality assessment of the included randomized
of the relevant evidence regarding the outcome of single clinical trial is shown in Table 5. The included randomized
visit REPs for the management of immature permanent clinical trial (25) was appraised as “some concerns” which
tooth. Within the paucity of studies, positive outcomes could be due to bias in the randomization process. The
appear to be associated with the use of sodium hypochlorite study identified as a randomized clinical trial but failed
(NaOCl) and EDTA as root canal irrigant solutions, in the to report on the method of randomization process and
presence of adequate dynamics of irrigation, namely the allocation concealment and hence were marked lower in
volume and agitation of the irrigant. The present review quality. However, allocation concealment was not possible

Single visit revascularization endodontics


includes five case reports, one randomized clinical trial and due to the inherent difference in methodology of the two
one animal study to assess the outcome of single visit REPs. interventions (immediate vs delayed induction). Inadequate
This approach has been followed due to limited number of randomization can lead to systemic differences between
studies in the review, however this is consider acceptable as the experimental and control group of subjects and can
allows to integrate the richness of the qualitative research lead to baseline differences. Allocation concealment
currently available to capture the whole phenomenon of conceals the experiment labels from the operator and the
interest (27). patients to avoid bias due to knowledge of the treatment
Case reports help us to gain knowledge and information or intervention. This can lead to spurious results affecting
on any new observation or procedure, report on rare the magnitude and direction of the effect. Hooijmans et
diseases or conditions, generate hypothesis and research al. (20) developed the SYRCLE’s risk of bias tool for animal
question on a problem and thus serves as an important studies and was adapted from the Cochrane’s risk of bias
educational tool and clinical resource (28). Generally, tool. This tool evaluates the quality based on ten domains
case reports/series are at the lowest level of the evidence assessing five biases. In da Silva et al. (26) study domains
pyramid due to increased risk of bias (29) but have played 1 to 6 were scored as unclear (Table 6), however it should
an important role in the evidence network (30). They form be mentioned that those were mostly related to animal
the first level of evidence in many instances which leads husbandry and not necessarily relevant, considering that
to well-designed observational or interventional studies. all groups were tested in each animal. Domain 7 to 10
In the specific case of REPs, two case reports had this role were scored yes. The biases include selection, performance,
(3,31). The evidence derived from systematic review of case detection, attrition and reporting. Selection bias can occur
reports/series will be low, however such reviews can be when randomization and allocation concealment are
used for clinical decision making (32). Hence the present inadequate. Performance bias is dependent on random
review was undertaken with five case reports, which can housing of the animals and blinding of the caregivers
provide early evidence and guidelines for future clinical and operators. Detection bias occurs due to inadequate
trials on the outcome of single–visit REPs. selection of animals for outcome assessment and blinding
of the examiners. Attrition bias is related to incomplete or
Quality of Included Case Reports, Randomized Clinical uneven loss of animals or exclusions. Selection of reported
Trial and Animal Study outcomes leads to reporting bias (20).
The quality of evidence derived from a review is largely
dependent on the quality of the studies included. The Pre-Operative Factors
quality assessment of included case reports are presented The age of patients ranged from 7 to 12 in case
in Table 4. Five case reports scored “yes” for all 8-checklist reports, whereas in the randomized clinical trial from 6 to
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Braz Dent J 30(6) 2019

25 (at screening stage). Case reports and the randomized successful single visit cases were associated with trauma.
clinical trial included both genders, however the divide The diagnosis of the teeth was necrotic pulp with periapical
was not clearly reported for the latter study. Regarding abscess or apical periodontitis for the randomized clinical
type of teeth, for case reports, mandibular teeth were trial (25) (personal communication with Dr. Tatiana Botero)
most commonly treated including a central incisor (n=1), and for most case reports, apart from the two studies,
second premolars (n=2) and mandibular first molars (n=3), which included four teeth in total (22,24). Partial necrosis
and finally, a maxillary central incisor (n=1). In the animal was reported in one case report, in the presence of an
study second and third maxillary premolars and second, invagination (21).
third, and fourth mandibular premolars immature teeth
were studied. The aetiology of the loss of vitality included Disinfection Strategies
caries (n=5), dens invaginatus (n=1), root fracture (n=1) The presence of infection has a negative impact on
and dental avulsion (n=1). In the animal study pulp necrosis the outcome of REPs (33), hence disinfection of the
and apical periodontitis was created experimentally. For root canal system plays a major role. Generally, NaOCl in
the randomized clinical trial tooth type and aetiology of copious volumes was used for root canal irrigation in all
loss of vitality were not clearly stated. However, the four included studies, at concentrations ranging from 2.5% to

Table 1. Characteristics of included case reports


Age Etiology of the
Author, year Country Gender Study design Tooth type Preoperative radiographic findings
(years) loss of vitality
Immature open apex, measuring 2 mm in
Mandibular Caries diameter. Condensing osteitis at the apical
Shin et al.
USA 12 Female Case report second and dens area with a large periradicular rarefaction
2009 (21)
premolar invaginatus 9 x·9 mm in size, extending from the
G. Rossi-Fedele et al.

apex to the distal crestal bone area

Maxillary Trauma, Probable periapical disease with


McCabe et al.
Ireland 7 Female Case report central oblique root an incomplete root development
2014 (10)
incisor fracture with wide open apex

Topcuoglu and Female: Case


Mandibular Healthy periapical tissues with incomplete
Topcuoglu, Turkey 8, 8, 9 2, reports Caries
first molars root development with wide open apices
2016 (24) Male:1 (n=3)

Continuation
Pulpal and
Periapical Disinfection Intracanal Duration of Radiographic
Author, year Clinical outcome
pretreatment Protocol coronal barrier Follow up outcome
diagnosis
No tenderness Complete
to percussion periradicular
White MTA
Partially necrotic 10 mL of 6% NaOCl, or palpation, bone healing and
Shin et al. (Dentsply Tulsa 2, 3 week, 7,
pulp with chronic saline, 10 mL of 2% Periodontal root maturation,
2009 (21) Dental, Tulsa, 13,19 months
periapical abscess CHX for 5 minutes pocket depths and complete resolution
OK, USA)
physiologic mobility of condensing
were normal. osteitis
30 ml of 5 % NaOCl
for 20 minutes,
Necrotic pulp MTA plug (MTA; 6 weeks, 3, Evidence of
McCabe et ultrasonics, 3ml of
with acute apical Angelus,Londrina, 6, 12, 18 Asymptomatic continued root
al. 2014 (10) 17% EDTA, final
periodontitis PR, Brazil) months development.
rinse 3 mL NaOCl
and 3 mL EDTA
Not sensitive
Platelet-
Every 3 to percussion Absence of
20 ml of 2.5% rich plasma,
Topcuoglu and months or palpation, periapical lesions
NaOCl, 10 ml of Biodentine
Topcuoglu, Necrotic pulp during an physiologic mobility and thickening of
sterile saline, 10 (Septodont,
2016 (24) 18-month and normal the canal walls
ml of 17% EDTA Saint Maur des
period probing depth and apical closure
Fosses, France)
around the teeth

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Braz Dent J 30(6) 2019

6%. The lower concentration was used for three cases in factors (37,38). Agitation of this solution was carried out
the absence of radiographic signs of apical periodontitis in one study using ultrasonication (10), whereas one case
(24), the randomized clinical trial and the animal study. In report (23) and the animal study (26) used apical negative
a previous systematic review, 97% of the clinical studies pressure with the EndoVac system. Ultrasonic activation
used NaOCl as the only irrigant or in combination with significantly reduces the bacteria load in root canal system
other irrigating solutions in REPs (34). compared to conventional syringe irrigation methods (39).
Chlorhexidine was used in association with NaOCl and One animal model study showed that no difference was
ethylenediaminetetraacetic acid (EDTA) in two studies observed in terms of bacterial load reduction between
(21,22). EDTA was commonly used, with the exception of EndoVac system to conventional irrigation combined
a case report (21) and the animal study (26). 17% EDTA with triple antibiotic paste in immature teeth with apical
has the ability to promote the survival of stem cells of the periodontitis (40). Further research has to be performed to
apical papilla (35), reverse the adverse effect on NaOCl confirm the ability of various irrigant agitation techniques
(36) and expose the dentin matrix to release growth and devices in REPs.

Table 2. Characteristics of included RCT

Author, Age Study Tooth Clinical


Country Gender Sample size Disinfection Protocol
year (years) design type condition
Pulp necrosis
20 mL of 2.5% NaOCl,
Botero et Randomized on an
Not Not 13 at randomization; 3 ml of saline, 3 ml

Single visit revascularization endodontics


al. 2017 USA 6 to 25 Clinical immature
specified specified 9 intra-canal bleeding of 17% EDTA for no
(25) Trial permanent
less than 2 minutes
tooth

Continuation
Author, Etiology for the loss intracanal Follow-up Radiographic Clinical outcome Radiographic Success
year of tooth vitality coronal barrier duration findings for success outcome for success rate

At least 1
White MTA 50%
open apex of
Botero et (ProRoot; 4 weeks, when
1 mm or more Absence of signs Decrease of
al. 2017 Not specified Dentsply Tulsa 3, 12, 24 intracanal
in diameter. or symptoms periapical lesion
(25) Dental, Tulsa, months bleeding
Periapical
OK, USA) occurred
radiolucency

Table 3. Characteristics of included animal study

Number
Author, Age Study
Country of Animal species Tooth type Intervention
year (month) design
samples
Minimal mechanical
Second and third instrumentation using 2.5%
da Silva maxillary premolars NaOCl at each change of file.
Animal 28 root
et al. 2010 Brazil 4 Mongrel dogs and second, third, and 10 mL of 2.5% NaOCl using
study canals
(24) fourth mandibular apical negative pressure
premolars (EndoVac System, Discus
Dental, Ontario, CA, USA)

Continuation
Author, Preoperative radiographic
Intracanal coronal barrier Duration of Follow up Histological outcome
year findings

Intracanal connective tissue


ProRoot grey MTA (Dentsply
Incomplete root formation ingrowth in all specimen and
da Silva Tulsa Dental, Johnson City,
and open apices. Periapical beginning of mineralisation.
et al. 2010 TN, USA) and silver amalgam 3 months
periodontitis as indicated by Normal alveolar bone
(24) (Sybraloy; Kerr Corporation,
periapical radiolucencies in 20 teeth, osteoclasts
Orange, CA, USA)
present in the remaining

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Intra-Coronal Barrier Materials clinical trial was 50%, which is lower than the multiple
Among the seven included studies, five studies used MTA visit success rate comparator in the same study (25) and
whereas two studies, used Biodentine as an intracoronal the success rates suggested in a previous systematic review
barrier. The MTA have been recommended in REPs due to for REPs (8). Although case reports were associated with
its biocompatibility, sealing ability and tissue-conductive successful treatment outcomes, it should be noted that
properties (41,42). The disadvantage of using MTA is these studies should not be used to assess treatment
occurrence of mild or moderate tooth discoloration after outcomes per se, considering that case reports presenting
single-visit REPs was reported in a case report (23) and positive reports are more likely to be published (43).
the randomized clinical trial (25). Conversely, the use of REPs outcomes are likely influenced by the duration of
Biodentine was justified in two studies (22,24), in order to follow up of the studies, as healing of apical periodontitis
prevent this treatment complication. Further in vitro and and root maturation, would require time. The final recall
in vivo studies have to be performed to study the potential for the clinical studies ranged between 18 and 24 months
use of other bioactive endodontic cements for REPs. (Tables 1 and 2), whereas the animal study had a 3-month
recall only, with favorable histological results, also when
Outcomes compared with the multiple-visit group in the same study
The limited evidence related to the component (Table 3). It should be highlighted that animal studies
studies suggests that single-visit REPs are unpredictable, present with experimentally induced disease, whereas a
considering that the success rate reported in the randomized well-established pathosis is commonly found in humans.
G. Rossi-Fedele et al.

Figure 1. Summary of the details and results of the search process.


532
Braz Dent J 30(6) 2019

Therefore the result of animal studies may not have the in the absence of medication, irrigation is crucial for
proposed clinical translation. the management of intra-canal infection, especially
The definition of success differed widely amongst in the presence of apical periodontitis. The use of high
component studies (Tables 1 and 2). The clinical studies concentrations of NaOCl followed by EDTA, in association
included symptoms and/or clinical signs, together with with agitation, should therefore be considered for single-
inconsistent radiographic criteria. The latter included further
root maturation using various descriptors, associated with
the reduction and/or disappearance of apical periodontitis,
Table 6. SYRCLE’s tool for assessing risk of bias for animal study
if previously present. Studies on patients did not include
histological assessment, for obvious ethical reasons. No Domain da Silva et al. 2010 (26)

1 Sequence generation Unclear


Limitations of the Study 2 Baseline characteristics Unclear
The included studies have several confounding factors
3 Allocation concealment Unclear
in their study design which may influence on outcomes, as
previously described. Only publications in English language 4 Random housing Unclear
were included in our review and no grey literature was 5 Blinding Unclear
searched, which may be a limitation in the study selection
6 Random outcome assessment Unclear
process. This may have reduced the number of potentially
eligible studies. 7 Blinding Yes

8 Incomplete outcome data Yes


Clinical Translation

Single visit revascularization endodontics


9 Selective outcome reporting Yes
REPs protocols, in general, include limited or no
10 Other sources of bias Yes
instrumentation and no root canal obturation. Therefore,

Table 4. JBI Critical Appraisal Checklist for Case reports

Topcuoglu and
Shin et al. McCabe et Chaniotis Aldakak et
JBI checklist questions Topcuoglu
2009 (21) al. 2014 (10) 2016 (23) al. 2016 (22)
2016 (24)
Were patient’s demographic
Yes Yes Yes Yes Yes
characteristics clearly described?
Was the patient’s history clearly described
Yes Yes Yes Yes Yes
and presented as a timeline?
Was the current clinical condition of the
Yes Yes Yes Yes Yes
patient on presentation clearly described?
Were diagnostic tests or assessment methods
Yes Yes Yes Yes Yes
and the results clearly described?
Was the intervention(s) or treatment
Yes Yes Yes Yes Yes
procedure(s) clearly described?
Was the post-intervention clinical
Yes Yes Yes Yes Yes
condition clearly described?
Were adverse events (harms) or unanticipated
Yes Yes Yes Yes Yes
events identified and described?
Does the case report provide takeaway lessons? Yes Yes Yes Yes Yes

Table 5. Revised Cochrane tool for assessing risk of bias for randomized clinical trial

Bias arising Bias due to


Bias due Bias in Bias in selection
from the deviations
Author, year to missing measurement of of the reported Overall bias
randomization from intended
outcome data the outcome result
process interventions
Botero et al.
? + + + + ?
2017 (25)

+symbol means ‘low risk of bias’; ? symbol means ‘some concerns.


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Braz Dent J 30(6) 2019

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may be considered in those cases where the intra-canal
2016;42:730-734.
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in the absence of clinical and radiographic manifestations procedure: A retrospective case series. J Endod 2016;42:1752-1759.
  8. Kahler B, Rossi-Fedele G, Chugal N, Lin LM. An evidence-based review
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Single visit revascularization endodontics


Received February 13, 2019
Accepted May 3, 2019

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