Fatores Outcomes
Fatores Outcomes
DOI: 10.1111/iej.13897
REVIEW ARTICLE
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© 2023 The Authors. International Endodontic Journal published by John Wiley & Sons Ltd on behalf of British Endodontic Society.
82 | wileyonlinelibrary.com/journal/iej
Int Endod J. 2023;56(Suppl. 2):82–115.
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GULABIVALA and NG 83
KEYWORDS
factors affecting, outcomes, periapical healing, retreatment, root canal treatment
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84 OUTCOMES OF ROOT CANAL TREATMENT
& Gulabivala, 2011; Ng, Mann, Rahbaran, et al., 2008). types rarely meet these expectations and have been ranked
Added to this are the facts that root canal system com- into a hierarchy (Figure 1) based on their methodological
plexity and clinician expertise may be confounding factors quality, design, validity, and applicability to patient care.
(Chambers et al., 2009; Yee, 2019). Nevertheless, endodon- The highest evidence level is deemed to be derived from a
tics has become a gadget-oriented discipline, with dentists synthesis of quality primary data (randomized controlled
keen to adopt new technology in the interests of efficiency, trials), by a select group of workers, using a systematic
efficacy and economy. and accepted process that identifies appropriate mate-
rial, screens for matching entry criteria, filters for quality,
extracts useable raw data, pools it, and calculates an esti-
Nature of expected and available mated overall outcome. Based on such pooled data, guide-
evidence and its value to service delivery lines may be agreed by consensus workshops to inform
and recommend best practice (Sanz Herrera et al., 2020;
Confidence and assurance in the validity and predict- Scholmerich, 2000). The intention is to propagate a stand-
ability of root canal treatment is desirable because there ardization of approach to raise overall levels of perfor-
remain elements within society that doubt the evidence mance by the dentist population working for the overall
(Meinig, 1996). Received wisdom suggests that high- patient population. With the methodological advances in
quality evidence is typically obtained from pooled out- evidence evaluation, tools and checklists have been devel-
come data from suitable studies ideally all following oped to guide assessment of risk of bias: RoB2 (https://
consensus guidelines, with a large and representative metho d s.cochr a ne.org/bias/resou r ces/rob-2 - r evis e d-
enough patient and dentist population. The anticipation cochrane-risk-bias-tool-randomized-trials); ROBINS-1
is that such pooled data, when homogenous may distil (https://methods.cochrane.org/methods-cochrane/robin
and rank key biological, technical and clinical factors that s-i-tool); Newcastle Ottawa Scale for observational studies
exert a dominant influence on outcomes. Available study (http://www.ohri.ca/programs/clinical_epidemiology/
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GULABIVALA and NG 85
oxford.asp), and to designate through grading, the cer- data serves the dual purpose of motivating and direct-
tainty of evidence into the categories of ‘very low’, ‘low’, ing practitioners to refine their technique and knowl-
‘moderate’ or ‘high’, when making recommendations in edge to enhance predictability of their own outcomes
clinical guidelines (https://gdt.gradepro.org/app/handb (Chambers, 2001).
ook/handbook.html). The merits of such standardized The flaw in the evidence-based system is that dentists
approaches are self-evident, but they also carry the risk following guidelines blindly, will not work, because the
of falling into the trap of ticking boxes without exercis- process does not place emphasis on the progressive im-
ing due diligence and intuitive analysis, and thinking provement and development of the individual dentist in
out of the box. The approach must not be allowed to sti- understanding the clinical problem and solving it from
fle productive and innovative synthesis, to facilitate do- first principles (Chambers, 2001). Improvement in the out-
main knowledge development (Greenhalgh et al., 2018). comes of individual dentists, the ultimate goal, requires
A proliferating mass of systematic reviews informs on the integrated correction and development in numerous do-
sufficiency or otherwise of the available evidence, often mains (cognitive, technical, clinical) through dedicated,
reaching the conclusion that the evidence quality is in- diligent practice by the dentist, in which the guidelines
adequate for reliably confident conclusions about best form only a small directional role (Chambers, 2001;
practice or generalizability to the population at large. The Scholmerich, 2000). Paradoxically, the best study out-
majority of the published outcome data may be deemed comes in the literature can be attributed to a larger pro-
of moderate or low quality and is thus less amenable to portion of “best individual performances” amongst the
mathematically robust summation. The outcome for the studied dentist cohorts, yet in the hierarchy of evidence,
clinician then is no useful guidance, unless they under- the opinion of such high performers (experts) is relegated
take a deep and personal intuitive synthesis that may add to the bottom of the pyramid. Exploration of the relation-
to their own domain knowledge, albeit without external ship between evidence-based outcomes and high expert
consensus. The evidence base for non-surgical root canal performance at an individual level, merits much deeper
treatment is more comprehensive than that for other en- consideration (Ericsson, 2009; Ericsson et al., 2018). The
dodontic procedures. Although the quality and scope of distribution of high expert performers across the cen-
the research does not always reach the highest prescribed tury of outcome data is not skewed towards the “era of
hierarchical levels, it does nevertheless provide a breadth evidence-based practice (1980–present)”, suggesting that
and depth of insight for the individual who is open to full the “evidence-base” per se, is not a prior requirement for
and deep exploration of the literature. expertise development. Such an idea may also help to dis-
In addition to predictability and consistency in treat- tinguish between domain knowledge (that which makes
ment delivery, patients also value prognostic accuracy an expert) and evidence-based knowledge (that which
(predicting, projecting, prophesising or foretelling) to helps to refine the conceptual basis for understanding the
aid decision-making in selection of treatment choices. problem and how to manage it, or domain knowledge).
Prognostication skill is an art predicated on mentally The evidence-base may contribute to domain knowledge
weighing the relative balance of different factors affecting but is not an essential requirement to derive an intuitive
treatment outcomes. Such insight is a part of the “expert conceptual understanding of the biology and biome-
domain knowledge”, a conglomerate derived through chanics of the problem, it is the latter that forms a plat-
active experience in the application of biological princi- form for expertise development (Ericsson, 2009; Ericsson
ples coupled with composite outcome data to surmount a et al., 2018) and predictability of outcomes.
spectrum of treatment challenges. Such skill is not gifted
by guidelines but is individually developed. The overall
tooth prognosis extends beyond endodontics (periodon- Purpose and nature of root canal
tic, restorative and occlusal aspects), where each element treatment and its outcome challenges
subsumes further subsidiary factors influencing overall
prognosis, therefore the clinician must go beyond end- Root canal treatment is a procedure used to either prevent
odontic guidelines and reach for a broader insight for pre- apical periodontitis or once established, to treat and re-
dictable management. solve it. These two ends of the biologic disease spectrum
Population- based summary outcome data may help also define the two ends of the outcome spectrum, since
clinicians to inform patients about the general outcome the highest success rates are attributed to periapical dis-
trend to be expected for their problem but only the den- ease prevention and the lowest to disease resolution, par-
tist's personal audit caseload, case-mix and outcome data ticularly when the measures of disease are at their worst
are likely to persuade the patient of the suitability of the (large, suppurative, symptomatic lesion). Prevention of
dentist's skill and knowledge for their care. Such personal apical periodontitis broadly encompasses prevention of
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86 OUTCOMES OF ROOT CANAL TREATMENT
primary dental diseases as it is their sequel (caries, tooth The pre-eminent biologically important outcome of such
surface loss, periodontal disease and traumatic injuries). treatment, intra-canal bacterial load control, is at the best,
More parochially, it is prevention of spread of pulpitis to a side-effect of the technical and chemical procedural
apical periodontitis through pre-emptive vital pulp ther- manipulations rather than a direct and conscious act of
apy, or partial/total pulpectomy. The absence of apical observable microbicide. The dentist may have conscious
periodontitis implies the absence of apical bacterial colo- or unconscious microbicide intent (clinician thinking
nization, probably coupled with vital, healthy pulp tissue about the microbes and their killing) but the greater part
apically. The prime requirement for management of such of the mental focus will generally be concentrated on the
a condition is asepsis during the technical execution of technical outcome; namely the “root- filling aesthetic”
instrumentation, irrigation and obturation. The expected (flow, centeredness, apical extension, smoothness, and
probability of retaining periapical health is 90%–99% if homogeneity). This dissociation between the technical
asepsis is treated as sacrosanct, regardless of the choice and biological elements, which in some practitioners
of clinical protocol (Ng, Mann, & Gulabivala, 2008; Ng, may cause cognitive dissonance (Seltzer & Bender, 2003),
Mann, Rahbaran, et al., 2008), tools or hands of the clini- was aptly captured by Noyes (1922), a hundred years ago
cian. That is, the success rates can be predictably and con- (“We are not trained to think in terms of biological con-
sistently high in the hands of a diverse group of dentists cepts, but we are to act in mechanical procedures”) and by
using different protocols. Naidorf (1972) 50 years ago (“The preoccupation of den-
In teeth associated with periapical lesions, the chal- tists with “techniques” has channelled endodontics into a
lenge is much more substantial in the form of removal state of technical excellence that often is not accompanied
of established bacterial biofilm in the apical root canal by a biologic awareness of the basic pathologic problems
anatomy. The larger the lesion, the greater the infection with which we are dealing or the biologic consequences of
diversity (Sundqvist, 1976), and the challenge of its erad- our therapy. The schism between clinicians & basic scien-
ication (Bystrom & Sundqvist, 1981). In this scenario, the tists is propagated by a tendency of each group to confer
responses to the adopted treatment protocols in the hands with themselves rather than with each other”). This prob-
of different clinicans vary substantially, offering a spec- lem remains prevalent today because despite advances in
trum of effectiveness in microbial control and thus out- biological understanding of the disease process, the princi-
comes. The predictablity of outcomes is therefore starkly ples of treatment have not changed and remain technically
different at the two ends of the biological spectrum. focussed.
The immediate effects of bacterial load reduction may Despite the attempts of mainly clinical academics to
be evident in the root canal system straightaway through change the status quo (Bergenholtz & Spangberg, 2004;
the culture test but periapical healing shows latency, tak- Naidorf, 1972; Noyes, 1922), the product market has
ing months, if not years to fully manifest. The majority largely persuaded the business part of the system that
of periapical lesions heal within 1 year (Azim et al., 2015; efficiency and profit should remain the key priority and
Ng et al., 2011a, 2011b) but some can take up to 4 years focus. Hence the danger of habituation with and over-
or longer (Strindberg, 1956). The follow-up of cases pre- reliance on type of tool and gadget. Clinical outcome re-
senting with widened apical periodontal ligament space search might yet prove the uniting element by aiding the
for 10 years revealed unfavourable future healing only synthesis of the different strands of influence (biological,
in a small proportion of the cases (28%, 4/14) (Halse & biomechanical, technical, clinical) into a coherent picture
Molven, 2004). The persistence of inflammation in the of how root canal treatment might work and thus what
periapical tissues (Nair et al., 2005) is attributed to per- may be required to evolve the procedure further to an even
sistent residual infection in the apical anatomy, plus the more effective or consistently predictable solution.
effect of any extruded root filling material (Matsumiya &
Kitamura, 1960; Nair et al., 2005; Vera et al., 2012).
Optimal technical completion of root canal treatment Outcome measures of root canal treatment
is one of the most tactile- skill-
dependent procedures
in the surgical field and attracts dental artisans with a The uncertainty in outcome, created by periapical healing
passion and obsession for such finely detailed work (in- latency, possibly led to alternative quality control meas-
cluding the desire to deploy available tools and gadgets), ures during root canal treatment, such as the culture test
committing the practitioner to a focus on the technical as deployed during the focal infection era. The test fell
elements. This does not absolve the clinician or process out of favour in contemporary practice, not least because
of disease management from the usual host of meta- root canal treatment had already become widely accepted
cognitive decision-making, including biological, patient- (Molander et al., 1996a, 1996b) but also the procedural
related, organization- related, and management- related. step was percieved to compromise cost-effectiveness. The
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GULABIVALA and NG 87
postoperative absence of clinical signs and symptoms, (Polycarpou et al., 2005) and may be due to neuropathy.
coupled with radiographic evidence of technically optimal It is a moot point whether the neuropathy is correlated to
root-filling have become established in routine practice as delayed healing and a subtle surrogate measure for ongo-
the immediate (and sometimes the final) outcome meas- ing healing.
ures at completion of the procedure (Bender et al., 1966a, The dichotomous criteria for discriminating successful
1966b). or failed periapical healing proposed by Strindberg (1956)
Prediction of prospective periapical healing is in- have been widely adopted or adapted and embrace both
formed by postoperative absence of signs of infection and radiographic and clinical elements (Table 1). Friedman
inflammation, including absence of pain, tenderness to and Mor (2004) suggested the alternative terms “healed”,
pressure/percussion of the tooth, tenderness to palpation “healing” and “diseased” to avoid seeding confusion from
of the associated soft tissues, swelling and sinus. In the the patients' perspective. Nevertheless, the terms concur,
medium term it may be informed by radiographic reduc- the “healed” category corresponding to Strindberg's (1956)
tion in periapical radiolucency size, ultimately to lead to “success”, and “healing” corresponding to (Bender
normal periodontal ligament space (Ng et al., 2007). The et al., 1966a, 1966b) “success” (Table 1). The length of
ideal histological goal would be periapical tissue regener- time taken for complete periapical healing requires ex-
ation with cementum formation over the apical termini to tended study periods, which are, in turn, accompanied
biologically isolate the root canal system. by recall rate declines at the longer follow-ups. Some ob-
Clinically, the periapical status of root-treated teeth servers therefore accept a looser (Ng et al., 2007) or more
is assessed using radiographic imaging, typically the lenient (Friedman & Mor, 2004) threshold for success at
conventional two- dimensional variety, which despite partial (reduced lesion size) rather than complete healing,
compressing 3D into 2D data and reducing sensitivity the latter described as “stricter” (Ng et al., 2007) or a “more
through anatomic superimposition, especially for molars stringent” (Friedman & Mor, 2004) measure. Adoption of
(Huumonen et al., 2003), gives a sufficient indication of shorter duration recall, tacitly assumes a continuously
progress. In order to standardize radiographic interpreta- linear healing scale to predict the longer term outcome
tion, a five point scale for measuring periapical healing, but healing-dynamics studies do not support this notion
the periapical index (PAI) (Orstavik, 1996; Orstavik & (Bystrom et al., 1987). Healing rates vary and those for
Horsted-Bindslev, 1993) has been used but it precludes di- large lesions are often faster and for small lesions slower
rect comparison with dichotomous data, except by pooling (Esfahani, 2016).
the five scores into “healthy” (PAI 1 or 2) or “diseased” This narrative review on the outcomes of root canal
(PAI 3–5) states (Orstavik et al., 1987). treatment seeks to understand the nature of root canal
Three-dimensional imaging in the form of cone-beam treatment through integration of outcome data with as-
computed tomography (CBCT), overcomes such anatom- sociated biological, chemical and biomechanical data to
ical superimposition and improves sensitivity (de Paula- offer explanations of the nature of the process and the
Silva et al., 2009; Kanagasingam, Hussaini, et al., 2017; probable reasons for the observed outcomes.
Kanagasingam, Lim, et al., 2017; Patel et al., 2009;
Petersson et al., 2012; Sogur et al., 2009; Stavropoulos
& Wenzel, 2007). Routine use of CBCT for diagnosing OUTCOMES OF NON- S URGICA L
periapical status is not recommended (Brown Jacobs ROOT CANAL TREATMENT
et al., 2014; Holroyd & Gulson, 2009; Patel et al., 2019;
Scarfe, 2011) owing to its higher radiation dosage (×2–3) Numerous systematic reviews and meta- analyses have
(Arai et al., 2001; Holroyd & Gulson, 2009). The higher been performed on outcomes of root canal treatment since
sensitivity of CBCT for judging periapical status (Kruse those published by the authors on the factors affecting pri-
et al., 2017, 2019; Liang et al., 2011; Patel et al., 2012), yields mary root canal treatment (Ng et al., 2007; Ng, Mann, &
lower healed rates and longer durations for complete heal- Gulabivala, 2008; Ng, Mann, Rahbaran, et al., 2008). The
ing. It may be noted though that the periapical diagnostic authors have continued to use their published methods to
accuracy of CBCT may be lower for root-filled teeth com- update their meta-analyses (with new and emerging data
pared with non-root-filled teeth (Kruse et al., 2019) due to to the end of 2020) (Random effect metaprop or metan,
beam-hardening artefacts. STATA IC version 16.1, STATA Corporation), although
Periapical healing is only judged to be successful when only published in textbook chapters. The updated meta-
the surrogate measures of both radiographic and clinical analyses reveal that 84% of vital pulpectomy cases retain
criteria have been satisfied (Friedman & Mor, 2004; Ng the absence of apical periodontitis (Figure 2) but apical
et al., 2007); persistent symptoms can arise in a small pro- periodontitis cases result in the absence of apical peri-
portion of cases despite complete radiographic resolution odontitis in 74% of cases (Figure 3).
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88 OUTCOMES OF ROOT CANAL TREATMENT
Strindberg (1956) Bender et al. (1966a, 1966b) Friedman and Mor (2004)
Success: Success: Healed:
Clinical: No symptoms Clinical: Clinical: Normal presentation
Radiographic: The contours, width and Absence of pain/swelling Radiographic: Normal presentation
structure of the periodontal margin were Disappearance of fistula
normal, or No loss of function
The periodontal contours were widened No evidence of tissue destruction
mainly around the excess filling. Radiographic: An eliminated or arrested area of
rarefaction after a post-treatment interval of
6 months to 2 years
Failure: Diseased:
Clinical: Presence of symptoms Radiolucency has emerged or
Radiographic: A decrease in the periradicular persisted without change, even
rarefaction, or when the clinical presentation
Unchanged periradicular rarefaction, or is normal, or
An appearance of new rarefaction or an Clinical signs or symptoms
increase in the initial rarefaction. are present, even if the
radiographic presentation is
normal.
Uncertain: Healing:
Radiographic: There were ambiguous Clinical: Normal presentation
or technically unsatisfactory control Radiographic: Reduced
radiographs which could not for some radiolucency.
reason be repeated; or
The tooth was extracted prior to the 3-year
follow-up owing to the unsuccessful
treatment of another root of the tooth.
Factors that affect periapical health status and can only be accounted for or investigated in observa-
following root canal treatment tional studies. Well-designed randomized controlled tri-
als, coupled with population-based observational studies,
Root canal treatment is subject to enormous variation therefore provide better complementary insight (Booth &
in the way it is performed depending on interpretation Tannock, 2014). In this context, the value attributed to
and execution of any given protocol by an operator, not a study is better judged by the quality and utility of the
to mention the variations imposed by the environment emergent data than the design, per se.
and patient requirements. Root canal treatment is a The factors that may potentially influence periapical
multi-step procedure, where each sequential step is de- status (healing, or maintenance of periapical health) after
pendent on the adequacy of the previous for its cumula- root canal treatment may be classified into three groups:
tive efficacy. From a research perspective, characterizing
and accurately recording variations in protocol execution • Patient and tooth factors (age, sex, general health or im-
is massively challenging because of the range and scope mune status, tooth anatomy, pre-operative pulpal and
of variables to be recorded. Not only the individual steps periapical status);
(factors), but also any interaction between them must be • Treatment factors (operator characteristics, tooth man-
accounted for. All of these factors cannot be randomized, agement and isolation, canal system access, working
only some may be amenable to control in well-designed length control at all stages, canal shaping/enlargement,
and executed randomized controlled trials, data on other irrigation, medication, culture test outcome and obtura-
factors may only be recorded and remain at risk of bias, tion); and
particularly due to recruitment or drop-out problems. • Postoperative restorative factors (amount, distribution
Strict participant (patient and dentist) selection may aid and quality of remaining tooth structure and its in-
control of cohorts and compliance with protocols but tegrity, type of restorative material, full or partial cov-
by virtue of that control, may limit the generalizability erage, timing of permanent restoration, quality and
of findings. In addition, the effects of pre-operative fac- maintenance of marginal adaptation, abutment or non-
tors and some treatment steps cannot be randomized abutment, and occlusal dynamics).
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GULABIVALA and NG 89
F I G U R E 2 Forest plot showing results of pooled and individual study's probability of maintained periapical health for preoperatively
vital teeth undergoing root canal treatment using strict criteria (Pooled probability = .84; 95% confidence interval: 0.80, 0.89) (Random effect
metaprop, STATA version 16.1).
Some of these factors have a profound impact on important factors already stand revealed, even though
periapical healing, whilst others show a negligible ef- the quality of individual studies may often be judged
fect or had not accrued sufficient evidence. Patient sub-optimal by various published study quality mea-
and tooth factors characterizing the nature of disease sures. Confidence in the reliability of the data may be
consistently show the most potent effect (periapical sta- asserted through the statistical measures deployed and
tus), whilst most of the treatment factors, individually, is often the most common form of indication in pub-
exert only a weak effect, except for the apical extent of lished works. It cannot be over-emphasized though that
root canal filling (treatment) relative to the root apex the prior deep personal study of the raw rather than the
(root canal terminus), the quality of root-filling, and the synthesized data, confers a much greater sense of per-
quality of the postoperative restorative care, which show spective, understanding and confidence in the findings.
profound influences on periapical health. Systematic re- It is the former type of knowledge rather than a sum-
views, triangulation from individual studies, and intui- mary synthesis that serves to knit together a thorough
tive synthesis (Ng, Mann, & Gulabivala, 2008; Ng, Mann, biological, clinical and technical understanding of how
Rahbaran, et al., 2008), suggest that the main and most the procedure works, forming a key part of the domain
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90 OUTCOMES OF ROOT CANAL TREATMENT
F I G U R E 3 Forest plot showing results of pooled and individual study's probability of periapical health for teeth with non-vital pulps
and associated periapical radiolucencies undergoing root canal treatment (Pooled probability = .75; 95% confidence interval: 0.70, 0.79)
(Random effect metaprop, STATA version 16.1).
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GULABIVALA and NG 91
knowledge underpinning expertise (Ericsson, 2009; find in favour of anterior teeth generally have not consid-
Ericsson et al., 2018). ered the confounding effect of periapical disease, which
Each of the main and subgroup of factors that may in- once accounted for, reveal that tooth type does not exert
fluence outcomes of root canal treatment are now anal- a strong influence on periapical healing rates. That the
ysed and synthesized with other evidence to understand studies collectively find no overall difference between an-
the probable underlying mechanisms. terior and posterior teeth is an extremely powerful mes-
sage about the factors influencing outcome rather than
being a confounded outcome as is sometimes supposed
Patient and tooth factors (Al-Nuaimi et al., 2018; Patel et al., 2012). The most logi-
cal and obvious explanation for this lack of difference in
Effect of age, sex, health periapical healing between anterior and posterior teeth
must lie in the dominance of the impact of “apical canal
The routinely collected demographic data on factors such complexities” (and their interaction with infection) rather
as the patient's age and sex, show no significant influ- than “canal system complexities” (Azim et al., 2015); the
ence on root canal treatment outcome, even though youth parameter of “apical canal complexities” may exhibit
and old age may be anticipated to produce some effect greater similarities between different tooth and root types.
through immune responsiveness. A proportion of the var-
iation in periapical healing outcomes may be attributed
to differences between individual patients' host responses Effect of pulpal and periapical status
(Ng et al., 2011a, 2011b; Yee, 2019). Although, the no-
tion is further supported by the weak influence of “gen- The preoperative pulp status (vital or necrotic) has no
eral health” of the patient on periapical healing, specific influence on the outcome of periapical healing (Rossi-
health conditions, such as diabetes (Doyle et al., 2006; Fedele & Ng, 2022), unless there is, in addition, an associ-
Fouad & Burleson, 2003) and “compromised innate im- ated periapical lesion (Rossi-Fedele & Ng, 2022), that is,
mune response” (Marending et al., 2005), may have a the canal system is infected. Necrotic pulp tissue neither
significant influence, although with limited evidence for causes apical pathosis nor influences its healing (Moller
the mechanistic pathway and strength of effect. Emerging et al., 1981). Periapical healing is predominantly and pow-
evidence suggests that polymorphisms of various genes erfully influenced by the presence and size of the preoper-
involved in periapical healing may have an effect on out- ative periapical lesion (Ng et al., 2011a, 2011b; Ng, Mann,
comes (Farmani, 2018; Mazzi-Chaves et al., 2018; Morsani & Gulabivala, 2008; Ng, Mann, Rahbaran, et al., 2008),
et al., 2011; Petean et al., 2019; Rocas et al., 2014; Silva- which therefore carries a huge confounding risk when an-
Sousa et al., 2020; Siqueira et al., 2009, 2011). alysing the influence of any other factor. The periapical le-
sion typically signals infection in the complex apical canal
anatomy, which is known to be difficult to control (Nair
Effect of tooth type et al., 2005; Vera et al., 2012). The even greater negative
influence of larger periapical lesions may be attributed to
The commonly accepted perception that single- rooted the greater diversity of bacteria (number of species and
teeth must exhibit a higher rate of periapical healing than their relative abundance) in such teeth (Sundqvist, 1976),
multi-rooted teeth, is shown to be untrue by the collec- making the infection even more difficult to control
tive data, as well as the majority of individual studies. This (Bystrom & Sundqvist, 1981). Other, mainly speculative
entirely plausible preconception is driven by the simpler explanations for a negative influence of larger lesions are
canal anatomy, easier access, and comfort of dentists to that they may have longer-standing infections with deeper
complete root canal treatment in such teeth. In sharp penetration of bacteria in dentinal tubules and accessory
contrast, posterior teeth harbour more difficult access, anatomy (Shovelton, 1964) and potentially represent
unpredictable canal numbers and location, complicated cystic transformation (Nair, 2006), or a more exaggerated
canal negotiation and enlargement due to severe and mul- host response that may in turn fail to switch off in the
tiple canal curvatures, as well as the perception of diffi- presence of residual bacteria (Nair et al., 2005).
culty and likelihood of failure (Laukkanen et al., 2021). Other negative preoperative factor influences on out-
The psychologically greater prospect of being daunted by comes, such as pain, tenderness of tooth to percussion,
treating molars may prevent dentists from embarking on tenderness of associated soft tissues to palpation, associ-
such treatments and thus there may be a bias in those un- ated swellings or sinus tracts, periodontal probing defects
dertaking posterior tooth root canal treatments. The rare of endodontic origin and root resorption may all represent
studies (Benenati & Khajotia, 2002; Field et al., 2004) that a more aggressive periapical host-microbial interaction
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92 OUTCOMES OF ROOT CANAL TREATMENT
with greater tissue destruction and therefore reduced po- tasks of gaining access, finding the canals, negotiating
tential for periapical tissue regeneration (Weiss, 1966). them without blockage, enlarging them without iatro-
The negative influence of sinus tract and swelling (chronic genic error, disinfecting the geometrically complex root
and acute forms of suppuration, respectively) may also canal space, and filling it completely without extrusion. It
be related to proliferation of microbiota into the periapi- takes a diligent and biologically insightful dentist to keep
cal tissues, presumably hindering or delaying periapical the technical and biological elements intertwined in mind
healing. and execution. For example, improvements in the tech-
nical quality of root-fillings through training in Nitinol
(NiTi) instrumentation and single-cone root-filling did
Effect of tooth integrity not result in a parallel improvement in periapical healing
status (Koch et al., 2014). This may suggest that reducing
Preoperative clinical evidence of compromised tooth the technical burden of instrumentation alone through
structure, such as in the form of reduced amount, distri- adoption of NiTi instruments, is insufficient. The ques-
bution, quality (sclerosed dentine) or integrity (cracks) tion of whether a “biologically oriented” or a “technically
of enamel or dentine may reduce the prospect of periapi- oriented” practitioner might enjoy higher rates of periapi-
cal healing (Al-Nuaimi et al., 2018; Sim et al., 2016; Tan cal healing is an interesting but sparsely explored research
et al., 2006). This important factor is considered further question.
under postoperative factors.
In summary, the preoperative clinical finding of peri-
apical lesion, particularly of large size, with preoperative Effect of operator skill and knowledge
pain (Friedman et al., 1995), sinus tract (Ng et al., 2011a, (competence)
2011b), swelling (Ng et al., 2011a, 2011b) and apical re-
sorption (Strindberg, 1956) are negative prognostic factors The general theme of the previous section is continued
significantly reducing the probability of periapical healing along a specific line in this section. The impact of opera-
after root canal treatment. The presence of these factors tor insight and skill (using the surrogate measure of train-
signals a clear message to the clinician of the potential ing qualification and experience) has been investigated
biological challenges facing management of the tooth to a limited extent. Clinicians with higher educational or
without yet having considered the technical treatment training backgrounds (amongst undergraduate students,
challenges. In addition, compromised coronal tooth struc- general dental practitioners, postgraduate students and
ture or the restoration interface, also reduces the prospect specialists) display outcome rates commensurate with
of periapical healing, presumably by reducing the pros- their training and experience level (Ng et al., 2007). It is
pect of sustaining control of the internal tooth environ- difficult to segregate the complex constellation of cogni-
ment and its infection. tive, technical and clinical skills expressed by the dentist
in completing the treatment. It is not just the refined and
insightful technical execution that matters, but also how
Treatment factors the overall understanding of the biological problem in-
fluences the operators' intra-operative decision-making,
The technical versus biological conundrum especially, the motivation and integrity with which the
procedure is performed (elements difficult to measure)
As already mentioned, the paradox of the importance of (Ericsson et al., 2018).
biological insight over technical skill in the performance The authors' Eastman study, using multi-level mod-
of root canal treatment was highlighted a 100 years ago elling, accounting for the relative influence of operator,
(Blayney, 1922; Noyes, 1922) and remains pertinent patient, tooth and procedure on periapical healing and
today. Although clinicians may psychologically feel that iatrogenic outcomes, revealed only a moderate degree of
their treatment imposes the greatest influence on periapi- operator influence (14% of total variation) on periapical
cal healing, through the effortful precision of their tech- healing and an even smaller degree (4% of total variation)
nical execution and consequent bacterial load reduction on iatrogenic errors (Yee, 2019). Meanwhile, patient-level
(Bystrom et al., 1985; Bystrom & Sundqvist, 1981, 1983, characteristics accounted for 17%, and tooth-level 69%, of
1985), the precise relationship between their practical the total variation of the healing outcome. Patient-level
(mechanical and chemical) steps and bacterial demise (26%), and tooth-level (70%) characteristics accounted for
are unclear and only rudimentarily charted. The techni- most of the variation of the iatrogenic error outcome. The
cal complexity of root canal treatment typically “diverts” findings imply that the dominant influence on outcomes
the dentist's attention towards the technically challenging comes from factors not completely under the direct and
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GULABIVALA and NG 93
independent control of the operator but are a function coronal salivary contamination has on an exposed pulp
of the nature of interaction of the operator with the pa- over many days (Cox et al., 1985), any minor contamina-
tient-and tooth-related factors. That is to say, the expertise tion during root canal treatment is unlikely to alter the
with which the operator negotiates the presenting clinical apical biofilm physiology and established host-microbial
and biological problem may have the greatest “operative” dynamics. The key value of rubber dam isolation is in se-
bearing on the outcome. Contemporary tools and proto- curing control of the operative field during the procedure
cols alone, do not yet allow direct and absolute control to allow the necessary meticulous completion of stepwise
(predictable management) over cases with high biological tasks of root canal treatment with control, precision, and
and technical complexity. diligence.
Deconstruction of root canal treatment into its Effect of access cavity design
procedural steps
The entry hole through the occlusal surface of the tooth
Root canal treatment may be deconstructed into proce- to the root canal system is called the “access cavity”. Its
dural components to evaluate their individual impacts on shape and location (or design) are dictated by the precise
the final composite outcome. The procedural components anatomical juxtaposition of the pulp chamber to the tooth
might include rubber dam isolation, access preparation, surface providing the most direct access to the chamber
canal system identification and location, canal negotia- and/or straight-line trajectory to the apical parts of the root
tion, length determination, canal enlargement parameters, canal system. The location, direction and size of the ac-
lavage and disinfection of the canal system (convention- cess cavity should be tailored to balance the needs of canal
ally called irrigation and medication), and obturation. The access and minimization of tooth structure damage that
afore-mentioned inter-dependence of the procedural steps might affect the tooth's strength or aesthetics (Mannan
means that to apportion the effect of treatment on periapi- et al., 2001), assuming the operator has appropriate and
cal healing to any one step, as well as to any interaction precise orientational control over the cutting tool.
between them, requires comprehensive prospective data The pendulum has gradually and rightly swung to-
collection coupled with sophisticated statistical analysis. wards adopting more conservative access cavities in the
interests of maintaining tooth strength, but the trend
has irrationally continued towards conservative ex-
Effect of rubber dam isolation tremes that may potentially compromise root canal de-
bridement; indeed, such miniscule cavities were once
The universally recommended but often neglected rub- labelled as “errors” in the annals of root canal treatment
ber dam isolation in modern root canal treatment has not (Stock, 1988).
been robustly tested for its effect on the outcome of peri- Nevertheless, 3D CBCT data have enabled the design
apical healing. Incidentally, one observational study on and execution of ultra- conservative access cavities (or
root canal retreatment (Van Nieuwenhuysen et al., 1994) “ninja access cavities”) aiming to preserve dentine and in-
found a significantly higher periapical healing rate when crease tooth survival (Plotino et al., 2017). A prime goal
rubber dam was used, compared with cotton roll isola- of restoring root-treated teeth is tooth structure preser-
tion. Another reported a significantly lower prevalence vation and protection, so that in biomechanical function,
of periapical lesion development after post placement they exhibit more favourable stress distribution (Wang
in root canal-treated teeth under rubber dam (Goldfein et al., 2020); however, whether these cavities increase
et al., 2013). The additional benefits listed for adopting fracture strength in vivo and elongate long-term tooth
rubber dam isolation include safety (prevention of instru- survival remains unknown (Ozyurek et al., 2018; Sabeti
ment inhalation), medico- legal compliance, improved et al., 2018). The most important question about ultra-
access, and a controlled and disinfected operative field conservative access cavity designs is whether they com-
(European Society of Endodontology, 2006). promise root canal system preparation, debridement and
A randomized controlled trial comparing root canal obturation, which has only been addressed in laboratory
treatment with or without rubber dam isolation is highly studies (Tufenkci & Yilmaz, 2020); longer-term clinical
unlikely to yield a significant difference in periapical heal- trials are awaited to demonstrate improved periapical
ing. This is because the major influence on outcomes is healing and tooth survival. In the meantime, conventional
conferred by the established infection in the apical anat- access cavities serve their purpose to aid predictable fa-
omy, which is unlikely to be altered by any transient cor- cilitation of root canal treatment without compromising
onal salivary contamination. Given the minimal effect periapical healing or survival outcomes.
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94 OUTCOMES OF ROOT CANAL TREATMENT
Effect of use of magnification and termini with a root canal instrument has been identified
illumination as the single most important treatment factor contributing
to a favourable periapical healing outcome in teeth with
Having accessed the pulp chamber, optimal visualization apical periodontitis (Ng et al., 2011a, 2011b; Ng, Mann, &
of its floor to identify all canal orifices and negotiate (or Gulabivala, 2008; Ng, Mann, Rahbaran, et al., 2008). The
“thread”) them with instruments for enlargement, bene- same may not be true for teeth without apical periodon-
fits from good illumination, and if possible, magnification. titis (Byström, 1986; Cvek et al., 1976), where reaching
Indeed, some operators even use magnification and illu- canal termini is not essential and may even jeopardize
mination for preliminary stages such as anaesthesia and periapical status (Chugal et al., 2003; Seltzer et al., 1969,
access cavity preparation, which makes little sense, since 2004). These findings make absolute biological sense.
these elements require broader 3D perspective for cor- In the case of teeth without apical periodontitis, it is
rect orientation, which may be lost under certain types of likely that the pulp stumps in the apical delta are still vi-
magnification. The virtues of magnification and illumina- able, healthy, and uninfected. This coupled with the fact
tion during the root canal location and negotiation phase that the narrowing of the neurovascular bundle with the
and indeed for most of the root canal treatment procedure approach to the exit, also concentrates the fibrous ele-
are almost universally extolled by Endodontists (Patel ment of the connective tissue (by reduction in the ground
& Rhodes, 2007) because of the “feeling” of control over substance), creating the “pulp stump”, where the pulp
the process. In addition, it may aid location of all canal typically tears on extirpation (Seltzer et al., 1969, 2004).
orifices, although each of these lead to a single pulp canal Maintaining such pulp stumps by preparing short of the
system, unless the canal is completely separate. It is worth canal terminus, better prevents the development of api-
noting that the canal orifices at the root apex are more cal periodontitis, subsequently (Ng et al., 2011a, 2011b;
important for periapical healing than those in the pulp Ng, Mann, & Gulabivala, 2008; Ng, Mann, Rahbaran,
chamber. In any case, systematic reviews have failed to et al., 2008; Seltzer et al., 1969).
identify objective evidence for improved periapical heal- In the case of teeth associated with apical periodontitis,
ing outcomes related to utilization of magnification (Del the entire purpose of root canal treatment is to gain full
Fabbro et al., 2009; Ng et al., 2011a, 2011b), other than access to the complex apical anatomy to enable its disin-
in assisting location of additional canals (Ng et al., 2011a, fection. Without securing this requisite, the treatment is
2011b). A definitive view on the benefit of a microscope on doomed to fail as there is little opportunity to influence the
periapical healing outcomes may perhaps emerge through apical infection, except by the fortuitous interception of
a randomized controlled trial but on current evidence and ecological shift in the microbiota incurred by any attempts
the fact that the main barrier to improved periapical heal- thereof. It is emphasized that access to the entire apical
ing is control of the invisible apical intra-radicular infec- anatomy (including all the multiple exits) must be secured
tion, a positive effect is highly unlikely. and not just the single exit that the negotiating file might
In the context of expertise development, it is also worth happen to traverse. Over-focus and over-instrumentation
noting that “threading” a canal “without looking” is some- of that randomly selected single exit (by dint of trajectory),
thing seasoned endodontists can do. It is a composite skill without adequate irrigation, may risk blocking the other
involving practical knowledge of anatomy, tactile sensitiv- apical canal delta tributaries and their infected exits. The
ity and mental visualization that incorporates the ability presence and infection of multiple apical exits is typically
to “mentally see” and physically traverse a “flight path” betrayed clinically by the size and distribution of the peri-
that enables the clinician to place a file into the canal with apical lesion about the root apex, a sign to which the in-
relative ease. Reliance on microscopes may potentially formed clinician will be alerted.
override the development of such a skill, which is a pre- It is well accepted that root canal system disinfection
lude to the tactile skill required for further apical negoti- should extend to its apical termini. The goal may be ex-
ation into the unknown curvatures and apical foramina pressed in different ways in the outcome literature as
beyond (Ericsson et al., 2018). extension to the “apical constriction”, “0.5–2 mm from
the radiographic apex”, or “cemento-dentinal junction”
(European Society of Endodontology, 2006). “Patency at
Effect of negotiation of instruments to the canal terminus” and “apical extent of canal instrumenta-
canal terminus tion” were the only significant prognostic factors for root
canal treatment amongst those related to mechanical
The ability to negotiate the main canal system channels preparation of canals (“type of instrument”, “patency at
(“canals” are expanded parts of the system that allow files canal terminus”, “apical size”, “taper and extent of canal
to traverse a path from coronal entry to apical exit) to their instrumentation”), which are putatively measures of the
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GULABIVALA and NG 95
apical extent of canal cleaning (Ng et al., 2011a, 2011b). believed that the canal terminus diameter should be en-
Achieving technical patency at the canal terminus signifi- larged (Crane, 1921), by at least three file sizes (Grossman,
cantly increased the odds of periapical healing 2-fold (Ng 1970). The purpose of canal enlargement has undergone
et al., 2011a, 2011b), whereas the odds of successful heal- a conceptual paradigm shift and is now described as suf-
ing was reduced by 12%–14% for every 1 mm of the canal ficient selective sculpting of the canal wall to facilitate the
short of the terminus that remained “un-instrumented” delivery of irrigants and medicaments for disinfection, fol-
(Chugal et al., 2003; Ng et al., 2011a, 2011b). It is worth lowed by delivery of the root filling material to the entire
noting that sometimes, the natural anatomy or iatro- boundary and volume of the root canal system (Gulabivala
genic faults preclude achievement of “mechanical” or et al., 2005). It is this paradigm shift, which has propelled
“physical” patency but nevertheless an electronic apex the focus and drive for research on root canal irrigation
locator (EAL) may still give a reading (Abdelsalam & over the last two decades; and seen the proliferation in
Hashem, 2020), albeit short of “zero”. This infers the exis- irrigation devices available commercially. The precise di-
tence of “electrical patency” or continuity of a conductive mensions and optimal shape to facilitate these elements
medium to the canal terminus. In such circumstances, ac- remain a matter of debate because available laboratory
tive irrigation with sufficient pressure may facilitate some and clinical studies suggest that a diverse range of shapes
apical debridement (Lorono et al., 2020) by allowing pene- and sizes can all potentially fulfil the purpose (Baugh &
tration of the irrigant further than the instrument. A com- Wallace, 2005). The question of precise dimensions is
pletely blocked canal would disable electrical continuity impossible to answer definitively because the combined
and hence complete circuit, so an EAL would show “no chemical and mechanical preparation effects (chemo-
reading”; a signal that the potential for apical irrigation is mechanical) cannot be divorced from each other as they
non-existent. are intimately interlinked and interdependent. The lack
It may be stated categorically and with confidence that of definitive correlation between the physical dimensions
one of the major goals of root canal treatment in teeth of the machined preparation and microbial control is un-
with apical periodontitis, is to obtain and maintain api- derstandable because microbial ecological shift rather than
cal canal patency for predictable root canal treatment (Ng size and shape of the prepared canal terminus influences
et al., 2011a, 2011b; Ng, Mann, & Gulabivala, 2008; Ng, the outcome (see section on “Quality control of root canal
Mann, Rahbaran, et al., 2008). This conceptually sim- disinfection and persistent bacteria”).
ple goal is, practically, one of the most difficult things to The prime reason for root canal enlargement is to en-
achieve and is where many root canal treatments floun- able irrigant delivery into the small volume of the root
der at an early stage in the hands of a novice. Obtaining canal system, which makes liquids behave like solids in
patency, and maintaining it, is a key tactile skill in root their flow characteristics; expansion of the canal volume
canal treatment and typically requires the use of stainless- marginally improves the flow of irrigant fluids. Other vari-
steel instruments for sensitive and controllable scouting ables that might influence fluid flow include the irrigant's
and negotiation. Such negotiation must be accompanied viscosity, density, length scale and velocity (Gulabivala
by judicious irrigation and lubrication with sodium hypo- et al., 2010).
chlorite and or EDTA (Ng et al., 2011a, 2011b) to avoid A variety of instruments of different cutting designs,
blockage, which is a risk throughout this process. Lack of tips, tapers, diameters, materials of construction and
mechanical negotiability of canals may be attributed to series transitions (multiple instrument series to sin-
many factors including the presence of undetected acute gle file), have been deployed to mechanically enlarge
curvatures, division of the main canal into a fine plexus root canal systems to defined apical sizes and tapers
of apical canals, natural obstructions (“denticles”, pulp (Schilder, 1974). Numerous laboratory studies tes-
stones, tertiary dentine), or dentine/organic debris accu- tify to their properties, efficacy and utility (Hülsmann
mulation because of poor instrument control or irrigation et al., 2005), but their efficacy in clinical canal enlarge-
(Seltzer et al., 2004). ment has been evaluated in only three prospective ob-
servational studies (Koch et al., 2014; Ng et al., 2011a,
2011b; Pettiette et al., 2001). In one (Ng et al., 2011a,
Effect of mechanical root canal 2011b), the better success rates for NiTi instruments
enlargement to the canal terminus (hand or rotary) compared with stainless steel instru-
ments were attributed to prior tactile skill development
In the original conceptualisation of root canal treat- using stainless steel files by the senior students. The
ment, the mechanical preparation of the canal held a pre- ability to gain and maintain apical patency as well as to
eminent place in debridement by virtue of its association avoid procedural errors would be better instilled in such
with removal of “infected material and dentine”. It was students through progressive and continual coaching.
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96 OUTCOMES OF ROOT CANAL TREATMENT
A further confounding factor in the study may be that bacterial debridement with larger apical preparations
such senior trainees would also be more likely to have (Card et al., 2002; Parris et al., 1994; Rollison et al., 2002).
established a better understanding of biological ratio- The principle of considering chemical and mechan-
nale and effective intra-operative decision-making. NiTi ical (or chemo- mechanical) debridement together, ap-
instruments also appear capable of achieving the same plies equally well to the apical size and taper of the canal.
in selected mild to moderate complexity primary root Guideline (European Society of Endodontology, 2006)
canal treatment cases undertaken by undergraduates recommendations stipulate only that canal preparation
(Pettiette et al., 2001). should be tapered from crown to apex; a minimum taper
The effect of apical size of canal preparation on treat- size is not indicated. Intuitively, this makes perfect sense
ment outcome has been considered in a number of stud- because of the natural tapering shape of roots. Even this pa-
ies (Hoskinson et al., 2002; Kerekes & Tronstad, 1979; Ng rameter elicits a paucity of sufficient direct evidence for its
et al., 2011a, 2011b; Saini et al., 2012; Souza et al., 2012; influence on root canal treatment outcome. Observational
Strindberg, 1956). Enlargement of the canal to three studies (Hoskinson et al., 2002; Ng et al., 2011a, 2011b;
sizes larger than the first file to bind apically led on av- Smith et al., 1993), incidentally reporting on the effect of
erage to an apical size of ISO 30, which was sufficient canal preparation taper on primary treatment and retreat-
for periapical healing in a randomized controlled trial ment outcome give no specific recommendation either.
(Saini et al., 2012). Observational studies (Hoskinson Smith et al. (1993) found a “flared” preparation (wide
et al., 2002; Ng et al., 2011a, 2011b; Strindberg, 1956), not taper) resulted in a significantly higher rate of periapi-
specifically designed to test the effect of apical canal size cal healing compared with a “conical” preparation (nar-
found no statistically significant influence attributable row taper), using loose criteria; the taper sizes were not
to this factor but all reported the same inverse trend of specified, and potential confounders were uncontrolled.
decreasing periapical healing rates with increasing size Other studies (Hoskinson et al., 2002; Ng et al., 2011a,
of apical preparation, which seems counter- intuitive 2011b) using strict criteria, found no significant differ-
and unexpected. Two explanations may be advanced ence between narrow (0.05) and wide (0.10) canal tapers,
for this clear trend from three independent studies. achieved using stainless steel ISO files. The latter study
One is that larger apical preparations may be prone to (Ng et al., 2011a, 2011b) also compared stainless steel file
incur iatrogenic errors, such as blockage, transportation stepback preparation (0.05 and 0.10) and tapers of 0.04,
and ledging. A second explanation is that larger apical 0.06, and 0.08 (achieved using non-ISO, greater taper,
preparations would generate more dentine debris with nickel–titanium instruments) but again found no signif-
a greater propensity to block bacterially contaminated icant difference in treatment outcome associated with
apical canal exits that had not been instrumented. The them. They cautioned that the absence of randomization
effect would be further confounded by a coupling with in their study could result in confounding from the ini-
a poor irrigation regimen, thus potentially jeopardizing tial canal size, instrument type and operator experience.
periapical healing. Creation of 0.05 (1 mm step-back) or 0.10 (0.5 mm step-
The apical stagnation zone and vapour lock phenom- back) tapers using stainless steel instruments demands
ena that hamper irrigation may act in concert with the trained, controlled, manipulation with tactile sensitivity
generated dentine and organic debris to allow it to congeal to avoid over-instrumentation, which can readily produce
from a “slurry” into “dentine mud”, to create either a pass- a much greater diversity of tapers and shapes, confound-
able (“pick-able”) or unpassable (“unpick-able”) block- ing the outcomes.
age. Faced with this scenario, the impatient or neophyte Despite the disparate and “sub-gold standard” level of
dentist typically forces the instruments to regain their evidence, triangulation of available data on the effects of
designated length(s), resulting in the classically described prepared canal taper on periapical healing outcome, in-
procedural errors of apical transportation, canal straight- tuitively suggests over-enlargement of canals is unneces-
ening, ledging and perforation (Gulabivala et al., 2010). sary to achieve periapical healing. Apical preparation size
These explanations do not account for the higher failure of ISO 30 coupled with a minimal 0.05 taper is more than
in initially large canals, where presumably immature roots sufficient, conditional upon adequate irrigation. The chem-
present a different debridement challenge. In such cases, ical, biological and hydrodynamic mechanisms required
where the canal shape is less amenable to planing by con- to be at play in “adequate irrigation”, however, remain elu-
ventional instruments, it is speculated that an intracanal sive, although there is plenty of circumstantial evidence
brush with a larger effective diameter may provide better and speculation from laboratory studies (Gulabivala
debridement (Gu et al., 2009). Available study outcomes et al., 2010; Lee et al., 2004). Collaborations between fluid
reject the intuitively “logical” notion of more effective dynamics specialists (Gulabivala et al., 2010), (micro)
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GULABIVALA and NG 97
biologists and endodontists (Gulabivala, 2004) may ulti- access to the infection in the apical canal anatomy and
mately yield these answers. coupling the technical goals of canal enlargement with
Procedural errors during root canal preparation are chemical debridement (Gulabivala et al., 2010). In conclu-
more common amongst novices or junior dentists and sion, none of the mentioned factors on their own, have any
are typically classified into canal blockage, uncontrolled significant impact on periapical healing, other than to indi-
canal shaping (ledging, apical zipping and transportation, vidually contribute to or collectively conspire to help achieve
straightening of canal curvature) tooth/root perforation the main goal of gaining patency and access to the apical
(sub-classified into pulp chamber or radicular levels), or infection for effective disinfection.
instrument separation. Amongst these, the effect of canal
blockage has been reported above, whilst the influence of
uncontrolled canal shaping has not been specifically inves- Effect of root canal irrigation
tigated. Iatrogenic root perforations result in significantly
lower chances of periapical healing (Cvek et al., 1982; de The role of root canal irrigation is inextricably linked
Chevigny et al., 2008a, 2008b; Imura et al., 2007; Marquis with mechanical preparation and the conceptual ground
et al., 2006; Ng et al., 2011a, 2011b; Sjogren et al., 1990). for this section has already been laid in the last section.
MTA® has found favour as a contemporary perforation To advance the discussion, a diverse range of neutral or
repair material, attributed to its biocompatibility and seal chemically active agents has been used to irrigate root
effectiveness (de Chevigny et al., 2008a, 2008b; Gorni canal systems. They have been used singly or in various
et al., 2016; Main et al., 2004; Mente et al., 2010). The fur- combinations in clinical practice but not all of them have
ther specific effects of location and size of perforation, been systematically or purposefully investigated through
time lapse before defect repair, adequacy of perforation appropriate laboratory, animal or clinical study models.
seal, and operators' experience, were found to have no The irrigants reported on include water/saline, local an-
significant influence on long-term outcome of root canal aesthetic solution, sodium hypochlorite, iodine, chlora-
treatment with iatrogenic perforation repaired using MTA mine, sulphuric acid, EDTA, hydrogen peroxide, organic
(Mente et al., 2014), However, a larger scale and longer acid, Savlon®, urea peroxide and Biosept® (quaternary
term follow-up study reported that perforations of larger ammonium compound) (Ng, Mann, & Gulabivala, 2008;
size, located in the middle third of canal and associated Ng, Mann, Rahbaran, et al., 2008). The majority of stud-
with a periodontal probing defect, had poorer healing out- ies used sodium hypochlorite as an irrigant (Ng, Mann,
comes (Gorni et al., 2016). & Gulabivala, 2008; Ng, Mann, Rahbaran, et al., 2008) for
Instrument separation during canal preparation may primary or secondary root canal treatment, consistent with
reduce periapical healing success rates significantly (Ng guidelines (European Society of Endodontology, 2006)
et al., 2011a, 2011b; Strindberg, 1956) when there is pre- recommending solutions possessing dual disinfectant and
existing apical pathosis (Spili et al., 2005). The stage at tissue-solvent properties.
which instrument separation occurs in relation to degree Root canal irrigation has been demonstrated to have a
of prior canal disinfection may also influence the out- significant impact on intracanal bacterial load reduction
come. The prevalence of such errors ranges from 0.5% to in clinical studies (Bystrom & Sundqvist, 1981, 1983), but
7.4% for stainless steel instruments (Panitvisai et al., 2010) counter-intuitively, the effect of different irrigants (with or
and 1.3% to 10% for rotary nickel–titanium instruments without active antibacterial effect, even of different NaOCl
(Madarati et al., 2013). The corono- apical location of concentrations) on periapical healing is not substantially
separated instruments in the canal system had no effect different (Adenubi & Rule, 1976; Harty et al., 1970; Smith
on treatment outcome, however, whether they were suc- et al., 1993). This stark and surprising observation must
cessfully bypassed or removed to regain apical patency also signal an important phenomenon demanding an
did make a positive impact on treatment outcome (Ng explanation.
et al., 2011a, 2011b; Ungerechts et al., 2014). First, to report the consolidated findings, one pro-
These disparate outcome data all converge to make spective observational study (Ng et al., 2011a, 2011b)
sense when viewed in the biological context of the pur- exploring the effect of irrigant on periapical healing
pose of root canal treatment as one of microbial load rates following root canal treatment found that a higher
reduction through disinfection or infection prevention concentration of sodium hypochlorite (5% vs. 2.5%)
through asepsis. Instead of over-focusing on the details of made negligible difference to treatment outcome. In
mechanical preparation protocol, instrument types, their other studies, too, higher concentrations of NaOCl did
mode of manipulation, their sequence of use or canal seg- not yield the expected improved periapical healing or
ment priorities, it would be better to conceptualize the bacterial load reduction (Bystrom & Sundqvist, 1985;
problem from the perspective of gaining and maintaining Cvek et al., 1976). This trend of absence of difference in
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98 OUTCOMES OF ROOT CANAL TREATMENT
bacterial load reduction (comparing 0.5% to 3.0% or 5.0% and sodium hypochlorite are both halogen- releasing
NaOCl) (Bystrom & Sundqvist, 1985; Ulin et al., 2020) or agents, acting on common protein groups (McDonnell &
periapical healing (comparing 0.5% or 1% to 5% NaOCl) Russell, 1999). The alternative agent, chlorhexidine had
(Cvek et al., 1976; Verma et al., 2019) is consistent across originally been justified on grounds of its substantivity in
studies. root dentine (Rosenthal et al., 2004), relative lack of tox-
The belief within the profession and the market that icity (Loe, 1973) and broad-spectrum efficacy (McDonnell
individual irrigant solutions did not possess all the req- & Russell, 1999). However, 2% chlorhexidine irrigant
uisite properties, led to the development of commer- has been shown to be less effective than 1% NaOCl in re-
cially branded and marketed mixed products to enhance ducing bacterial load to undetectable levels (70% vs. 80%
overall potency (QMix™ 2 in 1 [Dentsply, Tulsa Dental negative load, respectively) (Zandi et al., 2016), although
Specialties], BioPure MTAD [Dentsply Tulsa Dental there was no difference in periapical healing at 4-years
Specialties]). Such mixed solutions show promise in labo- (81% vs. 82%, respectively) (Zandi et al., 2019). In another
ratory studies (Pappen et al., 2010; Wang et al., 2012) con- study, the additional use of 0.2% chlorhexidine irrigant,
sistent with single pure solutions but again lack evidence surprisingly, reduced the success of treatment signifi-
(microbiological or periapical healing) in their clinical cantly (Ng et al., 2011a, 2011b). The use of chlorhexidine
applications. is currently deprecated for the toxic interaction product
The most commonly adopted adjunctive agent to (para-chloro-aniline) from its reaction with sodium hy-
NaOCl, Ethylenediaminetetraacetic acid (EDTA), pro- pochlorite, which is deemed cytotoxic and carcinogenic
foundly improves periapical healing rates by 1.3–2.3 odds (Basrani et al., 2007; Bui et al., 2008). Apart from mutually
for primary and secondary root canal treatment, respec- depleting the antibacterial moiety of both solutions, the
tively (Ng et al., 2011a, 2011b). The synergistic action of precipitate may potentially irritate periapical tissues and
alternate irrigation with sodium hypochlorite and EDTA block dentinal tubules or accessory anatomy, particularly
had already been demonstrated for bacterial load reduc- the apical infected anatomy. Chlorhexidine has also been
tion (Bystrom et al., 1985) but long-term (≥2 years) peri- associated with two types of immune sensitivity reactions
apical healing outcome (Byström, 1986) did not correlate (Rose et al., 2019; Teixeira de Abreu et al., 2017) and cou-
with their microbiological findings. The synergistic effect pled with the other issues is now not widely advocated for
between the two disinfectants had been attributed to the root canal irrigation, despite its continued promulgation.
chelating properties of the sodium salts of EDTA and re- The physical aspect of irrigation dynamics has taken
moval of the smear layer to expose deeper lying bacteria on a significantly more important conceptual dimen-
(Zehnder, 2006). sion in root canal disinfection over the last two decades
EDTA solution was originally recommended as a root (Gulabivala et al., 2010) and its beneficial effects have
canal irrigant to assist negotiation of narrow or sclerosed been repeatedly demonstrated in in vitro studies. However,
canals and for smear layer removal. EDTA has since also there is a paucity of clinical research evidence to under-
been attributed other functions, including the ability to aid pin its intuitively obvious advocacy for improved periapi-
loosening of compacted debris in the non-instrumented cal healing (Liang et al., 2013). The latter study failed to
canal anatomy, facilitating deeper penetration of sodium confirm a significant influence of ultrasonically agitated
hypochlorite solution into dentine by opening dentinal NaOCl irrigant on periapical healing. The lack of direct ef-
tubules (likely of dubious clinical value), and possibly fect on periapical healing may simply reflect the fact that
most importantly for aiding breakup and detachment of although such agitation may have a robust effect on the
biofilms adherent to root canal walls (Bryce et al., 2009; flow and mixing of irrigants in the part of the canal system
de Almeida et al., 2016; Gulabivala et al., 2005). Of all above the stagnation zone (Gulabivala et al., 2010), its ef-
these justifications, the last function is probably the most fect within the stagnation zone and therefore the encapsu-
important for improvement in periapical healing and the lated apical anatomy, where the critical infection remains,
least recognized for it because of the erroneous focus and is probably negligible (de Gregorio et al., 2010). The novel
obsession with the “smear layer”, which is merely surface- multi-sonic device, GentleWave system (Sonendo, Inc.)
deformed and displaced dentine. The question may be displayed the promising outcome of 92% healed rate but
posed why dentine has this unique property of “surface critical evaluation of the data showed that only 19% of the
smearing”; for which a hypothetical but plausible expla- teeth had necrotic pulps and the outcome was not strat-
nation might be that it is an evolutionary selection trait ified by periapical status (Sigurdsson et al., 2016). A fur-
designed to temporarily close exposed dentinal tubules. ther study on teeth with periapical lesions of sizes larger
The additional use of 10% povidone-iodine for irri- than PAI > 3, managed with the device protocol, showed
gation confers no supplementary benefit to treatment complete healing in 82% after 12 months (Sigurdsson
success, which may not be surprising given that iodine et al., 2018), which is on par with other approaches.
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GULABIVALA and NG 99
The lack of any obviously significant difference in peri- chemical equilibrium reaction. The multi-visit approach
apical healing between chemical agents of different types also allows a second or further opportunity for chemo-
and different concentrations is best explained by the phys- mechanical debridement and a chance to gauge the early
ical and chemical stagnation caused by the apical stagna- periapical host response through the presence/absence of
tion zone phenomenon. Fluid in the stagnation zone lacks exudate or pus, before placing the root filling.
flow due to the closed-end-tube effect of the canal and its There is a paucity of studies investigating the influence
small volume, confining the chemical exchange to diffu- of inter-appointment medicaments on treatment outcome.
sion, which is an extremely slow and inefficient process The use of a variety of root canal medicaments in outcome
(Gulabivala et al., 2010). The vapour lock effect, in addi- studies, without proper segregation of their use or effect,
tion may prevent adequate contact between the irrigant precludes definitive conclusions to be drawn about them.
and canal contents. It is therefore hardly surprising that The traditionally tested medicaments include calcium
chemical irrigants with different antibacterial potencies, hydroxide, creosote, and iodine solutions (Ng, Mann, &
may show commensurate bacterial load reduction in the Gulabivala, 2008; Ng, Mann, Rahbaran, et al., 2008), whilst
coronal two-thirds of the canal (sample-able part of the more recent agents include 2% chlorhexidine gel alone or
canal system), but regardless of their potency, all of them mixed with calcium hydroxide, and triple antibiotic pastes
are “neutralized by the buffer” of the stagnant fluid zone but they lack long-term clinical outcome data.
containing the apical infected anatomy (Nair et al., 2005; Calcium hydroxide, with its unique combination of
Vera et al., 2012). This explains the voluminous labora- properties, including antibacterial effect, tissue/toxin de-
tory literature on root canal system debridement, which naturation, and low aqueous solubility product (conferring
universally show a lack of proper “cleaning” in the apical a continuous-release capability and lasting effect), has en-
third of root canal systems (Gulabivala et al., 2010), as well abled it to serve as an inter-appointment medicament for
as the consequent lack of influence on periapical healing many years with predictable outcomes (Best et al., 2021;
(Ng, Mann, & Gulabivala, 2008; Ng, Mann, Rahbaran, Kandemir Demirci et al., 2020; Ng et al., 2011a, 2011b).
et al., 2008). However, its antibacterial ability has come under close
scrutiny, with opponents suggesting that the material is
not suitable for purpose (Sathorn et al., 2007). Although
Effect of number of treatment visits and a final and definitive resolution to this debate maybe yet
interappointment medicaments to arrive, the current evidence unfortunately divides the
discipline into proponents and antagonists of the agent,
As already established, the performance of pulpectomy in the authors firmly taking the former side.
the absence of apical periodontitis has very different dis- A mixture of calcium hydroxide and chlorhexidine has
infection requirements from those with established root been proposed based on the speculation of greater effec-
canal infection and apical periodontitis. In the former tiveness against E. faecalis (Basrani et al., 2003; Gomes
teeth, maintenance of asepsis is the prime requirement, et al., 2003; Schafer & Bossmann, 2005). Such targeting of
whilst facilitating residual pulp tissue removal using so- this species is unwarranted based on available evidence.
dium hypochlorite, which may be enhanced by calcium Nevertheless, clinical trials have revealed no differences
hydroxide dressing, where judged necessary, due to its tis- in efficacy amongst several tested: Ca(OH)2, 2% chlor-
sue denaturation properties (Hasselgren et al., 1988). In hexidine gel, mixture of Ca(OH)2 plus 2% chlorhexidine
the latter teeth, even rigorous disinfectant irrigation is not gel, or triple antibiotic paste (Arruda et al., 2018; Manzur
completely effective in eliminating all the adherent bacte- et al., 2007).
rial biofilm (Nair et al., 2005), leaving residual bacteria to Equally, advocates of single-visit treatment remain
multiply and recolonize the canal system (Byström, 1986; despite the definitive evidence of residual viable bac-
Bystrom & Sundqvist, 1985). It is therefore desirable to teria in the root canal system after chemo-mechanical
supplement chemo-mechanical debridement at the end debridement. In teeth lacking apical root canal in-
of the first visit with inter-appointment medication of fection and apical pathosis, the case for single- visit
the canal system using an agent capable of destroying or treatment is strong as it should better serve to prevent
incapacitating residual bacteria and denaturing residual bacterial contamination. In teeth with preoperative
toxins and tissues; such an agent should ideally have a apical pathosis, the biological rationale for single-visit
long-lasting effect that would be sustained over the entire treatment is less clear and the debate about the merits
inter-appointment period to prevent bacterial regrowth. and demerits of single versus multiple visit treatments
The long-lasting effect may be a function of either sus- remains an on-going controversy. The debate is fueled
tained high concentration or a slow- release device or by considerations of cost- effectiveness (Schwendicke
mechanism that acts as a buffer, allowing reversal of a & Gostemeyer, 2016), practical-sense, business-sense,
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100 OUTCOMES OF ROOT CANAL TREATMENT
postoperative pain (Nunes et al., 2021) and biological Effect of quality control of root canal
rationale (Spangberg, 2001). Randomized controlled disinfection and persistent bacteria
trials (Fonzar et al., 2017; Gesi et al., 2006; Molander
et al., 2007; Paredes-Vieyra & Enriquez, 2012; Penesis The focal infection era spawned the technique of
et al., 2008; Peters & Wesselink, 2002; Trope et al., 1999; quality-checking bacterial disinfection using an inter-
Weiger et al., 2000; Wong et al., 2015) on the issue have appointment culture test prior to root-filling; the meas-
found no significant influence attributable to number ure served a historic purpose in returning credibility
of visits but they all lack statistical power and are com- to root canal treatment at the time. Obturation would
promised by potential bias related to recruitment and only be embarked on if a negative culture test result was
management protocols for cases not completed within returned, “confirming” the absence of bacteria in the
the designated number of visits (Figini et al., 2007, (sample-able part of the) root canal system (Buchbinder
2008; Manfredi et al., 2016; Sathorn et al., 2005; Su & Wald, 1939; Frostell, 1963; Morse & Yates, 1941). Over
et al., 2011). The debate on the merits of single versus time, the perceived predictability and favourable prog-
multiple visit treatments will continue unabated given nosis of root canal treatment without microbiological
the respective strengths and nature of the motivational sampling was realized and this quality control practice
drivers amongst the opposing advocates. The issue may fell out of clinical favour because of its perceived defi-
only be resolved by properly documented, large random- ciencies (time-consuming nature, difficulty, inaccuracy,
ized controlled trials because unrecorded confounders laboratory-support-resource-rich) coupled with con-
(operator skill, biological or technical case complexity, cerns over cost- effectiveness and business imperative
patient compliance and recruitment bias) would con- (Molander et al., 1996a, 1996b). Despite the perceived
tinue to play out their biasing effect in non-randomized deficiencies, a preobturation negative culture result in-
studies. creased periapical healing success twofold (Figure 4).
Study %
.0273 1 36.7
Positive culture test results Negative culture test results
F I G U R E 4 Forest plot showing pooled and individual study's odds ratios (OR) for periapical health of teeth undergoing root canal
treatment with preobturation negative versus positive culture test results (Pooled OR = 1.6; 95% CI: 1.4, 1.9) (Random effect metan, STATA
version 16.1).
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GULABIVALA and NG 101
One study (Seltzer et al., 1963) showing a 10% higher suc- deprecated cotton wool dressing underneath the access
cess rate when a negative culture test was returned in the restoration serves as a useful diagnostic aid for leakage
presence of periapical disease, nevertheless, may have into the tooth by sign-posting the location and extent of
contributed to the beginning of the demise of the culture staining (Gulabivala & Ng, 2014), whereas other alterna-
test. Demonstration of the predictability of bacterial load tives (Sattar et al., 2017) are not as useful in this context.
reduction with various chemo- mechanical strategies The use of inter-appointment, antibacterial intra-canal
(Bystrom et al., 1985; Bystrom & Sundqvist, 1981, 1983, dressings, increased the frequency of negative cultures
1985; Sjogren & Sundqvist, 1987) may have consolidated at the subsequent visit to an average of 71% (range 25%–
its fate as a routine measure. 100%) (weighted pooled average) of cases (Gulabivala &
The effect of different stages and steps of root Ng, 2019a, 2019b).
canal treatment (mechanical preparation, irrigation, Bacterial taxa recovered from preobturation cultures
medication) on the intra- radicular microbiota have include Enterococcus, Streptococcus, Staphylococcus,
been evaluated in numerous studies (Akpata, 1976; Lactobacillus, Veillonella, Pseudomonas, Fusobacterium
Auerbach, 1953; Bence et al., 1973; Bystrom et al., 1985; species and yeasts. Some studies attribute statistical asso-
Bystrom & Sundqvist, 1981, 1983, 1985; Card et al., 2002; ciations between the presence of individual species and
Chu et al., 2006; Cvek et al., 1976; Dalton et al., 1998; treatment failure. As an example, one study noted an
Engström, 1964; Gomes et al., 1996; Grahnen & overall failure rate of 31% in cases with positive cultures,
Krasse, 1963; Ingle & Zeldow, 1958; Koontongkaew 55% for teeth with Enterococcus species and 90% for teeth
et al., 1988; Kvist et al., 2004; Lana et al., 2001; Markvart with Streptococcus species (Frostell, 1963). Another study
et al., 2013; Molander et al., 1990; Nicholls, 1962; with good quality root canal treatment on 54 teeth with
Orstavik et al., 1991; Paquette et al., 2007; Peciuliene asymptomatic apical periodontitis and an overall success
et al., 2000, 2001; Peters et al., 2002; Reit et al., 1999; Reit & rate of 74%, attributed 80% success in the absence of bac-
Dahlen, 1988; Shuping et al., 2000; Siqueira, Guimaraes- teria, 33% for those with detected canal bacteria before
Pinto, & Rocas, 2007; Siqueira, Magalhaes, & Rocas, 2007; obturation and 66% for those with Enterococcus faecalis
Sjogren et al., 1991, 1997; Sjogren & Sundqvist, 1987; (Sundqvist et al., 1998). It is stressed that these are merely
Stewart et al., 1961; Vianna et al., 2007; Wang et al., 2007; associations and not cause–effect relationships; a fuller
Xavier et al., 2013; Yared & Dagher, 1994), and a system- picture may only emerge by exploring the full interaction
atic review (Siqueira & Rocas, 2008), both qualitatively between the total microbial diversity and other treatment
and quantitatively. Some studies merely reported the pres- outcome factors.
ence or the absence of bacteria, whereas others identified An interpretive perspective is added to these clinical-
and quantified intra-radicular microbiota before and after microbiological findings from a controlled experimental
the designated stages of treatment. monkey-model study (Fabricius et al., 2006), involving
The effect of the steps upto and including “mechanical infection of monkey's teeth with four-or five-strain bac-
preparation” of the canal(s) on the microbiota has been terial microcosms to test the effect of debridement and
tested using “neutral” irrigants such as water or saline; obturation on periapical healing outcome. They found
such studies show that negative cultures were achieved that of the canals with residual bacteria following chemo-
in 31% (range 0%–79%) (weighted pooled average) of the mechanical debridement, 79% were associated with peri-
cases. The use of sodium hypochlorite (concentration apical non-healing, compared with only 28%, when no
range 0.5%–5.0%) irrigation during the steps upto and in- bacteria remained. Multiple residual species were more
cluding ‘mechanical preparation’, increased the frequency frequently associated with non-healing than single spe-
of negative cultures immediately after debridement to 52% cies survival. Absence of bacteria after chemo-mechanical
(range 13%–95%) (weighted pooled average) (Gulabivala debridement was associated with periapical healing, in-
& Ng, 2019a, 2019b). dependent of root-filling quality but bacterial persistence
Despite such microbial reduction, the majority was correlated to a greater degree with non-healing in
of studies report culture- reversals during the inter- the presence of poor-quality root-fillings than with tech-
appointment period if antibacterial dressing was nically well-performed root-fillings. Furthermore, when
avoided. Culture reversals may be attributed to either bacteria were detected after root- filling removal, 97%
regrowth of residual bacteria because of inadequate showed absence of periapical healing, compared with
chemo- mechanical debridement or recontamination only 18% when bacteria were not detected. The study re-
by bacterial leakage, from restorative margins or tooth emphasized that optimal periapical healing conditions
cracks. It is important to diagnostically distinguish be- are achieved by reducing bacteria below detection limits
tween the two causes because the former may be correct- before permanent root-filling and that obturation played
ible, and the latter potentially may not be. The currently an important role in helping to control residual infection.
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102 OUTCOMES OF ROOT CANAL TREATMENT
Regardless of the sampling technique, the use of a neg- Effect of root filling
ative culture result to inform progress of treatment has material and technique
a positive impact on treatment outcome. More recently,
alternative bacterial tests, such as, fluorescent vital dye Notwithstanding the observations on residual microbial
has been tested for use as a rapid chair-side root canal presence in the root canal system and its relationship with
microbial detection method to predict periapical healing obturation or root-fillings, investigation of the individual
with promising results (Knight et al., 2020). The evidence effects of obturation technique and root-filling material on
shows the value of such a quality-control measure to re- treatment outcome is complicated by the inter-action be-
turn root canal treatment to a biological fold. tween core root-filling material, sealer and placement tech-
nique. The most commonly used core root-filling material
in the majority of outcomes studies was gutta-percha with
Effect of acute exacerbation various types of sealer or gutta-percha softened in chloro-
during treatment form (chloropercha) (Ng, Mann, & Gulabivala, 2008; Ng,
Mann, Rahbaran, et al., 2008). The sealer types may be
Any invasive operative procedure is liable to elicit some classified into zinc oxide eugenol-based, glass ionomer-
pain or discomfort by virtue of its inherent injurious based or resin-based (Ng, Mann, & Gulabivala, 2008; Ng,
impact triggering an acute inflammatory response that Mann, Rahbaran, et al., 2008). Recently introduced ma-
may be superimposed on any pre-existing inflammatory terials such as Resilon®, SmartSeal®, Mineral Trioxide
or prevailing immune response. If the pre-existing pain Aggregate (Pace et al., 2014; Ree & Schwartz, 2017;
is severe, treatment should not make it substantially Simon et al., 2007), silicate-based (Bardini et al., 2020)
worse through the inflammatory process alone but may and bioceramic-based (Chybowski et al., 2018) materi-
do so through initiation of sensitization and neuropathy als have not penetrated clinical practice sufficiently to
by lowering of neural firing thresholds or broadening yield significant long-term data. The healing rate of teeth
of the field of involvement (Nixdorf et al., 2010, 2015). obturated with Resilon® (Resilon Research LLC) and
However, when preoperative pain is absent, mild or Epiphany sealer (Pentron Clinical Technologies) was re-
moderate, treatment may induce or make the pain worse portedly comparable with conventional gutta- percha/
for 24–48 h (Torabinejad et al., 1994); this is normal and sealer in 1–2-year follow-ups (Cotton et al., 2008) but 5-
patients should be fore- warned and fore- armed, psy- year follow-ups (Barborka et al., 2017; Strange et al., 2019)
chologically and if necessary, pharmaceutically. In rare showed higher failure rates. Apart from this exception,
situations, the trajectory of pain may worsen over the fol- root-filling material or placement technique, per se, have
lowing days, and this may be due to adverse alterations no significant influence on treatment outcome (Ng, Mann,
in the microbiota, immune reaction or neuropathic sen- & Gulabivala, 2008; Ng, Mann, Rahbaran, et al., 2008). The
sitization. The precise aetio-pathogenesis of such inter- impact of root-filling material is surprisingly manifested
appointment pain is ill-defined but could be triggered much more profoundly in its apical extent in relation to
by chemical, mechanical, thermal or microbial injury canal terminus and radiographic quality of obturation.
to the periradicular tissues, conditioned by psychologi-
cal (Seltzer & Naidorf, 1985a, 1985b) or neurological
influences (Nosrat et al., 2020). Although such pain did Effect of apical extent of root filling
not have a significant association with periapical heal-
ing in two studies (Kerekes & Tronstad, 1979; Sjogren The apical extent of root-fillings in relation to the root
et al., 1990), the London Eastman study (Ng et al., 2011a, apex, is one of the many intra-operative factors under the
2011b) found that pain or swelling occurring in 15% of control of the operator and is one of the most frequently
cases after chemo-mechanical debridement, was signifi- investigated factors, because it offers a readily and con-
cantly associated with reduced probability of periapical stantly available assessment measure in retrospective
healing. The speculative explanations may reside in in- studies. It is often analysed categorically by division into
complete chemo-mechanical debridement (either due to three types of root-filling extensions: (1) more than 2 mm
poor protocol compliance or greater microbial diversity) short of radiographic apex (short); (2) within 2 mm of
leading to a shift in canal microbial ecology favouring the radiographic apex (flush); and (3) beyond the radio-
the growth of more virulent micro-organisms or extru- graphic apex (long) (Ng, Mann, & Gulabivala, 2008; Ng,
sion of contaminated material during canal preparation Mann, Rahbaran, et al., 2008). This measure has a sig-
or obturation, resulting in an acute or chronic foreign nificant influence on periapical healing rates, regardless
body reaction or (transient) extra- radicular infection of preoperative periapical status (Ng et al., 2011a, 2011b;
(Siqueira, 2003). Ng, Mann, & Gulabivala, 2008; Ng, Mann, Rahbaran,
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GULABIVALA and NG 103
et al., 2008). “Flush” root-fillings are associated with the extent of extrusion (Ng et al., 2011a, 2011b; Ng, Mann, &
highest success rates (81%) and “long” root-fillings (ex- Gulabivala, 2008; Ng, Mann, Rahbaran, et al., 2008) but
truded) the lowest (66%) (Ng, Mann, & Gulabivala, 2008; they have the additional problem of potential bacterial
Ng, Mann, Rahbaran, et al., 2008). contamination of the extruded gutta-percha, although
Retrospective root canal treatment outcome studies this hypothesis is unproven.
fail to distinguish between the effects of apical extent of The data on periapical sealer extrusion draws contra-
instrumentation and apical extent of obturation because dictory conclusions. Extrusion of a glass ionomer-based
the former information is generally missing. The prospec- sealer significantly reduced periapical healing rates
tive Eastman study (Ng et al., 2011a, 2011b), measured (Friedman et al., 1995), whilst a zinc oxide eugenol based-
both these parameters and found them to affect periapical sealer showed no significant effect, although only a quar-
healing, independently and significantly. This is consis- ter of the cases had exhibited extrusion (Ng et al., 2011a,
tent with the observations already made about obtaining 2011b). The discrepancy may be attributed to the differ-
patency to the canal terminus and accuracy of length de- ences in sealer type and duration of treatment follow-up.
termination and its maintenance. The length measures of Radiographic assessment of sealer resorption may be com-
canal preparation and root-filling extension naturally cor- plicated by the radiolucency of its toxic components and
relate with each other because canals are normally filled the insufficient sensitivity of radiographic methods to de-
to the prepared canal length. The single measure “apical tect trace amounts (Ng et al., 2011a, 2011b). Radiographic
extent of root filling”, therefore informs about both the disappearance of extruded sealer is clearly due to disinte-
apical extent of canal cleaning and obturation. The ex- gration or dispersal of the radio-opaque component (bar-
ceptions were overextended instrumentation or extruded ium sulphate) but this may be independent of the sealer
cleaning agents without root filling extrusion, or extruded constituent eliciting a host reaction that may still be resi-
root filling material without apical over-extension during dent in the vicinity (Nair et al., 1990).
preparation. Some extruded sealers, glass ionomer-based (Friedman
The issue of apical extrusion of root-filling sealer sur- et al., 1995), zinc oxide eugenol- based (Huumonen
prisingly divides the discipline between polar opposite et al., 2003), silicone- based (Huumonen et al., 2003),
views, despite the extremely clear and one-sided outcome and Endomethasone® (Boggia, 1983), remained in the
data. Some endodontists pursue extrusion of “sealer puffs” periapical tissues after 1 year. Whilst traces of a calcium
through the main apical foramina and lateral/accessory hydroxide-based sealer (Sealapex®) could be detected after
canals as a “school of thought”, in the belief of its value as 3 years (Sari & Okte, 2008). Longer term studies show more
“good practice” (Nguyen, 1994). Their argument centres complete resorption of extruded sealer over time, for ex-
on the belief that sealer extrusion is only possible in the ample, 69% of zinc-oxide eugenol-based sealer after 4 years
presence of thorough apical debridement and is taken as a (Procosol®, Roth Elite®) (Augsburger & Peters, 1990),
measure of apical debridement quality and they therefore and 45%–85% of resin-based sealer after 4–10 years (AH
anticipate healing would follow predictably, albeit with Plus, Dentsply/DeTrey) (Goldberg et al., 2020; Ricucci
some delay. et al., 2016; Sari & Okte, 2008). Conversely, extruded
The collective outcome data are categorically clear, sealer has been known to persist even after 10 years in 40%
however, that extrusion of root filling material (gutta- of cases (Goldberg et al., 2020). Ng et al. (2011a, 2011b)
percha) hinders, delays or prevents periapical healing advanced two explanations for the difference between the
(Ng et al., 2011a, 2011b; Ng, Mann, & Gulabivala, 2008; effect of extruded core gutta-percha and zinc oxide/euge-
Ng, Mann, Rahbaran, et al., 2008). The biological nol sealer; the antibacterial properties of the latter may
mechanisms of action are persistent inflammation help to control residual microorganisms, whilst it is also
and foreign body reaction (Koppang et al., 1992; Nair more soluble and readily removed by host cells compared
et al., 1990; Sjogren et al., 1995; Yusuf, 1982). Gutta- with gutta-percha.
percha may be contaminated by magnesium and silicon The overwhelmingly clear conclusion must be that the
particles from the talc used in their manufacture (at penetration of a chemically active foreign material, devoid
least historically) and can induce a foreign body reac- of regenerative potential, into a wound, infected or unin-
tion (Nair et al., 1990). Experimental implantation of fected, would hardly enhance healing and is more likely
large pieces of gutta-percha subcutaneously in guinea to delay or prevent healing. It is best to avoid extrusion of
pigs were encapsulated in collagen, whilst fine particles root filling materials of any type to obtain the best periapi-
of gutta-percha induced an intense, localized tissue re- cal healing outcomes. The notion of using bio-inductive
sponse (Sjogren et al., 1995). Clinical data do not show materials that may support periapical healing is yet to be
an exactly parallel effect on periapical healing based on proven.
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104 OUTCOMES OF ROOT CANAL TREATMENT
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GULABIVALA and NG 105
Effect of imposed functional occlusal stresses for any iatrogenic procedural errors, including blockages
on root-treated teeth and finally, its shape may be modified into a more opti-
mal form to facilitate better irrigation and re-obturation.
The stresses imposed on root-treated teeth are a function, The periapical healing rates of root canal retreatment are
first, of the manner in which the patient uses them, and slightly lower compared with primary treatment. This is
secondly, their functional prominence in the occlusal attributed to persistently obstructed access to the apical
scheme. The pattern of static and dynamic occlusal loading infection; and/or potentially more resistant microbiota,
stresses in teeth is dictated by holding or guiding contacts, which the host immunity is unable to overcome.
as well as their status as single units or abutments (bridge/ The mean weighted probability of complete periapi-
denture). Prosthetic abutments (fixed or removable) may cal healing is 69%, about 6% lower than in the case of
bear more unfavourable loads, as may last-standing teeth primary treatment on teeth with apical periodontitis (Ng
in the dental arch (Matsumoto & Goto, 1970). Evidence et al., 2011a, 2011b; Ng, Mann, & Gulabivala, 2008; Ng,
suggests such teeth exhibit lower periapical healing rates, Mann, Rahbaran, et al., 2008).
presumably through development of cracks and fractures The factors influencing outcomes of periapical health
due to fatigue (Walton, 2002, 2003), or a greater propen- after root canal retreatment are identical to those affecting
sity for restorative margin failure. primary root canal treatment, except for elements peculiar
In conclusion, the prominent impact of restorative to secondary root canal treatment as mentioned above.
factors on periapical healing is highly suggestive of the Hence, a separate treatment of the data is unnecessary.
importance of tooth integrity as well as the restoration/ Of the potential prognostic factors unique to retreatment
margin integrity, whatever, the precise definition of that cases, the main one showing significant influence on out-
statement might prove to be in the future. At present, the come after treatment was the ability to remove or bypass
understanding of the nature of this phenomenon remains pre-existing root filling material or separated instruments
neophytic and is classed merely as “microleakage” or during retreatment to achieve canal patency at the termi-
“nanoleakage”. nus (Ng et al., 2011a, 2011b).
13652591, 2023, S2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/iej.13897 by Cochrane Portugal, Wiley Online Library on [09/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
106 OUTCOMES OF ROOT CANAL TREATMENT
or die because their nutritional source, the inflamma- balance in favour of the host immune defences, dampen-
tory exudate, reduces in concert with the dying bacteria. ing the inflammation and commencing a new phase in
Completion of active root canal treatment (or sometimes the interaction. Breaches in the tooth (cracks) or marginal
chemo-mechanical debridement) marks the beginning of integrity (leakage) may “passively” allow reversal of the
a new phase in the dynamic apical encounter, in which the targeted microbial demise and host interaction, hence the
apical immune mechanisms gradually re-exert control over remarkably powerful impact of this factor on outcomes.
the surviving intra-radicular apical infection. The precise This then is the reframed and re-stated principle of root
dynamic (Nair, 1997) may vary from tooth to tooth, and canal treatment. It strongly and logically argues for a two-
host to host, dependent on the relative strength of the two stage (two-visit) management of teeth with apical peri-
arms (infection versus host defences) of the interaction, odontitis, in which the debridement phase only is ideally
resulting in the typically variable but nearly-always ex- completed within one visit.
tended periapical healing period (1–4 years plus). Prognostication should therefore take account of the
The rates of periapical healing over the previous cen- feasibility of both biological (periapical lesion size and
tury show no significant differences because the principles symptoms) and technical (root canal system complex-
of root canal treatment had remained the same over that ity and operator competency) control of the root canal
period, despite conceptual and protocol variations. Whilst infection, as well as the prospect of sustaining any root-
the protocol changes have improved the efficiency and pre- canal-treatment-induced microbial control through tooth
dictability of the technical outcome, they have not altered the and restorative interface integrity. The endodontist must,
efficacy of periapical healing. This is perfectly logical be- therefore, also have insight about factors influencing tooth
cause none of the root canal treatment protocols over the restoration and survival.
last century have altered the nature of the intra-operative
or postoperative apical host/microbial dynamic. It should AUTHOR CONTRIBUTIONS
therefore not be expected that the biological outcomes The two authors contributed equally to conception, data
would be any different by chronological (decade of treat- analysis, writing and critical appraisal.
ment) or geographic (location in the world) distribution.
All the factors that have a direct effect on the apical CONFLICT OF INTEREST STATEMENT
host/microbial dynamic have a powerful prognostic ef- The authors have stated explicitly that there are no con-
fect on periapical healing (preoperative periapical status flicts of interest in connection with this article.
including signs and symptoms of infection and size of
lesion, patency to canal terminus, apical extent of canal DATA AVAILABILITY STATEMENT
instrumentation and root- filling, quality of restoration Data sharing not applicable to this article as no datasets
and remaining tooth structure). Whilst all the factors that were generated or analysed during the current study.
have no or only an indirect influence on the apical host-
microbial dynamic exert no or only a weak prognostic ef- ETHICAL APPROVAL
fect on periapical healing (age, sex, general health, tooth This investigation did not involve human or animal
type, rubber dam use, magnification and illumination use, subjects.
access cavity design, root canal instrumentation choice
and technique, dimensions of canal preparation, root ORCID
canal irrigation choice and technique, root filling material Kishor Gulabivala https://orcid.
choice and technique). Effective apical root canal irriga- org/0000-0002-2384-608X
tion and medication can have an impact on the apical dy- Yuan Ling Ng https://orcid.org/0000-0003-3712-8836
namic (Vera et al., 2012), as may the genetic expression of
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