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Journal of LSTR Therapy (International WEB version) VOL 8: 3-7, 2009

Endodontic Retreatment using 3Mix-MP without Removal of Previous Root Canal
Obturation
TAKUSHIGE T.

1, 2, D.D.S., Ph.D., HATAOKA H.1, D.D.S., ANDO M.1, D.D.S., HOSHINO E.2, D.D.S., Ph.D.

1

2

1

CDRG (Creative Dental Research Group), Sendai, Japan and Oral Ecology in Health and Infection Niigata
University Graduate School of Medical and Dental Sciences, Niigata, Japan
Abstract
This is a retrospective clinical study of 161 permanent teeth that needed retreatment because the previous treatment failed. Preoperative X-ray photos showed radiolucent periradicular lesions in all the cases. The re-treatment was carried out using 3Mix-MP
without removing previous root canal obturation. A ball-like particle (1 mm diameter) of standard preparation of 3Mix-MP was placed
and pressed onto previous obturation at the orifice of root canals, sealed by glass-ionomer cement and restored by resin inlays. A
good clinical outcome was defined as the lack of any mechanical allodynia to biting and the disappearance or reduced sizes ofradiolucent alveolar bone resorption, and without any other clinical symptoms. Using these criteria, a good clinical outcome wasfound in 158 cases. Remaining 3 cases were also good after giving a re-restoration to ensure tight sealing. These data suggestthat 3Mix-MP may be worth evaluating in prospective randomized clinical trials for root canal re-treatment including cases of socalled “repeated recurrent periapical disorders”.
Key words:
3Mix-MP, endodontic retreatment, LSTR, NIET, radiolucent lesions

Introduction
It is possible for bacteria residing in oral cavity to come into
caries lesions when caries cavity opens to oral cavity. Suchbacteria may invade into pulp tissue causing pulpitis, and, then,periapical disorders. Thus, any oral bacteria are possible tocause endodontic disorders (1-5).
It may not be so rare that such bacteria remain in endodontic
lesions even after endodontic treatment, causing recurrent
endodontic disorders.
In addition, recurrent endodontic
disorders may be caused by bacteria that invade newly
through micro-leakages around the restoration, although nonbacterial causes such as traumatic occlusion may also be
associated with the recurrent clinical symptoms. Recently
tooth-fracture happens in some cases after root canaltreatment, and bacteria may invade through the fracture to root
canal system, causing also recurrent endodontic disorders.
Using the conceptual framework that any kinds of oral
bacteria have possibly cause endodontic disorder including
recurrent ones after the previous endodontic treatment,
bacterial constituents of carious dentin (1), pulpitis lesions (3),infected root dentin and necrotic pulps (2, 4), periapical lesions
and infected cementum (5) have been analyzed under strict
anaerobic conditions to understand which bacteria are present
in these lesions. In addition, bacteria at other oral sites,
including dental plaque (6), tongue plaque (7), denture plaque(8), saliva (9), periodontal pockets (10) and osteomyelitis sites(11) have been also analyzed with strict anaerobic procedures
because these were possible sources of bacteria invading
endodontic lesions. These studies included a large number of
the “difficult to culture” species of bacteria (12). Importantly,
all of these bacteria were found to be sensitive against a
combination of three antibacterial drugs (3Mix), namely
ciprofloxacin, metronidazole and minocycline (5, 13-21),
together with other combinations (17). In addition, when was
mixed with macrogol (M) and propylene glycol (P), thecombination has been demonstrated to penetrate efficiently
dentinal lesions via dentinal tubules (22) and through previous
endodontic obturation(23), suggesting that bacteria in
Accepted: Aug. 1, 2009
Published: Aug 18, 2009

endodontic lesions could be killed by placement of 3Mix-MP at
the bottom of a carious lesion or on the previous root canalobturation. Thus, one important prediction of the LSTR
hypothesis is that local delivery of effective antibiotics in an
appropriate vehicle to endodontic lesions may lead to healingof cases of recurrent endodontic disorders without a need forconventional re-instrumentation and re-filling procedures.
The aim of this retrospective clinical study was to evaluate
the clinical outcomes of this hypothesis by following up
endodontic retreatment cases using local application of 3MixMP, which is called as “LSTR 3Mix-MP NIET therapy” (21, 2425) and, NIET means “Non-instrumentation endodontic
treatment”.

Materials and Methods
Patients and teeth involved in this study
A total of 161 teeth involved in this study. The patients, aged
from 19 to 78 years old, visited one of the clinics of Drs.
Takushige, Hataoka and Ando, Sendai, Japan, because theirprevious endodontic treatments done elsewhere have failed.
Prior to their inclusion to this study using LSTR 3Mix-MP
therapy, they were informed of the aim, expected clinicalresults, as well as the risks and alternative conventional
treatment, and they subsequently completed an approved
informed consent, although most of them would keenly like tobe obtain LSTR 3Mix-MP endodontic therapy after they haverecognized the previous treatment had failed.
Root canals of all the cases had been previously obturated.
Clinical and radiographic observations
Clinical symptoms, such as swelling, abscess, sinus tract,
induced pain on cold and hot conditions, pain on bite,
spontaneous pain, were recorded before and after thetreatment. Preoperative radiographs were taken prior totreatment to observe conditions of pulp chambers andperiodontium. Postoperative radiographs were also taken toobserve radiographic changes in periradicular lesions.

3

Takushige et al.

Preparation of 3Mix-MP
Commercially prepared chemotherapeutic agents, namely,
ciprofloxacin (Ciproxan, Bayer, Osaka, Japan), metronidazole(Trichocide, Green Cross, Osaka, Japan) and minocycline(Minomycine, Ledeale-Japan, Tokyo, Japan) were used.
Preparation procedures of 3Mix-MP were described elsewhere(21, 24-26). In short, after removal of the capsules or coating
materials that enclose the drug products, each of the drugs
was pulverized to fine powders using porcelain mortars andpestles, and then stored separately in a tightly capped
porcelain container to prevent exposure to light and humidity.
A small amount of silica gel in a bag was placed inside thecontainer to maintain low humidity. The powdered drugs wereused within a month of preparation. On the day of treatment,
powdered ciprofloxacin, metronidazole and minocycline weremixed in a ratio of 1:3:3 (by volume). The vehicle, of an
ointment consistency, was prepared separately by mixing
macrogol (M; Solbase, Meiji, Tokyo, Japan) and propylene
glycol (P) in a ratio of 1:1 (by volume). The 3Mix antibiotics
and MP vehicle were thoroughly mixed to form 3Mix-MP in aratio of 7:1 for standard consistency and, then, ball-likeparticles (1 mm diameter) of 3Mix-MP were prepared. 3MixMP preparation should be prepared and used on the day of
preparation.
Clinical procedure of LSTR root canal treatment without
removal of previous obturation
The clinical procedures are described elsewhere (24-26). In
brief, after previous coronal restoration was removed, a
medication cavity was prepared at the orifice of root canal, of
which size was 1 mm diameter x 2 mm depth, and the cavity
was irrigated with 12% EDTA solution, pH 7.0 to remove
smear layers.
Previous root canal obturation was left
intentionally. The cavity wall and bottom were dried up using a
cotton ball or an absorbing paper, and then, a 1 mm diameterball-like particle of 3Mix-MP was placed onto the bottom ofcavity. A care was taken not to leave 3Mix-MP dangling fromthe edges of medication cavity, but to adhere 3Mix-MP tightly
onto the previous root obturation, otherwise 3Mix-MP might
not penetrate through the obturation.
A NIET carrier (Japan Dental Supply, Tokyo, Japan) was
helpful for placement of the medication. Then, a first layer ofglass-ionomer cement (Fuji IX, GC, Tokyo) was applied to seal
3Mix-MP with care not to express 3Mix-MP out of the cavity.
The previous restoration cavity was then entirely sealed withthe second layer of glass-ionomer cement. Then, a widely
open-angled restoration cavity for a composite resin-inlay
restoration was made as small in size as possible. The wider
margin areas on enamel were provided to reinforce the seal
and to ensure sufficient adherence and retention of thecomposite resin-inlay restoration following etching with 35%
phosphoric acid solution. The resin-inlay, made using theClearfil composite resin (Kuraray, Tokyo, Japan) on the tooth,was cemented using the Panavia F 2.0 Estenia Cementing Kit(Kuraray, Tokyo, Japan) according to the manufacture’s
manual. In certain cases with undermined cusps, an onlay
form of the composite resin restoration was provided.
In
cases with extensive coronal destruction, metal inlays fixed byresin cement were used. In most cases, the treatment wascompleted in one visit.
Post-treatment observations, including those using postoperative radiographs, were made to assess the changes of
the clinical symptoms. In addition, any pain or discomfort on
biting or chewing on the treated tooth was noted.
Postoperative evaluation was done after the certain intervals(as longest, up to 14 years) indicated elsewhere.
The evaluation of outcomes was done whenever the patients
visited and finally when they visited most lately after the4

LSTR 3Mix-MP endodontic retreatment

treatment.
The three clinical outcomes were defined as follows. A“good” clinical outcome was defined as the lack of any
spontaneous pain, no mechanical allodynia to biting and theperiapical radiolucent lesion was disappeared or reduced insize.
Some cases were “under observation”, because thesize of radiolucent lesion was not changed, although noclinical symptoms and no mechanical allodynia to biting wereobserved. Thus, these cases were clinically good, and nofurther treatment was needed. An outcome of “failure” wasdefined by the deterioration of clinical symptoms, such as
abscess formation, increased size of periapical radiolucent
lesions, which needed the second LSTR 3Mix-MP endodontic
treatment with the same procedure. The size of lesion wasmeasured on X-ray photos, and the care was taken to use the
X-ray photos showing the same width of tooth root to compare
the change of lesion sizes.

Results
Clinical aspects before retreatment
A total of 161 teeth were involved in this study. All of thenhad been treated using conventional root canal preparation
and root canal filling as their previous treatment elsewhere. Allof them showed radiolucent periradicular lesions on X-ray
photos (width: 1 ~ 15 mm) with other clinical symptoms,
including swelling (61 cases). In 40 cases, swelling was
limited within attached gingiva, and apical areas in 18 cases,
and extended to facial areas in 3 cases. Sinus tracts wereobserved in 39 cases. A total 116 claimed pains fromdiscomfort with slight pain (19 cases) to severe spontaneous
pain (32 cases). Other claims included pain when the lesion
areas were pressed (29 cases), percussion pain (7 cases) andpain on bite (48 cases).
The previous root canal filling had been obturated using
lateral condensation technique in 43 cases, and using verticalcondensation technique in 16 cases. Single-point technique,which used a main gutta-percha point with root canal sealer,
had been used in 59 cases, and in 43 cases root canals had
been obturated only with root canal sealer (Table 1~4). The XRay photos showed the obturation were given until just near
the apex areas in 54 cases, and short not until apex areas in
107 cases.
It should be noted that fractured reamers were remained in 5
cases, and perforation to periodontium in 8 cases. Bifurcation
lesions were observed in 8 cases and root fracture lines were
found in 6 cases.
Some cases had been repeatedly treated for more than 1
year, and some teeth were notified as treatment-difficult and to
be extracted.
Clinical outcomes of endodontic retreatment
After the LSTR 3Mix-MP treatment, 46 cases (29 %) were
evaluated the outcomes within a year, 71 cases (44 %) after
between a year to 4 years, 26 cases after between 4 years to
7 years, 18 cases more than 7 years (Table 2).
In 108 cases among a total of 161 cases, periradicularlesions were disappeared on the postoperative X-ray photos.
The mean of lesion size was 3.8 mm (range: 1 ~ 15 mm). The
mean follow up period was 38 months (range; 3 ~ 144 months).
The outcomes were evaluated as good.
In 42 cases, the sizes of radiolucent lesions were reduced.
The radiolucent lesions of meanly 5.0 mm size (range: 1 ~ 15mm) shrank to meanly 1.5 mm (range: 5 ~ 1 mm). The mean
width of reduction was 3.4 mm (range: 0.5 ~ 12 mm). The
mean follow up period was 26 months (range: 4 ~ 168 months).
Thus, it was the tendency that the radiolucent lesions of larger
sizes needed more time to disappear (Table 2). Because theTakushige et al.

LSTR 3Mix-MP endodontic retreatment

lesions in these cases had been reducing to disappear, theTable 1. Lesions and previous obturation

outcomes of these 42 cases were also evaluated as good.

No. of cases (size of lesions before treatment)
Obturation on X-ray photos before treatement

Lesion on X-ray photos after treatment

Disappeared *Reduced*Not changed*
Lateral condensation (total: 43 cases)
Length:25
19
42
Just to apex
(mean size: 4.4 mm)(mean size: 4.4 mm)(mean size: 6.3 mm)(mean size: 1.5 mm)
Length:
18
10
8
0
Short
(mean size: 3.7 mm)(mean size: 3.1 mm)(mean size: 4.4 mm)
Vertical condensation (total: 16 cases)
Length:8242
Just to apex
(mean size: 4.8mm)(mean size: 3.5 mm)(mean size: 6.5 mm)(mean size: 2.5 mm)
Length: Short84
40(mean size: 4.4 mm)(mean size: 4.8 mm)(mean size: 4.0 mm)
A single point + root canal sealer (total: 59 cases)
Length:18
13
3
2
Just to apex
(mean size: 3.7 mm)(mean size: 3.3 mm)(mean size: 5.0 mm)(mean size: 4.0 mm)
Length: Short
41
25
12
4
(mean size: 3.9 mm)(mean size: 4.0 mm)(mean size: 4.3 mm)(mean size: 2.0 mm)
Root canal sealer only (total: 43 cases)
Length:2200Just to apex
(mean size: 4.5 mm)(mean size: 4.5 mm)
Length: Short
41
31
8
2
(mean size: 3.7 mm)(mean size: 3.6 mm)(mean size: 4.4 mm)(mean size: 2.5 mm)＊ Outcomes of the LSTR 3Mix-MP endodontic retreatment. Lesion size was measured before treatment.

In 8 cases, the size of lesions (mean: 2.6 mm) did not seemto reduce on the postoperative X-ray photos and those cases
were evaluated as “under observation” because there were noother clinical symptoms and the patients could bite on thetooth, respectively, without any discomforts (Table 2).
While, 3 cases got worse and were evaluated as “failed
cases”, because the sizes of radiolucent lesions seemed to
expand, although no other clinical symptoms/disorders wereobserved (Table 2). It might be ascribed by the breakdown of
margin areas and the formation of micro-leakages allowing thebacterial re-invasion. So, these cases were retreated using
the same procedures with special cares for tight restoration.
After the re-treatment, the cases were under observation

without any discomforts.
In this study, 3Mix-MP was placed on the previous root canalobturation. So, the previous root canal filling materials were
not removed, and clinical outcomes did not depend on
previous root canal obturation methods, because 96%, 88%,
92 % and 95% cases done by lateral condensation, verticalcondensation, single point, and root canal sealer, respectively,
were evaluated as good clinical outcome (Table 1). In thesame manner, the previous root canal obturation conditions
did not affect the clinical outcomes in this study. Thus, clinicaloutcomes were good in 87 % and 96% of cases of which root
canal obturation had been so called ‘just’ in length and short inlength, respectively (table 1).

Table 2. Clinical outcomes
Disappeared

Change of radiolucent lesions
ReducedNot changed

Worse

No. of cases

108 cases

42 cases

8 cases

3 cases

Mean size(Range)

3.8 mm(1 ~ 15 mm)

5.0 mm(1 ~15 mm)

2.6 mm(1 ~ 5 mm)

3.7 mm(3 ~ 5 mm)

Mean reduction

3.8 mm

3.4 mm

0 mm

-2 mm

Mean months of follow-up(Range)38 months(3 ~ 144)

26 months(4 ~ 168)

46 months(3 ~144)＊(＊)＊Under observation after re-restoration
Discussion

It was clearly demonstrated that excellent clinical outcomes
were obtained for the retreatment cases that had failed in

Journal of LSTR Therapy (International WEB version) VOL 8: 3-7, 20095

Takushige et al.

conventional endodontic treatment.
In the present
retrospective clinical study, we applied only 3Mix-MP
medication locally without removal of previous obturation for
the retreatment. This might mean that 3Mix-MP penetrated
previous root canal obturation in vivo and disinfect lesions,which had been demonstrated in our in vitro and in situ study(23，28). The present study also clearly demonstrated that,after disinfected, periradicular radiolucent lesions disappearedor reduced, thus the lesions repaired. We call this treatment
system as “Lesion Sterilization and Tissue Repair (LSTR)” anddo the clinical way to leave root canal system untouched as“Non-instrumentation Endodontic Treatment (NIET)”. Thus, thepresent study demonstrated that LSTR 3mix-MP NIET therapy
is excellent for endodontic retreatment.
The might be quite useful and convenient for dentists, who
are feeling conventional endodontic treatment is somewhat
complicated and needs matured clinical techniques, because
LSTR 3mix-MP NIET therapy is quite simple and easy, and yet
brings excellent clinical outcomes which should be one of theimportant factors for public dental treatment. Conventionally,
when root canals need retreatment after the previous treatment,
the previous root canal obturation has to be removed, andrepeat the same endodontic procedures including root canal
preparation and root canal obturation, but it may not be sure forthe dentists whether the retreatment is good enough if theprevious endodontic treatment had been done with the samemanner and failed.
The molecular sizes of 3Mix components are quite small and,thus, it is quite understandable that 3Mix-MP penetrated
endodontic obturation (23， 28), but the size of bacteria ismuch more bigger, so, if root canal obturation is tight, bacteria,
if any was in dentinal tubules of root canal walls, may be
packed and not immigrate to cause periradicular lesions.
However, it is also the fact that recurrent symptoms happen
often after the previous endodontic treatment. Conventionalroot canal obturation may not always perfect to seal up bacteria
within endodontic root canal system to prevent the immigration
to periradicular tissue.
The shapes of root canals arecomplicated with fin and isthmuses structures. It has beenclearly demonstrated that root canal obturation, even it seems
to be tight on two-dimensional X-ray photos, many defects arefound on three dimensional Micro-CT images (28). In addition,
minute air-bubbles formation and/or boundary problems
between root canal wall dentin and obturation materials may
also cause defects in the obturation and allow bacteria
immigrate.
It can be considered that the most important factor to cause
recurrent symptoms after previous endodontic treatment should
be bacteria remaining and surviving in lesions (2). Bacteriathat invade newly through the loose sealing may also cause
recurrent symptoms. If so, LSTR 3Mix-MP NIET therapy,
aiming first to eliminate causative bacteria (24), is quite
reasonable. Tight restoration, using glass-ionomer cement as
the first sealing and direct-method-resin-inlay cemented byresin cement as the second tight sealing, may keep lesion
sterile and induce new dentin and/or cementum formation
finally to seal lesions.
Softened dentin is recalcified tostrengthen the tooth structure and, at the same time, thedentinal tubules fill up with newly formed calcified crystals.
This new paradigm has been applied not only for endodontic
retreatment, but also general dental practices including dental
caries (24), pulpitis (26) and root canal treatment (25) without
removal of so called “infected dentin” including softened dentin,
pulp tissue, and root canal instrumentation and root canalobturation, and clinical outcomes have been excellent (24~26),
indicating that fundamental principles in these cases iselimination of causative bacteria from lesions (“Lesion
Sterilization”). Most cases have been done by one-visit
6

LSTR 3Mix-MP endodontic retreatment

treatment. Under sterile conditions, damaged lesion tissue iseasy repaired, which happens generally and commonly as the
final process of human infective inflammation. Of course, thisparadigm will not exclude conventional endodontic treatment,
and it is also clearly shown that when conventional endodontic
treatment is done properly, the clinical outcome is also good.
Because LSTR 3Mix-MP therapy is time-saving, simple andeasy but still excellent (24~26), and do not need expensive
dental machines/equipment and dental materials, this newparadigm using 3Mix-MP may most likely suit for public dental
practices or even for general dental practices if the endodontic
patients are abundant.
Conclusion:
Relapse of radiolucent lesions was successfully retreatedusing 3Mix-MP without removing previous obturation.
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Correspondent:
Professor HOSHINO Etsuro
Oral Ecology in Health and Infection,
Niigata University Graduate School of Medical and Dental Sciences
Gakkocho-dori 2, Niigata 951-8514 Japan
Fax: +81 (0)25-227-0806; Tel: +81 (0)25-227-2838; e-mail: hoshino@dent.niigata-u.ac.jp-------------------------------------------------------------------------------------------------------------------------------------------------------------------------Supported by the Grants-in-aid for Scientific Research (14406028, and 17390500) from the Ministry of Education, Culture, Sports, Science andTechnology, and by the grants for the Joint Research Program from the Japan Society for the Promotion of Science.

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Journal of LSTR Therapy (International WEB version) VOL 8: 3-7, 20097