Takushige SavePulp J LSTR

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Takushige & Hoshino LSTR 3Mix-MP SavePulp treatment

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Fig. Pulpitis cases treated by LSTR 3Mix-MP SavePulptherapy.

Clinical and radiographic observationsClinical symptoms, such as swelling, abscess, sinus tract,

induced pain on cold and hot conditions, pain on bite,spontaneous pain, were recorded before and after the

treatment. Preoperative radiographs were taken prior totreatment to observe development of caries lesions to pulpchambers and periodontium conditions. Postoperativeradiographs were also taken to observe re-calcification of softened dentin, closure of exposed pulps, and radiographicchanges in periradicular lesions.

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, 23, 24). In short, after removal of the capsules or coatingmaterials 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 cappedporcelain 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 anointment consistency, was prepared separately by mixingmacrogol (M; Solbase, Meiji, Tokyo, Japan) and propyleneglycol (P) in a ratio of 1:1 (by volume). The 3Mix antibioticsand 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. 3Mix-MP preparation should be prepared and used on the day of preparation.

Clinical procedure of LSTR therapy for pulpitisThe clinical procedures are described elsewhere (23). In brief,

previous restoration, if any, was removed. Softened dentinwas not removed intentionally unless the access cavity was


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Journal of LSTR Therapy (International WEB version) VOL 7: 1-5, 2008 3

Table 1. Clinical outcomes of 3Mix-MP pulpitis treatment

Clinical Outcome Cases with spontaneous pain Cases without spontaneouspain

Total

Good 222 (95%) 120 (94%) 342 (95%)Necrotic 2 ( 1%) 4 ( 3%) 6 ( 1%)

Root Canalre-treatment

9 ( 4%) 3 ( 2%) 12 ( 3%)

Total 233 127 360

Table 2. Clinical outcomes of pulpitis cases with spontaneous pain

Clinical Outcome OccasionalPain (%)

Pain atNight

Continuous pain Total

Good 179 (96%) 12 (86%) 31 (97%) 222 (95%)Necrotic 2 ( 1%) 0 ( 0%) 0 ( 0%) 2 ( 1%)


6 ( 3%) 2 (14%) 1 ( 3%) 9 ( 4%)

Total 187 14 32 233

Table 3Clinical outcomes of cases with spontaneous pain with or without pulp exposure

Clinical Outcome Cases with Pulp Exposure(%)

Cases without Pulp Exposure Total

Good 35 (92%) 187 (96%) 222 (95%)Necrotic 1 ( 2%) 1 (0.5%) 2 ( 1%)


2 ( 4%) 7 ( 4%) 9 ( 4%)

Total 38 195 233

(78 cases; 22%) or spontaneous pain (233 cases; 65%). Somecases were comprised of a combination of these criteria (Fig.1). Nearly all cases (357 of 360) were vital as defined by apositive pain sensation to a cold stimulus. About 30% of thecases (130 of 360) had mechanical allodynia as defined aspain to percussion with such a mirror handle.

Of the 264 cases with carious lesions extending to pulps, 262(99%) were hypersensitive to cold water, 74 (28%) hadexposed pulps, 95 (36%) had mechanical allodynia, 139 (53%)complained of spontaneous pain, and 28 (11%) hadperiradicular radiolucent areas. Out of 233 cases withspontaneous pain, 231 (99%) were hypersensitive to coldwater, 38 (16%) had exposed pulps, 139 (60%) had cariouslesions extending to pulps, 110 (57%) had mechanicalallodynia, and 23 (10%) had periradicular radiolucent areas.

Among these 233 patients, 187 (80%) complained of occasional spontaneous pain, 14 (6%) reported spontaneouspain at night, and 32 (14%) had experienced continuousspontaneous pain including pulsing pain.

Out of 78 cases with clinically exposed pulps, all werehypersensitive to cold water, 23 (29%) had mechanicalallodynia, 38 (49%) complained spontaneous pain, and 6 (8%)had periradicular radiolucent areas.

Patients were periodically examined for post-operativefindings several times when the patients visited the clinic andthe final follow-up examination was done 1232065 days after the treatment. As shown in Table 1, 342 (95%) cases out of 360 cases, treated with LSTR 3Mix-MP therapy, were classifiedas having a good outcome, because the pulps were vital andthe patients could bite on the teeth without discomfort whenevaluated more than one month after the treatment. Anadditional 12 (3%) cases required a second application of 3Mix-MP due to an initial failure to resolve symptoms; these

cases were associated with poor margins on the compositerestorations, and all subsequently met the criteria for a goodoutcome. An additional 6 cases were justified as pulpalnecrosis (dead pulps), and no clinical symptoms anddiscomfort were reported, meaning that the cases, as thedental treatment, were successful. Thus, the dead pulps after disinfected did not show any clinical symptoms and no further treatment was given.

We next evaluated various subsets of the 360 cases todetermine if prognostic factors were evident that could predictthe clinical outcome. Treatment with LSTR 3Mix-MP wasclassified as good regardless of the presence of spontaneouspain (Table 1) or the temporal nature of the pain report (Table2). In addition, the clinical outcome of cases with spontaneouspain and either the presence of absence of a clinically evidentvisual pulp exposure was similar (Table 3). Finally, thepresence of radiographic carious lesions extending to the pulp(Table 4) or clinically evident carious exposure of the pulp(Table 5) did not alter the outcome of the 3Mix-MP treatment.

It should be noted that these excellent clinical outcomes wereobtained even though carious dentin including softened dentinwas intentionally left in all cases. Visibly exposed holes topulps were not extended any more intentionally, and, instead,pulp tissue was disinfected with 3Mix-MP placed on overlyingdentin with closure of the exposing hole with glass-ionomer cement, and, as the result, the pulp was kept vital without anyclinical symptoms in 91% cases (Table 5).

No other adverse effects were observed in this case seriesincluding allergic reactions, a flare-up of pain or swelling, or bleeding from the exposed pulps.The decalcified areas on pre-operative X-ray photographs

increased radio-opaque density on post-operative onesapparently, indicating the areas were re-calcified. Although


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quantitative differentiation or determination of radio-opaquedensity was not easy, in most cases (85 %) re-calcificationwere apparently observed when checked after one year.

Table 4. Clinical outcomes of cases with carious dentinextending to the pulp

Table 5. Clinical outcomes of cases with exposed Pulp

Discussion

It has been reported that bacteria can invade pulp tissue evenunder conditions of shallow carious lesions or when clinicallyintact dentin still remains (2). This indicates that bacteria caninvade not only through a visible exposed holes opened to pulpchamber but also through certain dentinal tubules beneathcaries cavities, and inflammation and/or infection of pulp may

occur even in early stage of dentin caries. One implication of this finding is that complete elimination of bacteria may requireresection of a rather large area of dentin. However, this mayweaken tooth structure or expose the pulp tissue. Even so,bacteria may be present beneath any subsequent restorationwith eventual induction of pulpitis (25).

In the present study, we selected cases of pulpitis withcarious dentin extending to the pulp, as evidenced byradiographic examination. Cases with exposed pulps andcases with spontaneous pain also included in this study. It islikely that bacteria or their byproducts, may have alreadyinvaded the pulp tissue with subsequent inflammatory or immune host responses (2). The conventional treatment of cases classified as having irreversible pulpitis is to surgicalremove the pulp by a pulpectomy procedure. However, theLSTR hypothesis proposes that the local application of antimicrobial agents, such as the 3Mix-MP combinationevaluated in the present retrospective study, would disinfectthese lesions by eradicating bacteria in dentinal or pulpallesions. The results in the present clinical study support thisconcept since >90% of cases fulfilling the criteria of irreversible pulpitis were classified as having a good long-term outcome after local application of 3Mix-MP. In addition,we note prior short-term studies where cases of irreversiblepulpitis were symptomatically controlled and remained vitalafter systemic steroid injection (26). Interestingly, this systemicsteroid treatment led to significantly reduced pulpal levels of inflammatory mediators (27), suggesting that clinically

significant pulpal blood flow remains even in cases diagnosedas having irreversible pulpitis. Taken together, these findingssuggest that the definition of so-called irreversible pulpitisshould be reconsidered. We definitely call this pulpitistreatment as LSTR 3Mix-MP SavePulp therapy, because mostinflamed pulps were saved to be alive instead of the removal of pulp tissue in the conventional endodontic therapy.

The LSTR hypothesis predicts a successful clinical outcomeby local bacterial eradication. In addition to the treatment of pulpitis cases that are reported in the present study, permanent

teeth (21) and primary teeth (24) with periradicular lesions havebeen also successfully treated by 3Mix-MP endodontic therapy.These might indicate that 3Mix-MP therapy may have broadapplications for endodontic treatment by creating conditions for pulpal healing, revascularization or control of infection. For example, it is also possible to provide revisionary endodontictreatment (i.e. re-treatment) of cases with 3Mix-MP withoutremoval of previous root canal obturating materials (Takushige& Hoshino, unpublished data).

The results of this retrospective clinical study indicate thatLSTR therapy using 3Mix-MP, a mixture of metronidazole,ciprofloxacin and minocycline (3Mix), and macrogol andpropylene glycol (MP), provided excellent clinical outcomes intreatment of cases with caries dentin extended to pulps, caseswith exposed pulps and cases of pulpitis with spontaneous pain.These data provide a strong rationale for conductingprospective randomized clinical trials and offer the potential for a new model for treating infections of the pulpodentin complex.

References

1. Hoshino E: Predominant obligate anaerobes in human cariousdentin. J Dent Res 1985; 64: 1195-8.

2. Hoshino E, Ando N, Sato Mi, Kota K: Bacterial invasion of non-exposed dental pulp. Int Endod J 1992; 25: 2-5.

3. Ando N, Hoshino E: Predominant obligate anaerobes invading thedeep layers of root canal dentine. Int Endod J 1990; 23: 20-7.

4. Sato T, Hoshino E, Uematsu H, Noda T: Predominant obligateanaerobes in necrotic pulps of human deciduous teeth. Microb EcolHealth Dis 1993; 6: 269-75.

5. Kiryu T, Hoshino E, Iwaku M: Bacteria invading periapicalcementum. J Endod 1994; 20: 169-72.

6. Hoshino E, Sato Mi, Sasano T, Kota K: Characterization of bacterial deposits formed in vivo on hydrogen-ion-sensitive fieldtransistor electrodes and enamel surfaces. Jap J Oral Biol 1989; 31:102-6.

7. Hori R, Kohno S, Hoshino E: Tongue microflora in edentulousgeriatric denture-wearers. Microb Ecol Health Dis 1999; 11: 89-95.

8. Hoshino E, Sato Mi: Composition of bacterial deposits on fulldenture. Jap J Prosthet Dent 1988; 32: 762-6 (in Japanese withEnglish Abstract).

9. Sato Ma, Hoshino E, Nomura S, Ishioka K. Salivary microflora of geriatric edentulous persons wearing dentures. Microb Ecol Health Dis1993; 6: 293-9.

10. Uematsu H, Hoshino E: Predominant obligate anaerobes inhuman periodontal pockets. J Periodont Res 1992; 27: 15-9.

11. Hoshino E, Echigo S, Yamada T, Teshima T: Isolation of Propionibacterium acnes from sclerosing osteomyelitis of mandibles.Jap J Oral Biol 1984; 26: 48-51.

12. Nakazawa F, Hoshino E: Phylogenetic diversity among unknownoral bacterial species. J Oral Biosci 2005; 47: 52-9.

13. Hoshino E, Kota K, Sato Mi, Iwaku M: Bactericidal efficacy of metronidazole against bacteria of human carious dentin in vitro. CariesRes 1988; 22: 280-2.

14. Hoshino E, Iwaku M, Sato Mi, Ando N, Kota K: Bactericidalefficacy of metronidazole against bacteria of human carious dentin invivo. Caries Res 1989; 23: 78-80.

15. Hoshino E, Sato Mi, Uematsu H, Kota K: Bactericidal efficacy of metronidazole against bacteria of human periodontal pockets in vitro.Jap J Oral Biol 1991; 33: 483-9.

16. Sato T, Hoshino E, Uematsu H, Kota K, Iwaku M, Noda T:Bactericidal efficacy of a mixture of ciprofloxacin, metronidazole,

Clinical

Outcome

Cases with

ExposedPulp

Cases

without PulpExposure

Total

Good 67 (91%) 181 (95%) 248 (94%)Necrotic 4 ( 5%) 2 ( 1%) 6 ( 2%)


3 ( 4%) 7 ( 4%) 10 ( 4%)

Total 74 190 264

ClinicalOutcome

Cases withSpontaneous

Pain

Cases withoutSpontaneous

Pain

Total

Good 35 (92%) 36 (90%) 71 (91%)Necrotic 1 ( 3%) 3 ( 8%) 4 ( 5%)


2 ( 5%) 1 ( 2%) 3 ( 4%)

Total 38 40 78


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minocycline and rifampicin against bacteria of carious and endodonticlesions of human deciduous teeth in vitro. Microb Ecol Health Dis 1992;5: 171-7.

17. Sato T, Hoshino E, Uematsu H, Noda T: In vitro antimicrobialsusceptibility to combinations of drugs of bacteria from carious andendodontic lesions of human deciduous teeth. Oral Microbiol Immunol1993; 8: 172-6.

18. Sato I, Kurihara-Ando N, Kota K, Iwaku M, Hoshino E: Sterilizationof infected root-canal dentine by topical application of a mixture of ciprofloxacin, metronidazole and minocycline in situ. Int Endod J 1996;29: 118-24.

19. Hoshino E, Kurihara-Ando N, Sato I, Uematsu H, Sato. Mi, Kota K,Iwaku M: In-vitro antimicrobial susceptibility of bacteria taken frominfected root dentine to a mixture of ciprofloxacin, metronidazole andminocycline. Int Endod J 1996; 29: 125-30.

20. Hori R, Kohno S, Hoshino E: Bactericidal eradication from cariouslesions of prepared abutments by an antibacterial temporary cement. JProsthet Dent 1997; 77: 348-52.

21. Takushige T, Hoshino E: Clinical evaluation of 3Mix-MP method in

endodontic treatment. Jap J Conserv Dent 1998; 41: 970-4 (inJapanese with English Abstract).

22. Cruz EV, Kota K, Huque J, Iwaku M, Hoshino E: Penetration of propylene glycol through dentine. Int Endod J 2002; 35: 330-6.23. Hoshino E, Takushige T: LSTR 3Mix-MP method. Better andefficient clinical procedures of Lesion Sterilization and Tissue Repair (LSTR) therapy. DentalReview 1998; 666: 57-106 (in Japanese).

24. Takushige T, Cruz EV, M Asgor M, Hoshino E: Endodontictreatment of primary teeth using a combination of antibacterial drugs.Int Endod J 2004; 37: 132-8.

25. Brnnstrm M: Dentin and Pulp in Restorative Dentistry. Nacka,

Dental Therapeutics AB; 1981.26. Gallatin E, Reader A, Nist R, Beck M: Pain reduction in untreatedirreversible pulpitis using an intraosseous injection of Depo-Medrol. JEndod 2000; 26:633-8.

27. Isett J, Reader A, Gallatin E, Beck M, Padgett D: Effect of anintraosseous injection of depo-medrol on pulpal concentrations of PGE2 and IL-8 in untreated irreversible pulpitis. J Endod 2003; 29:268-71.

Correspondent:Professor HOSHINO EtsuroOral Ecology in Health and Infection,Niigata University Graduate School of Medical and Dental SciencesGakkocho-dori 2, Niigata 951-8514 JapanFax: +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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Takushige SavePulp J LSTR