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CLINICAL RESEARCH  临床研究

The Effect of Mineral Trioxide
三氧化二铝的影响Aggregate Obturation Levels
咬合强度on the Outcome of Endodontic
对牙髓治疗结果的影响Retreatment: An Observational
再治疗：观察Study 研究

Yoshi Terauchi, DDS, PhD,*Mahmoud Torabinejad, DMD,
马哈茂德-托拉比内贾德（Mahmoud Torabinejad），牙医博士、MSD, PhD, Kingsley Wong,
医学博士、博士， Kingsley Wong、MBBS, MPH, MMedStat, and
MBBS, MPH, MMedStat, andGeorge Bogen, BS, DDS 乔治-博根，医学学士，牙科医生

SIGNIFICANCE 意义The outcomes of this 其结果是retrospective cohort study
回顾性队列研究suggest that MTA obturation is
这表明 MTA 封堵术an effective option for 的有效选择retreatment of previously root
根治术canal-treated teeth with 经过水管处理的牙齿periapical lesions. MTA 根尖周病变MTAextrusion does not reduce the
挤压不会减少rate of periapical healing.
根尖周愈合率

Abstract 摘要

Introduction: No clinical studies have examined the effect of mineral trioxide aggregate (MTA) obturation levels on the outcome of endodontic retreatment. This retrospective study examined treatment outcomes in three cohorts that compared overfilling, flush filling, and underfilling after orthograde retreatment using MTA. Methods: Two hundred fifty patients with 264 teeth diagnosed with previously treated root canals and apical periodontitis retreated in a private endodontic practice were included. All teeth received MTA obturation and the extent of the final filling level was measured in relation to the major apical foramen. After 6month follow-ups, all nonhealing cases were treated surgically. After 24- to 72-month reviews, the effect of preoperative lesion size and the degree of MTA obturation level were assessed. Multiple linear regression and time-to-event analysis using Stata 17 software (StataCorp LLC, College Station, TX) were used to evaluate the data. Results: Within the three cohorts, 99 out of 108 overfilled teeth (91.7%), 90 out of 103 flush fills (87.4%), and 10 out of 53 underfilled teeth (18.9%) healed and were successfully retreated without surgery at 48 -months. When surgical outcomes were included, the combined healed proportion was . Preoperative lesion size was found to be an important predictor for retreatment nonhealing. A 1-mm increase in lesion size at baseline resulted in an estimated (95% Cl 1.04, 1.18)-38% (95% ) increase in the risk of surgery. Compared to overfilling and flush filling, underfilling was associated with an approximately three-fold increase in requiring surgery and characterized by delayed healing. Conclusion: MTA obturation is a viable retreatment option for teeth with nonhealing endodontic treatment. MTA overfills or flush fillings do not adversely affect healing outcomes. However, MTA underfilling increases the chances for nonhealing and surgical intervention. (J Endod 2023; : :1-11.)
导言：还没有临床研究考察过三氧化物矿物质骨料（MTA）封闭水平对牙髓再治疗结果的影响。这项回顾性研究考察了三个队列的治疗效果，比较了使用 MTA 进行正交再治疗后的过度充填、齐平充填和充填不足。研究方法研究纳入了 250 名患者，他们有 264 颗牙齿被诊断为曾接受过根管治疗，并在一家私人牙髓治疗诊所接受过根尖周炎再治疗。所有牙齿都接受了 MTA 封闭治疗，并根据主要根尖孔测量了最终充填水平的范围。经过 6 个月的随访，所有未愈合的病例都接受了手术治疗。经过 24 至 72 个月的复查，评估了术前病变大小和 MTA 闭塞程度的影响。使用 Stata 17 软件（StataCorp LLC, College Station, TX）进行多元线性回归和时间到事件分析来评估数据。结果：在三个队列中，108 颗过度充填牙中有 99 颗（91.7%）、103 颗齐平充填牙中有 90 颗（87.4%）、53 颗充填不足牙中有 10 颗（18.9%）在 48 个月后痊愈并成功修复，无需手术。如果将手术结果也包括在内，痊愈的综合比例为 。研究发现，术前病变大小是预测再治疗不愈合的一个重要因素。基线时病灶大小每增加 1 毫米，手术风险估计会增加 (95% Cl 1.04, 1.18)-38% (95% )。与过度充填和齐平充填相比，充填不足导致需要手术的风险增加了约三倍，并且具有延迟愈合的特点。 结论：对于牙髓治疗不愈合的牙齿来说，MTA 包埋是一种可行的再治疗方案。MTA 过度充填或冲洗充填不会对愈合结果产生不利影响。然而，MTA填充不足会增加不愈合和手术干预的几率。(J Endod 2023; : :1-11.)

KEY WORDS 关键词

MTA cement; obturation; overfill; periapical lesion; retreatment
MTA 骨水泥；封闭；过度充填；根尖周病变；再治疗
Obturation of the root canal system is an integral component of nonsurgical endodontic treatment. Ideally, the procedure should ensure that the entire root canal system is obturated without extrusion of the root-filling material beyond the apical constriction . This prevents irritation of the periradicular tissue , inhibits microbial recolonization, and denies residual microorganisms access to nutrients and potentially further propagation . The quality of root filling and obturation length have been shown by meta-analysis to be a significant prognostic factor for nonsurgical retreatment .
根管系统封闭是非外科根管治疗不可或缺的组成部分。理想情况下，该过程应确保整个根管系统被封堵，而根管填充材料不会挤出根尖收缩 。这样可以防止对根周组织的刺激 ，抑制微生物的重新定殖，并使残留的微生物无法获得养分和进一步繁殖的可能 。荟萃分析表明，根充质量和封闭长度是非手术再治疗的重要预后因素 。
Thermoplastic and cold-compaction obturation techniques have both been shown to provide acceptable obturation quality, but show limited resistance to microleakage . The two commonly-used obturation techniques have also been shown to have similar treatment outcomes . Importantly, an adequate coronal restoration has been shown to be a significant predictor of success . Moreover, the ability of gutta-percha and sealer to prevent microleakage is questionable in modern endodontic treatment . Consequently, bioceramic sealers have been developed for the purpose of improving the seal-ability, antimicrobial effect, and biocompatibility of conventional obturation methods . Although
热塑性和冷压实闭塞技术都被证明能提供可接受的闭塞质量，但对微渗漏的抵抗力有限 。这两种常用的密合技术也被证明具有相似的治疗效果 。重要的是，充分的冠状修复已被证明是成功的重要预测因素 。此外，在现代牙髓治疗中，古塔漆和封闭剂防止微渗漏的能力是值得怀疑的 。因此，人们开发了生物陶瓷封闭剂来改善传统封闭方法的封闭性、抗菌效果和生物相容性 。虽然
From the *Private Endodontic Practice, Tokyo, Japan; † Department of Endodontics, School of Dentistry, Loma Linda University, Loma Linda, California; #Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia; and Department of Endodontics, University of Queensland, School of Dentistry, Brisbane Queensland, Australia
来自： *私人牙髓病诊所，日本东京；† 牙科学院牙髓病系，洛马琳达大学，加利福尼亚州洛马琳达市；#特勒森儿童研究所，西澳大利亚大学，澳大利亚西澳大利亚州珀斯市；以及 牙科学院牙髓病系，昆士兰大学，澳大利亚昆士兰州布里斯班市。
Address requests for reprints to George Bogen, Department of Endodontics, University of Queensland, School of Dentistry, 4902/71 Eagle Street, Brisbane QLD 4000, Australia.
如需转载，请联系 George Bogen，地址：Department of Endodontics, University of Queensland, School of Dentistry, 4902/71 Eagle Street, Brisbane QLD 4000, Australia。
E-mail address: g.bogen@uq.edu.au 0099-2399/$ - see front matter
电子邮件地址：g.bogen@uq.edu.au 0099-2399/$ - 参见前页
Copyright © 2023 American Association of Endodontists.
版权所有 © 2023 年美国牙髓病学家协会。
j.joen.2023.04.004
absent in well-controlled clinical trials, bioceramic sealers combined with a well-fitted single gutta-percha cone have shown promising success rates in a retrospective cohort study . Despite these materials demonstrating advanced sealing properties, they may not have characteristics preferable to unmodified mineral trioxide aggregate (MTA) cement. Improved antibacterial properties, generation of an interfacial layer with dentin and consistent reformation of the periodontium may be expected when MTA cement is applied in retreament cases .
在一项回顾性队列研究中，生物陶瓷封闭剂与配合良好的单个古塔牙胶锥相结合，显示出良好的成功率 。尽管这些材料显示出先进的封闭性能，但它们的特性可能并不优于未改性的三氧化二矿骨水泥（MTA）。在再造病例中使用 MTA 水泥时，抗菌性能、与牙本质界面层的生成以及牙周的持续改建可能会得到改善 。
Obturation using unmodified MTA or other calcium silicate cements (CSCs) is also associated with some drawbacks that may not be crucial in teeth requiring retreatment. Staining teeth under full coverage restorations and slower setting-times do not necessarily adversely affect esthetic or biological outcomes . Additionally, removal and retreatment of set MTA may not be a critical factor in healing, as nonhealing in the majority of these cases often simplifies indicated surgical treatment . This can be advantageous where access to surgical sites is difficult and placement of retrograde fillings is challenging . Moreover, efficient obturation of canals using MTA or other CSCs is expected when operators become familiar with the handling properties of these materials.
使用未经改性的 MTA 或其他硅酸钙水门汀（CSCs）进行封闭也有一些缺点，但这些缺点对于需要再治疗的牙齿可能并不重要。全覆盖修复体下的牙齿着色和较慢的固位时间并不一定会对美学或生物学效果产生不利影响 。此外，去除和重新处理已镶嵌的 MTA 可能不是愈合的关键因素，因为在大多数情况下，不愈合通常会简化指定的手术治疗 。在难以进入手术部位和逆行充填具有挑战性的情况下，这可能是有利的 。此外，当操作人员熟悉了 MTA 或其他 CSC 材料的操作特性后，就可以使用这些材料有效地封闭牙槽骨。
Root canal retreatment presents a unique clinical challenge that is complicated by the need to remove prior obturation materials, overcome procedural errors, reduce bacterial contamination, and promote apical healing when pathosis is evident. Failure of root canal treatment can be attributed to both intraradicular and extraradicular infections involving biofilms, cysts, foreign body reactions, and cholesterol clefts . Frequently, teeth with long-standing apica periodontitis can also exhibit large lesions and inflammatory apical root resorption . Obturation using CSCs such as MTA does not predictably ensure successful treatment but has shown promise for cases with root resorption and open apices . However, it is often difficult to prevent unwanted extrusion of root filling material in cases with open apices without providing apical barriers .
根管再治疗是一项独特的临床挑战，由于需要去除先前的封固材料、克服程序错误、减少细菌污染以及在病变明显时促进根尖愈合，因此变得更加复杂。根管治疗失败可归因于根管内和根管外感染，包括生物膜、囊肿、异物反应和胆固醇裂 。患有长期根尖牙周炎的牙齿通常也会出现大面积病变和炎性根尖吸收 。使用 CSCs（如 MTA）进行封髓并不能确保治疗成功，但对于牙根吸收和根尖开放的病例却很有希望 。然而，在根尖开放的病例中，如果不提供根尖屏障，通常很难防止不必要的根充材料挤出 。
Furthermore, filling material extrusion has consistently been shown to adversely affect treatment outcomes .
此外，填充材料挤出一直被证明会对治疗效果产生不利影响 。
In cases refractory to primary orthograde treatment, retreatment procedures should focus on methods that promote the highest probability of periapical healing and limit secondary interventions . Although gutta-percha materials and bioceramic sealers are the generally accepted treatment modality, clinicians may want an alternative retreatment method for the more challenging nonhealing cases. A search of literature shows an absence of clinical studies that have examined the effect of the level of MTA root canal obturation on the healing rates of root canal retreatment in teeth exhibiting periapical disease. The aim of this retrospective study was to investigate the effect of MTA obturation levels on the outcome of endodontic retreatment.
对于初次正畸治疗无效的病例，再治疗程序应侧重于促进根尖周愈合概率最高的方法，并限制二次干预 。虽然古塔漆材料和生物陶瓷封闭剂是普遍接受的治疗方式，但临床医生可能需要另一种再治疗方法来治疗更具挑战性的不愈合病例。文献检索显示，目前还没有临床研究探讨 MTA 根管封固水平对根尖周病牙齿根管再治疗愈合率的影响。本回顾性研究旨在探讨 MTA 根管封闭水平对根管再治疗结果的影响。

MATERIALS AND METHODS 材料和方法

Study Design and Participants
研究设计和参与者

The study examined a patient pool comprised of cases treated between 2013 and 2022 by an endodontic specialist at a private practice in Tokyo, Japan. Informed consents were obtained from all adult patients and parents of all minors after discussing risks, benefits and outcomes of the treatment. Patients showing periapical radiolucencies or larger in diameter on preoperative cone-beam computed tomography (CBCT) imaging (FineCube; Yoshida Dental Mfg. Co., Ltd., Tokyo, Japan), received MTA obturation during endodontic retreatment. Patients included in the study were recalled a period of atleast 24-72 months for both orthograde and retrograde treatment outcomes.
这项研究调查了日本东京一家私人诊所的牙髓病专家在 2013 年至 2022 年期间治疗的患者病例。在与所有成年患者和未成年人的父母讨论了治疗的风险、益处和结果后，获得了他们的知情同意。在术前锥形束计算机断层扫描（CBCT）成像（FineCube；Yoshida Dental Mfg. Co., Ltd., Tokyo, Japan）中显示根尖周放射状突起直径大于或等于 的患者在牙髓再治疗期间接受了 MTA 包埋治疗。研究中的患者至少接受了 24-72 个月的正向和逆向治疗。
A total of 250 patients (out of 3327 ) met the inclusion criteria. Patients with unremarkable health histories, previous orthograde treatments, and adequate restorations were included. Furthermore, the possible influence of these factors was distributed between all three groups. Case selection also included patients showing periapical lesions measuring at least or greater in diameter and diagnosed with symptomatic or asymptomatic apical periodontitis. Teeth with detectable preoperative vertical root fractures (VRF), advanced periodontal disease, or deemed unrestorable were excluded. Data included tooth number, tooth type, gender, the pre/ postoperative maximum lesion diameter, maximum extent (amount) of the MTA overfill, underfill or flush fill, whether periapical surgery was required, and the time course to radiographic healing. Assessments were based on CBCT imaging with a maximum quantified image resolution of . MTA obturations or more beyond the major apical diameter were categorized as overfills ( ). Obturations even or less than above or below the major apica foramen were considered flush fills and MTA fills or greater below the major apical diameter designated as underfills ( ). All measurements were completed using FineCube software. Teeth that failed to demonstrate a measurable reduction in lesion size from CBCT review at 6 months after MTA retreatment were surgically treated using microsurgical techniques. Asymptomatic cases that showed reduction of the lesion size to or smaller in diameter on CBCT imaging at least 6 months or longer after retreatment or surgery were classified as healed. After 24 to 72-month reviews, the effect of pre-operative lesion size and the degree of MTA obturation level were assessed.
在 3327 名患者中，共有 250 名患者符合纳入标准。这些患者的健康状况均无异常，既往接受过矫治，并有足够的修复体。此外，这些因素可能造成的影响在所有三个组别中都有分布。病例选择还包括根尖周病变直径至少为 或更大且被诊断为有症状或无症状根尖牙周炎的患者。术前可检测到垂直根折（VRF）的牙齿、晚期牙周病或被认为不可修复的牙齿均不包括在内。数据包括牙齿数量、牙齿类型、性别、术前/术后最大病变直径、MTA过度填充、填充不足或冲洗填充的最大范围（量）、是否需要进行根尖周手术以及影像学愈合的时间过程。评估基于最大量化图像分辨率为 的 CBCT 成像。超出主要根尖直径 或更多的 MTA 闭塞被归类为过度充填 ( )。在主要根尖孔上下均匀或小于 的闭塞被认为是齐平填充 ，而在主要根尖直径以下 或更大的 MTA 填充被指定为欠填充 ( )。所有测量均使用 FineCube 软件完成。MTA 再治疗后 6 个月，CBCT 复查未能显示病变大小明显缩小的牙齿将采用显微外科技术进行手术治疗。再治疗或手术后至少 6 个月或更长时间后，CBCT 成像显示病变直径缩小至 或更小的无症状病例被归类为痊愈。 经过 24 到 72 个月的复查，评估了术前病灶大小和 MTA 闭塞程度的影响。

Nonsurgical Retreatment and MTA Obturation
非手术再治疗和 MTA 封堵术

All endodontic treatments were performed under dental dam isolation using the dental operating microscope. After disassembly of restorations or post and cores, root canal filling materials were removed initially with Terauchi File Retrieval Kit-S ultrasonic tips (Guilin Woodpecker Medical Instrument Co., Ltd, Guangxi, China) and an XP Shaper/Finisher (FKG Dentaire SA, La Chaux-de-Fonds, Switzerland). When or less of guttapercha remained apically, an XP Shaper/ Finisher rotating at in combination of a GPR hand instrument (Kohdent Roland Kohler Medizintechnik GmbH & Co. KG, Germany) was used with chloroform and removal confirmed radiographically. If separated instruments were present, they were removed prior to final obturation. The canals were then preflared with no. 2 or 3 Gates Glidden drills prior to negotiation of the apical third. The working length was established with an electronic apex locator (EAL) (Root ZX II; J Morita Corp, Kyoto, Japan) or Ai-Pex; (Guilin Woodpecker Medical Instrument Co.,Ltd, Guangxi, China) and confirmed radiographically. Definitive canal preparation was performed with either Vortex Blue/ProTaper Universal files (Dentsply Tulsa Dental Specialties, Johnson City, TN), EdgeTaper Platinum files (EdgeEndo, Albuquerque, NM), HyFlex EDM/CM files (Coltene Whaledent, Altstatten, Switzerland), or XP Shaper/Finisher files using QMix 2in1 chelation (Dentsply Tulsa Dental Specialties, Johnson City, TN). Root canal irrigation consisted of using sodium hypochlorite solution ( followed by hydrogen peroxide solution throughout the procedure. All the canals were instrumented to a minimum size of ISO 35 .
所有的根管治疗都是在牙科手术显微镜的牙坝隔离下进行的。在拆卸修复体或桩核后，首先使用 Terauchi File Retrieval Kit-S 超声波探头（桂林啄木鸟医疗器械有限公司，中国广西）和 XP Shaper/Finisher （FKG Dentaire SA，瑞士拉绍德封）去除根管充填材料。当 或更少的牙本质残留在牙根尖时，使用旋转速度为 的 XP Shaper/ Finisher 与 GPR 手动器械（Kohdent Roland Kohler Medizintechnik GmbH & Co. KG，德国）结合使用，并使用氯仿，通过放射影像确认清除情况。如果存在分离的器械，则在最终封堵前将其取出。然后使用 2 号或 3 号盖茨-格利登钻在根尖三分之一处进行预钻。使用电子根尖定位器（EAL）（Root ZX II; J Morita Corp, Kyoto, Japan）或 Ai-Pex；（桂林啄木鸟医疗器械有限公司，中国广西）确定工作长度，并通过X光片进行确认。根管预备采用 Vortex Blue/ProTaper Universal 锉刀（Dentsply Tulsa Dental Specialties，Johnson City，TN）、EdgeTaper Platinum 锉刀（EdgeEndo，Albuquerque，NM）、HyFlex EDM/CM 锉刀（Coltene Whaledent，Altstatten，Switzerland）或使用 QMix 2in1 螯合剂的 XP Shaper/Finisher 锉刀（Dentsply Tulsa Dental Specialties，Johnson City，TN）。根管冲洗包括在整个过程中使用 次氯酸钠溶液( ，然后使用 过氧化氢溶液 。所有根管的器械尺寸最小为 ISO 35。
Further removal of obturation material was accomplished with the use of the no. 25 XP Finisher rotating at 1000-2500 rpm. This was followed by irrigation with for 30 seconds and Qmix 2in1 (Dentsply Tulsa Dental Specialties, Tulsa, OK) for 30 seconds. Each root canal was then ultrasonically irrigated with using with the
使用 25 号 XP Finisher 以每分钟 1000-2500 转的速度旋转，进一步清除封闭材料。然后用 冲洗 30 秒，再用 Qmix 2in1 (Dentsply Tulsa Dental Specialties, Tulsa, OK) 冲洗 30 秒。然后用 对每个根管进行超声冲洗。
ProUltra PiezoFlow (Dentsply Tulsa Dental Specialties, Johnson City, TN) for sixty seconds. Finally, the root canals were saturated with for a further 1020 minutes, replenishing every 5 minutes before drying the canals with sterile paper points or a Stropko irrigator (DCI International, Newberg, OR).
ProUltra PiezoFlow（Dentsply Tulsa Dental Specialties，田纳西州约翰逊市）60 秒。最后，用 饱和根管 1020 分钟，每 5 分钟补充一次，然后用无菌纸点或 Stropko 冲洗器（DCI International，Newberg，OR）擦干根管。
The apical size was gauged with no. 35 to 60 NiTi K-file (Dentsply Tulsa Dental Specialties, Johnson City, TN). A shaping file 1 or two sizes smaller than the apical size was used to condense MTA during canal obturation . Gray or White ProRoot MTA (Dentsply Tulsa Dental Specialties, Johnson City, TN) was mixed with phosphate buffered saline on a glass slab and carried into the canal with a Buchanan Hand Plugger 0 (Kerr Corporation, Brea, CA). MTA was compacted with the selected rotary file in a few millimeter push/pull motion while rotating counterclockwise either manually or at 100 rpm using an endodontic motor. The rotary file was initially connected to an electronic apex locator that allowed increased accuracy during initial MTA placement. After apical closure was established, the file was moved coronally as the MTA plug was completed using various sized ultrasonic tips, pluggers, and rotary files. MTA compaction was advanced coronally from the apex to the level of the expected post insertion or core placement depth. No apical barrier membranes were used. Wet cotton pellets were placed over the MTA and the access cavity was temporally sealed with Cavit G (3M ESPE, St Paul, MN). The patients returned a week later for core or post and core placement and then recalled for an initial 3-month followup. Patients were further evaluated at 6 to 72 month observation periods.
使用 35 号至 60 号镍钛 K 型锉（Dentsply Tulsa Dental Specialties，田纳西州约翰逊市）测量根尖尺寸。使用比根尖尺寸小 1 或 2 号的整形锉，在牙道封闭过程中压缩 MTA 。在玻璃板上将灰色或白色 ProRoot MTA（Dentsply Tulsa Dental Specialties，田纳西州约翰逊市）与磷酸盐缓冲盐水混合，然后用 Buchanan Hand Plugger 0（Kerr Corporation，加利福尼亚州布雷亚）将其带入牙管。用选定的旋转锉以几毫米的推/拉动作压实 MTA，同时手动或使用根管马达以 100 转/分的速度逆时针旋转。旋转锉最初连接到电子根尖定位器上，从而提高了最初放置 MTA 时的精确度。建立根尖闭合后，在使用不同大小的超声波尖头、塞入器和旋转锉完成 MTA 塞入时，将锉刀向冠状方向移动。MTA 压实从根尖向冠状方向推进，直至预期的插入后深度或牙髓芯放置深度。未使用根尖阻隔膜。在 MTA 上放置湿棉球，然后用 Cavit G（3M ESPE，圣保罗，明尼苏达州）暂时密封通路腔。一周后，患者返回医院进行取芯或桩核植入，然后进行为期 3 个月的首次随访。患者在 6 至 72 个月的观察期内接受进一步评估。

Statistical Analysis 统计分析

Descriptive statistics were used to summarize the characteristics of the study cohorts (overfilling, flush filling, and underfilling). For each cohort, generalized linear regression models with Poisson distribution, log-link function, and robust standard error were used to estimate the unadjusted and adjusted risk ratios (RR) and their confidence intervals (Cl) of requiring surgery after endodontic treatment had failed. The median healing time was estimated from the time-to-healing functions generated using the Kaplan-Meier method, and the log-rank test was used to test the equality of the functions across the three cohorts (Fig. 1). The data were also fitted using the Cox proportional hazards regression models to estimate the unadjusted and adjusted hazard ratios (HR) of healing. The assumption of proportional hazards was tested using Schoenfeld residuals. In the regression models, the exposure variables of interest were MTA amount and lesion size at baseline and the covariates were age, gender and tooth type. A univariable analysis was first performed to determine the unadjusted RR and , followed by a multivariable analysis using all variables to obtain the adjusted estimates which were subsequently reported.
描述性统计用于总结研究队列（过度填充、齐平填充和填充不足）的特征。对于每个队列，采用泊松分布、对数连接功能和稳健标准误差的广义线性回归模型来估计牙髓治疗失败后需要手术的未调整和调整风险比（RR）及其 置信区间（Cl）。根据使用 Kaplan-Meier 方法生成的愈合时间函数估算中位愈合时间，并使用对数秩检验来检验三个队列中函数的相等性（图 1）。还使用 Cox 比例危险回归模型对数据进行拟合，以估算未调整和调整后的愈合危险比（HR）。使用 Schoenfeld 残差检验了比例危险假设。在回归模型中，相关暴露变量为基线时的 MTA 量和病变大小，协变量为年龄、性别和牙齿类型。首先进行单变量分析，以确定未调整的 RR 和 ，然后使用所有变量进行多变量分析，以获得调整后的估计值，并随后进行报告。
After combining the three cohorts into 1 , the same analysis for an individual cohort was repeated with MTA obturation level as an additional exposure variable of interest. All analyses were carried out using Stata (version 17.0, StataCorp LLC, College Station, TX), and the Kaplan-Meier curve was plotted using (version 4.2.2, R Foundation for Statistical Computing, Vienna, Austria) as well as the package "survminer" (version 0.4.9, https:// CRAN.R-project.org/package =survminer).
在将三个队列合并为一个队列后，重复对单个队列进行同样的分析，并将 MTA 闭塞水平作为额外的相关暴露变量。所有分析均使用 Stata（17.0 版，StataCorp LLC，德克萨斯州 College Station）进行，Kaplan-Meier 曲线使用 （4.2.2 版，R Foundation for Statistical Computing，奥地利维也纳）以及软件包 "survminer"（0.4.9 版，https:// CRAN.R-project.org/package=survminer）绘制。

RESULTS 结果

The baseline characteristics of the 264 teeth included in the study are shown in Table 1. The majority of the teeth were from female patients and the average age at the time of retreatment was 47.1 years ( , 48.3 years , and 50.1 years in the overfilling, flush filling, and underfilling cohort, respectively. Molars were the predominant tooth type in the nosurgery and surgery subgroups across the three cohorts. Seven teeth in the surgery subgroup and 1 in the nonsurgery subgroup were extracted. Five teeth were extracted because of VRF, and three teeth were extracted due to periodontal conditions
研究中 264 颗牙齿的基线特征如表 1 所示。大部分牙齿来自女性患者，再治疗时的平均年龄分别为 47.1 岁 ( 、48.3 岁 和 50.1 岁 。在三个队列的未手术亚组和手术亚组中，磨牙是主要的牙齿类型。手术分组中有 7 颗牙齿被拔除，非手术分组中有 1 颗牙齿被拔除。5 颗牙齿因 VRF 而拔除，3 颗牙齿因牙周病而拔除。

Overfilling Cohort 超额组群

At the 6-month follow-up appointment, close to of these teeth ( out of ) were classified as healed (Table 2). Ninety-nine of 108 teeth in this cohort ( ) were successfully retreated with MTA overfilling at the 48 -month recall period (overfill amount: 0.88 mm, SD: 0.52) (Table 2), (Fig. 2). The median healing time was 6 months , 6) (Fig. 1). In the nosurgery subgroup, the mean MTA overfill amount at baseline was (SD: 0.52) (Table 1). The median lesion size at baseline was (first quartile [Q1] 5.3 and third quartile [Q3] 8.1) (Table 1). In comparison, for teeth that required surgica intervention ( out of ), the median lesion size was (Q1 7.7, Q3 13.1). Two teeth in the surgery subgroup were eventually extracted due to VRF.
在 6 个月的复诊中，接近 的牙齿（ ， ）被归类为愈合（表 2）。在 48 个月的复诊中，108 颗牙齿中有 99 颗（ ）成功地进行了 MTA 包埋修复（包埋量：0.88 毫米，标度：0.52）（表 2），（图 2）。中位愈合时间为 6 个月 , 6）（图 1）。在未手术亚组中，基线时的平均 MTA 过度填充量为 （标清：0.52）（表 1）。基线时病变大小的中位数为 （第一四分位数 [Q1] 5.3，第三四分位数 [Q3] 8.1）（表 1）。相比之下，需要手术干预的牙齿（ out of ）的中位病变大小为 （Q1 7.7，Q3 13.1）。手术亚组中有两颗牙齿最终因 VRF 而被拔除。
Lesion size at baseline appeared to be associated with surgical intervention. With each millimeter increase in size resulting in an estimated 16% (adjusted RR 1.16, 95% CI ) increase in risk (Table 3). Among the tooth samples successfully retreated, increasing lesion size at baseline negatively impacted the healing time by (adjusted HR ) for each millimeter increase (Table 4).
基线时的病变大小似乎与手术干预有关。病变大小每增加一毫米，风险估计会增加16%（调整后RR为1.16，95% CI ）（表3）。在成功修复的牙齿样本中，基线时病变大小的增加对愈合时间有负面影响，每增加一毫米， （调整后 HR ）（表 4）。

Flush Filling Cohort 冲洗填充组群

The proportion of teeth reported to be healed at the 6 -month follow-up appointment after nonsurgical retreatment was ( out of 91). The healed proportion at the 6month recall after surgery was ( out of 12) (Table 2). The number of teeth successfully healed in the nosurgery subgroup increased to 90 out of 103 teeth (87.4%) after the 48-month follow-up (Table 2, Fig. 3). In this subgroup, the median healing time was six months ( 6, 6) (Fig. 1) and the median lesion size at baseline ( , Q1 4.7, Q3 8.3) was smaller than that of the surgery subgroup (9.5 mm, Q1 8.4, Q3 11.2) (Table 1). One tooth in the nosurgery subgroup with a VRF was extracted and two in the surgery subgroup were deemed refractory to treatment at 36 and 48 months. Similar to the previous cohort, increasing lesion size at baseline was associated with a heightened risk of surgery after retreatment (adjusted RR ) and delayed healing (adjusted ) (Tables 3 and 4).
据报告，非手术再治疗后 6 个月复诊时痊愈的牙齿比例为 ( 91 颗中的 )。手术后 6 个月复诊时痊愈的比例为 （12 人中有 人）（表 2）。在随访 48 个月后，103 颗牙齿中有 90 颗成功痊愈（87.4%）（表 2，图 3）。该亚组的中位愈合时间为 6 个月（ 6，6）（图 1），基线时的中位病变大小（ ，Q1 4.7，Q3 8.3）小于手术亚组（9.5 毫米，Q1 8.4，Q3 11.2）（表 1）。在 36 个月和 48 个月时，未手术亚组中一颗有 VRF 的牙齿被拔除，手术亚组中有两颗牙齿被认为难治。与之前的队列相似，基线时病变大小的增加与再治疗后手术风险的增加（调整后 RR ）和愈合延迟（调整后 ）有关（表 3 和表 4）。

Underfilling Cohort 学生人数不足

Contrary to the other two cohorts, the majority of teeth in this cohort were treated surgically ( out of ) (Table 2),
与其他两个队列相反，该队列中的大多数牙齿都是通过手术治疗的（ ， ）（表 2）、
Furthermore, most of the teeth ( out of ) in the surgery subgroup were healed at the 6-month follow-up appointment after surgery. However, only approximately ( out of ) of the teeth in the no surgery subgroup were observed to be healed at the same time point. Ten of the 53 teeth (18.9%) retreated with MTA underfilling healed without requiring surgery at the 24 -month review (Table 2, Fig. 4), and the median healing time was 24 months ( 6) (Fig. 1). In the nosurgery subgroup, the average amount of MTA underfilling at baseline was (SD: 0.75 ), slightly less than that in the surgery subgroup ( , SD: 0.99) (Table 1). The median lesion size at baseline of the nosurgery and surgery subgroup in this cohort was (Q1 4.6, Q3 7.8) and (Q1 6.7, Q3 10.0), respectively. Four out of 36 ( ) surgical cases were extracted at the time of surgery due to VRF and 1 due to nonhealing. There were more nonhealing teeth in the nosurgery subgroup ( out of )
此外，手术亚组中的大多数牙齿（ ， ）在术后 6 个月复诊时已经愈合。然而，在同一时间点，未手术亚组中只有约 （ 中的 ）颗牙齿被观察到愈合。在使用 MTA 下填充修复的 53 颗牙齿中，有 10 颗（18.9%）在 24 个月复查时愈合而无需手术（表 2，图 4），中位愈合时间为 24 个月（ 6）（图 1）。在未手术亚组中，基线时的平均 MTA 底填充量为 （标清：0.75），略低于手术亚组（ ，标清：0.99）（表 1）。该队列中，未手术亚组和手术亚组基线时病灶大小的中位数分别为 (Q1 4.6, Q3 7.8) 和 (Q1 6.7, Q3 10.0)。36 例手术病例中有 4 例（ ）在手术时因 VRF 而拔除，1 例因不愈合而拔除。非手术亚组（ out of ）中有更多的牙齿不愈合。
FIGURE 1 - Estimated Kaplan-Meier time to healing curve showing the probability of healing at follow-up appointments in patients retreated with MTA overfilling, flush filling, and underfilling . *excluded canine teeth . MTA, mineral trioxide aggregate.
图 1 - 估计的愈合 Kaplan-Meier 时间曲线，显示使用 MTA 过度充填、冲洗充填和充填不足治疗的患者在复诊时的愈合概率 。* 不包括犬齿 。MTA：三氧化物矿物质。
than in the surgery subgroup ( out of 38 , .
与手术分组相比（38 人中有 ， 。
For each millimeter of decreased MTA underfilling (ie, less underfilling), the surgery risk after retreatment was reduced by (adjusted RR 0.83, 95% CI 0.69, 0.99) (Table 3). As observed in other two cohorts, lesion size at baseline was a risk factor for surgery, with each millimeter increase in size resulting in an estimated (adjusted RR ) increase in risk. There were no notable associations between healing and MTA level or lesion size at baseline (Table 4)
MTA 填充不足每减少一毫米（即填充不足减少），再治疗后的手术风险就会降低 （调整后 RR 0.83，95% CI 0.69，0.99）（表 3）。与在其他两个队列中观察到的情况一样，基线时的病变大小也是手术的一个风险因素，病变大小每增加一毫米，估计手术风险就会增加 （调整后 RR ）。愈合与 MTA 水平或基线病变大小之间没有明显的关联（表 4）。

Combined Cohort 合并组群

The combined cohort's success fraction for nonsurgical retreatment in this retrospective study was ( out of 264 )
在这项回顾性研究中，合并组群的非手术再治疗成功率为 ( 264 人中有 )
(Table 2). When only the overfilling and flush filling cohorts were considered, the proportion increased to ( out of 211 ). The success fraction of non-surgical retreatment that healed using the MTA obturation technique was ( out of 108) for overfilling, ( out of 103 ) for flush filling, and ( out 53 ) for the underfilling cohorts. After long-term review, the healed proportion of MTA retreated teeth combined with nonhealing teeth requiring
(表 2）。如果只考虑过度充填和冲洗充填队列，比例则增加到 ( 211 个中的 )。使用 MTA 封固技术的非手术再治疗痊愈成功率为：过充填牙 （108 人中有 人），冲洗充填牙 （103 人中有 人），欠充填牙 （53 人中有 人）。经过长期复查，MTA 修复后的牙齿愈合比例与未愈合的牙齿相比需要
TABLE 1 - Baseline Characteristics of 264 Teeth Included by MTA Filling Level and Retreatment Group
表 1 - 按 MTA 填充程度和再治疗组划分的 264 颗牙齿的基线特征
Characteristics 特点 Overfilling  过度填充 Flush filling  冲洗填充 Underfilling  填充不足
No surgery 无手术 Surgery 外科手术 No surgery 无手术 Surgery 外科手术 No surgery 无手术 Surgery 外科手术
Number of teeth 齿数 9 (8.3) 91 (88.4)
Age , years 年龄 , 岁 47.2 (13.6) 46.6 (3.8) 48 (9.6) 51.0 (12.4)
Sex
Male 男
Female 女性 79 (79.8) 67 (73.6) 7 (58.3) 23 (63.9)
Tooth type 牙齿类型
Incisor 门齿 6 (6.6) 1 (2.8)
Canine 犬类 - - 2 (2.2) - - -
Premolar 前臼齿 8 (8.8)
Molar 臼齿 81 (81.8) 75 (82.4) 7 (58.3)

基线时的病变大小
Lesion size at
baseline

MTA 量 ,mm
MTA amount ,
mm
0 0
, number of teeth; MTA, Mineral Trioxide Aggregate; SD, standard deviation; Q1, first quartile; Q3, third quartile; mm, millimete
Q1，第一四分位数；Q3，第三四分位数；mm，毫微米。
The values are count and proportion unless otherwise stated
除非另有说明，否则数值均为计数和比例
*Presented as mean (standard deviation)
*以平均值（标准差）表示
Presented as median (1 quartile, quartile)
以中位数表示（1 四分位数， 四分位数）
surgery was ( out of 264 ) (Table 2).
（264 人中有 ）（表 2）。
MTA underfilling, as a group, was associated with at least a three-fold increase in requiring surgical intervention after retreatment when compared to flush filling (adjusted RR 3.08, 95% Cl 1.58, 6.01) and overfilling (adjusted RR 3.56, 95% CI 1.50, 8.49) (Table 3). However, there was no discernible difference in the risk between the overfilling and the flush filling cohorts (adjusted RR 1.16, 95% Cl 0.51, 2.62). Notably, an incremental increase in MTA level lessened the likelihood of having surgery by 24% (adjusted RR 0.76, 95% CI 0.62, 0.93) (Table 3, Fig. 5). Healing was delayed close to three-fold in the underfilling cohort compared to the flush filling (adjusted ) and overfilling cohorts (adjusted HR 0.34, 95% CI 0.12, 0.97). Nevertheless, the healing time was not affected by incremental change in the extent of MTA obturation level (adjusted HR 0.95, 95% CI ) (Table 4)
与冲洗填充（调整后 RR 为 3.08，95% Cl 为 1.58，6.01）和过度填充（调整后 RR 为 3.56，95% CI 为 1.50，8.49）相比，MTA 填充不足组再次治疗后需要手术干预的风险至少增加了三倍（表 3）。然而，过量灌注和冲洗灌注队列之间的风险没有明显差异（调整后 RR 1.16，95% Cl 0.51，2.62）。值得注意的是，MTA 水平每增加一个百分点，手术的可能性就会降低 24%（调整后 RR 0.76，95% CI 0.62，0.93）（表 3，图 5）。与齐平充填（调整后 ）和过度充填队列相比，充填不足队列的愈合延迟了近三倍（调整后 HR 0.34，95% CI 0.12，0.97）。然而，愈合时间不受 MTA 闭塞程度增量变化的影响（调整后 HR 0.95，95% CI ）（表 4）。

DISCUSSION 讨论

Nonsurgical root canal retreatment is a challenging procedure as the presence of previous iatrogenic errors, root canal filling materials, missed main or accessory canals and residual bacteria/biofilms in inaccessible areas create unique problems not typically present in the initial treatments .
非手术根管再治疗是一项极具挑战性的手术，因为先前的先天性错误、根管填充材料、遗漏的主根管或附属根管以及无法进入区域的残留细菌/生物膜都会造成独特的问题，而这些问题在最初的治疗中通常不会出现 。
Excluding the underfill cohort, the outcome for MTA overfilling and flush filling in this retrospective study compares favorably to the success rates in retreatment reported in previous studies . However, the underfilling cohort showed the lowest healing rate, requiring surgical intervention in the majority of cases at 6 months (69.4%) Importantly, this study retreated many compromised teeth not included in previous published studies. A large proportion of MTA obturated and underfilled teeth were challenging cases primarily attributed to blocked, ledged, or calcified canal systems (Fig. 4). Although direct comparison with previous outcome studies is difficult due to differences in methodology and criteria, the strict definition of success used in this study should limit any potential bias of the outcome rate.
除去充填不足的病例，这项回顾性研究中 MTA 过度充填和冲洗充填的结果与之前研究中报告的 再治疗成功率相比 。重要的是，这项研究修复了许多以前发表的研究中未包括的受损牙齿。很大一部分 MTA 闭塞和充填不足的牙齿都是具有挑战性的病例，主要原因是牙管系统堵塞、形成或钙化（图 4）。虽然由于方法和标准的不同，很难与之前的结果研究进行直接比较，但本研究对成功的严格定义应该可以限制结果率的任何潜在偏差。
The influence of preoperative lesion size on the outcome of nonsurgical endodontic treatment is not universally agreed upon. The results of this study found that preoperative lesion size was a significant predictor for requiring surgical intervention. For every millimeter increase in lesion size, the risk for requiring surgical treatment increased
术前病变大小对非外科根管治疗结果的影响并没有得到普遍的认同。本研究结果发现，术前病变的大小是需要手术干预的一个重要预测因素。病变大小每增加一毫米，需要手术治疗的风险就会增加
FIGURE 2 - MTA retreatment overfill. (A) Preoperative radiograph shows periapical lesions associated with maxillary right second molar (arrowS). (B, C) CBCT sagittal and coronal views show large periapical lesion surrounding palatal root with radiolucent material extrusion (arrows). (D, E) CBCT sagittal and coronal images showing small periapical lesions on both mesiobuccal (MB) and distobuccal roots (arrows). (F) CBCT axial view of large periapical lesion on palatal root extending to the MB root (arrow). (G) Microscope photograph shows fissure extending from the palatal root to the MB root (arrow). (H) Photograph of the groove filled with white MTA (arrow). (/) Postoperative radiograph shows MTA obturation in all canals with significant MTA overfill in the palatal root (arrow). (J) Six-month postoperative radiograph shows advancing remineralization of pre-existing periapical lesions (arrows). (K) Twenty-four-month postoperative follow-up radiograph shows normal periapical tissues with a permanent full coverage restoration. Twenty-four-month postoperative CBCT sagittal and coronal images revealing complete resolution of periapical lesions and circumferential bone reformation around palatal root (arrow). ( ) Twenty-four-month postoperative sagittal and coronal images displaying complete resolution of the periapical lesions on both buccal roots (arrowS). ( ) Twenty-four-month postoperative CBCT axial view shows remineralization of supporting bone between palatal and mesiobuccal roots (arrow). CBCT, cone-beam computed tomography; MTA, mineral trioxide aggregate
图 2 - MTA 再治疗过度填充。(A）术前X光片显示与上颌右第二磨牙相关的根尖周病变（箭头S）。(B、C）CBCT矢状切面和冠状切面显示腭根周围有大面积根尖周病变，并有放射性物质挤出（箭头）。(D、E）CBCT矢状切面和冠状切面显示中颊根（MB）和远颊根均有小的根尖周病变（箭头）。(F）CBCT 轴位图显示腭根有大的根尖周病变，并延伸至 MB 根（箭头）。(G）显微镜照片显示裂隙从腭根延伸至 MB 根（箭头）。(H）用白色 MTA 填充凹槽的照片（箭头）。(/)术后X光片显示所有的牙道都有MTA封堵，腭根部有明显的MTA过度填充（箭头）。(J）术后六个月的X光片显示，原有的根尖周病变正在重新矿化（箭头）。(K）术后二十四个月的随访X光片显示根尖周组织正常，并有永久性全覆盖修复体。 术后 24 个月的 CBCT 矢状面和冠状面图像显示根尖周病变完全消退，腭根周围骨质重新形成（箭头）。( ) 术后 24 个月的矢状面和冠状面图像显示，两个颊根的根尖周病变完全消退（箭头S）。( ) 术后 24 个月的 CBCT 轴向图像显示，腭根和颊中根之间的支撑骨重新矿化（箭头）。CBCT：锥束计算机断层扫描；MTA：三氧化物矿物质聚合体
by an estimated in overfilling, in flush filling, and in the underfilling cohort. Correspondingly, the nosurgery subgroup in the flush filling cohort demonstrated smaller median lesion sizes at baseline than those of the surgical subgroup. Furthermore, increasing lesion size at baseline was also associated with delayed healing in the overfilling and flush filling cohorts. There was inconclusive evidence that the risk of surgery differed by gender, age, and tooth type in the three cohorts.
据估计，过度填充组的中位病灶大小为 ，齐平填充组的中位病灶大小为 ，填充不足组的中位病灶大小为 。相应地，冲洗填充队列中的非手术亚组在基线时的病变中值大小小于手术亚组。此外，基线时病变大小的增加也与过度填充和冲洗填充组的延迟愈合有关。在三个队列中，手术风险因性别、年龄和牙齿类型而异的证据尚不确定。
Our findings related to the size of the lesions are in agreement with the results reported in a systematic meta-analysis, where orthograde retreatments with larger preoperative lesions were associated with significantly lower healing rates than those with smaller periapical lesions . The data also appear to support the concept that larger preoperative lesions may be more critical to
我们关于病变大小的研究结果与一项系统荟萃分析报告的结果一致，即术前病变较大的根尖周病变正中退修术的愈合率明显低于术前病变较小的根尖周病变正中退修术 。这些数据似乎也支持这样的观点，即术前病变较大的根尖周愈合率可能更低。
TABLE 3 - Estimated adjusted* Relative Risks of Requiring Surgery at 24-72 month Review as Predicted by Lesion Size at Baseline and MTA Filling Level
表 3 - 根据基线时的病变大小和 MTA 填充程度预测的 24-72 个月复查时需要手术的调整后*相对风险估计值
Variables 变量

过满 aRR 值
Overfilling
aRR
value

冲洗灌装 aRR 值
Flush filling
aRR value

注水不足 aRR ( 值
Underfilling
aRR (
value
Combined  合并
aRR value aRR 值
 MTA 数量（毫米
MTA amount,
mm
1.19 (.47, 3.03), . 719 n/a .83 (.  .83 (.

基线时的病变大小、
Lesion size at
baseline,
1.16 (.98, 1.36), . 080
MTA fillina level MTA fillina 级
Over 完毕 n/a n/a n/a .86 (.38, 1.95), . 724 ref
Flush 冲洗 n/a n/a ref
Under 根据 n/a n/a
TABLE 4 - Estimated adjusted* Hazard Ratios for Time Required for Retreatment Case Classification as Healed When Predicted by Lesion Size at Baseline and MTA Filling Level
表 4 - 根据基线时的病变大小和 MTA 填充程度预测的再治疗病例分类为痊愈所需时间的估计调整*危险比
Variables 变量

过满 aHR 值
Overfilling
aHR
value

冲洗填充（n = aHR 值
Flush filling
(n =
aHR
value

充气不足 aHR (95% Cl)， 值
Underfilling
aHR (95% Cl),
value
Combined  合并
aHR value aHR 值
 MTA 数量（毫米
MTA amount,
mm
1.27 (.39, 4.12), . 689 .95 (.67, 1.36), . 789

基线时的病变大小、
Lesion size at
baseline,
1.32 (.85, 2.06), . 215
MTA filling level MTA 装填水平
Over 完毕 ref
Flush 冲洗 ref 0.95 (0.62, 1.44), 0.794
Under 根据
n, number of teeth; MTA, Mineral Trioxide Aggregate; aHR, adjusted hazard ratio; ref, reference category; n/a, not applicable.
n，牙齿数量；MTA，矿物三氧化物骨料；aHR，调整后危险比；ref，参考类别；n/a，不适用。
*The hazard ratios were adjusted for other reported variables and covariates including age, sex and tooth type.
*危险比已根据其他报告变量和协变量（包括年龄、性别和牙齿类型）进行调整。
excluded canine teeth
排除犬齿
‡Lesion size at baseline violated the proportional hazards assumption. The covariate was categorized and included in the model as strata, and hence its results were not shown
基线时的肿块大小违反了比例危险假设。该协变量被分类并作为分层纳入模型，因此其结果未显示
healing outcomes than the actual MTA obturation level. In contrast, Sjogren et al., reported that the diameter of the preoperative lesion was not a significant predictor for treatment outcome . A possible explanation for reduced healing rates in teeth with large periapical lesions may be the presence of more established intraradicular or extraradicular biofilms. These can be more difficult to eradicate through conventional nonsurgical treatment . The improvement in success rates in the two cohorts over those in recent studies could be attributed to stringent irrigation protocol and/or the antibacterial and bioactive properties of MTA/CSC materials
与实际 MTA 闭塞水平相比，MTA 闭塞水平对愈合结果的影响更大。与此相反，Sjogren 等人报告说，术前病变的直径并不是治疗效果的重要预测因素 。根尖周病变较大的牙齿愈合率较低的一个可能原因是根尖内或根尖外存在较多的生物膜。这些生物膜更难通过传统的非手术疗法根除 。与最近的研究相比，这两个队列的成功率有所提高，这可能归功于严格的冲洗方案和/或 MTA/CSC 材料的抗菌和生物活性特性。
The underfilling cohort, although smaller in size, demonstrated slower healing in the nosurgery subgroup compared to the other two cohorts. Moreover, the majority of teeth in this sample required surgical
虽然填充不足队列的规模较小，但与其他两个队列相比，未手术亚组的愈合速度较慢。此外，该样本中的大多数牙齿 都需要手术治疗。
FIGURE 3 - MTA retreatment flush fill. (A) Preoperative radiograph of previously treated maxillary right lateral incisor displaying a large cast post and full coverage restoration with periapical lesion and apical root resorption. ( CBCT sagittal, coronal and axial images showing extent of lesion and perforation of the palatal bone (arrowS). (E) Microscope photograph of previous filling materials in a ledged labial space after post and core removal. (F) Microscope photograph of MTA obturated. (G) Immediate postoperative radiograph confirming flush MTA obturation. (H-J) Recall radiographs at 3,6 , and 24 months showing bone reformation of previous periapical defect. ( ) CBCT coronal view at 24 months showing osseous repair of the palatal plate (arrow). ( ) CBCT coronal and axial views confirming remineralization of lesion and reformation of palatal bone at 24 months (arrows). CBCT, cone-beam computed tomography; MTA, mineral trioxide aggregate.
图 3 - MTA 再治疗冲洗填充。(A) 先前治疗过的上颌右侧切牙的术前 X 光片，显示有一个大的铸造柱和全覆盖修复体，根尖周病变和根尖吸收。( CBCT 矢状、冠状和轴向图像显示病变范围和腭骨（箭头S）穿孔。(E)显微镜下的照片，显示拔除牙柱和牙髓后，唇侧间隙中的填充材料。(F) MTA封闭后的显微镜照片。(G)术后即刻拍片，确认 MTA 封堵齐平。(H-J)3、6 和 24 个月的复查照片，显示之前根尖周缺损的骨质改良情况。( ) 24 个月时的 CBCT 冠状切面显示腭板骨性修复（箭头）。( ) 24 个月时的 CBCT 冠状切面和轴向切面显示病灶再矿化和腭骨再造（箭头）。CBCT：锥形束计算机断层扫描；MTA：三氧化物矿物质聚合体。
FIGURE 4 - MTA retreatment underfill. (A) Preoperative radiograph shows previously treated maxillary left first and second molars (no. 14, 15) with periapical pathosis associated with mesiobuccal (MB) root no. 15 (arrow). (B) CBCT sagittal view reveals mucositis of the sinus floor (arrows) and the apical foramen location of the curved MB root (arrow). (C) Sagittal CBCT view shows extent of periapical lesion measuring in length (arrow). (D) Coronal CBCT view reveals periapical lesions associated with both MB and palatal roots no. 15 . (E) CBCT axial image demonstrates loss of supporting bone and cortical plate of buccal roots no. 15 (arrowS). (F) Periapical radiograph shows negotiation file blocked by previous ledge formation (arrow). (G) Periapical radiograph showing MTA retreatment obturation of both molars with bonded composite cores (no. 14, 15). Note obturation short of apical foramen no. 15. (H) Twenty-four-month postoperative radiographic displays recently placed full coverage restorations and remineralization of MB periapical lesion no. 15. (I) Twenty-four-month CBCT sagittal image reveals normal mucous membrane (arrows). Note transported MTA obturation at perforation site of ledged MB canal and osseous repair of periapical area (arrow) Twenty-four-month sagittal and coronal CBCT recall images confirming successful repair of periapical bone (arrow). (L) Twenty-four-month axial CBCT follow-up shows reformation of periradicular supporting bone. CBCT, cone-beam computed tomography; MTA, mineral trioxide aggregate.
图 4 - MTA 再治疗下填充。(A）术前X光片显示，之前治疗过的上颌左侧第一和第二磨牙（第 14、15 号）根尖周病变与第 15 号中颊根（MB）有关（箭头）。(B）CBCT矢状切面显示窦底粘膜炎（箭头）和弯曲的MB根尖孔位置（箭头）。(C）CBCT 矢状切面显示根尖周病变范围，长度为 （箭头）。(D)CBCT 冠状切面显示根尖周病变与 MB 和第 15 号腭根相关。(E) CBCT 轴向图像显示第 15 号颊根的支撑骨和皮质板缺失（箭头S）。15（箭头S）。(F) 根尖周 X 光片显示商谈锉被先前形成的壁架阻塞（箭头）。(G)根尖周X光片显示两颗磨牙（14号和15号）的MTA再治疗闭锁，并粘结了复合树脂核。注意在 15 号根尖孔的短处进行封闭。(H)术后二十四个月的X光片显示最近放置的全覆盖修复体和 15 号 MB 根尖周病变的再矿化。(I）24 个月的 CBCT 矢状图显示粘膜正常（箭头）。注意甲基溴导管穿孔处的 MTA 封堵和根尖周区域的骨修复（箭头） 24 个月的矢状位和冠状位 CBCT 回放图像证实根尖周骨修复成功（箭头）。(L)24个月的轴向CBCT随访显示，根尖周支持骨重新形成。CBCT：锥形束计算机断层扫描；MTA：三氧化物矿物质骨料。
intervention to resolve nonhealing lesions. Interestingly, the surgical cases in this cohort healed more rapidly than both the other cohorts at the six-month recall period. It might be surmised that nonnegotiable canals encountered during MTA retreatment that were blocked and could not be obturated flush or beyond the major apical foramen, had higher risk for surgical treatment.
干预来解决不愈合的病变。有趣的是，在 6 个月的回顾期内，该组别的手术病例比其他两组的愈合速度都要快。由此可以推测，在 MTA 再治疗过程中遇到的阻塞且无法与主要根尖孔齐平或超出主要根尖孔的不可通畅的根管，采用手术治疗的风险较高。
Nonnegotiable canals were most likely the result of complex anatomy, calcifications, missed apical bifurcations, previously transported canals, or ledged apical preparations (Fig. 4). In clinical practice, this can be an important consideration in the management and informed consent of patients undergoing retreatment that receive underfillings after MTA obturation.
不可通畅的根管很可能是由于复杂的解剖结构、钙化、错过根尖分叉、以前输送过的根管或根尖预备过高造成的（图 4）。在临床实践中，这可能是在 MTA 封堵后接受再治疗的患者在管理和知情同意方面的一个重要考虑因素。
The retreatment outcomes of different MTA obturation levels in this study suggest that healing rates may improve using unmodified MTA in cases where the level of filling is flush or beyond the major apical foramen (Figs. 2, 3 and 4). Additionally, after inclusion of all three cohort nonhealing cases treated surgically, the combined healing rate was noteworthy. This favorable outcome may be attributed to the many physicochemical properties of MTA. They include the formation of an interfacial hybrid apatite diffusion zone, generation of an alkaline , and the phenomenon of intratubular mineralization . During the setting process, leaflet-like crystals form along the length of the dentinal and intracanalicular tubules, subsequently neutralizing persistent microbial pathogens . However, this process may be ineffective in reducing extraradicular biofilms if the obturation material cannot come in direct contact with microorganisms.
本研究中不同 MTA 封堵水平的再治疗结果表明，在充填水平与主要根尖孔齐平或超出主要根尖孔的病例中，使用未改性的 MTA 可能会提高愈合率（图 2、图 3 和图 4）。此外，在纳入所有三组通过手术治疗的未愈合病例后，综合愈合率也值得注意。这种良好的结果可能归功于 MTA 的多种物理化学特性。其中包括形成界面混合磷灰石扩散区、生成碱性 以及管内矿化现象 。在凝固过程中，沿牙本质和牙本质内小管的长度方向形成叶状结晶，随后中和持续存在的微生物病原体 。但是，如果封闭材料不能与微生物直接接触，这一过程可能无法有效减少龈外生物膜。
Bacteria residing outside the canal system protected by biofilms can prevent healing and increase indications for surgical alternatives .
在生物膜的保护下，寄居在牙管系统外的细菌会阻碍愈合，并增加手术替代方案的适应症 。
The biocompatibility and bioactivity properties of MTA are further supported in this study as the degree of MTA extrusion was infrequently associated with nonhealing (Fig. 5). This result differs to that reported previously, where extrusion of root filling material was associated with compromised outcome and slower healing . MTA cement has been established to be welltolerated when in contact with periradicular tissues in studies examining apexification and perforation repairs . This can be a distinct advantage in cases with advanced apical root resorption and long-standing periapical pathosis.
本研究进一步证实了 MTA 的生物相容性和生物活性特性，因为 MTA 的挤出程度很少与不愈合有关（图 5）。这一结果与之前报道的结果不同，在之前的报道中，牙根充填材料的挤出与效果受损和愈合缓慢有关 。在对顶点化和穿孔修复进行的研究中，已证实MTA粘接剂在与根周组织接触时具有良好的耐受性 。这在根尖吸收晚期和根尖周病变长期存在的病例中具有明显优势。
Despite its relatively large sample size and long follow-up periods, there are some shortcomings in this study that deserve consideration. The retrospective nature of this investigation is its main drawback. Ideally, it would have been preferred that this study had been carried out in a randomized prospective format with adequate controls. However, setting up randomized clinical prospective studies with various cohorts such as level of obturation and appropriate controls that could include other obturation materials has its own difficulties and ethical issues. The only manner to set up randomized prospective clinical investigations with adequate controls is to carry them out in experimental animals.
尽管这项研究的样本量相对较大，随访时间较长，但仍有一些不足之处值得考虑。这项调查的回顾性是其主要缺点。理想情况下，本研究最好采用随机前瞻性研究的形式，并进行适当的对照。然而，设立不同组别的随机临床前瞻性研究（如封堵水平）和适当的对照组（可包括其他封堵材料）有其自身的困难和伦理问题。建立具有适当对照的随机前瞻性临床研究的唯一方法是在实验动物身上进行。
FIGURE 5 - MTA retreatment overfill. (A) Preoperative radiograph shows large osseous lesion associated with the maxillary right first (no. 3) and second molars (no. 2) (arrow). (B, C) CBCT sagittal and coronal views show large periapical lesions between the palatal roots of the molars extending to the crestal bone (arrowS). (D) CBCT coronal and sagittal views reveal lesions elevating the sinus floor (arrow). (E,F) CBCT axial and coronal images showing perforation of the palatal plate and loss of supporting bone (arrowS). (G) Microscope photograph showing hemorrhaging upon access in the MB canal no. 3 (arrow). (H) Postoperative radiograph shows MTA overfills in each canal of the first molar with new composite core. (I) Three-month postoperative radiograph shows MTA extrusion in no. 2 and advancing remineralization of osseous defects. (J) Forty-eight-month postoperative radiograph shows resolution of the pre-existing periapical lesions with a new coronal restoration. Postoperative 48 -month CBCT sagittal and coronal views shows complete reformation of the supporting bone no. 2, 3 (arrows). (M) Forty eight-month postoperative CBCT sagittal view of no. 2 showing resolution of lesions with a normal sinus floor. ( ) Axial and coronal CBCT recall images demonstrating reformation of the cortical bone and repair of osseous defects (arrows). CBCT, cone-beam computed tomography; MTA, mineral trioxide aggregate.
图 5 - MTA 再治疗过度填充。(A）术前X光片显示与上颌右侧第一磨牙（3号）和第二磨牙（2号）相关的大面积骨质病变（箭头）。(B、C）CBCT矢状切面和冠状切面显示，磨牙腭根之间的大面积根尖周病变延伸至牙槽骨（箭头S）。(D）CBCT 冠状切面和矢状切面显示病变抬高了窦底（箭头）。(E、F）CBCT 轴向和冠状切面显示腭板穿孔和支撑骨缺失（箭头S）。(G)显微镜照片显示 MB 管 3 号入口处出血（箭头）。箭头）。(H)术后X光片显示，第一磨牙的每个牙道都有MTA填充，并有新的复合材料内核。(I）术后三个月的 X 光片显示 2 号臼齿的 MTA 被挤出，骨质缺损正在重新矿化。(J)术后48个月的X光片显示，新的冠状修复体解决了原有的根尖周病变。 术后 48 个月的 CBCT 矢状切面和冠状切面显示 2 号和 3 号支撑骨完全修复（箭头）。(M）2 号患者术后 48 个月的 CBCT 矢状切面显示病变已愈合，窦底正常。（ ）CBCT 轴位和冠状位回放图像显示皮质骨重组和骨缺损修复（箭头）。CBCT：锥形束计算机断层扫描；MTA：三氧化物矿物质聚合体。
Notwithstanding, these studies also have their own disadvantages.
尽管如此，这些研究也有其自身的缺点。
Although the number of teeth in the underfilling cohort group was only approximately half of the two other cohorts, it is plausible that the inclusion of additional underfilling cases may have produced different data. However, it is also important to note that many nonhealing MTA retreament cases can be successfully managed by surgical intervention, supporting the ultimate goal of continued tooth retention. Hence, data outcome from surgical treatment was included in this study. Another limitation of this investigation is the fact that all of the cases were performed by one experienced operator (Y.T.). The results might have been different if this investigation was completed in multiple locations by various operators with different training and experience using MTA obturation.
虽然欠充填组的牙齿数量仅为其他两组的一半左右，但纳入更多的欠充填病例可能会产生不同的数据。不过，同样重要的是要注意，许多不愈合的 MTA 再融合病例可以通过手术干预成功控制，从而支持继续保留牙齿的最终目标。因此，本研究也包括了手术治疗的结果数据。这项研究的另一个局限性是，所有病例都是由一位经验丰富的操作者（Y.T.）完成的。如果这项调查是在多个地点由受过不同培训、具有不同 MTA 封固经验的不同操作者完成，结果可能会有所不同。
All teeth that received retreatment and demonstrated no measurable reduction in lesion size after CBCT review at 6-months were surgically treated. There still remains the probability that some of these MTA obturated cases could have healed allowing longer observation periods without surgica intervention . Studies have shown delayed healing can be expected in a large portion of teeth that have undergone conventional retreatment . However, long-term followup periods do not ensure that healing will emerge after retreatment . Accordingly, the slower healing dynamics and large number of nonhealing cases reflected in the underfilling cohort may have been the consequence of untreated apical canal spaces . The advantages of surgical intervention in these cases included expedited healing periods and reduction of possible late post-treatment complications
所有接受再治疗的牙齿在 6 个月后的 CBCT 复查中均显示病变大小没有明显缩小，因此对这些牙齿进行了手术治疗。在这些 MTA 包埋的病例中，仍有一些可能在较长的观察期内愈合，而无需手术干预 。研究表明，大部分接受过传统再治疗的牙齿可能会出现延迟愈合 。然而，长期随访并不能确保再治疗后的愈合 。因此，充填不足队列中反映出的较慢的愈合动态和大量未愈合病例可能是未处理根尖管间隙的结果 。在这些病例中，手术干预的优势包括加快愈合期和减少治疗后后期可能出现的并发症
Our findings show that approximately of teeth in the nosurgery overfill and flush fill subgroups showed definitive signs of healing at 6 months. This is higher than Orstavik's study where only of successfully treated teeth showed signs of healing at 6 months . Other studies have demonstrated delayed healing in retreated teeth by up to 17-27 years, especially in cases with extruded root filling materials . It appears that the time required for complete remineralization of apical defects may be shortened when unmodified MTA is used as an obturation material. The influence of MTA on the speed of healing needs to be further explored in future randomized clinical trials or case-controlled studies.
我们的研究结果表明，在非手术过度充填和齐平充填亚组中，约有 的牙齿在 6 个月时出现了明确的愈合迹象。这比 Orstavik 的研究结果要高，在 Orstavik 的研究中，只有 成功治疗的牙齿在 6 个月后出现愈合迹象 。其他研究表明，再治疗牙齿的愈合延迟时间长达 17-27 年，特别是在使用挤压根充材料的病例中 。看来，如果使用未改性的 MTA 作为封闭材料，根尖缺损完全再矿化所需的时间可能会缩短。MTA 对愈合速度的影响需要在未来的随机临床试验或病例对照研究中进一步探讨。

CONCLUSION 结 论

MTA obturation is a viable alternative to the conventional filling materials currently used during retreatment procedures. In addition, extrusion of MTA does not adversely influence the outcomes of nonsurgical retreatment. However, indications for surgical treatment increase after retreatment when MTA obturation cannot reach the apical foramen.
MTA 封堵剂是目前再治疗过程中使用的传统填充材料的可行替代品。此外，MTA 的挤出不会对非手术再治疗的效果产生不利影响。但是，当 MTA 封堵材料无法到达根尖孔时，再治疗后手术治疗的适应症就会增加。

CREDIT AUTHORSHIP CONTRIBUTION STATEMENT
荣誉作者贡献声明

Yoshi Terauchi: Conceptualization,
寺内优概念化、
Resources, Investigation, Data curation,
资源、调查、数据整理、
Writing - review & editing. Kingsley Wong:
写作 - 审阅和编辑。Kingsley Wong：
Software, Formal analysis, Data presentation,
软件、形式分析、数据展示、

Writing - review & editing. Mahmoud
写作 - 审阅和编辑。马哈茂德

Torabinejad: Methodology, Validation, Writing - review & editing. George
托拉比内贾德方法论、验证、写作--审查和编辑。乔治
Bogen: Conceptualization, Writing - original draft, Visualization, Writing - review & editing.
博根构思、写作--原稿、可视化、写作--审阅和编辑。

ACKNOWLEDGMENTS 致谢

Dr. Terauchi is the named inventor of the Terauchi File Retrieval Kit and has patent licensing arrangements and is the recipient of royalties from the promotion and distribution of TRFK products through Guilin Woodpecker Medical Instrument Co. Ltd, Guangxi, China. Other authors deny any conflicts of interest related to this study.
寺内博士是寺内档案检索工具包的发明人，他通过桂林啄木鸟医疗器械有限公司获得专利许可，并从 TRFK 产品的推广和销售中获得版税。中国广西桂林啄木鸟医疗器械有限公司。其他作者否认与本研究有任何利益冲突。

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  1. n, number of teeth; MTA, Mineral Trioxide Aggregate; aRR, adjusted risk ratio; ref, reference category; , not applicable.
    n，牙齿数量；MTA，矿物三氧化物骨料；aRR，调整风险比；ref，参考类别； ，不适用。
    *The risk ratios were adjusted for other reported variables and covariates including age, sex and tooth type.
    *风险比已根据其他报告变量和协变量（包括年龄、性别和牙齿类型）进行调整。
    excluded canine teeth .
    排除犬齿 。