Survival Analysis and Other Clinical Outcomes of Immediate Implant Placement in Sites with Periapical Lesions: Systematic Review Chun-Teh Lee, DDS, MS1/Sung-Kiang Chuang, DMD, MD, DMSc2/Janet Stoupel, DMD, MS3 Purpose: Immediate implantation has become one of the therapeutic options for replacement of a hopeless tooth. In the case of a tooth with a periapical lesion, this approach remains controversial. The aims of this article were to systematically review the evidence on immediate implants in sites with periapical lesions with reference to: (1) survival rates, (2) changes in crestal bone levels and marginal tissues, (3) complication rates, and (4) comparison of clinical outcomes with other implant treatments. Materials and Methods: An electronic search was conducted in MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE for articles published between January 1990 and August 2013. Publications were screened, and data extraction and quality assessment were performed. Implant survival rates were calculated using predicted Kaplan-Meier survival analysis. Crestal bone level changes, soft tissue outcomes, complications, and procedure characteristics were analyzed descriptively. Results: Initially, 301 articles were identified. Three prospective controlled trials of immediate implant placement in sites with periapical lesions with a follow-up period of at least 1 year were selected for the survival analysis. The predicted cumulative 5-year survival rate of immediate implants in sites with periapical lesions was 96.23%. Bone and gingival level changes were comparable to those of implants placed in sites without periapical pathology. The complication rates, reported in only one study, were 15.4% (2/13) in sites with periapical lesions and 6.7% (1/15) in healthy sites. Conclusion: Limited evidence suggests that immediate implant placement in sites with periapical lesions leads to clinical outcomes comparable to those of immediate implants in healthy sites. Additional prospective controlled trials with large sample sizes and long-term follow-up are needed to further investigate these results. Int J Oral Maxillofac Implants 2015;30:268–278. doi: 10.11607/jomi.3619 Key words: dental implants, evidence-based dentistry, oral pathology

T

he concept of immediate implant placement was introduced by Schulte and Heimke in 1976.1 The earliest clinical studies of this approach were published in English about 25 years ago.2,3 Several studies have demonstrated similar survival and success rates for immediate and delayed implant placement.4,5

1Postdoctoral

Research Fellow, Division of Periodontology, Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA. 2 Associate Professor, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital and Harvard School of Dental Medicine, Boston, Massachusetts, USA. 3Assistant Clinical Professor, Division of Periodontics, Section of Oral and Diagnostic Sciences, College of Dental Medicine, Columbia University, New York, New York, USA. Correspondence to: Dr Chun-Teh Lee, Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston MA 02115, USA. Fax: +617-432-1897. Email: [email protected] ©2015 by Quintessence Publishing Co Inc.

Examination of peri-implant histology confirms similar healing patterns for immediate and delayed implants.6 In many clinical situations, an implant may be placed immediately to replace an unrestorable tooth with a periapical lesion. However, the outcomes of immediate implants placed in sockets with periapical lesions have been addressed in only a few prospective trials.7 The question thus arises: to what extent does the presence of a periapical lesion alter decision-making in the surgical protocol of immediate implant placement, and how does it affect the clinical outcomes? The diagnostic term for a periapical lesion of a tooth is “apical periodontitis,” according to the American Association of Endodontists consensus recommendation8 (Appendix 1). From a mechanical point of view, stabilization of the immediate implant in a site with a periapical lesion may present challenges beyond the usual considerations associated with immediate or delayed implantation. For example, osseous fenestrations may be present in sites with periapical lesions.9–11 The use of a wider or longer implant may be considered, in addition to

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alterations in placement direction or underpreparation of the socket osteotomy, to achieve primary stability of the implant. Regenerative materials may or may not be utilized. These adjustments in turn may influence hard and soft tissue healing, as compared to other implant treatments. In addition, the bacterial status of the periapical lesion has to be further elucidated. While some studies have described the lesion solely as an inflammatory response to a bacterial niche in the necrotic root canal, others have reported the presence of bacterial pathogens in the periapical lesion itself.12–14 If the latter is true, then periapical infection of the surgical site may present an additional risk factor for the survival and success of the immediate implant. Several studies have investigated the outcomes of immediate implant placement in “infected sites,” a term that is used inclusively for sites with periodontal, periapical, or combined lesions.15–19 However, periodontal and periapical infections are defined by different histopathologic mechanisms,14,20 and a diagnosis of one or the other implies different choices in the timing of implant placement. In the present review, the discussion is limited to periapical lesions of solely endodontic etiology. Previous reviews of this topic either did not focus on immediate implant placement in “periapical infected sites” primarily7,21 or did not provide complete discussion of clinical results and procedure characteristics of prospective trials.22 Moreover, these reviews have included case reports, case series, retrospective studies, and animal studies, with varied study quality controls and varied definitions of “infected sites.” The aim of this systematic review was to analyze the clinical outcomes, including survival rates, bone level changes, marginal gingival changes, and complications, in prospective clinical trials of immediate implant placement in sites demonstrating periapical pathology. The procedures of these selected studies were also discussed in the descriptive review.

MATERIALS AND METHODS This systematic review was performed according to previously outlined recommendations23 and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) principles.24

Focused Question

The focused question was proposed by following the PICO (Problem, Intervention, Comparison, Outcome) principle. “What are the survival rate and other clinical outcomes, such as the changes in the bone level, soft tissue margin, and complication rate, of immediate

Articles identified after search of databases and journals n = 301

Articles identified after review of titles and abstracts (n = 25)

Articles eligible for data analysis (n = 5)

Exclusion of articles with unrelated titles and abstracts Eligibility evaluated in detail: • Prospective randomized or nonrandomized controlled clinical design • Clear definition of inclusion and exclusion criteria in surgical sites • Immediate implant placement in sites with periapical lesions as primary investigation goal • Complete information on primary clinical outcomes • At least 1 year of follow-up Articles excluded; same cohort reported (n = 2)

Articles included in the final data analysis (n = 3) Fig 1   Search strategy.

implant placement in sites with periapical lesions? Are these outcomes comparable to those of immediate implant placement in healthy sites or delayed implant placement?”

Search Strategy and Selection Criteria

A search was conducted in the PubMed (MEDLINE), EMBASE, and Cochrane library databases for articles published between January 1990 and August 2013 by using different combinations of specific terms. The detailed search method in PubMed is described in Appendix 2. In addition to the database search, a hand search was performed of the following journals: Clinical Implant Dentistry and Related Research, Journal of Periodontology, Journal of Clinical Periodontology, International Journal of Periodontics & Restorative Dentistry, Clinical Oral Implants Research, International Journal of Oral & Maxillofacial Implants, Journal of Oral Implantology, Journal of Prosthetic Dentistry, International Journal of Prosthodontics, and Journal of Prosthodontics. Finally, the reference lists of identified articles were searched to identify any additional relevant publications. The International Journal of Oral & Maxillofacial Implants 269

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Table 1  Summary of Study Characteristics Study

Study design and no. of implants

GBR

Followup

Loading time

Surgical sites

Insertion torque

Implant type

Lindeboom et al46

Randomized controlled trial; 25 immediate/ infected sites, 25 delayed/infected sites

Autogenous bone and collagen membrane

1y

6 mo after surgery

Maxillary anterior teeth and premolars (asymptomatic)

> 25 N/cm

Frialit-2 Synchro

Crespi et al47

Prospective controlled trial; 15 immediate/ infected sites, 15 immediate/healthy sites

Not performed

2y

3 mo after surgery

Anterior teeth and premolars (asymptomatic)

> 25 N/cm

Seven, TPS

Jung et al45 (Truninger et al,44 Siegenthaler et al43)

Prospective controlled trial; 17 immediate/ infected sites (4 subjects dropped out before implant placement and one subject missed 5-y exam); 17 immediate/ healthy sites (1 subject dropped out before implant placement and 1 subject missed 5-y exam)

Bovine bone and collagen membrane

5y

3 mo after surgery

Anterior teeth and premolars (symptomatic cases included: pain, suppuration, fistula)

NA

Straumann

GBR = guided bone regeneration; TPS = titanium plasma spray.

Chosen studies had to feature the following: 1. A prospective‑ randomized or nonrandomized controlled clinical design to examine immediate implant placement in sites with periapical lesions 2. Detailed information of inclusion and exclusion criteria, especially the criteria for surgical site selection 3. Clinical outcomes of immediate implant placement in sites with periapical lesions as primary investigation goal, and complete information on survival rates 4. A follow-up period of at least 1 year Excluded from all analyses were articles not in English, animal experiments, and retrospective studies (including case reports or case series), and studies that did not have at least one comparative group in addition to the group of immediate implant placement in sites with periapical lesions.

Quality Assessment

All the studies included in this review were evaluated by the Cochrane Collaboration’s tool for risk bias assessment.25 The tool was designed for the assessment of the quality of randomized trials and has been modified to assess nonrandomized clinical trials.26,27 Studies were judged to have a low or high risk of bias for different assessment items. A designation of “unclear” was given when information was not reported clearly. Agreement on quality assessment was reached though discussion between two authors (CL, JS), and the interexaminer agreement was analyzed by kappa coefficient.

Data Extraction

The following data were extracted from the studies included in this systematic review: survival rate of implants, bone level changes, gingival level changes, and complication rates. All data were extracted by two authors (CL, JS) with a specially designed form and confirmed by a third author (SC).

Data Analysis

The primary outcome of the study was the implant survival rate following immediate placement in sites with periapical lesions. The periapical lesion at the apex of the tooth to be replaced with an implant in these studies fell under the definition of “apical periodontitis” according to the American Association of Endodontists consensus. Crestal bone level changes, gingival level changes, and complication rates were examined as secondary outcomes. Because there were small sample sizes, a low number of selected studies, few or no failure events, and/ or incompletely reported secondary outcomes, it was not possible to perform a meta-analysis with forest plots to compare the outcomes of immediate implant placement in sites with periapical lesions with those of other groups. Therefore, the information regarding the survival data points from the selected studies was extracted for Kaplan-Meier survival analysis, and log-rank tests were subsequently performed to predict the 1-year and 5-year cumulative survival rates of different groups.28,29 An available statistical software package (SAS v. 9.3) was utilized for analyses. A P value ≤ .05 was considered statistically significant. A

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Table 2  Assessment of Risk of Bias of Included Studies Lindeboom et al46

Crespi et al47

Jung et al45

Random sequence generation

Low risk

NA

NA

Allocation concealment

Low risk

NA

NA

Blinding of patients and surgeons

NA

NA

NA

Blinding of outcome assessment

High risk

High risk

High risk

Incomplete outcome data, selective reporting

Low risk

Low risk

Low risk

Group imbalance

High risk

Low risk

Low risk

Sample size

High risk

High risk

High risk

Follow-up time

High risk

High risk

Low risk

Radiographic outcome

High risk

Low risk

Low risk

Clinician bias

Unclear

Low risk

Low risk

Source of potential bias

Other sources of bias

Random sequencing generation, allocation concealment, blinding of patients and surgeons: Only Lindeboom et al performed randomization for group assignment. The randomization was performed by computer software. Surgeon blinding was logistically impossible in these studies, so this assessment item was not performed. Blinding of outcome assessment: No study mentioned recruiting an independent examiner for clinical outcome evaluation without prior familiarity with the characteristics of the surgical sites. Incomplete outcome data and selective reporting: No evidence of either was reported in any of the studies. Group imbalance: Lindeboom et al utilized more wide implants in the test group than in the delayed placement group. The other two studies had homogenous implant size and length distribution between test and control groups. Sample size: No information was given in any of the studies for the recruitment of the specific sample size. Follow-up time: Only Jung et al provided a 5-year follow-up and was considered a long-term follow-up study with a low risk of bias.45 Radiographic outcome: Lindeboom et al did not utilize customized image-taking devices. The other two studies had individualized devices to standardize radiographic images. Clinician bias: The same clinician performed all surgeries in Crespi et al and Jung et al. No information regarding the number of surgeons was given in Lindeboom et al.

descriptive analysis was performed to evaluate crestal bone levels, gingival levels, and complication rates because of the inability to conduct a meta-analysis.

RESULTS The search strategy is illustrated in Fig 1. Three hundred one articles containing the aforementioned search terms were initially identified (conducted by CL). Following review of the titles and abstracts, 25 articles were considered relevant to immediate implant placement in sites with periapical lesions. Studies were excluded for various reasons: two were animal studies30,31; several did not have the correct study design (retrospective studies,32–34 case reports,35–37 case series,19,38–40 no comparison group,17 review articles7,21,22); and four combined their analyses of surgical sites with periapical and periodontal lesions.15,16,41,42 Five studies met all the selection criteria for this systematic review (Fig 1). Three of the five articles were the same study at three incremental follow-up periods,43–45 so the one

with the longest follow-up period was selected for survival analysis.45 Finally, three studies were selected that included complete information on survival rates and changes in crestal bone and gingival levels: one randomized clinical trial with 1 year of follow-up46 and two prospective controlled clinical trials45,47 with 2 and 5 years of follow-up. Jung et al45 did not mention complications; therefore, Siegenthaler et al43 was selected for the descriptive analysis of complications. All articles were included with agreement of the three authors (CL, SC, JS). The characteristics of each study are summarized in Table 1.

Risk of Bias

The quality assessment of the three studies is summarized in Table 2.48 The kappa coefficient between the two authors (CL, JS) was 0.93. Some assessment items were specified for randomized trial, so they were not available for the two nonrandomized controlled trials. Three of nine assessment items were judged as “low risk” in Lindeboom et al.46 Four or five of seven evaluation items were considered “low risk” in Crespi et al47 and Jung et al,45 respectively. The International Journal of Oral & Maxillofacial Implants 271

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Table 3  Comparison of Predicted Cumulative Survival Rate (CSRs) Compared by Log-Rank Test 1-year CSR (%)

5-year CSR (%)

P*

A: Immediate implant placement in sites with periapical lesions

96.23

96.23

.1442 (A vs B and C)

B: Immediate implant placement in healthy sites

97.44

97.44

.3704 (B vs A and C)

C: Delayed implant placement in sites with periapical lesions

97.62

97.62

.4382 (C vs A and B)

Group

*The P value was calculated by comparison using the log-rank test in different groups; each group was compared to the other two groups, respectively.

Characteristics of Cases and Study Design

Only Jung et al45 included teeth with acute clinical symptoms (10/17 cases) in a group of immediate implants in periapical infected sites: pain, suppuration, fistulas, or a combination of these.45 These clinically symptomatic cases were not analyzed separately from the asymptomatic cases. The rest of the selected studies recruited only asymptomatic cases for their test groups (immediate implant placement in sites with periapical lesions), and diagnosis was based on radiographic periapical radiolucency. The main purpose of the Lindeboom et al study46 was to compare the outcomes of implants placed in sites with periapical lesions at two points in time: immediately following extraction and debridement versus delayed implant placement. The stated aims of the other two articles45,47 were to evaluate immediate implant placement in sites with periapical pathology and to compare them to immediate implant placement in healthy sites. However, these studies were not randomized clinical trials, since the condition of the surgical sites did not lend itself to randomization.

Survival Rates

Lindeboom et al demonstrated a 92% (23/25) survival rate for immediate implants in sites with periapical lesions.46 Crespi et al47 and Jung et al45 showed a 100% survival rate at 2 years (15/15) and at 5 years (12/12), respectively. In Jung et al, four subjects in the test group and one in the control group were excluded from analyses because of a lack of primary stability. The 1-year predicted cumulative survival rates were 96.23%, 97.44%, and 97.62% for immediate implants in sites with periapical lesions, immediate implants in healthy sites, and delayed implants in sites with periapical lesions, respectively. The 5-year predicted cumulative survival rate was not different from the 1-year survival rate. There was no statistically significant difference between these three groups (Table 3).

Interproximal Crestal Bone Levels

Average crestal bone level loss in the groups observed in Lindeboom et al46 and Crespi et al47 was 0.0 to 0.5 mm between baseline (time of surgery) and the end of follow-up period, which was 1 or 2 years, respectively (Table 4). The cohort reported in Siegenthaler et al43 and Jung et al45 demonstrated 1.5 to 2.0 mm of crestal bone loss during the first year, followed by changes within 0.3 mm up to the fifth year of follow-up (Table 4).

Gingival Levels

In Crespi et al,47 the mean gingival level changes at four sites (buccal, mesial, distal, palatal) were less than 0.1 mm from baseline (time of surgery) to 2 years postoperatively (Table 4). Gingival level changes were no more than 0.2 mm in different sites from 3 months (definitive crown delivery) to 5 years in Jung et al45 (Table 4). Lindeboom et al46 reported only on buccal gingival level relative to adjacent teeth and papilla score49 during 1 year of follow-up, without reporting absolute gingival level change (Table 4). In the group of immediate implants in sites with periapical lesions, 61% (14/21) of cases had the same gingival level as adjacent teeth at 1 year and 78% (18/23) of cases had a papilla score of 3 (complete fill of the interproximal space).48 In the delayed implant placement group, 84% (21/25) of cases had the same gingival level as adjacent teeth, and 72% (18/25) of cases had a papilla score of 3.

Complications

Only one study reported complications (suppuration) between implant placement and definitive crown delivery.43 The complication rates were 15.4% (2/13) and 6.7% (1/15) in sites with periapical lesions and in healthy sites, respectively. These results are summarized in Table 4.

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Table 4  Summary of Extracted Data Study

Survival rate

Bone level change

Gingival level

Complication rate

Lindeboom et al46

Delayed (D): 25/25 Infected (I): 23/25

Baseline to 1 y: Mesial: D, 0.52 ± 0.16 mm; I, 0.49 ± 0.11 mm Distal: D, 0.52 ±0.14 mm; I, 0.53 ± 0.12 mm

No. of cases with the same buccal gingival margin as adjacent teeth at 1 y: D, 21/25; I, 14/25 Papilla scores: D: score 3, 18/23; score 2, 5/23 I: score 3, 18/25; score 2, 7/25

NA

Crespi et al47

Healthy (H): 15/15 Infected (I): 15/15

Baseline to 2 y: Mesial: H, 0.18 mm; I, 0.17 mm Distal: H, 0.16 mm; I, 0.16 mm

Marginal gingival level change (baseline to 2 y, mean of four sites): H, 0.07 mm; I, 0.05 mm

NA

Jung et al45 (Truninger et al44 Siegenthaler et al43)

Healthy (H): 15/15 Infected (I): 12/12

1 y to 5 y: Mesial: H, –0.1 mm; I, 0.2 mm Distal: H, 0.2 mm; I, –0.3 mm

Gingival level change (3 mo to 5 y): Mesial: H, 0 mm; I, 0.2 mm Buccal: H, –0.1 mm; I, 0.1 mm Distal: H, –0.1 mm; I, 0.2 mm

Suppuration during healing after surgery: 1/15 H, 2/13 I

A negative number indicates a gain in bone or gingival level. Papilla scores49: Score 2 = at least one-half of the height interproximal space is filled; score 3 = complete closure of the interproximal space. Lindeboom et al46: D = delayed implant placement in sites with periapical lesions; I = immediate implant placement in sites with periapical lesions. Crespi et al47 and Jung et al45: H = immediate implant placement in healthy sites; I = immediate implant placement in sites with periapical lesions.

DISCUSSION Implant Survival

The predicted cumulative survival rates of the present review are comparable to survival rates of other studies or reviews with long-term follow-up (≥ 5 years) after delayed implant placement48,50,51 and to estimated survival rates after immediate implant placement (2-year survival rate of 98.4%).52 Moreover, the predicted cumulative survival rates for immediate implants placed in sites with periapical lesions, immediate implants placed in healthy sites, and delayed implant placement in sites with periapical lesions were not statistically different. This highlights the similar clinical feasibility of the three procedures. All of the surviving implants in the selected studies also complied with the International Congress of Oral Implantologists’ criteria for success.53 However, because of the small number of selected studies, more controlled clinical trials need to be conducted.

Crestal Bone Response

Laurell and Lundgren54 demonstrated 0 to 1.0 mm of bone level change around implants placed in healed sites, measured at loading and up to 5 years afterward. Lang et al,52 in a systematic review of immediate implants, confirmed that the crestal bone loss around immediate implants was within 0.2 mm after the first year of service during at least 3 years of follow-up, fulfilling one of the classic criteria for success outlined

by Albrektsson et al.55 Crestal bone changes reported in the studies included in the present review were within the minimal changes expected from previous reports and were not significantly different between implants placed in sites with periapical lesions and those placed in healthy sockets.

Soft Tissue Response

Lindeboom et al46 demonstrated less favorable buccal gingival levels after immediate implantation in sites with periapical lesions than buccal gingival levels after delayed implantation in sites with periapical lesions. These differences in gingival level changes may be affected by different marginal tissue remodeling rates and different handling of the soft tissue flap, especially if primary closure is desired after immediate procedures. However, no data on baseline gingival measurements were reported, making interpretation difficult. On the other hand, in two studies that compared immediate implants in sites with periapical lesions and those in healthy sockets,45,47 the changes in the position of the midbuccal or interproximal gingival margins were minimal and similar, although only Jung et al45 performed a statistical comparison (no significant difference). Based on the results of other studies, a limited amount of midbuccal gingival change is usually expected in immediate implant placement.56 In a longterm prospective study, the buccal gingival level The International Journal of Oral & Maxillofacial Implants 273

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change around immediate implants during 2 to 8 years of follow-up (mean, 4 years) was 1.13 ± 0.87 mm.57 A limited change (usually less than 1 mm) in the midbuccal margin position following immediate implant placement during 1 to 3 years of follow-up was described in a systematic review.56 The same study also reported stable interproximal gingival levels (mean recession of less than 0.5 mm). In general, the soft tissue changes after immediate implantation in sites with periapical lesions were comparable to those seen after other immediate implant treatments.

Clinical Complications

Siegenthaler et al43 reported a limited number of complications during the period between implant placement and definitive restoration. The other two studies included in this review did not report any biologic complications. In addition to common biologic complications, such as peri-implant mucositis, peri-implantitis, suppuration, and other symptoms of infection, retrograde peri-implantitis may be of particular concern when implants are placed in sites with a history of endodontic infection.58 Lefever et al,59 in a retrospective study, demonstrated that a history of periapical lesions or root canal therapy was associated with 13.6% and 8.2%, respectively, of a total of 59 cases of retrograde peri-implantitis. However, interpretation of the results should be guarded, because extraction and debridement of the socket of the involved teeth were not standardized or described in the study. In the present review, there were no reports of retrograde peri-implantitis in the selected studies.

Implant Placement Protocol in Sites with Periapical Lesions

Immediate implant placement in sites with periapical lesions is supported by the present limited evidence. However, the question arises whether the procedural protocol of this therapy should be modified from the usual and accepted protocols for other implant placement approaches. The procedural characteristics of the three studies included in this review were examined within the context of the available evidence on the respective topic. Prophylactic Antibiotics. All three studies included in this review introduced prophylactic antibiotics, regardless of the presence or absence of clinical symptoms of infection. However, the antibiotic regimens were different in each study: one prophylactic dose of clindamycin 600 mg 1 hour before surgery and no postoperative antibiotics,46 Clamoxyl 750 mg 1 hour before surgery and continued three times a day for 5 days postoperatively,45 and amoxicillin 1 g 1 hour before surgery and twice a day for 1 week postoperatively.47

Only the study of Jung et al45 included patients with clinical symptoms, in conjunction with the periapical lesions of the teeth to be replaced with immediate implants. From a biologic point of view, a high concentration of antibiotics systemically during the procedure may reduce the likelihood of bacteremia and postoperative infection. However, studies that examined antibiotic prophylaxis prior to periodontal, endodontic, or implant treatments have not unequivocally demonstrated an advantage of this approach in terms of a significant reduction of postoperative infections or more favorable long-term outcomes.60–62 Lang et al52 demonstrated the lowest failure rate after immediate implant therapy with postoperative antibiotics (0.51%), as compared to prophylactic antibiotics only (1.87%) or a combination of prophylactic and postoperative antibiotics (0.51%). However, the number of implants included in the group with the prophylactic regimen was significantly lower than those in the other two groups. On the other hand, Esposito et al63 suggested that 2 g of amoxicillin given orally 1 hour preoperatively significantly reduced failures associated with delayed implant placement (relative risk = 0.40). One of the selected studies46 included in the present review employed a live culture method to assess the bacterial profiles of the periapical lesions. However, the method of bacterial harvesting utilized in this study might carry an inherent risk of sample contamination.14 In addition, the study did not address quantitative species representation in the sample, making the presence of pathogens in the sample difficult to interpret, since low counts of pathogens may be indigenous to a clinically healthy oral environment.64 Controversy exists regarding the persistence of endodontic bacterial colonization in periapical lesions after the infected tooth is removed, or, for that matter, whether it is present beyond the confines of the infected root prior to the extraction.14 Moreover, no single species is considered to play a dominant role in endodontic infection, making antibiotic selection empirical.13 Although prophylactic antibiotics were given in most studies of immediate implant placement in sites with periapical lesions,7 including the three clinical trials reviewed here, a specific protocol for an antibiotic regimen cannot be recommended based on the limited evidence that is currently available. Socket Curettage and Irrigation. Meticulous debridement of the periapical lesion was emphasized in all three studies included in the present review. A pathologic change in tissue is anticipated in a socket with a periapical lesion. Several articles65–67 demonstrated that 70% to 90% of sites with periapical radiolucency had a histologic diagnosis of dental granuloma

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or cyst. Prior to placing an implant into an extraction socket with a periapical lesion, any inflammatory periapical soft tissue should be debrided to allow blood clot formation around the implant, which in turn will lead to angiogenesis, fibrogenesis, and finally osteogenesis in the site.68,69 In two of the three studies included in this review,45,47 irrigation was performed following extraction and debridement. There is limited evidence regarding any clinical benefit of supplementing mechanical debridement with topical antimicrobials or irrigation. Irrigation of the extraction socket may have an adverse effect on the formation of blood clot and healing of the socket.70 The infected pulp tissue itself is considered the niche for endodontic pathogens, and the periapical lesion is the inflammatory response to the infected intraradicular tissue. A high success rate, close to 80%, of nonsurgical endodontic retreatment of teeth with periapical lesions has supported this concept,71–73 and cases of failure are rarely caused by residual extraradicular microflora.14 Also, bacterial species have been found only rarely in periapical lesions under microscopic observation.12,74–76 Several studies demonstrated microbial presence in the periapical lesion by culture or molecular techniques. However, unintentional sample contamination cannot be ruled out; plus, mere detection of the pathogens does not confirm a causal effect between the infection and the extraradicular pathogens. Therefore, meticulous degranulation may be critical in immediate implant placement in sites with periapical lesions, although the clinical advantage of antimicrobial irrigation is debatable. Attainment of Primary Stability. One of the main requirements for success of immediate implants is primary stability. The osseous structure apical or lateral to the socket should be sufficient for implant stabilization.77 In cases of immediate implants in sites with periapical pathology, primary stability may be more challenging, since the lesion is accompanied with the loss of bony structure. Siegenthaler et al43 observed that four times as many immediate implants in sites with periapical pathology lost primary stability during surgery, compared to immediate implants in intact periapical sites (four cases vs one case). A larger armamentarium in implant choices may be needed when planning immediate implants with periapical pathology, as demonstrated by Lindeboom et al,46 who used a higher proportion of wider or longer implants in the test group (44% > 5-mm-diameter implants used for 11 of 25 implants) than for the delayed implants in the control group (24% > 5-mm-diameter implants used for 6 of 25 implants). Use of Graft/Barrier for Periapical Fenestration. Fenestration of the cortical bone in the area of periapical pathology is a common finding. Cone beam

computed tomography showed that 67% (356/523 cases) of endodontically treated teeth with periapical lesions and radiolucency had buccal bony defects.78 Jung et al and Lindeboom et al45,46 utilized grafts and barriers to fill the bone-implant gap and sites with dehiscence or fenestration. Crespi et al47 did not utilize regenerative materials, since all sockets in that study had intact bony walls. In cases with fenestration accompanying a periapical lesion, consideration must be given to the extent of cortical bone loss and the position of the implant in relation to the fenestration. One potential complication of the healing in such a defect is repopulation of the lesion with soft tissue, precluding bone formation in the site. One animal study of immediate implant placement in sites with periapical lesions demonstrated that the use of a barrier over the fenestration could increase the bone-to-implant contact percentage,31 but all implants, with or without a barrier over the apical fenestration, achieved adequate primary stability and met the criteria for clinical success. On the other hand, Garrett et al79 and Bernabe et al80 demonstrated no difference in radiographic or histologic outcomes of healing with or without guided bone regeneration following periapical surgery in animal and human studies. It is interesting to note that, in an experimental study,65 the periosteum was left intact. Therefore, the periosteum may function as a natural barrier and source of osteogenic cells in these cases,81 provided that fenestrations have been induced artificially. In case of a naturally occurring fenestration secondary to a periapical lesion, the periosteum is no longer present, and wound healing of such a site may necessitate the use of an artificial barrier to ensure predictable bone formation.82 More specific and long-term studies are needed to elucidate the wound-healing pathways in periapical lesions in conjunction with implant placement and the role of regenerative materials in these instances.83

Limitations

Because of the small number of selected studies and insufficient data regarding the clinical outcomes, a meta-analysis could not be conducted in the present review. Additional controlled clinical trials reporting clinical outcomes during long-term follow-up periods are needed to further elucidate the topics reviewed.

CONCLUSIONS Based on this review, the predicted cumulative survival rates at 1 and 5 years of this mode of therapy (96.23%) were similar to those of immediate implants placed into healthy sites (97.44%) and to those of delayed implants placed into previously periapically infected The International Journal of Oral & Maxillofacial Implants 275

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sites (97.62%) (P > .05). In addition, the success parameters assessed in this review—namely, buccal soft tissue levels and interproximal soft tissue levels, as well as crestal bone changes following implant placement—were similar for immediate implants placed into periapical lesions and into healthy sites. Therefore, immediate implant placement in sites with periapical lesions carries clinical outcomes comparable to those of other implant treatments, based on the present limited evidence.

ACKNOWLEDGMENTS The authors would like to express their appreciation to Dr Gunnar Hasselgren, Professor of Clinical Dentistry, Division of Endodontics, College of Dental Medicine, Columbia University, for his valuable and constructive guidance in writing this review. The authors reported no conflicts of interest related to this study.

APPENDIX 1 A tooth with apical pathology may be diagnosed clinically as one of the following8: symptomatic apical periodontitis, asymptomatic apical periodontitis, acute apical abscess, or chronic apical abscess. Symptomatic apical periodontitis is characterized by a painful response to percussion, biting, or palpation with or without apical radiolucency. Asymptomatic apical periodontitis is characterized by apical radiolucency without any clinical symptoms. When pulpal infection leads to an inflammatory reaction causing significant symptoms such as spontaneous pain, tenderness of the tooth to pressure, suppuration, and swelling of associated tissues with rapid onset, the diagnosis is acute apical abscess. When the onset o f symptoms is gradual with little or no discomfort, but accompanied with intermittent discharge of suppuration through an associated sinus tract, it is diagnosed as chronic apical abscess.

APPENDIX 2 The detailed search method in PubMed: immediate implant*[TW] OR ((implant placement*[TW] OR implant installation*[TW]) AND immedia*[TW]) OR fresh socket*[TW] OR extraction socket*[TW] OR (implant*[TW] AND (placed immediately[TW] OR immediately placed[TW] OR immediate placement*[TW] OR installed immediately[TW] OR immediately install*[TW]))AND(periapical [TW] OR lesion*[TW] OR infec*[TW])AND(survival [TW] OR success [TW] OR bone[TW] OR gingiva*[TW]) TW= Text Words; it includes all words and numbers in the title, abstract, other abstract, MeSH terms, MeSH subheadings, publication types, substance names, personal name as subject, corporate author, secondary source, comment/correction notes, and other terms. MH= MeSH terms.

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