Identification of keystone taxa in root canals and periapical lesions of post-treatment endodontic infections: Next generation microbiome research.

AIM: The aim of this study was to analyse and compare the microbiome present in root canals and periapical lesions of teeth with post-treatment infections, and to identify the presence of keystone taxa in both habitats using next-generation sequencing analysis. METHODOLOGY: Apices and periapical lesions of patients with post-treatment apical periodontitis were surgically extracted. Specimens were cryo-pulverized, bacterial DNA was extracted, and the V3-V4 hypervariable regions of the 16S rRNA gene were sequenced using the Illumina Miseq platform. Bioinformatic analysis was carried out with Mothur software, whilst diversity indices were obtained using operational taxonomic units (OTUs). The diversity indices were compared with the Kruskal-Wallis test, and community composition differences were explored with Permutational Multivariate Analysis of Variance (PERMANOVA). A bacterial functional study was performed with the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis. Co-occurrence network analyses were performed using the Sparse Correlations for Compositional data (SparCC). Eigencentrality, clr-based abundance and ubiquitousness were applied to infer keystone taxa. P values <.05 were considered statistically significant. RESULTS: Thirty-two apices and thirty-nine periapical lesions were sequenced and analysed. A similar alpha-diversity (p < .05) and community composition (p = .91) was observed for apices and lesion samples. The most abundant OTUs identified amongst all samples included Fusobacterium nucleatum, Prevotella loescheii, Streptococcus intermedius, Porphyromonas gingivalis, Parvimonas micra, Synergistetes bacterium, Tannerella forsythia and Peptostreptococcus stomatis. The metabolic pathways with >0.81% abundances included membrane transport, genetic information processing and metabolic pathways. F. nucleatum was identified as a keystone taxon as it showed ubiquitousness, an eigenvector centrality value of 0.83 and a clr-based abundance >4. CONCLUSIONS: The microbiome in apices and periapical lesions of post-treatment endodontic infections showed a similar diversity and taxonomic composition. Co-occurrence network analyses at OTU level identified F. nucleatum as a keystone taxon candidate in these infections.

Outcome of nonsurgical management of large cyst-like periapical lesions using a modified apical negative pressure irrigation system: a case series study.

OBJECTIVE: To assess the effectiveness of a self-constructed modified apical negative pressure irrigation (ANPI) system employing commonly used clinical instruments in nonsurgical root canal therapy (NSRCT) for large cyst-like periapical lesions (LCPLs). METHODS: From 2017 to 2022, 35 patients diagnosed with LCPLs (5-15 mm) via preoperative clinical and radiographic evaluations of endodontic origin underwent NSRCT combined with ANPI. These patients were subjected to postoperative clinical and radiographic follow-up at 3 months, 6 months, 1 year, 2 years, 3 years, and 4 years, with a CBCT scan specifically conducted at 6-month follow-up. Through the reconstruction of three-dimensional cone beam computed tomography (CBCT) data, an early prognosis was facilitated by monitoring changes in lesion volume. Various treatment predictors-including sex, type of treatment, lesion size, preoperative pain, jaw, type of teeth involved, sealer extrusion, and the number of root canals-were meticulously analyzed. The evaluation of post-treatment outcomes leveraged both clinical observations and radiographic data collected during the follow-up periods. The Kruskal‒Wallis test and one-way ANOVA were also conducted to determine the independent factors influencing treatment outcomes. A significance level of 5% was established. RESULTS: Thirty-five teeth from 35 patients with a median age of 28 years (range 24-34) were treated; the median follow-up duration was 19 months (range 12-26). The overall success rate was 91.4%, with a median lesion reduction of 77.0% (range 54.2-96.4%) at 6 months. Patients under 30 years of age exhibited a significantly greater success rate than older patients did (100.0% vs. 80.0%, p = 0.037). Other factors, such as sex, jaw, treatment type, preoperative pain, cyst size, tooth location, sealer extrusion, and the number of roots, did not significantly impact treatment outcomes. CONCLUSIONS: Despite limitations related to the observational case-series study design and relatively small sample size, our findings suggest that utilizing the ANPI in the NSRCT for LCPLs may hold promise. The notably higher success rate in patients younger than 30 years is worth noting.

The roles of stress-induced premature senescence and Akt/FoxO1 signaling in periapical lesions.

OBJECTIVES: There is little knowledge about oxidative stress-induced senescence involvement in apical periodontitis. Here, we explored its molecular mechanism in periapical lesions. METHODS: Ten cases of radicular cysts and five cases of periapical granulomas were randomly selected. Immunohistochemical analysis was performed to detect the expression and correlation between Senescence-associated factor polymerase I and transcript release factor (PTRF) and Akt/FoxO1 signaling. Human periodontal ligament cells (hPDLCs) pretreated with LY294002 were exposed to H2 O2 -induced oxidative stress conditions and then cell proliferation, senescence, apoptosis, and associated signaling were evaluated by EdU labeling, ß-galactosidase assay, RT-qPCR, and western blot analysis, respectively. RESULTS: Polymerase I and transcript release factor and Akt/FoxO1 signaling were more frequently expressed in the radicular cyst than in periapical granulomas. Notably, cells in radicular cysts showed Akt activation, FoxO1 phosphorylation, and cytoplasmic translocation. In vitro, prominent H2 O2 -induced senescence was observed in hPDLCs. LY294002, a PI3K inhibitor, attenuated the expression levels of senescence (Klotho, P16INK4), apoptosis (Bad, Fas), phosphorylated Akt, and phosphorylated FoxO1; however, did not affect cell proliferation. CONCLUSIONS: Our data indicated that senescence is present in clinical periapical lesions, and Akt/FoxO1 signaling is involved in the H2 O2 -induced cellular senescence, which could serve as a potential therapeutic target.

Elevated Foxo3a and Fas-ligand expression in human periapical granulomas as a potential treatment target.

OBJECTIVE: Periapical granuloma is a common periodontitis type involving chronic inflammation; however, the efficacy of current therapies is limited. Its molecular pathogenesis also remains obscure. Forkhead box transcription factor class o3a (Foxo3a) and Fas-ligand (FasL) are associated with chronic inflammation. Therefore, in this study, we aimed to clarify the roles of Foxo3a and FasL in periapical granuloma pathophysiology. SUBJECTS AND METHODS: Periapical lesions were obtained from patients during endodontic surgery and tooth extraction; those diagnosed with periapical granulomas using haematoxylin and eosin staining were further analysed. Immunohistochemical analysis was performed for Foxo3a and FasL, and real-time polymerase chain reaction was performed for FOXO3A, FASL and interleukin (IL)-1ß. Healthy gingival tissues were also examined as controls. RESULTS: Neutrophils, lymphocytes and plasma cells in the periapical granulomas, but not healthy tissues, expressed Foxo3a. Dual-colour immunofluorescence imaging revealed Foxo3a and FasL co-expression in leukocytes. FOXO3A, FASL and IL-1ß mRNA levels in healthy gingival tissues were significantly lower than those in the periapical granulomas. Additionally, FOXO3A and IL-1ß expressions were negatively correlated. CONCLUSIONS: Phosphorylated Foxo3a may reduce IL-1ß release by inhibiting apoptosis through FasL in periapical periodontitis and prevent exacerbation. Thus, Foxo3a is a potential therapeutic agent for periapical periodontitis.

Microbiome in paired root apices and periapical lesions and its association with clinical signs in persistent apical periodontitis using next-generation sequencing.

AIM: To assess and compare the microbiome of paired root apices and periapical lesions from cases with failed endodontic treatment and to associate the microbiome and bacterial metabolic pathways in both sites with asymptomatic apical periodontitis (AAP) and symptomatic apical periodontitis (SAP), using next-generation sequencing (NGS). METHODOLOGY: Matched root apices and periapical lesions of patients with failed root canal treatments were surgically extracted. Specimens were cryopulverized, bacterial DNA was extracted and the V3-V4 hypervariable regions of the 16 S rRNA gene were amplified and sequenced using the Illumina Miseq platform. Diversity and community composition were studied in the paired samples, as well as in AAP and SAP cases. Diversity indices were compared in each case by means of the Wilcoxon matched-pairs signed rank and Mann-Whitney U tests. Differences in the community composition were explored with multivariate statistical analysis and Linear discriminant analysis Effect Size (LEfSe). Bacterial functional study was performed through the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis. RESULTS: Twenty-one paired apices and lesions were successfully sequenced and analysed, identifying a total of 21 phyla and 600 genera. A higher alpha-diversity was observed in the periapical lesions, although no global differences in the community composition between the two sites were found (p = .87), the most prevalent genera being Fusobacterium, Porphyromonas and Streptococcus. Prevotella, Clostridiales_vadinBB60_group, Bosea, Phreatobacter, Afipia and Xanthobacteriaceae_unclassified were enriched in SAP samples, while Pseudopropionibacterium, Campylobacter and Peptoniphilus were significantly more abundant in AAP cases (p < .05). Metabolic pathways involved in the amino acid metabolism or degradation and flagellum assembly were more abundant in SAP samples, whereas glucose metabolism-related pathways were associated with AAP. CONCLUSIONS: The bacterial community composition was similar in the apices and periapical lesions. The microbiome was different in AAP and SAP samples, gram-negative bacteria showing higher relative abundances in SAP cases. An association was observed between amino acid degradation and flagellum assembly pathways, and the development of tenderness to percussion or palpation.

Ex vivo study of IL-6 expression and function in immune cell subsets from human periapical lesions.

AIM: Even though IL-6 is a key inflammatory cytokine in periapical lesions (PLs), its function in stable periapical disease is unknown. Therefore, the aim of this study was to investigate the following: first, the ex vivo production of IL-6 by clinically different PLs; next, subsets of immune cells expressing IL-6 in PLs according to their inflammatory status and finally, modulatory effect of IL-6 on T-cell cytokine production in cell cultures. METHODOLOGY: Inflammatory cells were isolated from a total of 95 human PLs. Detection of IL-6+ cells within the myeloid and lymphoid populations was performed by multicolour flow cytometry. ELISA and FlowCytomix Microbeads Assay were used to measure cytokine levels in culture supernatants. To study the role of IL-6 in PLs, mononuclear cells (MNC) from symptomatic (Sy) or asymptomatic (Asy) PLs were treated with IL-6 or Tocilizumab, an IL-6R blocking antibody. The differences between groups were tested by unpaired t-test, Mann-Whitney or Friedman tests. RESULTS: The levels of IL-6 in PL MNC culture supernatants were significantly higher compared with total PL cells and PL granulocytes (p < .001). MNC from Sy PLs produced significantly higher levels of IL-6 than MNC from Asy PLs (p < .001). Flow cytometry analysis showed that NKT cells, CD8+ T cells and M2 macrophages (MØ), were dominant IL-6+ cells, in contrast to CD4+ T cells. However, CD8+ and CD4+ T cells contributed the most to IL-6 production. IL-6hi producing MNC cultures had higher levels of Th1 (IFN-γ), Th17 (IL-17A), Tfh (IL-21) and RANKL, whereas Th2 (IL-4) and Tregs cytokines (IL-10, TGF-ß) were lower compared with IL-6low -producing cultures. Exogenous IL-6 stimulated 17A, IL-21 and RANKL, independently of PL activation status, but decreased IFN-γ, IL-4 and IL-33 levels in IL-6hi -producing cultures. Tocilizumab increased IL-10 and TGF-ß in IL-6low -producing cultures. All differences were p < .05. CONCLUSIONS: Most immune cells from Sy PLs expressed higher levels of IL-6 compared with Asy PLs, which correlated with IL-6 production in culture. Analysis of cytokines suggested a dominant pro-inflammatory T-cell response and osteodestructive function of IL-6 in PLs judging by Th17/Tfh cell activation, Tregs inhibition and increased RANKL/OPG ratio. Excessive IL-6 production decreased Th1/Th2 responses.

Histone Demethylase Jmjd3 Regulates the Osteogenic Differentiation and Cytokine Expressions of Periodontal Ligament Cells.

Periodontal ligament (PDL) cells are critical for the bone remodeling process in periapical lesions since they can differentiate into osteoblasts and secrete osteoclastogenesis-promoting cytokines. Post-translational histone modifications including alterations of the methylation status of H3K27 are involved in cell differentiation and inflammatory reaction. The histone demethylase Jumonji domain-containing 3 (Jmjd3) specifically removes methylation of H3K27. We investigated whether Jmjd3 is involved in the osteogenic differentiation and secretion of PDL cells' inflammatory factors. Jmjd3 expression in periapical lesions was examined by immunostaining. Using siRNA specific for Jmjd3 or the specific Jmjd3 inhibitor GSK-J4, we determined Jmjd3's roles in osteogenic differentiation and cytokine production by real-time RT-PCR. The locations of Jmjd3 and NF-κB were analyzed by immunocytochemistry. Compared to healthy PDLs, the periapical lesion samples showed higher Jmjd3 expression. Treatment with GSK-J4 or Jmjd3 siRNA suppressed PDL cells' osteogenic differentiation by suppressing the expressions of bone-related genes (Runx2, Osterix, and osteocalcin) and mineralization. Jmjd3 knockdown decreased the expressions of cytokines (TNF-α, IL-1ß, and IL-6) induced by lipopolysaccharide extracted from Porphyromonas endodontalis (Pe-LPS). Pe-LPS induced the nuclear translocations of Jmjd3 and NF-κB; the latter was inhibited by GSK-J4 treatment. Jmjd3 appears to regulate PDL cells' osteogenic differentiation and proinflammatory cytokine expressions.

Microbial identification from traumatized immature permanent teeth with periapical lesions using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

BACKGROUND: This study aims at identifying the microbiota in traumatized immature permanent teeth with periapical lesions using Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). METHODS: The study included 16 immature maxillary central incisors with periapical lesions in 13 patients. Field decontamination and negative control samples were performed before and after access cavity preparation. Root canal samples were taken using sterile stainless-steel hand files following field decontamination. In-office inoculation and pure sub-cultures were performed. Bacterial isolates were prepared for MALDI-TOF MS (Bruker, Billerica, MA USA) analysis using the formic acid extraction method. A comparison of the prevalence of isolated microorganisms was done using a one-sample chi-square test. Comparisons between identified microbial species with the, cone beam computed tomography periapical index (CBCT PAI) scores and lesion volume were also conducted. The Chi-square test was applied to investigate the association between the categorical variables . RESULTS: Out of the forty isolates recovered from the 16 traumatized teeth included in the present study with the mean patients' age of 10.93 ± 1.77, 37 isolates were reliably identified by MALDI-TOF MS. Twelve teeth (62.5%) were polymicrobial. The recovered bacteria belonged to five phyla, 15 genera and 25 species. Firmicutes were the predominant phylum (P < 0.001) over Bacteroidetes, Proteobacteria, Actinobacteria and Fusobacteria. Gram positive bacteria were significantly more prevalent than Gram negative (p = 0.03). Facultative anaerobes were the most prevalent (P < 0.001) compared to the obligate anaerobes and the obligate aerobes. The latter were the least prevalent. Statistically, significant differences existed in the comparison between CBCT PAI scores according to bacterial gram staining. CONCLUSION: Traumatized immature permanent teeth with periapical lesions showed a significant predominance of Gram-positive facultative anaerobes. MALDI-TOF MS provided accurate identification of numerous viable endodontic microbes.

Bacteria and virulence factors in periapical lesions associated with teeth following primary and secondary root canal treatment.

AIM: This cross-sectional study aimed to investigate the microbial profile and to quantify the levels of endotoxins (LPS) and lipoteichoic acid (LTA) present in periapical lesions associated with root filled teeth and those that had received root canal retreatment. It also aimed to investigate the association between microorganisms and their virulence factors with clinical and radiographic features. METHODOLOGY: Patients with periapical lesions in teeth with post-treatment endodontic disease following primary root canal treatment (n = 19) and unsuccessful root canal retreatment (n = 13) were treatment planned for endodontic microsurgery, where the periapical lesions were collected. Clinical and radiographic data were also collected. For microbiological analysis, nested polymerase chain reaction was used to detect 17 bacterial species. Levels of LPS and LTA were determined using limulus amebocyte lysate and enzyme-linked immunosorbent assays, respectively. The Student t-test or Wilcoxon-Mann-Whitney tests were applied to compare the data on LPS and LTA with clinical and radiographic features. The associations between the clinical and radiographic features and the bacterial species were analysed using the Fisher's exact test. A significance level of 5% was adopted. RESULTS: Bacterial DNA, LPS and LTA were detected in all samples. Parvimonas micra was the most commonly detected species in all groups, followed by Enterococcus faecalis, Fusobacterium nucleatum and Porphyromonas endodontalis. The type of endodontic treatment, whether a primary root canal treatment or retreatment, was not associated with the presence of any bacterial species in periapical lesions. The levels of LPS and LTA in periapical lesions of root filled teeth were not significantly different from those that had been retreated. Associations between the levels of LPS and LTA with clinical signs and symptoms were found. No association was found between specific bacteria and clinical features. CONCLUSION: Periapical lesions associated with teeth after primary root canal treatment and retreatment had similar polymicrobial composition. The levels of LPS and LTA in periapical lesions associated with teeth after primary root canal treatment and retreatment were similar, and both were associated with the same symptomatology.

Blockade of fatty acid signalling inhibits lipopolysaccharide-induced macrophage recruitment and progression of apical periodontitis.

AIM: To examine the role of palmitic acid in lipopolysaccharide (LPS)-stimulated chemotaxis of macrophages and the potential contribution of saturated fatty acid in signalling during the pathogenesis of apical periodontitis. METHODOLOGY: J774, a mouse macrophage cell line, was used in the experiments. After treatment with LPS, proteolytic maturation of sterol regulatory element-binding protein-1c (SREBP-1c) and expression of fatty acid synthase (FASN) were examined by Western analysis. Levels of palmitic acid were measured by reverse phase-high performance liquid chromatography-mass spectrometry. Knockdown of SREBP-1c and FASN was accomplished by small interfering RNA technology. Secretion of CC-chemokine ligand 2 (CCL2) and cellular chemotaxis were assessed by enzyme-linked immunosorbent assay and transwell migration assay, respectively. Sulfo-N-succinimidyl oleate (SSO) treatment was used to inhibit fatty acid signalling in vitro and also in a rat model of apical periodontitis. All data were first subjected to Levene's test. In vitro data were then analysed using ANOVA followed by Tukey's multiple comparison test. Data from animal experiments were analysed by independent t-tests. The significant level was set at 0.05. RESULTS: LPS stimulated proteolytic maturation of SREBP-1c and FASN expression in macrophages and significantly enhanced palmitic acid synthesis (P < 0.05). Knockdown of SREBP-1c attenuated LPS-enhanced FASN expression. Knockdown of FASN significantly suppressed LPS-enhanced palmitic acid synthesis (P < 0.05). LPS and exogenous palmitic acid significantly enhanced CCL2 secretion and macrophage chemotaxis (all P < 0.05). Inhibition of FASN expression significantly alleviated LPS-augmented CCL2 secretion (P < 0.05). SSO significantly suppressed CCL2 secretion and macrophage chemotaxis augmented by LPS and palmitic acid (all P < 0.05). In a rat model of induced apical periodontitis, SSO treatment significantly attenuated progression of apical periodontitis and macrophage recruitment (all P < 0.05). CONCLUSIONS: LPS/SREBP-1c/FASN/palmitic acid signalling contributed to tissue destruction caused by bacterial infection. Modulation of lipid metabolism and signalling may be helpful for the management of apical periodontitis.

Differential Diagnosis of Cysts and Granulomas Supported by Texture Analysis of Intraoral Radiographs.

The aim of this study was to evaluate whether textural analysis could differentiate between the two common types of lytic lesions imaged with use of radiography. Sixty-two patients were enrolled in the study with intraoral radiograph images and a histological reference study. Full textural analysis was performed using MaZda software. For over 10,000 features, logistic regression models were applied. Fragments containing lesion edges were characterized by significant correlation of structural information. Although the input images were stored using lossy compression and their scale was not preserved, the obtained results confirmed the possibility of distinguishing between cysts and granulomas with use of textural analysis of intraoral radiographs. It was shown that the important information distinguishing the aforementioned types of lesions is located at the edges and not within the lesion.

Assessment of bone healing after mineral trioxide aggregate and platelet-rich fibrin application in periapical lesions using cone-beam computed tomographic imaging.

OBJECTIVES: The aim of this study was to compare the effects of mineral trioxide aggregate (MTA) and platelet-rich fibrin (PRF) use on periapical healing in surgically treated periapical lesions using three-dimensional (3D) cone-beam computed tomographic (CBCT) imaging. MATERIALS AND METHODS: A total of 40 periapical lesions undergoing apical surgery were selected between December 2016 and November 2017. The participants were randomly divided into four study groups: control, MTA, PRF, and MTA+PRF. No interventions were made in the control group except root-end resection. Routine radiographs were taken in the 3rd, 6th, and 12th months. The volume and density of periapical lesions at the 1-year follow-up were compared with the pre-op values using the MIMICS software program. Primary healing of the periapical tissues was evaluated, and the outcomes were noted. RESULTS: Post-op volume values were significantly decreased, and density values were significantly increased according to the pre-op measurements. In the post-op volume evaluation between the groups, significant differences were observed in the MTA and MTA+PRF groups compared with the control group (p < 0.005). However, no substantial significance was noted between the control and PRF groups. There were no significant differences in post-op density calculations between all groups. CONCLUSION AND CLINICAL RELEVANCE: High success rates were achieved using MTA in periapical lesions in endodontic microsurgery. The application of PRF to the surgical cavity may not necessarily improve outcomes. Further studies are needed with long-term follow-up. TRIAL REGISTRATION NUMBER: NCT03743987 (The Effect of MTA and PRF Application in Periapical Lesions).

Morphological characteristics of radicular cysts using computed tomography.

The purpose of this study was to evaluate computed tomography (CT) findings of radicular cysts with a focus on location, size, and condition of the surrounding bone. Subjects comprised 60 men and 86 women (mean age 47.2 years) with histopathologically confirmed radicular cysts who underwent CT examination between 2012 and 2014. Mesiodistal and buccolingual diameters were measured at the location where the lesion appeared to be largest on CT axial images. Of the 146 cases, 103 lesions were in the maxilla and 43 were in the mandible. Mesiodistal diameter of the maxillary lesions was significantly larger than that of the mandibular lesions. However, the ratio of mesiodistal diameter to buccolingual diameter in the mandible was significantly larger than that in the maxilla. Bone expansion was more significant in the maxilla than in the mandible. Mesiodistal and buccolingual diameters in only the maxilla and perilesional sclerotic radiolucency in images of both jaws were significantly associated with the severity of clinical symptoms. The findings suggest that radicular cysts in the maxilla are accompanied by bone expansion in the mesiodistal and buccolingual directions and those in the mandible progress in the mesiodistal direction without bone expansion. Clinical acute symptoms (pain and swelling) are correlated with lesion size in the maxilla; such a correlation is not clear for mandibular lesions, and discovery of mandibular lesions may, therefore, be delayed.

Assessment of conformity between clinical (radiological) and histopathological diagnoses of chronic inflammatory periapical lesions treated with apicoectomy. Clinical and histopathological diagnoses of periapical lesions. Research article.

OBJECTIVES: Periapical inflammation is one of the most common pathologies within the jaws, leading to the destruction of periodontal ligaments, bone resorption and the formation of periapical granulomas or radicular cysts. The final diagnosis can be made only on the basis of histopathological examination. The aim of the study was to assess the conformity between clinical and histopathological diagnosis of inflammatory periapical lesions treated with apicoectomy. MATERIALS AND METHODS: The case histories of 52 patients subjected to surgical treatment at the Clinic of Conservative Dentistry with Endodontics between 2008 and 2018 were analyzed. Demographic data (age, gender), clinical (radiological) diagnosis, and data on the presence of sinus tracts and causal tooth were obtained from patients' records. RESULTS: In the light of clinical and radiological examination, 32 (61.5%) periapical granulomas, 18 (34.6%) radicular cysts and 2 (3.9%) periapical scars were diagnosed, whereas the result of histopathological examination revealed granuloma in 34 (65.4%) cases and in 18 (34.6%) - radicular cyst. For clinical diagnosis of granuloma, the result coincided with the result of the histopathological examination in 28 cases, and in the case of cysts in 14. The analysis showed a significant relationship between the clinical and histopathological diagnoses (p <0.05). CONCLUSIONS: The study emphasizes the importance of histopathological assessment for the proper diagnosis of periapical lesions. CLINICAL RELEVANCE: The article emphasizes the high importance of histopathological examination for the correct diagnosis of chronic inflammatory periapical lesions.

Effects of alpha-lipoic acid therapy on experimentally induced apical periodontitis: a biochemical, histopathological and micro-CT analysis.

AIM: To investigate the possible therapeutic effects of alpha-lipoic acid (ALA) in a model of chronic apical periodontitis in rats by analysing biochemical, histopathological and micro-CT parameters. METHODOLOGY: The study was approved by the Animal Ethics Committee of the Near East University. Thirty-two Wistar rats were divided into four groups of eight rats each: Control Group; ALA Group; AP Group; AP + ALA Group. In the AP and AP + ALA groups, the pulp chambers of the mandibular first molars were surgically exposed and were left open to the oral environment for 4-weeks to allow the establishment of periapical lesions. The rats in the Control and AP groups were treated intraperitoneally with saline solution (with a daily dose of 100 mg kg-1 , for 28 days after periapical lesion induction). The rats in the ALA and AP + ALA groups were treated intraperitoneally with ALA (with a daily dose of 100 mg kg-1 , for 28 days after periapical lesion induction). After decapitation, the trunk blood was collected for the assessment of biochemical parameters. The mandibles were surgically removed and dissected for histopathologic analysis and further scanned with micro-CT. Groups of data were compared with a two-way analysis of variance (two-way anova) followed by Sidak's multiple comparison tests. Values of P < 0.05 were regarded as significant. RESULTS: TNF-α, IL-1ß, MMP-1, MMP-2 levels were significantly lower in AP + ALA group compared with AP group (P < 0.05). There was a significant difference between the AP and AP + ALA groups according to assessment of the inflammatory scores (P < 0.05). The periapical inflammatory infiltrates were significantly more severe (P < 0.05) in the AP group. The AP + ALA group exhibited lower values both in terms of surface area and volume of resorption cavities than the AP group and this difference was significant (P < 0.05). CONCLUSION: alpha-lipoic acid treatment provided therapeutic effects on the inhibition of periapical bone loss.

WNT signalling pathway in oral lesions.

Wingless-Integrated/Beta-catenin (WNT/-catenin) signalling pathway is one of the principal intercellular signalling pathways in humans. It plays an intrinsic role in the cellular proliferation, differentiation and regeneration along with many other cellular functions. Epigenetic deoxyribonucleic acid methylations and silencing of WNT signalling pathway genes have a significant role in malignant transformation of oral lesions such as oral submucous fibrosis, oral leukoplakia, oral lichen planus and erythroplakia. The increase in WNT inhibitory proteins along with inflammatory factors cause bone loss in periapical lesions, such as chronic apical periodontitis. This review discusses the molecular genetics of potentially malignant oral lesions, sheds light on our understanding of WNT/-catenin signalling in bone loss pertaining to periapical lesions, and alteration of this pathway for therapeutic benefits.

Digital Orthopantomography vs Cone Beam Computed Tomography-Part 1: Detection of Periapical Lesions.

AIM: Digital orthopantomography (OPT) is usually the first examination step in supervising an incoming patient. Cone beam computed tomography (CBCT) is the most refined and affordable method to search for different dental lesions. The aim of this paper is to evaluate the effectiveness of OPT and CBCT in detecting periapical lesions in different dental groups. MATERIALS AND METHODS: An OPT and a CBCT scan of the dental arches of 45 patients were examined. The presence of AP was pointed out for OPT and CBCT. Sensitivity, specificity, predictive values, and accuracy were calculated for OPT, using CBCT as the reference standard. RESULTS: OPT showed low sensitivity (40.0), positive predictive value (90.4), negative predictive value (90.0), accuracy (90.0), and high specificity (99.2). It was found to have higher sensitivity in the lower front and premolar areas, while the lowest was found in the upper molar area. CONCLUSIONS: OPT can be used for endodontic diagnosis in the lower central and premolar sections, but CBCT plays a decisive role in the evaluation of molar areas and in the endodontic treatment planning, when a close relationship between apex and important anatomical structures exists. CLINICAL SIGNIFICANCE: CBCT exposes the patient to higher doses of radiations when compared with OPT, but CBCT, with its more selective sensitivity and the possibility to offer a three-dimensional (3D) rendering of dental and periodontal structures, is an elective choice for uncertain cases and for specific dental areas.

Pooled analysis of 1-year recall data from three root canal treatment outcome studies undertaken using cone beam computed tomography.

AIM: To provide an estimate of the proportion of successful outcomes of primary and secondary root canal treatments (retreatments) determined by periapical radiographs and cone beam computed tomography (CBCT), a pooled analysis of the data collected from three previous prospective clinical outcome studies was undertaken. METHODOLOGY: The analysis pooled the 1-year results for 354 teeth, including 123 primary treatments and 231 retreatments. All root canals were instrumented with ProTaper Universal and filled using a warm vertical condensation technique. Comparisons of favourable results between root canal treatments and retreatments and between different tooth types were made using chi-square/Fisher's exact test. RESULTS: The overall percentage of favourable results was 91% using periapical radiographs and 80% for CBCT (P < 0.001). With CBCT, the percentage of favourable results for primary treatments (84.7%) was not significantly different (P = 0.316) from that of retreatments (77.9%). When assessed by tooth group, the overall percentage of favourable results with CBCT was 75.5%, 90.6% and 91.1% for molar, premolar and anterior teeth, respectively. When CBCT is used to assess the outcome, the proportion of favourable outcomes in molars was significantly lower than that of premolars and anterior teeth (P < 0.05). Teeth with root fillings terminating more than 2 mm short of the radiographic apex had less favourable outcomes (73%) compared to long (83%) and adequate root filling length (84%). CONCLUSIONS: The proportions of favourable outcomes of primary root canal treatments and retreatments assessed with CBCT were lower when compared to periapical radiographs, and also lower than those historically reported by periapical radiograph-based outcome studies. Considering the very high favourable outcome of anterior teeth and premolars compared to molar teeth, future studies assessing the effect of new materials and techniques on the outcome of root canal treatments should be based on preoperative and postoperative CBCT images, and focus on molar teeth.

A prospective study assessing the effect of coronal tooth structure loss on the outcome of root canal retreatment.

AIM: To evaluate the outcome of secondary root canal treatment (retreatment) on posterior teeth in relation to the residual volume of coronal tooth structure, measured with an intraoral scanner, using periapical radiography and cone beam computed tomography (CBCT). METHODOLOGY: A total of 137 posterior teeth in 121 patients were assessed clinically and radiographically using periapical radiographs and CBCT scans at baseline and 1 year after root canal retreatment. The increase or decrease in the size of preoperative periapical radiolucencies and development of new radiolucencies were assessed by a consensus panel consisting of two pre-calibrated examiners. A clinical impression was obtained for each tooth after completion of root canal retreatment, before the placement of the temporary restoration and following cast restoration placement to produce two casts. All casts were scanned using an intraoral digital scanner and the three-dimensional volume of remaining tooth structure calculated. Teeth were also classified according to the number of remaining coronal walls before core build-up. χ2 test was used to determine the association between the outcome of root canal retreatments and the volume of remaining coronal tooth structure. RESULTS: At the 1-year recall, teeth retaining less than 30% of their original tooth structure volume had a significantly higher proportion of unfavourable outcomes (χ2 , P < 0.05, odds ratio [OR], 2.58; 95% CI, 1.026-6.487). CONCLUSIONS: The loss of tooth structure volume is an objective parameter that can be used to predict the probability of success of root canal retreatments. At 1-year follow-up, the percentage of unfavourable outcomes of root canal retreated teeth was significantly higher when less than 30% of the original tooth tissue structure was present at baseline.

Retrospective analysis of nonendodontic periapical lesions misdiagnosed as endodontic apical periodontitis lesions in a population of Taiwanese patients.

OBJECTIVE: We aimed to evaluate nonendodontic periapical lesions clinically misdiagnosed as endodontic periapical pathoses in a population of Taiwanese patients. MATERIALS AND METHODS: Cases (2000-2014) of histopathological diagnoses of nonendodontic periapical lesions were retrieved from all cases with a clinical diagnosis of radicular cyst, apical granuloma, or apical periodontitis in the institution. These cases were regarded as misdiagnosed nonendodontic periapical lesions, of which the types and frequencies, in addition to the demographic data, were determined. RESULTS: Four thousand and four specimens were clinically diagnosed as endodontically associated pathoses, of which 118 cases (2.95%) received a histopathological diagnosis of a nonendodontic pathologic entity, the most frequent lesion being keratocystic odontogenic tumor (KCOT, n = 38, 32.20%), followed by fibro-osseous lesion (n = 18, 15.25%), and dentigerous cyst (n = 13, 11.02%). Nine malignant lesions in the periapical area [squamous cell carcinoma (n = 7, 5.93%), adenoid cystic carcinoma (n = 1, 0.85%), and Langerhans cell histiocytosis (n = 1, 0.85%)] were also noted. CONCLUSIONS: A wide variety of histopathological diagnoses, including benign odontogenic and non-odontogenic cystic and tumorous lesions and infectious diseases, as well as malignant lesions, was noted in these 118 cases of nonendodontic periapical lesions. Squamous cell carcinoma was the most predominant malignancy of nonendodontic periapical lesions misdiagnosed as apical periodontitis lesions from imaging examination overlooking the clinical findings. CLINICAL RELEVANCE: The current data form a useful basis for clinicopathological investigation and educational teaching regarding nonendodontic periapical lesions misdiagnosed as endodontic apical periodontitis lesions.