Miroslav Andric

Functional endoscopic sinus surgery as an adjunctive treatment for closure of oroantral fistulae: a retrospective analysis.

OBJECTIVE The objective of this study was to report results of functional endoscopic sinus surgery (FESS) for treatment of chronic maxillary sinusitis of dental origin in a series of patients with oroantral fistulae (OAF). STUDY DESIGN Fourteen patients were treated by FESS and OAF closure by local flap. Data on severity of symptoms, diagnostic endoscopy, and coronal CT scan findings, as well as intraoperative course and complications, were recorded. The follow-up period lasted up to 2 years, comprising clinical examinations and control CT scans. RESULTS All OAF healed uneventfully. All patients reported improvement in severity of sinusitis symptoms, which was confirmed through results of clinical examinations and control CT scans. No significant complications were recorded. No revision surgery was needed in any case. CONCLUSION These results indicate that FESS, combined with OAF closure by buccal flap, might be an effective and safe option for treatment of selected cases of chronic odontogenic sinusitis with OAF.

Human cytomegalovirus and Epstein-Barr virus in etiopathogenesis of apical periodontitis: a systematic review.

INTRODUCTION During the last decade, a hypothesis has been established that human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) may be implicated in the pathogenesis of apical periodontitis. The aim of this review was to analyze the available evidence that indicates that HCMV and EBV can actually contribute to the pathogenesis of periapical lesions and to answer the following focused question: is there a relationship between HCMV and EBV DNA and/or RNA detection and the clinical features of human periapical lesions? METHODS The literature search covered MEDLINE, Science Citation Index Expanded (SCIexpanded), Scopus, and The Cochrane Library database. Quantitative statistical analysis was performed on the pooled data of HCMV and EBV messenger RNA transcripts in tissues of symptomatic and asymptomatic periapical lesions. RESULTS The electronic database search yielded 48 hits from PubMed, 197 hits from Scopus, 40 hits from Web of Science, and 1 from the Cochrane Library. Seventeen cross-sectional studies have been included in the final review. The pooled results from quantitative systematic method analysis showed no statistically significant relationship between the presence of HCMV and EBV messenger RNA transcripts (P = .083 and P = .306, respectively) and the clinical features of apical periodontitis. CONCLUSIONS The findings of HCMV and EBV transcripts in apical periodontitis were controversial among the included studies. Herpesviruses were common in symptomatic and large-size periapical lesions, but such results failed to reach statistical significance. Further studies, including those based on an experimental animal model, should provide more data on herpesviruses as a factor in the pathogenesis of periapical inflammation.

Human Cytomegalovirus and Epstein-Barr Virus Genotypes in Apical Periodontitis Lesions

INTRODUCTION Different genotypes of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) possess specific pathogenic abilities because of various interactions with the hosts immune system and differences in cell tropism. The aim of this study was to determine the distribution of HCMV and EBV genotypes in apical periodontitis lesions in relation to their clinical and histopathologic features. METHODS One hundred samples of apical periodontitis lesions and 25 control samples (healthy pulp tissue) were collected. The presence of HCMV glycoprotein B (gB) and EBV nuclear antigen-2 genotypes was analyzed by nested polymerase chain reaction and restriction fragment length polymorphisms analysis. RESULTS EBV and HCMV were detected in apical periodontitis lesions at significantly higher frequencies than in healthy pulp controls (P = .020 and P = .020, respectively). HCMV gB type II was significantly more frequent compared with gB type I in the examined groups (P = .036). No HCMV gB type III or IV products were found. In both periapical lesions and controls, EBV-1 occurred more often compared with EBV-2 (P = .001). Dual EBV and HCMV coinfection was more frequently detected in large-size periapical lesions (P = .038). CONCLUSIONS Both HCMV and EBV are associated with inflammatory processes of periapical bone destruction. HCMV gB type II and EBV-1 are the most prevalent genotypes in apical periodontitis lesions.

Pro-inflammatory cytokine levels in human apical periodontitis: Correlation with clinical and histological findings

This study aimed to compare the levels of tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) between apical periodontitis lesions with different clinical and histological features. Based on clinical data and history of disease, 100 human apical periodontitis lesions were categorised as either asymptomatic or symptomatic lesions. According to histological examination, lesions were divided into periapical granulomas and radicular cysts. Pulp tissues of 25 impacted wisdom teeth were used as controls. Homogenised tissue samples were centrifuged and supernatants were used for the determination of cytokine levels by enzyme-linked immunosorbent assay. Significantly higher levels of IL-1β and IL-6 were found in symptomatic lesions compared with asymptomatic lesions and control tissues (P < 0.001, P < 0.001, respectively). The concentration of IL-1β was significantly higher in radicular cysts compared with periapical granulomas (P = 0.003). Symptomatic lesions, as judged by high local production of IL-1β and IL-6, represent an immunologically active stage of the disease.

Survivin gene promoter polymorphism ‐31G/C as a risk factor for keratocystic odontogenic tumor development

Several single nucleotide polymorphisms in survivin gene promoters, notably -31G/C, have been shown to modulate the expression and activity of the survivin protein. Consequently, the -31G/C polymorphism has been identified as a risk factor for the development of several types of tumors. The aim of this study was to investigate a possible association between the -31G/C polymorphism and the risk for keratocystic odontogenic tumor (KCOT) development. DNA from 52 biopsy specimens of KCOTs and from 82 buccal swabs of healthy individuals was subjected to PCR restriction fragment length polymorphism analysis to identify individual genotypes. The distribution of genotypes in KCOT and control groups, respectively, was: GG: 30 (57.7%) vs. 26 (31.7%); CG: 17 (32.7%) vs. 45 (54.9%); and CC: 5 (9.6%) vs. 11 (13.4%), respectively. These differences were statistically significant. The G allele was more common in the KCOT group than in the control group: 76 (74%) vs. 96 (59%), respectively. Logistic regression analysis showed that GC heterozygotes had a considerably decreased susceptibility for KCOTs compared with GG homozygotes. The same was true for GC+CC vs. GG. The GG genotype of the -31G/C polymorphism might be a risk factor for KCOT development.

Epstein-Barr virus infection induces bone resorption in apical periodontitis via increased production of reactive oxygen species

Chronic inflammatory processes in periapical tissues caused by etiological agents of endodontic origin lead to apical periodontitis. Apart from bacteria, two herpesviruses, Epstein-Barr virus (EBV) and Human cytomegalovirus (HCMV) are recognized as putative pathogens in apical periodontitis. Although previous reports suggest the involvement of EBV in the pathogenesis of apical periodontitis, its exact role in periapical bone resorption has not yet been fully elucidated. We hypothesize that EBV infection in apical periodontitis is capable of inducing periapical bone resorption via stimulation of reactive oxygen species (ROS) overproduction. Increased levels of ROS induce expression of receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL). RANKL binding to receptor activator of nuclear factor κB (RANK) present on the surface of preosteoclasts induces their maturation and activation which consequently leads to bone resorption. The potential benefit of antiviral and antioxidant-based therapies in periapical bone resorption treatment remains to be assessed.

Keratocystic Odontogenic Tumors – Clinical and Molecular Features

Keratocystic odontogenic tumors (KCOTs) are certainly among the most studied lesions in oral pathology, which is not a surprise considering their perplexing clinical behavior and complicated mechanism of pathogenesis. In fact, the specific KCOT features are the reason for numerous discussions regarding the true nature and classification of these lesions, which are still debated in the scientific community.Until recently these lesions were known as odontogenic keratocysts (OKCs), a term first used by Philipsen in 1956. In the beginning, the term was used to describe any jaw cyst in which keratin was formed. However, it became obvious that some other types of jaw cysts, such as radicular and residual cysts, may exhibit keratinization as well, leading to the conclusion that specific histological features of OKCs and not solely the presence of keratin, should be used to distinguish these lesions from other cysts of the jaws [1]. Researchers soon realized that OKCs show aggressive clinical behavior and high recurrence rates, features which are not typical for other odontogenic cysts [2]. Be‐ sides that, it has been noted that OKCs are among the most prominent feature of Nevoid Basal Cell Carcinoma Syndrome (NBCCS), also known as Gorlin-Goltz syndrome. Finally, numerous studies have shown that genetic factors are predominant in etiology of these le‐ sions and that some mechanisms of pathogenesis, typical for neoplastic lesions, are also in‐ volved in formation of OKCs [3]. Therefore, in 2005 these lesions were reclassified as Keratocystic Odontogenic Tumors (KCOTs) and defined as benign, odontogenic, unior multicystic intraosseous tumors, with characteristic parakeratinized squamous epithelium lining, having a potential for aggressive and infiltrative growth [4]. However, since KCOTs also exhibit some cysts-like features, including response to decompression [5], the tumoral

Herpesviruses in Periapical Pathoses: An Updated Systematic Review

Apical periodontitis represents a chronic inflammation and destruction of periradicu‐ lar tissue caused by polymicrobial infection of endodontic origin. The aim of this systematic review was to make an update on findings related to Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) presence in periapical pathoses and to correlate these findings with clinical, histopathological and radiographic features of periapical lesions. Methods were based on the preferred reporting items for systemat‐ ic reviews and meta-analyses (PRISMA) statement. A search was performed using PubMed, Web of Science and SCOPUS. Search key words included the following medical subjects heading terms: (periapical disease OR apical periodontitis OR periapical lesions OR periapical abscess) AND (viruses OR herpesvir*). A manual search involved references from articles retrieved for possible inclusion. The search, evalua‐ tion, and critical appraisal of articles were performed by two independent judges. Collected data were analyzed using the measures of descriptive statistics. The final review has included twenty nine articles related to herpesviral presence periapical pathoses. Qualitative analysis indicated that EBV HCMV, and HHV-8 were the most prevalent species in periapical pathoses. Our findings suggest that there is wide variety of herpesviruses detection rates in periapical pathoses in relation to their clinical, histopathological and radiographic features.

The Role of Varicella Zoster Virus in the Development of Periapical Pathoses and Root Resorption: A Systematic Review

Introduction Varicella zoster virus (VZV) and subsequent herpes zoster (HZ) infection have been proposed as a causative agent of periapical pathoses and root resorption. This review aimed to identify, synthesize, and present a critical analysis of the available data on the association among VZV, subsequent HZ infection, and the development of periapical pathoses and root resorption and to analyze the level of evidence of available studies. Methods The literature search covered MEDLINE, Science Citation Index Expanded, and Scopus. A qualitative critical appraisal of the included articles was performed. Results The electronic database search yielded 66 hits from PubMed, 73 hits from Web of Science, and 107 from Scopus. Seven case reports and 3 cross‐sectional studies were included in the final review. When summarized, in 7 patients with a history of a previous HZ attack and with no other apparent cause, 23 teeth were diagnosed with apical periodontitis, 8 teeth with internal and 1 tooth with external root resorption. The cross‐sectional studies investigated the presence of VZV DNA in samples of acute apical abscess. The VZV DNA was found only in 2 of 65 samples. Conclusions All studies included in this systematic review had a low level of evidence (4 and 5). Still, the potential role of VZV in the etiopathogenesis of periapical pathoses and root resorption cannot be ruled out. Future investigations should be directed toward the analysis of VZV pathologic effects on pulp blood vessels, which might cause local ischemia and tissue necrosis. HighlightsThe literature search covered MEDLINE, Science Citation Index Expanded, and Scopus.Seven case reports and 3 cross‐sectional studies were included in final review.Only 1 of 7 case reports comprehensively analyzed the association among clinical manifestations of a previous HZ attack, the detection of VZV DNA, and the presence of apical periodontitis and root resorption.All available and included studies in this systematic review had a low level of evidence (4 and 5).A potential role of VZV in the etiopathogenesis of periapical pathoses and root resorption cannot be ruled out.

Survivin, cyclin d1 and p21hras in keratocystic odontogenic tumors before and after decompression

OBJECTIVES The aim of this study was to investigate survivin, cyclin D1, and p21hras expression in keratocystic odontogenic tumors before and after decompression, as well as in pericoronal follicles. A potential correlation between the expression levels of these proteins was also investigated. MATERIALS AND METHODS We analyzed eighteen keratocystic tumors treated by decompression and subsequent enucleation along with seven pericoronal follicles using immunohistochemistry. RESULTS Keratocystic tumor samples, both before and after decompression, were positive for each of the investigated proteins. In pericoronal follicles, survivin exhibited cytoplasmic staining in contrast to nuclear staining in keratocystic tumors. Cyclin D1 expression was negative in pericoronal follicles, and p21hras expression was similar in both groups. Survivin showed significantly higher expression after decompression, while cyclin D1 and p21hras remained unchanged (P = 0.039, P = 0.255, P = 0.913, respectively). There was no correlation between these proteins neither before nor after decompression. CONCLUSIONS Within the limits of the study, we can conclude that following decompression, keratocystic odontogenic tumors preserve distinct immunohistochemical profiles of cyclin D1 and p21hras expression, despite substantial reduction in size of the lesions. Significant increase of survivin expression after decompression might be attributed to higher level of epithelial proliferation caused by this procedure.