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Problems that lead to persistent apical periodontitis include: inadequate aseptic control, poor access cavity design, missed canals, inadequate instrumentation, debridement and leaking temporary or permanent restorations. Even when the most stringent procedures are followed, apical periodontitis may still persist as asymptomatic radiolucencies, because of the complexity of the root canal system formed by the main and accessory canals, their ramifications and anastomoses where residual infection can persist. Further, there are extraradicular factors \u2013 located within the inflamed periapical tissue \u2013 that can interfere with post\u2010treatment healing of apical periodontitis. The causes of apical periodontitis persisting after root canal treatment have not been well characterized. During the 1990s, a series of investigations have shown that there are six biological factors that lead to asymptomatic radiolucencies persisting after root canal treatment. These are: (i) intraradicular infection persisting in the complex apical root canal system; (ii) extraradicular infection, generally in the form of periapical actinomycosis; (iii) extruded root canal filling or other exogenous materials that cause a foreign body reaction; (iv) accumulation of endogenous cholesterol crystals that irritate periapical tissues; (v) true cystic lesions, and (vi) scar tissue healing of the lesion. This article provides a comprehensive overview of the causative factors of non\u2010resolving periapical lesions that are seen as asymptomatic radiolucencies post\u2010treatment.<\/jats:p>","DOI":"10.1111\/j.1365-2591.2006.01099.x","type":"journal-article","created":{"date-parts":[[2006,3,10]],"date-time":"2006-03-10T10:13:58Z","timestamp":1141985638000},"page":"249-281","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":841,"title":["On the causes of persistent apical periodontitis: a review"],"prefix":"10.1111","volume":"39","author":[{"given":"P. N. 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