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Background and Objectives Head and neck cancer surgery has a high risk of infection, becausesurgical fields are exposed to the oral cavity and the pharynx during surgery. The purposeof this study is to evaluate the usefulness of prophylactic metronidazole by identifying factorscontributing to postoperative fistulas in clean-contaminated head and neck cancer surgery. Subjects and Method A total of 234 patients underwent mucosa-opening surgery betweenJanuary 2002 and October 2015. Of those, 167 patients received conventional prophylactic antibioticsand 67 patients received metronidazole in addition to the conventional prophylactic antibiotics. Various clinical factors were evaluated to find association with postoperative fistula. Results The multivariate analysis showed that the tumor site, advanced T stage, and the preoperativetreatment were significantly associated with fistula formation, and the prophylacticuse of metronidazole significantly reduced the number of postoperative fistulas. Conclusion In cases where the incidence of postoperative fistulas are more likely to increase,such as in the advanced T stage, in oral/pharyngeal cancer, and preoperative non-surgical treatment,prophylactic metronidazole may be useful for preventing postoperative fistulas

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