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quality RCTs and small-sample sized studies prevent to draw any fi rm conclusion. To our knowledge, this study is the fi rst meta-analysis trying to de fi ne the best surgical technique able to reduce the subjective and objective FS incidence. Our results showed that that TPFF, FFG, and ADM seem to provide better results in reducing both sub jective and objective FS incidence if compared to no treat ment. Although the analysis revealed a partial overlapping between the TPFF, FFG, and ADM groups regarding their ef fi cacy to prevent FS, it is worth nothing that pooled data for the FFG showed a greater heteroge neity compared to ADM and TPFF. However, the higher level of heterogeneity for the FFG is partially related to the greater number of studies included. This factor should be considered for the interpretation of the results. Fat is a favorable graft material following parotidectomy due to several features. In particular, it is readily available from multiple potential donor sites (e.g., abdominal wall), and it could be easily harvested without prolonging operative time. Donor site complica tions are uncommon, 47,58 and the scar could be easily hid den. Moreover, no increase in post-operative complication at the level of the parotid bed was demonstrated. In partic ular, graft-related complications (e.g., graft necrosis) are extremely rare, and are signi fi cantly related to graft site adjuvant radiotherapy. 58 On the other hand, the main limit of fat allografting is the unpredictable reabsorption rate, which may vary from 20% to 90% of the volume. 84,85 Transplantation with dermis or an overcorrection between 15% and 30% have been used to overcome this issue. 13,59,86 ADM implantation is an effective heterologous mate rial able to prevent FS following parotidectomy. In particu lar, ADM does not require an additional surgical donor site or increasing operative time. However, its use is limited by the not negligible risk of complications such as infection, extrusion, limited volume, and resorption. 66,73 In particular, ADM resorption seems to occur mostly over the fi rst 6 months after treatment. 87 In addition, a higher rate of ser omas has been described with ADM grafts, but the use of prolonged suction drainage seems to prevent this undesir able effect. 6 Moreover, there is no report in the current liter ature on revision surgery after ADM implantation. Given the heterologous nature of the implant, a potential greater risk of facial nerve injury due to increased adhesions should not be underestimated. Finally, the higher cost of the graft compared to autogenous tissue fl aps should be considered in the selection of the preventive treatment. Although only a minority of included patients were treated with the TPFF, it seems to provide an optimal reduction of FS incidence. One of the advantages of this fl ap is its proximity to the parotid bed that allows to maintain its vascularization reducing the risk of fl ap necrosis. 38,49 In addition, it can supply suf fi cient volume to overlay the sur gical fi eld after total parotidectomy, while the resulting donor site scar can be well hidden in the temporal hairline. On the other hand, the invasive approach needed to harvest the fl ap with prolonged operative time, and potential com plications such as alopecia and injury to the frontal branch of the facial nerve 38 are the most important disadvantages. Our data suggested that the role of the SCM and the SMAS fl aps in the prevention of FS should be partially

revised. According to literature data, these techniques are the most widely used in preventing FS after parotidectomy. However, our analysis showed that they seem to be less effective than the other interventions. On the other hand, both treatment strategies determine a signi fi cant reduction of both subjective and objective FS incidence if compared to no treatment. This meta-analysis is subjected to some limitations. The main limit of this meta-analysis is related to the relatively low quality of included studies. In particular, only seven RCTs 6,19 – 24 have been included, while the majority of papers were retrospective non-randomized studies. 13,38,39,41,42,44,48,49,51,53 – 55,57,58,61 – 67,70,72,74,75,78,82,83 In addition, the majority of RCTs compared one of the interventions to observation, while only one paper 24 directly compared two different treatment strategies. We decided to perform a network meta-analysis given that multiple strategies have been proposed for the FS preven tion in the current literature. However, we were forced to use an arm-based approach due to the absence of RCTs comparing different techniques. Consequently, compara tive retrospective and single-arm studies were also included in the analysis. Although multiple indirect inter vention comparisons have been performed, the possibility to merge data from multiple studies allow to perform cumulative analysis of large samples, improving the robustness of the results in the context of low quality evi dence from the current literature. Our results showed that three techniques (FFG, ADM, and TPFF) are proba bly better than the most commonly used SCM and SMAS fl aps. As a consequence, further RCTs should be con ducted to compare these techniques to better de fi ne the best surgical strategy able to prevent the FS. The second limit of this study was that only the FS inci dence was compared between different techniques. The choice of a speci fi c surgical technique in the prevention of FS should consider also the aesthetic outcome in terms of both incidence and social impact. Facial asymmetry could repre sent the most relevant sequelae after parotidectomy, and no clear data are available in the current literature on the best technique able to reduce facial depression. The aesthetic outcome was measured in many included papers, but the methods employed were highly subjective and heteroge neous between studies, and a formal meta-analysis could not be performed on this outcome. Moreover, some studies may have been designed to assess the cosmetic outcome, and the prevention of FS was reported only as a secondary outcome with a potential impact on our analysis. Although the FFG seems to represents the best compromise between FS prevention and aesthetic outcome, further studies are needed to compare different surgical techniques from these perspectives to better clarify the best treatment for the reconstruction of the surgical fi eld after parotidectomy. Third, although we tried to include only homogeneous studies in terms of surgical technique, some differences surely exists among included papers. On the other hand, if a multicenter randomized trial with a homogenous proto col is designed for the primary assessment of FS preven tion, differences between surgical techniques are surely reduced. In addition, the reporting of subjective FS may be different between different centers. However, this aspect

Laryngoscope 131: August 2021

De Virgilio et al.: Surgical prevention of Frey syndrome

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