Methods of Fat Tissue Processing for Human Vocal Cord Injection: A Systematic Review Giselle M. Truzzi, Henrique F. Pauna, Patricia Bette, Reinaldo J. Gusmão, Agrício N. Crespo, and Graziela O. Semenzati, Campinas, SP, Brazil Summary: Objectives. We analyzed different methods used to process autologous fat tissues for vocal fold injec- tion (VFI). VFI is a safe procedure that preserves the folds’ original elasticity and vibration properties and rarely triggers foreign-body reactions, but is often a temporary treatment due to fat reabsorption. To avoid it, selecting a technique that provides as many viable implantable adipocytes as possible is mandatory. Study Design. This is a systematic review. Methods. Data were collected from PubMed, Embase, Ovid, and Cochrane Library. Authors systematically re- viewed databases for papers on autologous fat tissue processing methods involving human injections in vocal folds and vocalization outcomes that evolved the acoustic analysis of the voice before and after the surgical procedure, in- dependently of the follow-up time. Results. Nine out of the 517 articles met selection criteria for analysis. No standardized technique was found. Conclusion. There is no standardized technique for processing fat tissue for vocal fold injection. Further research is needed to point out the best available technique. Key Words: Vocal fold–Autologous fat tissue–Processing methods–Voice–Injection laryngoplasty. INTRODUCTION Several articles described many materials to be injected into the human vocal fold in cases of glottic insufficiency. Brunnings was the first to describe such attempt using paraffin injections, in 1911. Several methods came out after the initial study, using materi- als such as silicone and Teflon, trying to restore the glottic function with minimally invasive interventions. 1 These grafts, however, can trigger an intense inflammatory reaction, which some- times leads to granuloma formation, and may be reabsorbed or rejected to different degrees. For those reasons, new materials are being developed, and several autologous grafts have been described and tested in animal models. 2–4 Autologous bioimplants, especially autologous fat tissue (AFT), deserve attention for various reasons: it is rapidly obtained, with low costs, and presents a small risk to stimulate inflammatory reactions; additionally, its viscosity is similar to that of the lamina propria of the vocal fold. 5–8 The use of AFT has been associ- ated with adequate improvement of the voice and laryngeal function. 8,9 However, the techniques employed for processing har- vested tissue, as well as the volume to be injected, can alter the quantity of viable adipocytes and graft absorption. 4 There is still some controversy over the use of fat tissue, for not much is known about the lastingness of the graft, its resorp- tion rate, and its effectiveness on the functional recovery of the larynx. 7,8 Aware of that gap, the authors of the present study system- atically reviewed the literature regarding the use of fat tissue in human vocal folds. Additionally, we intended to find tech- niques for processing fat tissue that minimize tissular damage and optimize its application and graft durability, leading to a better vocal quality. OBJECTIVES This study aimed to evaluate the methods for processing AFT to be injected in human vocal folds and correlate it to phona- tion function. MATERIALS AND METHODS For this systematic review, we followed the norms of the Co- chrane Collaboration. Authors considered the method of fat tissue injection in human vocal folds as the “intervention,” and the quality of voice (preoperative and postoperative) was taken as “clinical outcome.” The literature research started on August 8, 2014, and was updated on September 2, 2015. The authors searched the following terms in medical data- bases (namely PubMed, Embase, Ovid, and Cochrane Library [http://onlinelibrary.wiley.com/cochranelibrary/search]): (Fats, Subcutaneous or Subcutaneous Fats or Adipose Tissue, Subcu- taneous or Fat, Subcutaneous or Subcutaneous Adipose Tissue) and (Cord, Vocal or Cords, Vocal or Vocal Cord or Vocal Fold or Fold, Vocal or Folds, Vocal or Vocal Folds or Vocal Liga- ment or Ligament, Vocal or Ligaments, Vocal or Vocal Ligaments). No searching filters were applied. To search the Literatura Latino-Americana e do Caribe em Ciências da Saúde database, we used the following strategy: MH vocal cords or MH pliegue vocales or MH prega vocal and MH Autoenxerto or Autotransplante or Transplantação Autóloga or Enxerto Autólogo. We also searched Google, using the Medical Subject Head- ings terms, to find texts or papers considered “cinereous.” Inclusion criteria The authors selected every study published in English or Latin languages that described the processing techniques of the fat tissue to be injected in human vocal folds and included the acoustic Accepted for publication August 18, 2016. From the Department of Otorhinolaryngology, Head and Neck Surgery, University of Campinas (UNICAMP), Campinas, SP, Brazil. Address correspondence and reprint requests to Giselle M. Truzzi, Department of Otorhinolaryngology, Head and Neck Surgery, University of Campinas (UNICAMP), PO BOX 6111, Campinas, São Paulo 13081-970, Brazil. E-mail: giselledmt@gmail.com Journal ofVoice, Vol. ■■, No. ■■, pp. ■■-■■ 0892-1997 © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jvoice.2016.08.012 ARTICLE IN PRESS