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Mes SD, Smajlović E, Heijnen BJ, Hendriksma M, Jansen JC, Langeveld APM, Sjögren EV. Multidimensional assessment of voice quality after injection augmentation of the vocal fold with autologous adipose tissue or calcium hydroxylapatite. Eur Arch Otorhinolaryngol 2021; 279:1967-1978. [PMID: 34846572 DOI: 10.1007/s00405-021-07193-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 11/17/2021] [Indexed: 11/28/2022]
Abstract
PURPOSE The purpose of this study was to evaluate short- and long-term outcome of injection augmentation with autologous adipose tissue (AAT) and calcium hydroxylapatite injection (CAHA) in patients with a unilateral vocal fold paralysis (UVFP). DESIGN/METHODS A retrospective cohort study was performed in patients diagnosed with UVFP, who had received injection augmentation with AAT or CAHA. Multidimensional voice analysis was performed before, 3 and 12 months after injection. This analysis included patient self-assessment (Voice Handicap Index-30), perceptual (overall dysphonia grade according to the GRBAS scale), aerodynamic (MPT, s/z ratio) and acoustic (fundamental frequency, dynamic range) parameters. Effects were assessed using a linear mixed model analysis. RESULTS Forty-six patients were available for evaluation, with a total of 53 injection augmentations (AAT n = 39; CAHA n = 14). We found significant improvement of patient self-assessment and perceptive voice outcome at 3 months, which were maintained at 12 months. In the CAHA group, s/z ratio and dynamic range of extreme frequencies also improved significantly over time. No statistically significant differences were found between the two treatments (AAT vs. CAHA). No major complications were reported. CONCLUSION This study, using a guide-line recommended panel of outcome parameters, shows a high success rate of injection augmentation with AAT or CAHA for patients with UVFP at 12 months with significant improvement in most voice outcome parameters, although voices do not completely normalize. There is no significant difference in outcome between the two materials.
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Affiliation(s)
- Stephanie D Mes
- Department of ENT, Head and Neck Surgery H5-Q, Leiden University Medical Center, Albinusdreef 2, Postbus 9600, 2300 RC, Leiden, The Netherlands.
| | - Edela Smajlović
- Department of Otorhinolaryngology, Head and Neck Surgery, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Bas J Heijnen
- Department of ENT, Head and Neck Surgery H5-Q, Leiden University Medical Center, Albinusdreef 2, Postbus 9600, 2300 RC, Leiden, The Netherlands
| | - Martine Hendriksma
- Department of ENT, Head and Neck Surgery H5-Q, Leiden University Medical Center, Albinusdreef 2, Postbus 9600, 2300 RC, Leiden, The Netherlands
| | - Jeroen C Jansen
- Department of ENT, Head and Neck Surgery H5-Q, Leiden University Medical Center, Albinusdreef 2, Postbus 9600, 2300 RC, Leiden, The Netherlands
| | - Antonius P M Langeveld
- Department of ENT, Head and Neck Surgery H5-Q, Leiden University Medical Center, Albinusdreef 2, Postbus 9600, 2300 RC, Leiden, The Netherlands
| | - Elisabeth V Sjögren
- Department of ENT, Head and Neck Surgery H5-Q, Leiden University Medical Center, Albinusdreef 2, Postbus 9600, 2300 RC, Leiden, The Netherlands
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Stefanie Buchberger AM, Nitiu R, Pinther M, Graf S, Skodacek D, Regn S, Kreutzer K, Storck K. Fibrin Gel Suspended Autologous Chondrocytes as Cell-based Material for long-term Injection Laryngoplasty. Laryngoscope 2020; 131:E1624-E1632. [PMID: 33368380 DOI: 10.1002/lary.29300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 10/27/2020] [Accepted: 11/18/2020] [Indexed: 11/10/2022]
Abstract
OBJECTIVES/HYPOTHESIS Injection laryngoplasty of materials for unilateral vocal-fold paralysis has shown various results regarding the long-term stability of the injected material. We evaluated a fibrin-gel based cell suspension with autologous chondrocytes in-vitro and in-vivo as long-term-stable vocal-fold augmentation material in an animal model. STUDY DESIGN This study compises an in vitro cell-culture part as well as an in vivo animal study with New Zealand White Rabbits. METHODS In in-vitro experiments, auricular chondrocytes harvested from 24 New Zealand White Rabbits cadavers were cultivated in pellet cultures to evaluate cartilage formation for 4 weeks using long-term-stable fibrin gel as carrier. Injectability and injection volume for the laryngoplasty was determined in-vitro using harvested cadaveric larynxes. In-vivo 24 Rabbits were biopsied for elastic cartilage of the ear and autologous P1 cells were injected lateral of one vocal cord into the paraglottic space suspended in a long-term-stable fibrin gel. Histologic evaluation was performed after 2, 4, 12, and 24 weeks. RESULTS During 12-week pellet culture, we found extracellular matrix formation and weight-stable cartilage of mature appearance. In-vivo, mature cartilage was found in two larynxes (n = 6) at 4 weeks, in four (n = 6) at 12 weeks, and in five (n = 6) at 24 weeks mostly located in the paraglottic space and sometimes with spurs into the vocalis muscle. Surrounding tissue was often infiltrated with inflammatory cells. Material tended to dislocate through the cricothyroid space into the extraglottic surrounding tissue. CONCLUSIONS A cell-based approach with chondrocytes for permanent vocal-fold augmentation has not previously been reported. We have achieved the formation of structurally mature cartilage in the paraglottic space, but this is accompanied by difficulties with dislocated material, deformation of the augmentation, and inflammation. LEVEL OF EVIDENCE N/A Laryngoscope, 131:E1624-E1632, 2021.
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Affiliation(s)
- Anna Maria Stefanie Buchberger
- Department of Phoniatrics and Pedaudiology, Ear-Nose-Throat, Head and Neck Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
| | - Ramona Nitiu
- Department of Ear-Nose-Throat, Head and Neck Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
| | - Melina Pinther
- Department of Ear-Nose-Throat, Head and Neck Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
| | - Simone Graf
- Department of Phoniatrics and Pedaudiology, Ear-Nose-Throat, Head and Neck Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
| | - Daniel Skodacek
- Department of Ear-Nose-Throat, Head and Neck Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
| | - Sybille Regn
- Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany
| | - Kilian Kreutzer
- Department of Maxillofacial Surgery, University clinic of the Charité Berlin, Berlin, Germany
| | - Katharina Storck
- Department of Ear-Nose-Throat, Head and Neck Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
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Five-year results of vocal fold augmentation using autologous fat or calcium hydroxylapatite. Eur Arch Otorhinolaryngol 2020; 278:1139-1144. [PMID: 33226462 DOI: 10.1007/s00405-020-06479-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 11/05/2020] [Indexed: 10/22/2022]
Abstract
PURPOSE To evaluate 5-year voice outcomes of vocal fold augmentation (VFA) using autologous fat (AF) injection via direct microlaryngoscopy versus office-based calcium hydroxylapatite (CaHA) injection. METHODS Retrospective study of patients who underwent VFA between 2012 and 2015, with a 5-year follow-up. Patients with a glottic gap of ≤ 3 mm caused by unilateral vocal fold paralysis or vocal fold atrophy were included in the study. VFA was performed using AF injection via direct microlaryngoscopy in 17 patients, and using office-based CaHA injection in 19 patients. Subjective satisfaction with voice, voice handicap index (VHI), and maximal phonation time (MPT) were analyzed pre-injection, and at 12 and 60 months post-VFA. RESULTS Altogether 36 patients underwent VFA between 2012 and 2015, of whom 5 were excluded within 1 year post-VFA, and 2 were excluded between 1 and 5 years post-VFA. Of the remaining 29 patients, 3 (10.3%) underwent re-intervention at between 1 and 3 years post-VFA. Thus, the 5-year follow-up included 26 patients (72.2%; 11 males and 15 females). At 5 years after surgery, 73.1% of the patients were satisfied with their voice, with no significant between-group difference (P = 0.307). The mean improvement of VHI was 28.8 ± 17.82 in the autologous fat group versus 33 ± 26.24 in the CaHA group (P = 0.458). MPT improvement was also similar between the two groups: 6.2 ± 4.26 for the autologous fat group versus 6.3 ± 4.34 for the CaHA group (P = 0.667). CONCLUSIONS Both AF injection via direct microlaryngoscopy and office-based CaHA injection yielded good and comparable 5-year results.
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Safety and feasibility of fat injection therapy with adipose-derived stem cells in a rabbit hypoglossal nerve paralysis model: A pilot study. Auris Nasus Larynx 2020; 48:274-280. [PMID: 32828592 DOI: 10.1016/j.anl.2020.08.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 07/19/2020] [Accepted: 08/03/2020] [Indexed: 11/21/2022]
Abstract
OBJECTIVE The aim of this study is to establish a unilateral tongue atrophy model by cutting the hypoglossal nerve and to evaluate the safety and feasibility of a fat injection of adipose-derived stem cells (ADSCs) to restore swallowing function. METHODS A total of 12 rabbits were randomized to three groups; the ADSCs+fat group (n=4), the fat group (n=4) and the control group (n=4). All rabbits were treated with denervation of the left hypoglossal nerve and their conditions including body weight and food intake were checked during follow-up periods (8 weeks). At 4 weeks after the transection of the nerve, rabbits received the injection therapy into the denervated side of the tongue with 1.0mL fat tissue premixed with 0.5mL ADSCs in the ADSCs+fat group, 1.0mL fat tissue premixed with 0.5mL PBS in the fat group and 1.5mL PBS in the control group. Rabbits were euthanized 8 weeks post-treatment and resected tongues were collected, formalin-fixed and paraffin embedded. To evaluate the change of the intrinsic muscles of the tongue, muscle fibers around the treatment area was analyzed by evaluating 5 consecutive hematoxylin-eosin slides per rabbit. RESULTS Food intake did not decrease upon nerve denervation, and none of the rabbits displayed adverse effect such as aspiration, surgical wound dehiscence or infection. No significant body weight changes were found between the three groups at 4 and 8 weeks after nerve transection (p>0.05). In the control group, the denervated side of tongue had significantly smaller muscle fiber areas and diameters compared to the non-denervated side (p<0.05). The ADSCs+fat group demonstrated a larger area of inferior longitudinal muscle fibers compared to the control and the fat groups (582±312µm2 vs. 405±220µm2 and 413±226µm2; p<0.05). A significant thicker lesser diameter of inferior longitudinal muscle fibers was found in the ADSCs+fat group compared to the control and the fat groups (24±8µm vs. 20±6µm and 20±7µm; p<0.05). CONCLUSION The rabbit tongue atrophy model was found suitable for the assessment of muscle change after nerve transection. Fat injection therapy with ADSCs demonstrated great potential to prevent the muscle atrophy after denervation and to promote the muscle regeneration around the injection area.
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Feasibility of virtual surgical simulation in the head and neck region for soft tissue reconstruction using free flap: a comparison of preoperative and postoperative volume measurement. Int J Oral Maxillofac Surg 2020; 50:316-322. [PMID: 32826125 DOI: 10.1016/j.ijom.2020.07.025] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2020] [Revised: 05/25/2020] [Accepted: 07/22/2020] [Indexed: 01/17/2023]
Abstract
In the head and neck region, preoperative evaluation of the free flap volume is challenging. The current study validated preoperative three-dimensional (3D) virtual surgical simulation for soft tissue reconstruction by assessing flap volume and evaluated fat and muscle volume changes at follow-up in 13 head and neck cancer patients undergoing anterolateral craniofacial resection. Patients received 3D virtual surgical simulation, and the volume of the planned defects was estimated by surgical simulation. Following en bloc resection of the tumor, the defect in the skull base was covered using a rectus abdominis myocutaneous flap. Following surgery, computed tomography scans were acquired at day 1 and at 6 and 12 months. Virtual planned defect was on average 227 ml (range, 154-315) and was 10% smaller than the actual flap volume in patients without skin involvement of the tumor. Between day 1 and 12 months post-surgery, the volume of fat and muscle tissue in the free flap dropped by 9% and 58%, respectively. Our results indicate that 3D virtual surgical simulation provides essential information in determining the accurate volume of the required free flap for surgical defect repair and may thus help improve surgical planning and functional and esthetic outcome.
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Lahav Y, Malka-Yosef L, Shapira-Galitz Y, Cohen O, Halperin D, Shoffel-Havakuk H. Vocal Fold Fat Augmentation for Atrophy, Scarring, and Unilateral Paralysis: Long-term Functional Outcomes. Otolaryngol Head Neck Surg 2020; 164:631-638. [PMID: 32777994 DOI: 10.1177/0194599820947000] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVE There is a debate regarding the durability of fat implants. Our experience and recent publications suggest fat implantation may deliver a long-lasting improvement. This study aims to present the long-term outcomes for vocal fold fat augmentation using strict harvesting, preparing, and implantation protocols. STUDY DESIGN A prospective cohort conducted between 2014 and 2020 (recruitment 2014-2017). SETTING An academic tertiary referral center. SUBJECTS AND METHODS Twenty-two patients with glottic insufficiency were enrolled: 11 had unilateral vocal fold paralysis (UVFP), and 11 had atrophy or scar. Harvested fat was injected unilaterally or bilaterally into multiple sites. Six of these patients also had simultaneous microlaryngoscopic removal of other benign glottic lesions. Outcome measurements included video stroboscopy; Grade, Roughness, Breathiness, Asthenia, Strain (GRBAS) score; Voice Handicap Index (VHI); and acoustic analysis, performed preoperatively, 3, 12, 24, and 36 months after surgery. RESULTS Ten augmentations were unilateral and 12 bilateral. Comparing the preoperative and 36-month postoperative periods, the mean VHI score improved from 73.45 (±22.78) to 44.88 (±28.93), P = .001, and the mean GRBAS decreased from 8.64 (±3.89) to 2.82 (±2.3), P = .001; 24 months postoperatively, the mean fundamental frequency decreased from 163.88 Hz (±41.61) to 150.44 Hz (±41.47), P = .012. Stroboscopic analysis revealed statistically significant improvement in mucosal wave propagation, phase closure, and phase symmetry. Best results were achieved in the UVFP subgroup. Computed tomography scans demonstrated long-term viability of the implanted adipose tissue. CONCLUSION Fat is an excellent source of autologous graft. With careful patient selection and proper surgical technique, fat is suitable for long-term correction of glottic insufficiency. Fat augmentation should be considered as a long-lasting or even permanent solution, rather than temporary.
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Affiliation(s)
- Yonatan Lahav
- Department of Otolaryngology Head and Neck Surgery, Kaplan Medical Center, Rehovot, Israel.,Faculty of Medicine, The Hebrew University, Jerusalem, Israel
| | - Liron Malka-Yosef
- Department of Otolaryngology Head and Neck Surgery, Kaplan Medical Center, Rehovot, Israel.,Faculty of Medicine, The Hebrew University, Jerusalem, Israel
| | - Yael Shapira-Galitz
- Department of Otolaryngology Head and Neck Surgery, Kaplan Medical Center, Rehovot, Israel.,Faculty of Medicine, The Hebrew University, Jerusalem, Israel
| | - Oded Cohen
- Department of Otolaryngology Head and Neck Surgery, Kaplan Medical Center, Rehovot, Israel.,Faculty of Medicine, The Hebrew University, Jerusalem, Israel
| | - Doron Halperin
- Department of Otolaryngology Head and Neck Surgery, Kaplan Medical Center, Rehovot, Israel.,Faculty of Medicine, The Hebrew University, Jerusalem, Israel
| | - Hagit Shoffel-Havakuk
- Department of Otolaryngology Head and Neck Surgery, Rabin Medical Center, Petach-Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Yang JZ, Qiu LH, Xiong SH, Dang JL, Rong XK, Hou MM, Wang K, Yu Z, Yi CG. Decellularized adipose matrix provides an inductive microenvironment for stem cells in tissue regeneration. World J Stem Cells 2020; 12:585-603. [PMID: 32843915 PMCID: PMC7415251 DOI: 10.4252/wjsc.v12.i7.585] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 05/27/2020] [Accepted: 05/30/2020] [Indexed: 02/06/2023] Open
Abstract
Stem cells play a key role in tissue regeneration due to their self-renewal and multidirectional differentiation, which are continuously regulated by signals from the extracellular matrix (ECM) microenvironment. Therefore, the unique biological and physical characteristics of the ECM are important determinants of stem cell behavior. Although the acellular ECM of specific tissues and organs (such as the skin, heart, cartilage, and lung) can mimic the natural microenvironment required for stem cell differentiation, the lack of donor sources restricts their development. With the rapid development of adipose tissue engineering, decellularized adipose matrix (DAM) has attracted much attention due to its wide range of sources and good regeneration capacity. Protocols for DAM preparation involve various physical, chemical, and biological methods. Different combinations of these methods may have different impacts on the structure and composition of DAM, which in turn interfere with the growth and differentiation of stem cells. This is a narrative review about DAM. We summarize the methods for decellularizing and sterilizing adipose tissue, and the impact of these methods on the biological and physical properties of DAM. In addition, we also analyze the application of different forms of DAM with or without stem cells in tissue regeneration (such as adipose tissue), repair (such as wounds, cartilage, bone, and nerves), in vitro bionic systems, clinical trials, and other disease research.
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Affiliation(s)
- Ji-Zhong Yang
- Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
| | - Li-Hong Qiu
- Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
| | - Shao-Heng Xiong
- Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
| | - Juan-Li Dang
- Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
| | - Xiang-Ke Rong
- Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
| | - Meng-Meng Hou
- Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
| | - Kai Wang
- Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
| | - Zhou Yu
- Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
| | - Cheng-Gang Yi
- Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
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M. Dominguez L, Villarreal R, Simpson CB. Voice Outcomes of Lipoinjection Versus Medialization Laryngoplasty for Nonparalytic Glottic Insufficiency. Laryngoscope 2018; 129:1164-1168. [DOI: 10.1002/lary.27573] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/20/2018] [Indexed: 11/09/2022]
Affiliation(s)
- Laura M. Dominguez
- Department of Otolaryngology, UT Health San Antonio San Antonio Texas U.S.A
| | | | - C. Blake Simpson
- Department of Otolaryngology, UT Health San Antonio San Antonio Texas U.S.A
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