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1.
Biochem Biophys Res Commun ; 732: 150401, 2024 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-39033554

RESUMEN

The pathophysiology of laryngopharyngeal reflux (LPR) and its impact on the vocal fold is not well understood, but may involve acid damage to vocal fold barrier functions. Two different components encompass vocal fold barrier function: the mucus barrier and tight junctions. Mucus retained on epithelial microprojections protects the inside of the vocal fold by neutralizing acidic damage. Tight junctions control permeability between cells. Here we developed an in vitro experimental system to evaluate acidic injury and repair of vocal fold barrier functions. We first established an in vitro model of rat vocal fold epithelium that could survive at least one week after barrier function maturation. The model enabled repeated evaluation of the course of vocal fold repair processes. Then, an injury experiment was conducted in which vocal fold cells were exposed to a 5-min treatment with acidic pepsin that injured tight junctions and cell surface microprojections. Both of them healed within one day of injury. Comparing vocal fold cells treated with acid alone with cells treated with acidic pepsin showed that acidic pepsin had a stronger effect on intercellular permeability than acid alone, whereas pepsin had little effect on microprojections. This result suggests that the proteolytic action of pepsin has a larger effect on protein-based tight junctions than on phospholipids in microprojections. This experimental system could contribute to a better understanding of vocal fold repair processes after chemical or physical injuries, as well as voice problems due to LPR pathogenesis.


Asunto(s)
Pepsina A , Uniones Estrechas , Pliegues Vocales , Animales , Pepsina A/metabolismo , Pepsina A/farmacología , Pliegues Vocales/efectos de los fármacos , Pliegues Vocales/patología , Pliegues Vocales/metabolismo , Pliegues Vocales/lesiones , Ratas , Uniones Estrechas/metabolismo , Uniones Estrechas/efectos de los fármacos , Ratas Sprague-Dawley , Masculino , Reflujo Laringofaríngeo/metabolismo , Reflujo Laringofaríngeo/tratamiento farmacológico , Reflujo Laringofaríngeo/patología , Concentración de Iones de Hidrógeno
2.
Am J Pathol ; 192(5): 771-782, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35189097

RESUMEN

Macrophages aid in wound healing by changing their phenotype and can be a key driver of fibrosis. However, the contribution of macrophage phenotype to fibrosis following vocal fold injury remains unclear. Peroxisome proliferator-activated receptor-γ (PPARγ) is expressed mainly by macrophages during early wound healing and regulates the macrophage phenotype. This study aimed to evaluate the effects of pioglitazone (PIO), a PPARγ agonist, on the macrophage phenotype and fibrosis following vocal fold injury in rats. PIO was injected into the rat vocal folds on days 1, 3, 5, and 7 after injury, and the vocal fold lamina propria was evaluated on days 4 and 56 after injury. Moreover, THP-1-derived macrophages were treated with PIO, and the expression of proinflammatory cytokines under lipopolysaccharide/interferon-γ stimulation was analyzed. PIO reduced the expression of Ccl2 both in vivo and in vitro. Furthermore, PIO decreased the density of inducible nitric oxide synthase+ CD68+ macrophages and inhibited the expression of fibrosis-related factors on day 4 after injury. On day 56 after injury, PIO inhibited fibrosis, tissue contracture, and hyaluronic acid loss in a PPARγ-dependent manner. These results indicate that PPARγ activation could inhibit accumulation of inflammatory macrophages and improve tissue repair. Taken together, these findings imply that inflammatory macrophages play a key role in vocal fold fibrosis.


Asunto(s)
PPAR gamma , Tiazolidinedionas , Animales , Fibrosis , Hipoglucemiantes/farmacología , Activación de Macrófagos , PPAR gamma/genética , Pioglitazona/farmacología , Ratas , Tiazolidinedionas/farmacología , Pliegues Vocales/metabolismo
3.
Cell Tissue Res ; 394(1): 163-175, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37460682

RESUMEN

The maintenance of planar polarity in airway multiciliated cells (MCCs) has been poorly characterized. We recently reported that the direction of ciliary beating in a surgically inverted tracheal segment remained inverted beyond the time required for the turnover of cells, without adjustment to global distal-to-proximal polarity. We hypothesized that the local maintenance of tissue-level polarity occurs via locally reproduced cells. To provide further insight regarding this hypothetical property, we performed allotransplantation of an inverted tracheal segment between wild-type (donor) and tdTomato-expressing (host) rats, with and without scratching the mucosa of the transplants. The origin of cells in the transplants was assessed using tdTomato-specific immunostaining. Ciliary movement and structures were observed by high-speed video and electron microscopy to analyze MCC orientations. Variabilities in the orientations of closely and distantly located MCCs were analyzed to evaluate the local- and broad-scale coordination of polarity, respectively. The epithelium was maintained by donor-derived cells in the non-scratched inverted transplant over 6 months, beyond one cycle of turnover. The inverted orientation of MCCs was also maintained throughout the non-scratched transplant. MCCs regenerated in the scratched transplant were derived from the host and exhibited diverse orientations across the transplant. However, the orientations of adjacent regenerated MCCs were often coordinated, indicating that airway MCCs can locally coordinate their orientations. A steady-state airway may maintain MCC orientation by locally reproducing MCCs via the local coordination of polarity. This local coordination enables the formation and maintenance of tissue-level polarity in small regions after mucosal injury.

4.
Int J Clin Oncol ; 28(4): 521-530, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36780098

RESUMEN

BACKGROUND: Endoscopic laryngopharyngeal surgery (ELPS) is a minimally invasive transoral surgery for superficial pharyngeal and laryngeal cancer, but dysphagia occasionally occurs post-treatment. We investigated dysphagia following ELPS and its risk factors. METHODS: Of the 145 patients who underwent ELPS, 92 were evaluated in this study using the Hyodo score, Functional Outcome Swallowing Scale, Eating Assessment Tool-10 along with the total scores for the three items of the method of intake, time, and food preoperatively and on postoperative 1, 3, and 6 months. We examined the 6-month trends of these values. Furthermore, the fasting period post-surgery, the need for swallowing rehabilitation by a speech therapist, and postoperative pneumonia episodes were set as outcomes reflecting the short-term swallowing function. We determined the associations between these outcomes and patient background factors. RESULTS: Postoperatively, the Hyodo score worsened at 1 month but recovered at 3 months. The Hyodo scores of all patients who underwent postcricoid ELPS did not worsen. The diameter of the resected specimen (DRS) was significantly associated with the need for swallowing rehabilitation and postoperative fasting time. A DRS ≥ 35 mm was considered the threshold for the need of swallowing rehabilitation, postoperative pneumonia, and prolonged postoperative fasting time. CONCLUSION: ELPS exerts a temporal and limited impact on the swallowing function, which recovers within 3 months in every swallowing evaluation. This necessitates additional care during the treatment of patients with mucosal defects ≥ 35 mm, owing to the significant association between the DRS and short-term swallowing function.


Asunto(s)
Trastornos de Deglución , Neoplasias Laríngeas , Humanos , Deglución , Trastornos de Deglución/etiología , Endoscopía/efectos adversos , Endoscopía/métodos , Neoplasias Laríngeas/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos
5.
Endocr J ; 70(10): 969-976, 2023 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-37635058

RESUMEN

The operative procedure in the surgical treatment of parathyroid carcinoma differs from that of benign hyperparathyroidism. However, preoperative differentiation is often difficult. This study elucidated how clinicians diagnose parathyroid carcinoma and the relationship between preoperative diagnosis and the operative course. Using a retrospective chart review, twenty cases of parathyroid carcinoma from nine participating centers were examined. In 11 cases with preoperative suspicion of malignancy, at least one of these three features was found: elevated serum calcium level (>14 mg/dL), palpable mass, and irregular margin on ultrasonography. Although an intact parathyroid hormone (iPTH) threshold to suspect malignancy has not been established, six cases showed marked iPTH elevation exceeding 8.0 times the upper limit of normal. One case was excluded from analysis due to hemodialysis. Compared with the four cases that showed calcium elevation, the iPTH threshold might represent better sensitivity. Among 9 cases of benign preoperative diagnosis, six cases were performed with pericapsular resection. In three cases where malignancy was suspected in the middle of the operation, the recommended en bloc resection with ipsilateral thyroid lobectomy was not performed but a parathyroidectomy with surrounding soft tissue. In contrast, 10 preoperatively suspected cases underwent en bloc resection, and one case underwent pericapsular resection followed by supplementary ipsilateral hemithyroidectomy due to the uncertain pre- and intraoperative findings to determine the diagnosis. In conclusion, the surgical procedure for parathyroid carcinoma strongly depends on the preoperative diagnosis. The presence of excessive iPTH levels might contribute to improved preoperative diagnostic sensitivity for parathyroid carcinoma.


Asunto(s)
Hiperparatiroidismo , Neoplasias de las Paratiroides , Humanos , Neoplasias de las Paratiroides/diagnóstico , Neoplasias de las Paratiroides/cirugía , Neoplasias de las Paratiroides/patología , Calcio , Estudios Retrospectivos , Hormona Paratiroidea
6.
Biochem Biophys Res Commun ; 601: 31-37, 2022 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-35220011

RESUMEN

Post-radiation fibrosis of the vocal folds is thought to cause vocal impairment. However, the mechanism by which this occurs has been poorly documented, probably because of the lack of an appropriate experimental animal model. The purpose of this study was to establish a simple and reproducible mouse model of laryngeal radiation to investigate the development of vocal fold fibrosis over time. C57BL/6 mice individually placed in a lead shield were irradiated with a single dose of 20 Gy. At 1, 2, and 6 months after irradiation, larynges were harvested and subjected to histological examination and gene expression analysis. Irradiated vocal folds showed time-dependent tissue contraction and increased collagen deposition, with no significant difference in the changes in hyaluronic acid levels. Transcriptional analysis revealed upregulated expressions of TGF-ß1 and iNOS at 6 months, but downregulated expressions of Acta2, Col1a1, Col3a1, and MMP8. Moreover, elevated TGF-ß1 and reduced downstream gene expression levels indicated the existence of an inhibitory factor over the TGF-ß/Smad pathway. Discrepancies in histological and transcriptional studies of collagen might suggest that radiation-induced vocal fold fibrosis could be caused by the elongated turnover of collagen. Overall, we established a mouse model of radiation-induced vocal fold fibrosis using a simple protocol. Further investigations are warranted to elucidate the pathogenesis of irradiation-induced fibrosis in vocal folds.


Asunto(s)
Factor de Crecimiento Transformador beta1 , Pliegues Vocales , Animales , Colágeno/genética , Colágeno/metabolismo , Modelos Animales de Enfermedad , Fibrosis , Ratones , Ratones Endogámicos C57BL , Factor de Crecimiento Transformador beta1/metabolismo , Pliegues Vocales/metabolismo , Pliegues Vocales/patología
8.
Eur Arch Otorhinolaryngol ; 273(5): 1221-5, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26742908

RESUMEN

In the management of laryngeal pre-cancerous lesions such as dysplasia or carcinoma in situ (CIS), it is important that lesion regression occur without any complications. As a minimally invasive treatment option, photocoagulation therapy using angiolytic lasers has been attracting attention. Therapeutic effects have been reported for this type of treatment, however, vocal function after treatment has not been well discussed. In this retrospective case series, we examined the therapeutic effects of photocoagulation therapy on laryngeal dysplasia and the impact on vocal function. Twenty-four patients with laryngeal dysplasia or CIS were treated with photocoagulation therapy using angiolytic lasers. Two patients were treated under general anesthesia, the remaining 22 patients were treated with topical anesthesia. Before and after treatment the extent of the lesion and vocal function was evaluated by endoscopic examination and acoustic and aerodynamic analyses, respectively. More than 50 % disease regression was observed in 20 of 24 patients. Acoustic and aerodynamic analyses revealed improvement in pitch perturbation quotient with no impairment in other parameters. Photocoagulation therapy using angiolytic lasers has proven to be feasible and safe for the treatment of laryngeal dysplasia.


Asunto(s)
Carcinoma in Situ , Neoplasias Laríngeas , Laringoscopía/métodos , Laringe , Fotocoagulación/métodos , Lesiones Precancerosas , Anciano , Anciano de 80 o más Años , Anestesia Local/métodos , Carcinoma in Situ/patología , Carcinoma in Situ/cirugía , Femenino , Humanos , Japón , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/cirugía , Laringe/patología , Laringe/cirugía , Fotocoagulación/instrumentación , Masculino , Persona de Mediana Edad , Lesiones Precancerosas/patología , Lesiones Precancerosas/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Calidad de la Voz
9.
Auris Nasus Larynx ; 51(4): 703-707, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38749306

RESUMEN

OBJECTIVE: Laryngeal framework surgery is a widely accepted treatment for unilateral vocal fold paralysis with good functional outcomes. Recently, with the aging of the population, opportunities to perform this procedure in elderly patients have increased; however, the safety and efficacy of this procedure in elderly patients has not been established. Therefore, this study aimed to investigate the safety and functional outcomes of laryngeal framework surgery in elderly patients. METHODS: Between January 2008 and December 2017, 97 patients with unilateral vocal fold paralysis underwent laryngeal framework surgery, and 71 among them completed pre- and post-operative voice function evaluations. The clinical course of these 71 patients were retrospectively reviewed. RESULTS: Out of 71 patients, 35 were assigned to the younger group (< 65 years) and 36 to the elderly group (≥ 65 years). Complications included post-operative edema and submucosal hematoma that were safely managed in all cases, and no differences were identified between the groups. Significant improvements were observed in maximum phonation time (MPT), mean flow rate, alternating current/direct current ratio, pitch perturbation quotient, amplitude perturbation quotient, and noise-to-harmonic ratio in both groups, and multivariate analysis of variance revealed greater improvement in the younger group in MPT. CONCLUSION: Laryngeal framework surgeries for unilateral vocal fold paralysis are safe and effective, regardless of age. Better improvement was observed in the younger group in the MPT suggesting that the effects of laryngeal framework surgeries is more likely to be present in the younger group than in the elderly.


Asunto(s)
Parálisis de los Pliegues Vocales , Humanos , Parálisis de los Pliegues Vocales/cirugía , Parálisis de los Pliegues Vocales/fisiopatología , Anciano , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Factores de Edad , Complicaciones Posoperatorias , Resultado del Tratamiento , Fonación , Calidad de la Voz , Anciano de 80 o más Años , Adulto , Laringoplastia/métodos
10.
Auris Nasus Larynx ; 51(4): 713-716, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38796982

RESUMEN

OBJECTIVE: To develop phonosurgery skills, surgical training of the actual larynx is essential. In our institution, the Japanese deer (Cervus Nippon aplodontids) larynx is used in phonosurgery training. This study aimed to examine the similarities and differences between the Japanese deer and human larynx and to demonstrate their utility in vocal surgery practice. METHODS: A comparative study was conducted using 30 Japanese deer larynges and 51 human donor larynges, evaluating the overall framework, dimensions, and angle of the thyroid cartilage, vocal cord length, and location of the arytenoid cartilage muscular process. The changes and movements of the vocal folds during contraction and relaxation of each internal laryngeal muscle were also visually analyzed. RESULTS: The larynx size of Japanese deer is intermediate between that of human males and females. The adduction and abduction of the vocal folds induced by contraction of the posterior and lateral cricoarytenoid muscles, as well as the extension of the vocal folds induced by contraction of the cricothyroid muscle, behaved in the same manner as in the human larynx. CONCLUSION: The morphology of the Japanese deer larynx is similar to that of the human larynx, making it suitable for use in dissection and surgical practice. Owing to the recent animal damage problem and the popularity of gibier cuisine, large quantities of Japanese deer larynx are available at low prices. We believe that the Japanese deer larynx is the most appropriate animal for phonosurgery training so far.


Asunto(s)
Ciervos , Músculos Laríngeos , Laringe , Pliegues Vocales , Animales , Laringe/cirugía , Laringe/anatomía & histología , Masculino , Humanos , Pliegues Vocales/cirugía , Pliegues Vocales/anatomía & histología , Femenino , Músculos Laríngeos/cirugía , Músculos Laríngeos/anatomía & histología , Cartílago Aritenoides/cirugía , Cartílago Aritenoides/anatomía & histología , Cartílago Tiroides/cirugía , Cartílago Tiroides/anatomía & histología , Japón , Pueblos del Este de Asia
11.
Laryngoscope ; 134(8): 3537-3541, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38280184

RESUMEN

OBJECTIVE: This study aimed to evaluate the significance of background noise in machine learning models assessing the GRBAS scale for voice disorders. METHODS: A dataset of 1406 voice samples was collected from retrospective data, and a 5-layer 1D convolutional neural network (CNN) model was constructed using TensorFlow. The dataset was divided into training, validation, and test data. Gaussian noise was added to test samples at various intensities to assess the model's noise resilience. The model's performance was evaluated using accuracy, F1 score, and quadratic weighted Cohen's kappa score. RESULTS: The model's performance on the GRBAS scale generally declined with increasing noise intensities. For the G scale, accuracy dropped from 70.9% (original) to 8.5% (at the highest noise), F1 score from 69.2% to 1.3%, and Cohen's kappa from 0.679 to 0.0. Similar declines were observed for the remaining RBAS components. CONCLUSION: The model's performance was affected by background noise, with substantial decreases in evaluation metrics as noise levels intensified. Future research should explore noise-tolerant techniques, such as data augmentation, to improve the model's noise resilience in real-world settings. LEVEL OF EVIDENCE: This study evaluates a machine learning model using a single dataset without comparative controls. Given its non-comparative design and specific focus, it aligns with Level 4 evidence (Case-series) under the 2011 OCEBM guidelines Laryngoscope, 134:3537-3541, 2024.


Asunto(s)
Aprendizaje Profundo , Ruido , Trastornos de la Voz , Humanos , Estudios Retrospectivos , Trastornos de la Voz/diagnóstico , Trastornos de la Voz/fisiopatología , Trastornos de la Voz/etiología , Calidad de la Voz/fisiología , Masculino , Femenino , Redes Neurales de la Computación
12.
Tissue Eng Part A ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-38970444

RESUMEN

Tracheal cartilage provides structural support to the airways to enable breathing. However, it can become damaged or impaired, sometimes requiring surgical resection and reconstruction. Previously, we clinically applied an artificial trachea composed of a polypropylene mesh and collagen sponge, with a favorable postoperative course. However, the artificial trachea presents a limitation, as the mesh is not biodegradable and cannot be used in pediatric patients. Compared to a polypropylene mesh, regenerated cartilage represents an ideal material for reconstruction of the damaged trachea. The use of mesenchymal stem cells (MSCs) as a source for cartilage regeneration has gained widespread acceptance, but challenges such as the invasiveness of harvesting and limited cell supply persist. Therefore, we focused on the potential of human-induced pluripotent stem cell (hiPSC)-derived mesenchymal stem cells (iMSCs) for tracheal cartilage regeneration. In this study, we aimed to regenerate tracheal cartilage on an artificial trachea as a preliminary step to replace the polypropylene mesh. iMSCs were induced from hiPSCs through neural crest cells and transplanted with a polypropylene mesh covered with a collagen sponge into the damaged tracheal cartilage in immunodeficient rats. Human nuclear antigen (HNA)-positive cells were observed in all six rats at 4 weeks and in six out of seven rats at 12 weeks after transplantation, indicating that transplanted iMSCs survived within the tracheal cartilage defects of rats. The HNA-positive cells coexpressed SOX9, and type II collagen was detected around HNA-positive cells in four of six rats at 4 weeks and in three of seven rats at 12 weeks after transplantation, reflecting cartilage-like tissue regeneration. These results indicate that the transplanted iMSCs could differentiate into chondrogenic cells and promote tracheal cartilage regeneration. iMSC transplantation thus represents a promising approach for human tracheal reconstruction.

13.
Auris Nasus Larynx ; 51(4): 774-778, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38875994

RESUMEN

OBJECTIVE: Tracheoesophageal puncture (TEP) is one of the most established methods for voice reacquisition following total laryngectomy. The most difficult complication following TEP is the management of saliva leakage or secretion into the trachea due to TE fistula enlargement. In this study, we devised a new strategy to close TE fistulas and confirmed its safety and effectiveness. METHODS: Skin incision: If the tracheal mucosa around the voice prosthesis appears intact and normal, an arcuate incision, from 10 to 2 o'clock, is made on the skin 5 mm superior to the edge of the stoma. However, if the surrounding tracheal mucosa is fragile because of leaking, the incision is made on the superior edge of the stoma, with later reconstruction of the posterior tracheal wall. Separation of the trachea and esophagus: If the esophagotracheal spatium appears normal and is easy to dissect, the connective pipes can be found easily. After cutting the pipe, a ligature alone is sufficient for the tracheal side; however, the esophageal wall is closed with Gambee sutures. If the esophagotracheal spatium is compromised and the posterior tracheal wall is fragile (due to saliva leakage), we remove the posterior wall and reconstruct the area using the superior skin flap. We performed our novel method on four patients with intractable conditions; postradiotherapy for laryngeal cancer, total pharyngo-laryngo-esophagectomy (TPLE) with jejunum reconstruction, TPLE with gastric lifting reconstruction, and in a patient who underwent cervicothoracic incisional drainage for descending necrotizing mediastinitis. RESULTS: None of the cases showed postoperative leakage from the fistula, and oral intake was resumed without difficulty. CONCLUSION: This study showed that this strategy based on TE fistula conditions is effective even in difficult-to-treat cases.


Asunto(s)
Esófago , Neoplasias Laríngeas , Laringectomía , Tráquea , Fístula Traqueoesofágica , Humanos , Fístula Traqueoesofágica/cirugía , Laringectomía/métodos , Masculino , Neoplasias Laríngeas/cirugía , Persona de Mediana Edad , Tráquea/cirugía , Esófago/cirugía , Anciano , Complicaciones Posoperatorias/cirugía , Colgajos Quirúrgicos , Punciones , Femenino , Laringe Artificial
14.
Auris Nasus Larynx ; 51(6): 911-916, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39265196

RESUMEN

OBJECTIVE: Airway stenosis impairs the quality of life of patients. However, the epidemiology and pathophysiology of airway stenosis remain underexplored owing to its rarity. Airway stenosis may go undetected for a long period without accurate diagnosis or treatment owing to the lack of established treatment guidelines. Thus, clinical information must be accumulated and analyzed to generate evidence-based treatment strategies for this rare entity. METHODS: A retrospective nationwide epidemiological survey was conducted targeting patients with pharyngeal, laryngeal, or tracheal stenosis in Japan. The initial survey was conducted across 1393 facilities between 2013 and 2017 to evaluate the treatment of airway stenosis. The clinical information of the patients was collected via a secondary survey. RESULTS: The primary survey revealed that airway stenosis was treated at only 43 % of the facilities over the 5-year period. The secondary survey revealed that 284 cases were registered across 57 facilities. The number of patients with acquired stenosis exceeded that of those with congenital stenosis. The larynx or cervical trachea was the most common site of stenosis, and intubation or tracheostomy was the most common cause of stenosis. Approximately 76 % of patients underwent surgical treatment, and tracheostomy was the most common procedure. Stenosis persisted in > 70 % of patients at the last visit. CONCLUSIONS: This study clarified the clinical background of patients with pharyngeal, laryngeal, and tracheal stenosis in Japan and the surgical treatment received. The findings of this study confirmed the rarity of airway stenosis and the difficulty in treating this entity.

15.
Tissue Eng Part A ; 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38832872

RESUMEN

Investigating the infection mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the airway epithelium and developing effective defense strategies against infection are important. To achieve this, establishing appropriate infection models is crucial. Therefore, various in vitro models, such as cell lines and primary cultures, and in vivo models involving animals that exhibit SARS-CoV-2 infection and genetically humanized animals have been used as animal models. However, no animal model has been established that allows infection experiments with human cells under the physiological environment of airway epithelia. Therefore, we aimed to establish a novel animal model that enables infection experiments using human cells. Human induced pluripotent stem cell-derived airway epithelial cell-transplanted nude rats (hiPSC-AEC rats) were used, and infection studies were performed by spraying lentiviral pseudoviruses containing SARS-CoV-2 spike protein and the GFP gene on the tracheae. After infection, immunohistochemical analyses revealed the existence of GFP-positive-infected transplanted cells in the epithelial and submucosal layers. In this study, a SARS-CoV-2 infection animal model including human cells was established mimicking infection through respiration, and we demonstrated that the hiPSC-AEC rat could be used as an animal model for basic research and the development of therapeutic methods for human-specific respiratory infectious diseases.

16.
Auris Nasus Larynx ; 51(3): 575-582, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38547566

RESUMEN

OBJECTIVE: Transoral surgery is a minimally invasive treatment but may cause severe dysphagia at a lower rate than chemoradiotherapy. METHODS: We compared clinical information, surgical complications, and swallowing function in patients who underwent transoral nonrobotic surgery for laryngo-pharyngeal squamous cell carcinoma between 2015 and 2021 in a multicenter retrospective study. RESULTS: Six hundred and forty patients were included. Postoperative bleeding was observed in 20 cases (3.1%), and the risk factor was advanced T category. Postoperative laryngeal edema was observed in 13 cases (2.0%), and the risk factors were prior radiotherapy, advanced T stage, and concurrent neck dissection in patients with resected HPC. Dysphagia requiring nutritional support was observed in 29 cases (4.5%) at 1 month postoperatively and in 19 cases (3.0%) at 1 year postoperatively, respectively. The risk factors for long-term dysphagia were prior radiotherapy and advanced T category. Short-term risk factors for dysphagia were prior radiotherapy, advanced T category, and concurrent neck dissection, while long-term risk factors for dysphagia were only prior radiotherapy and advanced T category. CONCLUSION: Prior radiotherapy, advanced T stage, and concurrent neck dissection increased the incidence of postoperative laryngeal edema and short-term dysphagia, but concurrent neck dissection did not affect long-term dysphagia. Such features should be considered when considering the indication for transoral surgery and postoperative management.


Asunto(s)
Trastornos de Deglución , Neoplasias Laríngeas , Disección del Cuello , Neoplasias Faríngeas , Complicaciones Posoperatorias , Humanos , Masculino , Estudios Retrospectivos , Trastornos de Deglución/etiología , Femenino , Neoplasias Laríngeas/cirugía , Persona de Mediana Edad , Anciano , Complicaciones Posoperatorias/epidemiología , Neoplasias Faríngeas/cirugía , Factores de Riesgo , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Estadificación de Neoplasias , Adulto , Edema Laríngeo/etiología , Carcinoma de Células Escamosas/cirugía , Hemorragia Posoperatoria/epidemiología , Anciano de 80 o más Años , Cirugía Endoscópica por Orificios Naturales
17.
Head Neck ; 46(1): 118-128, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37897205

RESUMEN

BACKGROUND: Late laryngopharyngeal cancers after transoral surgery include not only local recurrences but also metachronous multiple cancers. METHODS: We compared clinical information, surgical outcomes, and late laryngopharyngeal cancers in patients who underwent transoral nonrobotic surgery for laryngopharyngeal squamous cell carcinoma without lymph node metastases between 2015 and 2021 in a multicenter retrospective study. RESULTS: Four hundred and fifty-seven patients were included. Positive surgical margins were found in 121 patients (26.5%). Twenty-two patients (4.8%) received additional treatment. Positive horizontal margins of invasive carcinoma (p = 0.003) and positive horizontal margins of carcinoma in situ only (p = 0.032) were independent risk factors for local recurrence, and prior radiotherapy (p = 0.001) for metachronous multiple cancers. Local control was significantly worse without additional treatment (p = 0.049), but there was no significant difference in survival. CONCLUSIONS: Patients with positive margins had an increased frequency of local recurrence, but salvage therapy was effective.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Hipofaríngeas , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Estudios Retrospectivos , Carcinoma de Células Escamosas/cirugía , Recurrencia Local de Neoplasia/patología
18.
Head Neck ; 46(8): 1913-1921, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38294099

RESUMEN

BACKGROUND: Hypopharyngeal carcinoma is likely to spread to the lymph nodes, but there is no established strategy for management in transoral surgery. METHODS: We compared oncologic and functional outcomes in a retrospective multicenter study of patients who underwent transoral surgery for hypopharyngeal carcinoma between 2015 and 2021. RESULTS: Two-hundred and thirty-two patients were included. Comparing patients with and without adjuvant radiotherapy, 3-year regional recurrence-free survival (RRFS) was not significantly different in pN2b and pN2c, but was significantly worse in pN3b without adjuvant radiotherapy. In patients without neck dissection, the 3-year RRFS was 85.6%, 76.8%, and 70.0% for T1, T2, and T3 primary lesions, respectively, and was significantly worse for T2 or higher (p = 0.035). CONCLUSIONS: In the absence of extracapsular invasion, regional control did not deteriorate without adjuvant therapy. If prophylactic neck dissection is not performed, careful follow-up is necessary if the primary lesion is T2 or greater.


Asunto(s)
Neoplasias Hipofaríngeas , Metástasis Linfática , Disección del Cuello , Humanos , Neoplasias Hipofaríngeas/patología , Neoplasias Hipofaríngeas/mortalidad , Neoplasias Hipofaríngeas/cirugía , Neoplasias Hipofaríngeas/terapia , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/terapia , Estadificación de Neoplasias , Anciano de 80 o más Años , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Radioterapia Adyuvante , Supervivencia sin Enfermedad , Cirugía Endoscópica por Orificios Naturales/métodos
19.
Auris Nasus Larynx ; 50(1): 94-101, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35701287

RESUMEN

OBJECTIVES: Intraoperative cone beam computed tomography (CBCT) imaging has the potential to facilitate the surgical procedure. The current preliminary retrospective chart review investigated the benefits of intraoperative CBCT during laryngoplasty. METHOD: This study examined 26 cases that underwent intraoperative CBCT imaging during laryngoplasty, with one patient who counted twice due to first and revision surgery. The visual quality of structures of interest (glottal shape, thyroid cartilage, arytenoid cartilage, and implants) was determined using intraoperative CBCT during laryngoplasty. Each patient also underwent an aerodynamic assessment. RESULTS: CBCT provided unique information, such as surgical landmarks in severe scarring, the subglottal shape, and the rotation angle of the arytenoid cartilage during arytenoid adduction. Nonetheless, 26.9% (7 of 26) of cases were affected by motion artifact, due to the long acquisition time. When motion artifact-negative cases were evaluated, 100% of glottal shape and more than 89% of thyroid cartilage were well visualized. All arytenoids were well-visualized in patients ≥ 50 years of age and without motion artifact, while CBCT failed to visualize the arytenoids in 2 of 4 patients who were < 50 years, due to the lack of calcifications. After medialization surgery, the yields of improved maximal phonation times (MPTs) in the motion artifact-negative and -positive groups were 8.7 sec and 3.4 sec, respectively (p = 0.032; Welch's t test). This comparison indicates intraoperative CBCT would contribute in MPT improvement, if CBCT is taken in measurable quality. CONCLUSION: The potential benefits of intraoperative CBCT during laryngoplasty were demonstrated. A corollary, prospective study is warranted to further confirmation.


Asunto(s)
Enfermedades de la Laringe , Laringoplastia , Parálisis de los Pliegues Vocales , Humanos , Laringoplastia/métodos , Parálisis de los Pliegues Vocales/diagnóstico por imagen , Parálisis de los Pliegues Vocales/cirugía , Fonación , Estudios Retrospectivos , Estudios Prospectivos , Cartílago Aritenoides , Tomografía Computarizada por Rayos X , Enfermedades de la Laringe/cirugía , Resultado del Tratamiento
20.
Magn Reson Med Sci ; 22(1): 79-85, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-35249911

RESUMEN

PURPOSE: To evaluate whether readout-segmented echo-planar imaging (RS-EPI) diffusion-weighted imaging (DWI) can reduce image distortion and improve the lesion identification in parathyroid adenomas (PTAs) compared to single-shot EPI (SS-EPI) DWI, and to determine whether PTAs can be differentiated from other soft tissue structures of the head and neck region by using the apparent diffusion coefficient (ADC) value. METHODS: We retrospectively analyzed the preoperative MR images including DWI of 24 patients with surgically confirmed PTA. RS-EPI and SS-EPI DWI were evaluated by two independent readers for the identification of the lesions and distortion. The ADC values of the PTAs were compared with those of thyroid glands and cervical lymph nodes. RESULTS: RS-EPI provided significantly less distortion compared to SS-EPI. RS-EPI tended to have better lesion identification compared with SS-EPI without a statistically significant difference. On SS-EPI, the PTAs had significantly higher ADC values compared with the cervical lymph nodes. On RS-EPI, the PTAs had significantly higher ADC values compared with the thyroid glands and cervical lymph nodes. CONCLUSION: RS-EPI reduces the DWI distortion in PTAs. The ADC value obtained using RS-EPI enables the differentiation of PTAs from nearby structures, such as thyroid glands and cervical lymph nodes.


Asunto(s)
Neoplasias de las Paratiroides , Humanos , Neoplasias de las Paratiroides/diagnóstico por imagen , Neoplasias de las Paratiroides/cirugía , Imagen Eco-Planar/métodos , Estudios Retrospectivos , Imagen de Difusión por Resonancia Magnética/métodos , Difusión
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