Publications by authors named "Ichiro Tateya"

117 Publications

Airway ciliated cells regenerated on collagen sponge implants acquire planar polarities towards nearby edges of implanted areas.

J Tissue Eng Regen Med 2021 May 19. Epub 2021 May 19.

Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Tissue-engineered tracheae have been developed to replace defective tracheae. However, the direction of ciliated cells in the regenerated epithelium remains unclear. We investigated planar polarity formed in the regenerated airway epithelium after tracheal graft implantation. We partially resected the rat trachea and implanted a collagen scaffold. The direction of the basal foot was assessed by transmission electron microscopy. Immunofluorescence staining was performed to examine the biased distribution of Vangl1 and Frizzled6 proteins. The direction of mucociliary transport was analyzed by video microscopy. Our results showed that the basal feet of cilia in the proximal and distal regions of the implanted areas were respectively oriented toward the proximal and distal directions. The biased distribution of Vangl1 and Frizzled6, and the directions of mucociliary transport showed that planar polarities formed in the regenerated epithelium were oriented toward the proximal, distal, left, and right directions in the proximal, distal, left, and right regions of the implanted area. These polarities persisted until nine months after implantation. Hence, the results suggest that planar polarities formed in epithelia regenerated on tracheal grafts are directed toward the nearby edges of implanted areas and are preserved for a prolonged period. The polarities can, at least partially, contribute to clearing external materials from the implanted areas by transporting them to a normal region.
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http://dx.doi.org/10.1002/term.3220DOI Listing
May 2021

Transoral surgery for superficial head and neck cancer: National Multi-Center Survey in Japan.

Cancer Med 2021 Jun 15;10(12):3848-3861. Epub 2021 May 15.

Department of Gastroenterology, Kobe City Medical Center General Hospital, Kobe, Japan.

Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real-world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1-75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2-357). Adverse events occurred in 12.7%. Life-threatening complications occurred in 0.5%, but there were no treatment-related deaths. During a median follow-up period of 46.1 months (range 1-113), the 3-year overall survival rate, relapse-free survival rate, cause-specific survival rate, and larynx-preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment. Clinical trials registry number: UMIN000008276.
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http://dx.doi.org/10.1002/cam4.3927DOI Listing
June 2021

High-grade salivary gland carcinoma with the ETV6-NTRK3 gene fusion: A case report and literature review of secretory carcinoma with high-grade transformation.

Pathol Int 2021 Jun 13;71(6):427-434. Epub 2021 Apr 13.

Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.

Secretory carcinoma or mammary analog secretory carcinoma is an entity of salivary gland carcinoma that is characterized by the ETV6-NTRK3 gene fusion. Although it is generally considered to be a low-grade malignancy, some cases of secretory carcinoma with high-grade transformation (SCHG) have been reported. We herein describe a case of SCHG composed almost exclusively of the high-grade component. The patient presented with a growing mass in the buccal mucosa and underwent surgery. Tumor cells showing high-grade nuclear atypia were arranged in solid or cribriform nests with comedo-like necrosis. A differential diagnosis included high-grade salivary gland carcinoma, such as salivary duct carcinoma. Immunohistochemically, tumor cells were focally positive for S-100 and negative for mammaglobin and showed nuclear positivity for pan-Trk. A reverse transcription polymerase chain reaction assay showed that the tumor harbored the ETV6-NTRK3 gene fusion. A histological review of microscopic slides of the tumor did not reveal a typical secretory carcinoma component, except for a very focal area. We ultimately diagnosed this tumor as SCHG. This case underscores the importance of recognizing the histological spectrum of SCHG and the utility of pan-Trk immunohistochemistry to detect secretory carcinoma, which may be targeted by tyrosine kinase inhibitors.
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http://dx.doi.org/10.1111/pin.13100DOI Listing
June 2021

Evaluation of Velopharyngeal Closure Function With 4-Dimensional Computed Tomography and Assessment of Radiation Exposure in Pediatric Patients: A Cross-Sectional Study.

Cleft Palate Craniofac J 2021 Mar 31:10556656211001732. Epub 2021 Mar 31.

Department of Dentistry and Oral-Maxillofacial Surgery, Fujita Health University, School of Medicine, Kutsukake, Toyoake, Aichi, Japan.

Objective: Some patients with cleft palate (CP) need secondary surgery to improve functionality. Although 4-dimensional assessment of velopharyngeal closure function (VPF) in patients with CP using computed tomography (CT) has been existed, the knowledge about quantitative evaluation and radiation exposure dose is limited. We performed a qualitative and quantitative assessment of VPF using CT and estimated the exposure doses.

Design: Cross-sectional.

Setting: Computed tomography images from 5 preoperative patients with submucous CP (SMCP) and 10 postoperative patients with a history of CP (8 boys and 7 girls, aged 4-7 years) were evaluated.

Patients: Five patients had undergone primary surgery for SMCP; 10 received secondary surgery for hypernasality.

Main Outcome Measures: The presence of velopharyngeal insufficiency (VPI), patterns of velopharyngeal closure (VPC), and cross-sectional area (CSA) of VPI was evaluated via CT findings. Organ-absorbed radiation doses were estimated in 5 of 15 patients. The differences between cleft type and VPI, VPC patterns, and CSA of VPI were evaluated.

Results: All patients had VPI. The VPC patterns (SMCP/CP) were evaluated as coronal (1/4), sagittal (0/1), circular (1/2), and circular with Passavant's ridge (2/2); 2 patients (1/1) were unevaluable because of poor VPF. The CSA of VPI was statistically larger in the SMCP group ( = .0027). The organ-absorbed radiation doses were relatively lower than those previously reported.

Conclusions: Four-dimensional CT can provide the detailed findings of VPF that are not possible with conventional CT, and the exposure dose was considered medically acceptable.
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http://dx.doi.org/10.1177/10556656211001732DOI Listing
March 2021

Treatment outcomes of transoral robotic and non-robotic surgeries to treat oropharyngeal, hypopharyngeal, and supraglottic squamous cell carcinoma: A multi-center retrospective observational study in Japan.

Auris Nasus Larynx 2021 Jun 22;48(3):502-510. Epub 2021 Feb 22.

Department of Otorhinolaryngology-Head and Neck Surgery, Yokohama City University, School of Medicine, Yokohama, Japan.

Objectives: The aim of this multicenter retrospective cohort study was to compare efficacy and subsequent postoperative treatment between transoral robotic surgery (TORS) and any non-robotic transoral surgery in Japanese patients with early oropharyngeal squamous cell carcinoma (OPSCC), hypopharyngeal SCC (HPSCC), or supraglottic SCC (SGSCC).

Materials And Methods: Clinical information and surgical outcomes were compared between patients with early-stage OPSCC, HPSCC, and SGSCC who underwent TORS (TORS cohort) and those who underwent non-robotic transoral surgery, including transoral videolaryngoscopic surgery (TOVS), endoscopic laryngopharyngeal surgery (ELPS), and transoral laser microsurgery (TLM) (non-robotic cohort). The data of the Head and Neck Cancer Registry of Japan (registry cohort) were used to validate the comparison. The main outcomes were the presence of positive margins under pathology and the requirement for postoperative therapy, including radiotherapy or chemoradiotherapy.

Results: Sixty-eight patients in the TORS cohort, 236 patients in the non-robotic cohort, and 1,228 patients in the registry cohort were eligible for this study. Patients in the TORS cohort were more likely to have oropharyngeal tumor disease and T2/3 disease than those in the other cohorts (P<0.001 and P=0.052, respectively). The TORS cohort had significantly fewer patients with positive surgical margins than the non-robotic cohort (P=0.018), as well as fewer patients who underwent postoperative treatment, although the difference was not significant (P=0.069). In the subgroup analysis of patients with OPSCC, a total of 57 patients in the TORS cohort, 73 in the non-robotic cohort, and 171 in the registry cohort were eligible for the present study. Patients with OPSCC who underwent TORS were more likely to have lateral wall lesions than those in the other cohorts (P=0.003). The TORS cohort also had significantly fewer patients with positive surgical margins than the non-robotic cohort (P=0.026), and no patients in the TORS cohort underwent any postoperative treatment for OPSCC, although the difference was not significant (P=0.177).

Conclusions: Our results suggest that TORS leads to fewer positive surgical margins than non-robotic transoral surgeries. The clinical significance of TORS may be further validated through the results of all-case surveillance for patients who underwent TORS running in Japan in the future.
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http://dx.doi.org/10.1016/j.anl.2021.01.024DOI Listing
June 2021

Management of tracheostomy in COVID-19 patients: The Japanese experience.

Auris Nasus Larynx 2021 Jun 9;48(3):525-529. Epub 2021 Jan 9.

Department of Otolaryngology - Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, North 15 West 7, Sapporo 060-8638, Japan. Electronic address:

Objective: Involvement in the tracheostomy procedure for COVID-19 patients can lead to a feeling of fear in medical staff. To address concerns over infection, we gathered and analyzed experiences with tracheostomy in the COVID-19 patient population from all over Japan.

Methods: The data for health-care workers involved in tracheostomies for COVID-19-infected patients were gathered from academic medical centers or their affiliated hospitals from all over Japan.

Results: Tracheostomies have been performed in 35 COVID-19 patients with a total of 91 surgeons, 49 anesthesiologists, and 49 surgical staff members involved. Twenty-eight (80%) patients underwent surgery more than 22 days after the development of COVID-19-related symptoms (11: 22-28 days and 17: ≥29 days). Thirty (85.7%) patients underwent surgery ≥ 15 days after intubation (14: 15-21 days, 6: 22-28 days, and 10: ≥29 days). Among the total of 189 health-care workers involved in the tracheostomy procedures, 25 used a powered air-purifying respirator (PAPR) and 164 used a N95 mask and eye protection. As a result, no transmission to staff occurred during the 2 weeks of follow-up after surgery.

Conclusion: No one involved in tracheostomy procedures were found to have been infected with COVID-19 in this Japanese study. The reason is thought to be that the timing of the surgery was quite late after the infections, and the surgery was performed using appropriate PPE and surgical procedure. The indications for and timing of tracheostomy for severe COVID-19 patients should be decided through multidisciplinary discussion.
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http://dx.doi.org/10.1016/j.anl.2021.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794599PMC
June 2021

Hyperactive sensorimotor cortex during voice perception in spasmodic dysphonia.

Sci Rep 2020 10 14;10(1):17298. Epub 2020 Oct 14.

Human Brain Research Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Spasmodic dysphonia (SD) is characterized by an involuntary laryngeal muscle spasm during vocalization. Previous studies measured brain activation during voice production and suggested that SD arises from abnormal sensorimotor integration involving the sensorimotor cortex. However, it remains unclear whether this abnormal sensorimotor activation merely reflects neural activation produced by abnormal vocalization. To identify the specific neural correlates of SD, we used a sound discrimination task without overt vocalization to compare neural activation between 11 patients with SD and healthy participants. Participants underwent functional MRI during a two-alternative judgment task for auditory stimuli, which could be modal or falsetto voice. Since vocalization in falsetto is intact in SD, we predicted that neural activation during speech perception would differ between the two groups only for modal voice and not for falsetto voice. Group-by-stimulus interaction was observed in the left sensorimotor cortex and thalamus, suggesting that voice perception activates different neural systems between the two groups. Moreover, the sensorimotor signals positively correlated with disease severity of SD, and classified the two groups with 73% accuracy in linear discriminant analysis. Thus, the sensorimotor cortex and thalamus play a central role in SD pathophysiology and sensorimotor signals can be a new biomarker for SD diagnosis.
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http://dx.doi.org/10.1038/s41598-020-73450-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566443PMC
October 2020

A novel method for live imaging of human airway cilia using wheat germ agglutinin.

Sci Rep 2020 09 2;10(1):14417. Epub 2020 Sep 2.

Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Multiciliated epithelial cells in the airway are essential for mucociliary clearance. Their function relies on coordinated, metachronal and directional ciliary beating, appropriate mucus secretion and airway surface hydration. However, current conventional methods for observing human airway ciliary movement require ciliated cells to be detached from airway tissues. Determining the directionality of cilia is difficult. We developed a novel method to stain airway epithelial cilia to observe their movement without releasing ciliated cells. Human tracheae were obtained from patients (n = 13) who underwent laryngectomies to treat malignancies or swallowing disorders. The tracheae were treated with fluorescently labeled wheat germ agglutinin, which interacts with the acidic mucopolysaccharides present on the cilia. Epithelial surfaces were observed using an epi-fluorescence microscope equipped with a water-immersion objective lens and a high-speed camera. Ciliary movement was observable at 125 fps (13/13 samples). Ciliated cells in close proximity mostly exhibited well-coordinated ciliary beats with similar directionalities. These findings indicated that wheat germ agglutinin renders ciliary beats visible, which is valuable for observing human airway ciliary movements in situ.
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http://dx.doi.org/10.1038/s41598-020-71049-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468155PMC
September 2020

Endoscopic laryngopharyngeal surgery for hypopharyngeal lesions.

Oral Oncol 2020 07 20;106:104655. Epub 2020 Apr 20.

Department of Otolaryngology Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Japan.

Objectives: Transoral approaches for laryngeal/pharyngeal malignancies have been widely accepted as minimally invasive treatment options; however, hypopharyngeal lesions treated by transoral surgery have rarely been reported due to the difficulties in visualizing the hypopharynx. Since 2010, we have treated superficial hypopharyngeal lesions with endoscopic laryngopharyngeal surgery (ELPS), and herein report the outcomes of this transoral procedure.

Materials And Methods: One hundred and eighteen patients with superficial hypopharyngeal lesions were treated by ELPS from February 2010 to February 2017, and the clinical courses of the patients were reviewed.

Results: Four females and 114 males (average: 65.6 y-o) were included in this study. Some patients had multiple lesions and a total of 154 superficial hypopharyngeal lesions (dysplasia: 29, Tis: 52, T1: 44, T2: 20, T3: 9) were treated with ELPS. Ten patients had only dysplasia and no carcinoma. Five patients presented with nodal metastases and 11 patients had simultaneous oropharyngeal lesions. In all cases, the hypopharynx was well visualized with sufficient working space, and no cases required a change in surgical approach. All post-operative complications were safely managed. In regard to the oncological outcomes, of the 108 patients with malignant lesions, the 3-year and 5-year overall survival (OS) rate was 93.6% and 85.5%, respectively.

Conclusions: During ELPS, the hypopharynx was well visualized providing sufficient working space for the resection. The procedure was safe and feasible for superficial hypopharyngeal lesions and exhibited very good oncological outcomes. ELPS is thought to be a very effective surgical alternative for superficial hypopharyngeal lesions.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104655DOI Listing
July 2020

Recurrent laryngeal nerve regeneration using a self-assembling peptide hydrogel.

Laryngoscope 2020 10 5;130(10):2420-2427. Epub 2019 Dec 5.

Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Objectives/hypothesis: To regenerate defected recurrent laryngeal nerves (RLNs), various methods have been developed. However, no consistently effective treatments are currently available because of their insufficient functional recovery. RADA16-I, a self-assembling peptide used clinically as a hemostat, reportedly supports neurite outgrowth and functional synapse formation in vitro. The purpose of this study was to investigate the effect of RADA16-I hydrogels on transected RLNs in rats.

Study Design: Animal experiments with controls.

Methods: Fifteen adult rats were divided into the following three groups: RADA16-I (+), RADA16-I (-), and neurectomy. A 6-mm gap of the left RLN was bridged using an 8-mm silicone tube in the RADA16-I (-) and RADA16-I (+) groups. Subsequently, RADA16-I hydrogel was injected into the tube in the RADA16-I (+) group. The surgical incisions were closed without any further treatment in the neurectomy group. After 8 weeks, laryngoscopy and electrophysiological and histological examinations were performed to evaluate the effect of RADA16-I on nerve regeneration and thyroarytenoid muscle atrophy.

Results: Although most rats in the three groups exhibited no improvements of their vocal fold movement, partial recovery was observed in one rat in the RADA16-I (+) group. The neurofilament-positive areas and the number of myelinated nerves in the RADA16-I (+) group were significantly higher than in the RADA16-I (-) group. The area of the left thyroarytenoid muscle in the RADA16-I (+) group was significantly larger than that of the neurectomy group.

Conclusions: Our results suggested that RADA16-I hydrogel was effective for RLN regeneration.

Level Of Evidence: NA Laryngoscope, 130:2420-2427, 2020.
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http://dx.doi.org/10.1002/lary.28434DOI Listing
October 2020

A summary of the Clinical Practice Guideline for the Diagnosis and Management of Voice Disorders, 2018 in Japan.

Auris Nasus Larynx 2020 Feb 4;47(1):7-17. Epub 2019 Oct 4.

Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Japan.

Objective: To develop a summary of the first version of the Clinical Practice Guideline of Voice Disorders for Diagnosis, Management, and Treatment in Japan by the Clinical Practice Guideline Committee of the Japan Society of Logopedics and Phoniatrics and The Japan Laryngological Association. The 2018 recommendations, based on a review of the scientific literature, are intended to serve as clinical practice guidelines for the diagnosis, management, and treatment of voice disorders in Japan.

Methods: A summary of the original version of the Clinical Practice Guideline of Voice Disorders for Diagnosis, Management, and Treatment in Japan was described. Recommendations for the diagnosis, management, and treatment of voice disorders were prepared. Twelve clinical questions (CQs) regarding the diagnosis, management, treatment, and effectiveness of therapy for voice disorders were also prepared.

Results: A summary of the first version of the clinical practice guidelines for the diagnosis, management, and therapy of voice disorders was prepared and is presented. Additionally, answers to the 12 CQs on the diagnosis, management, treatment, and effectiveness of voice disorder therapy were prepared, and include evidence-based recommendations.

Conclusion: These guidelines present a summary of the standard approaches for the diagnosis and treatment of voice disorders and relevant CQs that consider the medical environments in Japan. We hope that the guidelines will assist physicians in clinical settings for patients with voice disorders.
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http://dx.doi.org/10.1016/j.anl.2019.09.004DOI Listing
February 2020

Real-World Outcomes and Prognostic Factors in Patients Receiving Nivolumab Therapy for Recurrent or Metastatic Head and Neck Carcinoma.

Cancers (Basel) 2019 Sep 6;11(9). Epub 2019 Sep 6.

Department of Otolaryngology - Head & Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.

Recently, a global phase III study demonstrated that nivolumab markedly improved patient outcomes in recurrent or metastatic head and neck carcinoma (RMHNC). However, the efficacy of nivolumab in patients who are ineligible for clinical trials is unknown. We investigated nivolumab efficacy in real-world patients and prognostic factors associated with the response to nivolumab. This study was conducted at 11 institutes associated with Kyoto University and its Affiliated Hospitals-Head and Neck Oncology Group. In total, 93 patients with RMHNC who received nivolumab between May 2017 and May 2018 were retrospectively reviewed. Objective response rate (ORR), overall survival, and progression-free survival (PFS) were evaluated. Univariate and multivariate analyses were performed to identify prognostic factors. The ORRs in patients with squamous cell carcinoma (SCC) and non-SCC were 21.8% and 0%, respectively. In patients with SCC and non-SCC, the 1-year PFS rates were 28.7% and 8.9%, respectively. The hazard ratio (HR) for risk of PFS events (SCC versus non-SCC) was 2.28 (95% confidence interval: 1.21-4.1; log-rank = 0.007). Univariate and multivariate analyses revealed radiotherapy history, platinum-refractory carcinoma, and treatment-related adverse events (TRAEs) as important prognostic factors associated with PFS in patients with SCC. In a real-world setting, non-SCC and platinum-refractory carcinoma were associated with a poorer prognosis, and a history of radiotherapy to the primary tumor, and the occurrence of TRAEs were associated with a better prognosis. These findings could be useful for clinicians and patients when selecting a treatment strategy.
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http://dx.doi.org/10.3390/cancers11091317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770631PMC
September 2019

Dedifferentiated liposarcoma of the thyroid gland: A case report.

Mol Clin Oncol 2019 Sep 18;11(3):219-224. Epub 2019 Jun 18.

Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.

Liposarcoma is one of the most common soft tissue tumors that affect adults. Liposarcoma is typically identified in the retroperitoneum, trunk and extremities as a slow-growing mass, yet is rare in the thyroid gland. Herein, we report a case of dedifferentiated liposarcoma that developed in the thyroid gland, and performed a literature review. A 66-year-old male with a history of well-differentiated liposarcoma in the thymus presented with a rapidly enlarging mass in the thyroid gland. Malignancy was suspected due to the local extension of the tumor, and complete resection of the tumor was achieved. Tissue diagnosis from the tumor following surgery revealed that dedifferentiated liposarcoma, and tumor progression was difficult to control with adjuvant radiation and chemotherapy. This is, to the best of our knowledge, the first case to report dedifferentiated liposarcoma in the thyroid gland, and the difficulty in initial diagnosis as well as the aggressive features of dedifferentiated liposarcoma are highlighted.
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http://dx.doi.org/10.3892/mco.2019.1882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636207PMC
September 2019

Curved Laryngopharyngoscope With Flexible Next-Generation Robotic Surgical System for Transoral Hypopharyngeal Surgery: A Preclinical Evaluation.

Ann Otol Rhinol Laryngol 2019 Nov 20;128(11):1023-1029. Epub 2019 Jun 20.

Department of Otolaryngology-Head and Neck Surgery, Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital, Bunkyo-ku, Tokyo, Japan.

Objectives: The indication of transoral robotic surgery for hypopharyngeal cancer is limited because of poor accessibility. The aim of this study was to explore the efficacy of a curved laryngopharyngoscope used in combination with a next-generation flexible robotic surgical system for accessing and resecting the hypopharynx.

Methods: A comparative evaluation of the curved laryngopharyngoscope versus standard straight-blade retractors using the flexible robotic surgical system was conducted on 2 cadavers. End points measured included visualization, accessibility, and ease of dissection for accessing and resecting the hypopharynx.

Results: Visualization, accessibility, and dissection were superior with the curved laryngopharyngoscope in all subareas of the hypopharynx. The advantages of accessibility and visualization were much more evident in the cadaver with a high body mass index.

Conclusions: These preclinical data suggest that using a curved laryngopharyngoscope in combination with a flexible robotic surgical system may lead to technical innovations concerning transoral surgery of the hypopharynx.
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http://dx.doi.org/10.1177/0003489419856391DOI Listing
November 2019

Re-introducing the same chemotherapy after exposure to anti-PD-1 therapy.

Int Cancer Conf J 2019 Apr 12;8(2):86-88. Epub 2019 Feb 12.

1Department of Medical Oncology, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507 Japan.

Cytotoxic chemotherapy after exposure to nivolumab (nivo), an anti-programmed death-1 (PD-1) antibody, has been associated with good response compared with historical data in various cancers including head and neck squamous cell carcinoma (HNSCC). In a previous report, different chemotherapy regimens were used before and after treatment with nivo. This HNSCC case is the first report of a good response when the same cytotoxic chemotherapy regimen was used before and after nivo. In addition, the efficacy of anti-epidermal growth factor receptor antibody after nivo treatment may be better than without exposure to nivo.
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http://dx.doi.org/10.1007/s13691-019-00360-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498283PMC
April 2019

A retrospective multicenter study of sublingual gland carcinoma in Japan.

Auris Nasus Larynx 2020 Feb 17;47(1):111-115. Epub 2019 May 17.

Department of Otolaryngology - Head & Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address:

Objective: Salivary gland carcinoma is rare among head and neck cancers. Sublingual gland carcinoma, a type of salivary gland carcinoma, is even rarer; therefore, the number of cases at a single institute is too small for sufficient evaluation of tumor characteristics. We conducted a multicenter, retrospective analysis of sublingual gland carcinomas in patients who visited 12 institutions associated with the Kyoto Hospital and Affiliated Facilities Head and Neck Clinical Oncology Group.

Methods: Thirteen previously untreated patients who visited the institutions between 2006 and 2015 were enrolled. The overall survival (OS) and disease-free survival (DFS) rates for all patients and by disease stage were analyzed. Statistical analyses were performed for all patients with respect to disease stage.

Results: Eight of thirteen patients were diagnosed with adenoid cystic carcinoma on pathological study. A significant difference in OS rate was observed between patients with Stage I-III and Stage IV disease; however, the difference in DFS rate by disease stage was not significant.

Conclusion: Stage IV disease was identified as a poor prognostic factor in patients with sublingual gland carcinoma. However, even patients with Stage I-III disease experienced relatively short DFS. Distant metastasis is a serious problem among patients with sublingual gland carcinoma.
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http://dx.doi.org/10.1016/j.anl.2019.04.006DOI Listing
February 2020

Evaluation of Cilia Function in Rat Trachea Reconstructed Using Collagen Sponge Scaffold Seeded with Adipose Tissue-Derived Stem Cells.

Anat Rec (Hoboken) 2020 03 5;303(3):471-477. Epub 2019 Apr 5.

Department of Otolaryngology, Head and Neck Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.

The tracheal lumen is essential for conducting air to the lung alveoli and for voice production. However, patients with severe tracheal stenosis and malignant tumors invading the trachea often require tracheal resection. Recently, various reported tissue engineering methods for tracheal reconstruction show that regeneration of ciliated epithelium in the reconstructed areas, as well as preservation of the luminal structure is possible. However, only few studies report on the mucociliary transport function in reconstructed tracheae. We investigated mucociliary transport function within rat tracheal epithelium, reorganized after autologous adipose tissue-derived stem cell (ASC) transplantation. Rat ASCs were expanded in culture, and then seeded in a collagen sponge, which was physically supported with a polypropylene framework. The ASC-seeded collagen sponge was transplanted into the rat tracheal defect. We then examined the motility and transport function of cilia generated in the transplanted area using ciliary beat frequency (CBF) and microsphere movement analyses. Our data suggested that autologous ASC transplantation promoted ciliogenesis, consistent with previous reports. The CBF analysis revealed that motility of the cilia generated in the ASC group was comparable to that observed in the normal rat tracheal epithelium. Transport function in the ASC group was higher than that in the control group. These data suggested that autologous ASC transplantation increased ciliated cells in the reconstructed area without significantly disrupting cilia motility, thereby promoting transport function regeneration. Autologous ASC transplantation is expected to be beneficial in morphological and functional regeneration of tracheal epithelium. Anat Rec, 303:471-477, 2020. © 2019 American Association for Anatomy.
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http://dx.doi.org/10.1002/ar.24104DOI Listing
March 2020

Transplantation of multiciliated airway cells derived from human iPS cells using an artificial tracheal patch into rat trachea.

J Tissue Eng Regen Med 2019 06 24;13(6):1019-1030. Epub 2019 Apr 24.

Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Tracheal resection is often performed for malignant tumours, congenital anomalies, inflammatory lesions, and traumatic injuries. There is no consensus on the best approach for the restoration of tracheal functionality in patients with tracheal defects. Artificial grafts made of polypropylene and collagen sponge have been clinically used by our group. However, 2 months are required to achieve adequate epithelialization of the grafts in humans. This study aimed to investigate the feasibility of transplantation therapy using an artificial trachea with human-induced pluripotent stem cell (hiPSC)-derived multiciliated airway cells (hiPSC-MCACs). Collagen vitrigel membrane, a biocompatible and absorbable material, was used as a scaffold to cover the artificial trachea with hiPSC-MCACs. Analyses of hiPSC-MCACs on collagen vitrigel membrane were performed by immunocytochemistry and electron microscopy and by assessing ciliary beat frequency. Along with the artificial trachea, hiPSC-MCACs were transplanted into surgically created tracheal defects of immunodeficient rats. The survival of transplanted cells was histologically evaluated at 1 and 2 weeks after the transplantation. The hiPSC-MCACs exhibited motile cilia on collagen vitrigel membrane. The surviving hiPSC-MCACs were observed in the endotracheal epithelium of the tracheal defect at 1 and 2 weeks after transplantation. These results suggest that hiPSC-MCAC is a useful candidate for tracheal reconstruction.
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http://dx.doi.org/10.1002/term.2849DOI Listing
June 2019

Collagen sponge scaffolds containing growth factors for the functional regeneration of tracheal epithelium.

J Tissue Eng Regen Med 2019 05 9;13(5):835-845. Epub 2019 Apr 9.

Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Tracheal epithelia have barrier and mucociliary clearance functions that prevent invasion of extraneous particles and infectious materials. Hence, following tracheal reconstructions, functional and morphological regeneration of epithelia is required to prevent respiratory declines and infectious diseases. Although growth factors (GFs) promote the regeneration of tracheal epithelial morphologies, it remains unclear whether tracheal grafts containing GFs are beneficial for regeneration of tracheal epithelial functions. Thus, we fabricated collagen sponge scaffolds containing insulin-like GF-1 (IGF-1) and the basic fibroblast, hepatocyte, and epidermal GFs (bFGFs, HGFs, and EGFs, respectively), and we evaluated the effects of the grafts on the functional regeneration of tracheal epithelia. Partial tracheal defects were imposed surgically, and collagen sponges containing IGF-1, bFGF, HGF, or EGF were then transplanted to defect sites. Subsequent immunofluorescence studies suggested that EGF and bFGF contribute to regular distributions of tight junction molecules, and tracer permeability assays suggested that EGF and bFGF promote regeneration of barrier function. Increased ciliogenesis was also observed using scanning electron microscopy in reconstructed regions treated with EGF- and bFGF-supplemented collagen sponges. However, bFGF-supplemented collagen sponges led to greater microsphere transport than did EGF-supplemented sponges. The present data suggested that collagen sponge scaffold containing bFGF promotes functional regeneration of tracheal epithelial tissues.
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http://dx.doi.org/10.1002/term.2835DOI Listing
May 2019

Alterations in macrophage polarization in injured murine vocal folds.

Laryngoscope 2019 04 30;129(4):E135-E142. Epub 2018 Dec 30.

Department of Otolaryngology Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Objectives: Macrophages are prominent inflammatory cells in wounds, and their phenotypes are altered during wound healing. They are reported to contribute to not only inflammatory responses but also tissue remodeling. However, few studies in vocal fold biology have focused on the function of macrophages. The purpose of this study was to investigate macrophage polarization and distribution in injured murine vocal folds.

Study Design: Animal experiments with controls.

Method: Unilateral vocal fold stripping was performed on C57BL/6 mice, and larynges were harvested 1, 3, 5, 7, and 14 days postinjury. Immunohistochemical analysis of the vocal fold lamina propria was performed to detect the expression of classically activated (M1) and alternatively activated (M2) macrophage markers (inducible nitric oxide synthase [iNOS] and CD206, respectively) in F4/80 macrophages.

Results: The proportion of F4/80 iNOS cells out of all F4/80 cells tended to increase from day 1. F4/80 iNOS cell percentage tended to be high at days 1 through 7 and declined to close to a normal level by day 14. F4/80 CD206 cell percentage tended to decrease at day 1 and then to increase the rest of the time. In the normal vocal fold, the majority of F4/80 macrophages were only positive for CD206. F4/80 iNOS CD206 cells were observed at days 1 through 7.

Conclusion: The main population of injured sites gradually shifted from M1 to M2 marker-positive macrophages in murine vocal folds. However, coexistence of M1 and M2 markers in the same macrophages was observed. Our results suggest that macrophage phenotypes are regulated by complex tissue-derived signals and exhibit dynamic changes during wound healing.

Level Of Evidence: NA Laryngoscope, 129:E135-E142, 2019.
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http://dx.doi.org/10.1002/lary.27523DOI Listing
April 2019

Characterization of aged rat vocal fold fibroblasts.

Laryngoscope 2019 03 19;129(3):E94-E101. Epub 2018 Nov 19.

Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Objectives/hypothesis: To elucidate the aging physiology of the vocal folds, we examined the characters of aged vocal fold fibroblasts (VFFs) in various conditions.

Study Design: In vitro study.

Methods: VFFs from young (12-week-old) and aged (19-month-old) Sprague-Dawley rats were compared. Proliferative capacity, ratio of myofibroblast to fibroblast, myofibroblast function, and extracellular matrix production were examined in the following conditions: naïve, basic fibroblast growth factor (bFGF) supplemented, and hepatocyte growth factor (HGF) supplemented.

Results: Aged VFFs demonstrated reduced proliferation by cell counting, though the ratio of Ki-67-positive cells showed no difference. Aged VFFs exhibited an increased expression of α-smooth muscle actin (α-SMA); however, they demonstrated no enhanced contractile ability in a gel contraction assay. Type I collagen protein was increased age dependently, accompanied with decreased Mmp1 and unchanged Col1a1 transcription. Type I collagen protein and α-SMA represented quite similar reduction patterns to bFGF or HGF administration.

Conclusions: The following possible characteristics of aged VFFs were implied: long duration of mitosis, increased myofibroblast population size with certain dysfunctions, reduced type I collagen turnover, and correlation between α-SMA expression and type I collagen metabolism. Further investigations of these features will help to clarify presbyphonia's pathology and establish treatment strategies.

Level Of Evidence: NA Laryngoscope, 129:E94-E101, 2019.
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http://dx.doi.org/10.1002/lary.27464DOI Listing
March 2019

Endoscopic laryngo-pharyngeal surgery for elderly patients.

Auris Nasus Larynx 2019 Apr 8;46(2):279-284. Epub 2018 Sep 8.

Department of Otolaryngology Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Japan.

Objective: Due to the rising number of elderly patients and advances in endoscopic devices, early laryngeal and pharyngeal cancers are increasingly found in elderly patients. In these cases, minimally invasive endoscopic larygo-pharyngeal surgery (ELPS) may be indicated. However, the safety and efficacy of ELPS in elderly populations has not been established. The purpose of this study was to investigate the safety, outcomes and feasibility of ELPS in very elderly patients.

Methods: Between February 2010 and April 2016, 29 pharyngeal cancerous or pre-cancerous lesions in 19 patients aged 75 years or older were treated with ELPS. Twenty-six resections were performed in total, and the patients' clinical courses were reviewed.

Results: Sixteen patients had multiple comorbidities and moderate to severe comorbidities were observed in 17 patients. The average surgical time and hospitalization period was 54.3min and 18.8 days, respectively. On average, oral intake began 4.4days after the procedure, and all patients eventually received nourishment by mouth; no percutaneous endoscopic gastrostomy dependency was observed. Complications included post-operative bleeding and aspiration pneumonia in two cases each, and all complications were safely managed. The 3-year overall survival rate was 90.2% and the 3-year disease-specific survival rate was 100%.

Conclusion: ELPS was safely performed in elderly patients, suggesting that it is a feasible treatment option for pharyngeal lesions in very elderly patients.
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http://dx.doi.org/10.1016/j.anl.2018.08.008DOI Listing
April 2019

Survival in patients with submandibular gland carcinoma - Results of a multi-institutional retrospective study.

Auris Nasus Larynx 2018 Oct 7;45(5):1066-1072. Epub 2018 Feb 7.

Department of Otolaryngology - Head & Neck Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Objective: Clinical studies demonstrating the prognostic factors in submandibular gland carcinoma are limited because the tumor is relatively rare. The aim of this study was to identify clinical outcomes and prognostic factors in submandibular gland carcinoma.

Methods: The study included 65 patients with submandibular gland carcinoma who underwent initial surgical treatment at the Kyoto University and its affiliated hospitals.

Results: The 3-year overall survival (OS), disease specific survival, locoregional control (LRC), and no distant metastasis (NDM) rates were 74.2%, 74.2%, 90.0%, and 64.8%, respectively. In the current follow-up study, 16 patients died of the disease, 5 patients were alive with recurrence, 43 patients were alive without disease, and 1 patient died of unrelated disease without recurrence. All patients who died of the disease had developed distant metastasis. Based on univariate analysis, tumor grade (high grade) and lymph node metastases (≥N2) were significant prognostic factors for OS and LRC. It also revealed tumor grade (high grade), T classification (≥T3), and lymph node metastases (≥N2) were significant for distant metastasis. Multivariate analysis showed the following significant prognostic factors: lymph node metastases (≥N2) for OS, LRC, and NDM, and high tumor grade for NDM.

Conclusion: Our study suggested death of submandibular gland carcinoma occurred mainly due to distant metastasis. The significant predictors of distant metastasis were lymph node metastases (≥N2) and tumor grade (high grade).
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http://dx.doi.org/10.1016/j.anl.2018.01.011DOI Listing
October 2018

Long-term preservation of planar cell polarity in reversed tracheal epithelium.

Respir Res 2018 02 2;19(1):22. Epub 2018 Feb 2.

Department of Otolaryngology-Head & Neck Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Background: Planar cell polarity (PCP) coordinates the patterning and orientation of cells and their structures along tissue planes, and although its acquisition during the formation of airway epithelium has been described, the mechanisms for its maintenance and reconstruction are poorly understood. We aimed to clarify whether ambient environment change by orthotropic autologous transplantation affected PCP at the cellular level.

Methods: We performed orthotropic autologous transplantation by inverting tracheal segments in rats, and then performed morphological evaluation by microscopy. The PCP of the tracheal epithelium was assessed over time by analyzing the directions of mucociliary transport and ciliary beat, the positional relationship between the basal body and basal foot, and the bias of Vang-like protein 1 (Vangl1) at 2, 4, and 6 months postoperatively.

Results: After 2 months, the directions of mucociliary transport and ciliary beat were preserved toward the lung in the inverted tracheal segments. The positional relationship between the basal body and the basal foot, and the bias of Vangl1, also indicated preservation of PCP in the inverted tracheal segments. Similar results were obtained at 6 months.

Conclusion: The PCP of ciliated epithelium was preserved in reversed trachea, even after long-term observation.
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http://dx.doi.org/10.1186/s12931-018-0726-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797350PMC
February 2018

Unknown primary squamous cell carcinoma of the head and neck: retrospective analysis of 80 cases.

Acta Otolaryngol 2018 Jun 8;138(6):590-596. Epub 2018 Jan 8.

a Department of Otolaryngology - Head & Neck Surgery , Graduate School of Medicine, Kyoto University , Kyoto , Japan.

Objectives: The management of patients with cervical metastasis in head and neck cancer of unknown primary (HNCUP) remains controversial. This current multicenter retrospective study investigated the treatment outcomes of patients with HNCUP.

Methods: The study included patients who were treated curatively at 12 institutions in Japan from January 2006 to December 2015.

Results: Eighty patients with HNCUP were included. The median follow-up period was 34 months. The three-year overall survival (OS), disease-specific survival (DSS), regional relapse-free survival (RRFS), local progression-free survival (LPFS), and distant metastasis-free survival (DMFS) rates were 72.5%, 80.3%, 74.0%, 89.7%, and 86.9%, respectively. Nodal status was a significant factor for OS, DSS, RRFS, and DMFS; and extracapsular extension (ECE) was significant for OS and DSS. There was a distinct difference between the survival rates of patients with N1-2a and N2b-3 disease. RT was a significant positive factor for LPFS (3-year LPFS, RT 93.0% vs. no RT 83.0%, p = .043).

Conclusions: For N2a as well as N1 disease without ECE, a single treatment modality, including ND or RT alone is acceptable. When ND alone is performed, thorough monitoring should be continued during follow-up to identify the emergence of the primary lesion.
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http://dx.doi.org/10.1080/00016489.2017.1422141DOI Listing
June 2018

Flexible next-generation robotic surgical system for transoral endoscopic hypopharyngectomy: A comparative preclinical study.

Head Neck 2018 Jan 11;40(1):16-23. Epub 2017 Nov 11.

Division of Head and Neck Surgery, Department of Otolaryngology, Stanford University, Palo Alto, California.

Background: The purpose of this cadaveric study was to determine the efficacy of a flexible, next-generation robotic surgical system for transoral robotic hypopharyngectomy.

Methods: A comparative evaluation study of the flexible versus rigid robotic surgical systems for the hypopharynx was conducted using 3 cadavers. Endpoints for assessment were visualization of the hypopharynx, access to the hypopharynx, and difficulty of dissection. Hypopharyngectomy was performed on 3 other cadavers using the da Vinci Sp surgical system.

Results: Access to the apex of the pyriform sinus and the esophageal inlet was easier with the da Vinci Sp than with the da Vinci Si. Dissection with the da Vinci Sp was easier in all areas of the hypopharynx than with the da Vinci Si. Robotic hypopharyngectomy was successfully completed on all cadavers using the da Vinci Sp surgical system.

Conclusion: Preclinical testing in human cadavers suggests that flexible robotic surgery may facilitate successful transoral hypopharyngectomy.
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http://dx.doi.org/10.1002/hed.24868DOI Listing
January 2018

Survival in patients with parotid gland carcinoma - Results of a multi-center study.

Am J Otolaryngol 2018 Jan - Feb;39(1):65-70. Epub 2017 Oct 24.

Department of Otolaryngology - Head & Neck Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Background: Parotid gland carcinoma is a rare malignancy, comprising only 1-4% of head and neck carcinomas; therefore, it is difficult for a single institution to perform meaningful analysis on its clinical characteristics. The aim of this study was to update the clinical knowledge of this rare disease by a multi-center approach.

Methods: The study was conducted by the Kyoto University Hospital and Affiliated Facilities Head and Neck Clinical Oncology Group (Kyoto-HNOG). A total of 195 patients with parotid gland carcinoma who had been surgically treated with curative intent between 2006 and 2015 were retrospectively reviewed. Clinical results including overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), local control rate (LCR), regional control rate (RCR), and distant metastasis-free survival (DMFS) were estimated. Univariate and multivariate analyses were performed to identify prognostic factors.

Results: The median patient age was 63years old (range 9-93years), and the median observation period was 39months. The OS, DFS, DSS, LCR, RCR, and DMFS at 3years were 85%, 74%, 89%, 92%, 88%, and 87%, respectively. Univariate analysis showed age over 74, T4, N+, preoperative facial palsy, high grade histology, perineural invasion, and vascular invasion were associated with poor OS. N+ and high grade histology were independent factors in multivariate analysis. In subgroup analysis, postoperative radiotherapy was associated with better OS in high risk patients.

Conclusion: Nodal metastases and high grade histology are important negative prognostic factors for OS. Postoperative radiotherapy is recommended in patients with advanced high grade carcinoma.
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http://dx.doi.org/10.1016/j.amjoto.2017.10.012DOI Listing
August 2018

Process of tight junction recovery in the injured vocal fold epithelium: Morphological and paracellular permeability analysis.

Laryngoscope 2018 04 31;128(4):E150-E156. Epub 2017 Oct 31.

Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Objectives/hypothesis: The vocal fold epithelium that includes tight junction (TJ)-based barrier function protects underlying connective tissues from external insults. TJs play an important role to control paracellular permeability of not only solutes but also ions, and preserve the vocal fold homeostasis. However, the distribution of TJs and paracellular diffusion barrier across the entire vocal fold epithelium are still unknown. The aim of this study was to identify the distribution of TJs in the vocal fold epithelium and to characterize the recovery process of TJ-based paracellular diffusion barrier in a rat model of vocal fold injury.

Study Design: Animal experiments with controls.

Methods: Normal and vocal fold-injured rats were used. Larynges were harvested for immunohistochemical examination of TJ proteins. For functional analysis, a tracer permeability assay was performed using EZ-Link Sulfo-NHS-LC-Biotin.

Results: TJ proteins occludin and zonula occludens 1 signals were localized to the junctional regions of the most luminal cell layers of the vocal fold epithelium. The injured region had been recovered with epithelium at 5 days postinjury, but the paracellular diffusion barrier assays revealed that biotinylation reagents diffused into the lamina propria at 5 days postinjury, and were blocked at the epithelium at 14 and 28 days postinjury.

Conclusions: It was strongly suggested that TJs in the vocal fold epithelium exist at the junctional regions of the first layer of stratified squamous epithelium. TJ-based paracellular diffusion barrier following vocal fold injury is recovered by 14 days postinjury, and this period corresponds with the time course of structural changes in the regenerating epithelium layer.

Level Of Evidence: NA. Laryngoscope, 128:E150-E156, 2018.
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http://dx.doi.org/10.1002/lary.26959DOI Listing
April 2018

A phase I/II exploratory clinical trial for intracordal injection of recombinant hepatocyte growth factor for vocal fold scar and sulcus.

J Tissue Eng Regen Med 2018 04 25;12(4):1031-1038. Epub 2017 Dec 25.

Department of Otolaryngology, Kitano Hospital, Osaka, Japan.

Vocal fold scar and sulcus are intractable diseases with no effective established treatments. Hepatocyte growth factor (HGF) has preclinically proven to have potent antifibrotic and regenerative effects on vocal fold scar. The current Phase I/II clinical trial aims to examine the safety and effectiveness of intracordal injection of a recombinant human HGF drug for patients with vocal fold scar or sulcus. This is an open-label, dose-escalating, first-in-human clinical trial. Eighteen patients with bilateral vocal fold scar or sulcus were enrolled and divided into three groups: Step I received 1 μg of HGF per vocal fold; Step II received 3 μg of HGF; and Step III received 10 μg of HGF. Injections were administered once weekly for 4 weeks. The protocol treatment was performed starting with Step I and escalating to Step III. Patients were followed for 6 months post-treatment. Local and systemic safety aspects were examined as primary endpoints, and therapeutic effects were assessed as secondary endpoints using voice handicap index-10; maximum phonation time; vocal fold vibratory amplitude; grade, rough, breathy, asthenic, strained scale; and jitter. The results indicated no serious drug-related adverse events in either the systemic or local examinations. In whole-subject analysis, voice handicap index-10, vocal fold vibratory amplitude, and grade, rough, breathy, asthenic, strained scale were significantly improved at 6 months, whereas maximum phonation time and jitter varied. There were no significant differences in phonatory data between the step groups. In conclusion, intracordal injection of a recombinant human HGF drug was safe, feasible, and potentially effective for human patients with vocal fold scar or sulcus.
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http://dx.doi.org/10.1002/term.2603DOI Listing
April 2018

Complications After Endoscopic Laryngopharyngeal Surgery.

Laryngoscope 2018 07 10;128(7):1546-1550. Epub 2017 Oct 10.

Department of Otolaryngology-Head and Neck Surgery.

Objectives/hypothesis: Endoscopic laryngopharyngeal surgery (ELPS), a hybrid of head and neck surgery and gastrointestinal endoscopic treatment, has been attracting attention as a new therapeutic modality for superficial laryngopharyngeal cancers. Although this technique is less invasive than traditional open procedures, some complications including postoperative bleeding, subcutaneous emphysema, or aspiration pneumonia can occur after treatment. The purpose of this study was to investigate the complications associated with ELPS to better understand the indications for this procedure.

Study Design: Retrospective medical chart review.

Methods: One hundred five patients with 159 laryngeal or pharyngeal lesions were treated with ELPS between August 2009 and September 2015 at Kyoto University Hospital. In total, 147 resections were performed, and complications after the resections were reviewed.

Results: Of the 147 resections, postoperative bleeding, subcutaneous emphysema, and aspiration pneumonia were observed in 10, 17, and 10 cases, respectively. All cases with postoperative bleeding and aspiration pneumonia occurred in patients over 65 years of age. A history of taking anticoagulation/platelet medications, and macroscopic 0-IIa lesions were shown to correlate with postoperative bleeding after ELPS. Resection of lesions in the pyriform sinus was found to be associated with subcutaneous emphysema.

Conclusions: All complications after ELPS were safely managed. A history of taking anticoagulation/platelet medications and macroscopic 0-IIa lesions were identified as risk factors for postoperative bleeding, whereas resection of pyriform sinus lesions was found to be a risk factor for subcutaneous emphysema. These risk factors should be carefully considered when treating pharyngeal and laryngeal lesions by ELPS.

Level Of Evidence: 4. Laryngoscope, 128:1546-1550, 2018.
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http://dx.doi.org/10.1002/lary.26953DOI Listing
July 2018