Publications by authors named "Hirohito Umeno"

94 Publications

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.3927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209601PMC
June 2021

Role of colony-forming tissue stem cells in the macula flava of the human vocal fold in vivo.

Laryngoscope Investig Otolaryngol 2021 Apr 22;6(2):283-290. Epub 2021 Mar 22.

Department of Otolaryngology-Head and Neck Surgery Kurume University School of Medicine Kurume Japan.

Objectives: Our previous investigations showed that tissue stem cells in the maculae flavae (a stem cell niche) form colonies in vivo like stem cells in vitro. However, the roles of colony-forming cells in the maculae flavae in vivo have not yet been determined.This study investigated the metabolism of the colony-forming tissue stem cells in the maculae flavae of the human adult vocal fold.

Study Design: Histologic analysis of the human vocal folds.

Methods: Three normal human adult vocal folds were investigated under transmission electron microscopy and light microscopy including immunohistochemistry.

Results: Mitochondrial cristae of the colony-forming cells in the maculae flavae were sparse. Hence, the microstructural features of the mitochondria suggested that their metabolic activity and oxidative phosphorylation were low. Colony-forming cells strongly expressed glucose transporter-1 and glycolytic enzymes (hexokinase II, glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase A). The colony-forming cells did not express phosphofructokinase-1 but did express glucose-6-phosphate dehydrogenase indicating the cells relied more on the pentose phosphate pathway. Since the colony-forming cells expressed lactate dehydrogenase A, cells seemed to rely more on anaerobic glycolysis in an anaerobic microenvironment.

Conclusions: The present study is consistent with the hypothesis that the colony-forming tissue stem cells in the maculae flavae of the human adult vocal fold seemed to rely more on anaerobic glycolysis using the pentose phosphate pathway for energy supply in vivo. Microstructural features of the mitochondria and expressed glycolytic enzymes of the colony-forming cells in the maculae flavae suggested that the oxidative phosphorylation activity was low.In an anaerobic microenvironment in vivo, there is likely a complex cross-talk regarding the metabolism between the colony-forming aggregated cells along the adhesion machinery and chemical signaling pathways, which reduces toxic oxygen species and is favorable to maintaining the stemness and undifferentiated states of the tissue stem cells.

Level Of Evidence: NA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lio2.550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035955PMC
April 2021

Distribution of Label-Retaining Cells and their Properties in the Newborn Vocal Fold Mucosa.

J Voice 2021 Apr 14. Epub 2021 Apr 14.

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

Objectives: There is growing evidence that the cells in the maculae flavae (MFe) are candidates for tissue stem cells of the vocal fold mucosa and the MFe are a stem cell niche. Distribution of label-retaining cells and their properties in the postnatal vocal fold mucosa were investigated.

Methods: Oral administration of bromodeoxyuridine (BrdU) was given to pregnant Sprague-Dawley rats and the label-retaining cells in the postnatal vocal fold mucosa were observed by immunohistochemistry. Immunoreactivity to antibodies directed to Ki-67 was studied to investigate the cell cycle.

Results: At day 1 after birth, BrdU positive cells were identified in the MFe (60.1 ± 1.7%), epithelium (58.7 ± 10.6%) and lamina propria (52.4 ± 7.8%) of the vocal fold mucosa. At day 56 after birth, the number of BrdU positive cells in the epithelium (4.8 ± 2.2%) and lamina propria (32.3 ± 16.5%) were significantly lower compared to day 1 after birth (P < 0.05). However, the number of BrdU positive cells remaining in the MFe was still high (56.2 ± 2.5%). The label-retaining cells were distributed throughout the MFe. Few Ki-67 positive cells were identified in the MFe indicating they were resting cells.

Conclusions: The results of this study are consistent with the hypothesis that the cells in the postnatal MFe are candidates for tissue stem cells. At birth, these cells are already present in the MFe of the newborn vocal fold and they are likely ready to start the growth and development of the vocal fold mucosa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvoice.2021.03.003DOI Listing
April 2021

Long-term outcomes of basic fibroblast growth factor treatments in patients with vocal fold scarring, aged vocal fold, and sulcus vocalis.

Auris Nasus Larynx 2021 Oct 24;48(5):949-955. Epub 2021 Feb 24.

Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.

Objective: Fibrotic changes in the vocal fold mucosa have been observed in patients with vocal fold scarring, aged vocal fold, and sulcus vocalis, which often lead to severe voice disorders. Previous research suggests that the basic fibroblast growth factor (b FGF) improves variations in vocal fold properties [1,2]. Although clinical studies on b FGF treatments have been conducted [3,4,5], these studies only demonstrated the efficacy of this drug over a short period. The present study is the first to investigate the long-term efficacy of b FGF treatment.

Methods: b FGF injections were performed in six patients from January of 2016 to December of 2017 at our institution. Patient follow-up continued for at least two years after the last injection. Three patients had vocal fold scarring, two had aged vocal fold atrophy, and one patient had sulcus vocalis. Each vocal fold was injected with 10 µg of b FGF four times. Voice and stroboscopic examinations were performed after surgery (at one month, three months, six months, one year, two years). Fundamental frequency, maximum phonation time (MPT), mean flow rate (MFR), amplitude perturbation quotient (APQ), pitch perturbation quotient (PPQ), and noise-to-harmonic ratio (NHR), and voice handicap index-10 (VHI-10) were examined and compared statistically between the pretreatment time and at each posttreatment time point.

Results: The speaking F0 had an obvious decreasing tendency, with significant differences suggesting the increase in volume in the vocal folds. Aerodynamic parameters also showed small improvements. The most remarkable improvement was observed in the acoustic parameters, indicating that the treatment could improve the vocal fold to make vibrations symmetrically and regularly for a long period. Achievement of symmetry and regularity on vocal fold vibrations suggested the property changes had happened in the vocal folds. Consequently, the score of VHI-10 had improved, indicating high patient satisfaction with this treatment.

Conclusion: b FGF injections could be a reliable treatment option for diseases that deteriorate the property of vocal fold.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anl.2021.02.004DOI Listing
October 2021

Glycolytic activity of the tissue stem cells in the macula flava of the human vocal fold.

Laryngoscope Investig Otolaryngol 2021 Feb 23;6(1):122-128. Epub 2021 Jan 23.

Department of Otolaryngology-Head and Neck Surgery Kurume University School of Medicine Kurume Japan.

Objectives: In our previous studies, the features of the mitochondria of tissue stem cells in the maculae flavae of the human vocal fold suggested that their metabolic activity and oxidative phosphorylation was low. This study investigated the metabolic activity, especially glycolysis of the tissue stem cells in the maculae flavae of the human adult vocal fold.

Study Design: Histologic analysis of the human vocal folds.

Methods: Three normal human adult vocal folds obtained from autopsy cases were investigated using immunohistochemistry.

Results: Among the three phenotypes of cells in the human adult maculae flavae, the vocal fold stellate cell-like cells strongly expressed glucose transporter-1. Three phenotypes of cells in the human adult maculae flavae expressed glycolytic enzymes (hexokinase II, glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase A) indicating the tissue stem cells in the maculae flavae relied more on glycolysis. The cells did not express phosphofructokinase-1 but did express glucose-6-phosphate dehydrogenase indicating the cells relied more on the pentose phosphate pathway. The cells expressed lactate dehydrogenase A indicating the maculae flavae of the human adult vocal fold was likely to be an anaerobic microenvironment.

Conclusions: The present study is consistent with the hypothesis that the tissue stem cells in the maculae flavae of the human vocal fold seem to rely more on anaerobic glycolysis, especially by the pentose phosphate pathway, for energy supply. The metabolism of the tissue stem cells in the maculae flavae of the human adult vocal fold is likely to prevent toxic reaction oxygen species and be favorable to maintaining the stemness and undifferentiated states of the tissue stem cells in the stem cells system.

Level Of Evidence: NA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lio2.525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883606PMC
February 2021

Primary Pituitary Adenoid Cystic Carcinoma: A Rare Salivary Gland-Like Tumor in the Sella.

Head Neck Pathol 2021 Jan 4. Epub 2021 Jan 4.

Department of Neurosurgery, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka, 830-0011, Japan.

Adenoid cystic carcinoma (ACC) is a tumor of the exocrine glands that originates primarily from the minor and major salivary glands, nasopharynx, and lacrimal glands. ACC grows slowly but is locally aggressive and prone to recurrence. It is uncommon for ACCs to develop in the pituitary gland as a primary tumor. We present a case of primary pituitary ACC extending to the sphenoid sinus resembling an invasive adenoma in a 71-year-old woman with a history of nasal epistaxis. We reviewed other reported cases of pituitary ACCs with retrospective validation of whether the tumor was primary or not. The intrasellar tumor exhibited MYB rearrangement with enlargement and destruction of the sella turcica and dural tears toward the sphenoid sinus, which would be consistent for a tumor originating from the pituitary gland. Including our case, only four intrasellar and one suprasellar ACC have been confirmed as primary tumors. All intrasellar ACCs had the characteristic of some form of invasion of neighboring structures with evidence of hyperprolactinemia. ACC could develop in the pituitary gland as a form of salivary gland-like tumor derived from the ectopic salivary gland rests. ACCs rarely arise from the pituitary gland; however, the accurate determination of primary occurrence is difficult because of the invasive nature of these tumors, and the anatomical relationship with the sphenoid sinus and the cavernous sinus. Excessive bleeding from the tumor or unexpected internal carotid artery injury should be avoided during surgery for primary and secondary pituitary ACC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12105-020-01256-7DOI Listing
January 2021

Recurrent aspiration pneumonia precipitated by obstructive sleep apnea.

Auris Nasus Larynx 2021 Aug 6;48(4):659-665. Epub 2020 Dec 6.

Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.

Objective: The clearance of the pharynx by deglutition and the respiratory phase patterns associated with deglutition are important in protecting airways and lungs against aspiration. The deglutition and respiratory phase patterns during sleep in patients (without swallowing disorders while awake) with obstructive sleep apnea (OSA) precipitating recurrent intractable aspiration pneumonia were investigated.

Methods: After videoendoscopic and videofluorographic examinations of swallowing showed subjects had no swallowing disorders while awake, two adults with recurrent intractable aspiration pneumonia precipitated by severe OSA were examined via time-matched digital recordings of polysomnography and surface electromyography of the muscles (thyrohyoid and suprahyoid muscles) related to swallowing and compared with the same patients before and under CPAP therapy.

Results: CPAP therapy cured recurrent intractable aspiration pneumonia. Swallows following and/or followed by inspiration (uncoordinated deglutition with respiration), which were frequently observed before CPAP therapy, were markedly reduced under CPAP therapy. On the other hand, swallows following and/or followed by expiration (coordinated deglutition with respiration) markedly increased under CPAP therapy. Deglutition was related to the sleep stage. The deeper the sleep stage, the lower the deglutition frequency. Before and under CPAP therapy, swallowing was infrequent and absent for long periods. However, respiratory phase patterns associated with sleep-related deglutition in patients with OSA under CPAP therapy markedly improved.

Conclusions: In patients (without swallowing disorders while awake) with OSA precipitating recurrent intractable aspiration pneumonia, the high rate of uncoordinated deglutition with respiration (swallows following and/or followed by inspiration) during sleep were markedly reduced and the rate of coordinated deglutition with respiration (swallows following and/or followed by expiration) was markedly increased under CPAP therapy. Sleep-related deglutition and respiratory phase patterns are likely to adversely influence aspiration pneumonia in patients with OSA. CPAP therapy improved not only apnea-hypopnea during sleep and sleep quality but also sleep-related deglutition, especially respiratory phase patterns associated with deglutition in patients with OSA. CPAP therapy may decrease the risk of aspiration and greatly improve aspiration-related diseases such as aspiration pneumonia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anl.2020.11.021DOI Listing
August 2021

Epithelium of the human vocal fold as a vibrating tissue.

Auris Nasus Larynx 2021 Aug 28;48(4):704-709. Epub 2020 Nov 28.

Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.

Objectives: The human adult vocal fold mucosa, especially, superficial layer of the lamina propria (Reinke's space) has attracted notice as an important vibrating structure. However, fine structures of the stratified squamous epithelium of the human adult vocal fold, which is another histological component of the mucosa, remain enigmatic.

Methods: Three normal human adult vocal folds and epiglottises and three newborn vocal folds were investigated. Observations using transmission electron microscopy and light microscopy including immunohistochemistry were performed.

Results: The most obvious feature of the epithelium of the human adult vocal folds was that the intercellular spaces between adjacent epithelial cells were large (984 ± 186 nm) compared with the stratified squamous epithelium of the human adult epiglottis and the human newborn vocal fold. Even though intercellular spaces between adjacent epithelial cells of the human adult vocal fold were large, desmosomes at the junctions of two adjacent epithelial cells made firm intercellular adhesion. Tonofilaments composed of the bundles of intermediate filaments anchored to the desmosomes. Desmosomes formed a continuous cytoskeletal network throughout the epithelial cells and epithelium of the human adult vocal fold. In addition, a great deal of E-cadherin (adhesive glycoprotein) was present between epithelial cells especially the lower half of the stratified squamous epithelium of the human adult vocal fold.

Conclusions: From the functional morphological point of view, stratified squamous epithelium of the human adult vocal fold seems to form a structural framework of tensile strength with pliability suitable structure for vibration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anl.2020.11.011DOI Listing
August 2021

Heterogeneity and hierarchy of the tissue stem cells in the human newborn vocal fold mucosa.

Laryngoscope Investig Otolaryngol 2020 Oct 29;5(5):903-910. Epub 2020 Sep 29.

Department of Otolaryngology-Head and Neck Surgery Kurume University School of Medicine Kurume Japan.

Objectives: There is growing evidence that the cells in the maculae flavae (MFe) are tissue stem cells and the MFe are a stem cell niche of the human vocal fold mucosa. Heterogeneity and hierarchy of tissue stem cells in the MFe of newborn vocal fold were investigated in vivo.

Study Design: Histologic analysis of the human vocal folds.

Methods: Five normal human newborn vocal folds were investigated under transmission electron microscopy and light microscopy.

Results: Cobblestone-like polygonal cells, vocal fold stellate cell-like cells, and fibroblast-like spindle cells were intermingled in the newborn MFe in vivo, indicating that the cells in the MFe had heterogeneity. However, cobblestone-like polygonal cells were predominant. Free ribosomes were well developed in the cytoplasm. The cells in some cases formed gap junctions with each other. The cells in some cases were attached to other cells and formed cell junctions with each other. These findings indicated cells in the newborn maculae flavae possessed features of mesenchymal cells (cells in mesenchyme). Colony-forming-unit-like cell aggregate was observed, indicating the cells in the newborn MFe had stemness. The cobblestone-like polygonal cells expressed SSEA-3 (a human pluripotent stem cell marker), indicating they were at the top of a cellular hierarchy in the stem cell system.

Conclusions: The cells in the MFe of the human newborn vocal fold mucosa had heterogeneity and hierarchy in the stem cell system in vivo. At birth, newborn maculae flavae are ready to start the growth of the vocal fold mucosa as a vibrating tissue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lio2.470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585242PMC
October 2020

Prognostic Value of Tumor Proportion Score in Salivary Gland Carcinoma.

Laryngoscope 2021 05 6;131(5):E1481-E1488. Epub 2020 Oct 6.

Department of Pathology, Kurume University School of Medicine, Kurume, Japan.

Objective: Limited information is available regarding the role of programmed death ligand 1 (PD-L1) expression and CD8 tumor-infiltrating lymphocyte (TIL) density in the tumor immune microenvironment (TIM) of patients with salivary gland carcinoma (SGC). This study aimed to assess the association between the prognosis of SGC patients and the probability of PD-L1 expression in tumor and/or immune cells using the tumor proportion score (TPS), mononuclear immune cell density score (MIDS), combined positive score (CPS), and CD8 TIL density in the TIM.

Study Design: Retrospective cohort study.

Methods: We retrospectively reviewed 73 SGC patients treated with definitive surgery between 2000 and 2015. Immunohistochemical analysis was used to assess TPS, MIDS, CPS, and CD8 TIL density, followed by prognostic evaluation of these immune-related parameters.

Results: Histological grade was associated with TPS, MIDS, and CPS based on PD-L1 expression, and these scores exhibited a significant association with CD8 TIL density. Patients with positive TPS had an unfavorable disease-free survival and overall survival. Multivariate analyses indicated that the TPS was a significant and independent prognostic factor.

Conclusion: Our results suggest that TPS might be a useful prognostic biomarker in SGC patients receiving definitive surgery. Laryngoscope, 131:E1481-E1488, 2021.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lary.29120DOI Listing
May 2021

CD8+ T Cell Infiltration Predicts Chemoradiosensitivity in Nasopharyngeal or Oropharyngeal Cancer.

Laryngoscope 2021 04 15;131(4):E1179-E1189. Epub 2020 Sep 15.

Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan.

Objectives: Limited information exists regarding the associations between pre-existing immune parameters in the tumor immune microenvironment (TIM) and either chemoradiosensitivity or prognosis for patients with squamous cell carcinoma of the nasopharynx or oropharynx involving virus-related or nonvirus-related tumors.

Study Design: Retrospective cohort study.

Methods: We retrospectively reviewed 141 patients with EBV+, p16+, or EBV- and p16- statuses who are receiving chemoradiotherapy. We performed immunohistochemistry using pretreatment biopsy specimens to analyze the programed death ligand 1 (PD-L1) levels in tumor and immune cells and CD8+ tumor-infiltrating lymphocyte (TIL) density. We evaluated chemoradiosensitivity and prognosis with respect to these immune-related parameters.

Results: Virus-related tumors showed associations with both PD-L1 expression and high CD8+ TIL density. Patients with higher CD8+ TIL density or greater numbers of PD-L1+ tumor and immune cells showed significant rates of favorable local recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS). Multivariate analyses demonstrated that higher CD8+ TIL density is an independent, significant, and favorable predictive factor for LRFS (P = .005) and OS (P = .003), although it is not a significant predictor of PFS (P = .077).

Conclusions: Higher CD8+ TIL density represents a useful and favorable biomarker of chemoradiosensitivity in patients receiving chemoradiotherapy for nasopharyngeal or oropharyngeal cancer.

Level Of Evidence: 3 Laryngoscope, 131:E1179-E1189, 2021.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lary.29097DOI Listing
April 2021

Dysphagia Precipitated by Cervical Lordosis in the Aged.

Ear Nose Throat J 2020 Aug 25:145561320946644. Epub 2020 Aug 25.

Department of Otolaryngology-Head and Neck Surgery, 26333Kurume University School of Medicine, Kurume, Japan.

A lordotic curve of the cervical spine in the aged is a physiological curvature of the cervical spine. The swallowing disorder precipitated by lordosis of the cervical spine in the aged, the swallowing function and intervention were reported on. An 86-year-old woman complained of swallowing difficulty for a few months. A lordotic curve (physiological curvature) of the cervical spine was observed. In the neutral neck position, the cervical lordotic angle was 29° using the Cobb C2-C7 method. When the lordotic curve of the cervical spine was intentionally straightened, the lordotic angle became 0°, the laryngeal elevation changed from 0.5 times the height of a cervical vertebra to 1.75 times, the laryngeal elevation delay time changed from 0.5 seconds to 0.23, the percent laryngeal elevation changed from 50% to 72% and pharyngeal transit time changed from 0.83 seconds to 0.75. Lordosis of the cervical spine inhibited laryngeal elevation and influenced the swallowing function. In cases in which lordotic curvature of the cervical spine adversely influences the swallowing function in the aged, rehabilitation to manage the lordosis of the cervical spine is useful. For the purpose of effective intervention, not only diagnostic but also therapeutic videofluorographic examination of swallowing is very important.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0145561320946644DOI Listing
August 2020

Predictive value of CD8/FOXP3 ratio combined with PD-L1 expression for radiosensitivity in patients with squamous cell carcinoma of the larynx receiving definitive radiation therapy.

Head Neck 2020 12 18;42(12):3518-3530. Epub 2020 Aug 18.

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

Background: Little is known about immune-related radiosensitivity in patients with squamous cell carcinoma of the larynx (SCC-L) treated with radiation therapy (RT).

Methods: We retrospectively reviewed 91 patients with SCC-L treated with RT or chemoradiation therapy and performed immunohistochemical examination to analyze PD-L1 level on tumor cells, CD4 tumor-infiltrating lymphocytes (TILs), CD8 TIL, and FOXP3 TIL using pretreated biopsy specimens. The association between these immune-related parameters and radiosensitivity was evaluated.

Results: Multivariate analyses showed that high CD8/FOXP3 ratio combined with negative PD-L1 expression was an independent and significant favorable predictive factor for local control, compared with the other groups.

Conclusions: We showed that high CD8/FOXP3 ratio combined with negative PD-L1 expression might be a useful biomarker of radiosensitivity in patients with SCC-L receiving definitive RT. We propose that coassessment of CD8/FOXP3 ratio and PD-L1 expression level in tumor cells can help predict potential radiosensitivity in patients with SCC-L.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.26416DOI Listing
December 2020

Pathophysiology of current odontogenic maxillary sinusitis and endoscopic sinus surgery preceding dental treatment.

Auris Nasus Larynx 2021 Feb 3;48(1):104-109. Epub 2020 Aug 3.

Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.

Objective: The successful management of odontogenic maxillary sinusitis (OMS) involves a combination of medical treatment with dental surgery and/or endoscopic sinus surgery (ESS). However, there is no consensus for the optimal timing of ESS. Although several studies have emphasized dental surgery as the primary treatment modality for OMS, there is recent evidence to suggest that ESS alone may be an effective treatment approach. The purpose of this study is to retrospectively investigate the pathophysiology of the current intractable OMS and the role ESS, especially ESS preceding dental treatment, plays in its pathophysiology.

Methods: Ninety-seven adults (60 males and 37 females, 48 ± 12 years) who underwent ESS for intractable OMS were retrospectively examined.

Results: In a great deal of the cases (85 cases, 87.6%), causative teeth of OMS were periapical lesions after root canal treatment (endodontics). The root canal procedures were not sufficient; hence, the root-canal-treated teeth had periapical lesions causing OMS. In postoperative nasal endoscopy and cone-beam CT scans for all patients, the natural ostiums and the membranous portions of the maxillary sinuses were enlarged and the ostiomeatal complexes remained widely open. The ventilation and drainage of all patients' maxillary sinuses seemed to be successfully restored. Temporary acute sinusitis recurrence after primary ESS for OMS was observed in 10 cases (11.8%) when the patients caught a cold. However, since the natural ostium and the membranous portion of the maxillary sinuses and the ostiomeatal complexes remained widely open, antibiotic administration alone without dental treatment cured the temporary acute sinusitis. Regarding the causative teeth (endodontic treated teeth), in 83 out of 85 cases (97.6%), causative teeth were able to be preserved with only antibiotic treatment and without dental retreatment. In two cases, extraction of the teeth was necessary because the teeth became mobile. Regarding the causative teeth after dental restoration, in 2 out of 2 cases (100%), causative teeth were able to be preserved with antibiotic treatment alone.

Conclusion: ESS is highly indicated for OMS requiring surgery. The treatment results of intractable OMS are exceptionally good once the ventilation and drainage of the maxillary sinus is successfully restored after surgery. Consequently, ESS can be considered the first-line therapy for intractable OMS caused by root canal treatment (endodontics) and dental restoration, followed by close dental follow-up and dental treatment when necessary.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anl.2020.07.021DOI Listing
February 2021

Changes in immune parameters between pre-treatment and recurrence after (chemo) radiation therapy in patients with head and neck cancer.

Sci Rep 2020 07 20;10(1):11973. Epub 2020 Jul 20.

Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Kurume University, Asahimachi 67, Kurume, Fukuoka, 830-0011, Japan.

Squamous cell carcinoma of the head and neck (SCCHN) has a high recurrence rate after (chemo) radiation therapy [(C)RT]. The relationship between the changing levels of immune checkpoint molecules and immune cells in pre-(C)RT tissues and locally recurrent tissues in the irradiated field, after (C)RT completion, is not known. This study aimed to assess the changes in these immune parameters between pre-(C)RT tissue and the same area after local recurrence post-(C)RT. We retrospectively reviewed 30 (C)RT-treated patients with SCCHN. We performed immunohistochemical analyses on these immune parameters using paired tissue samples obtained pre-(C)RT and at local recurrence sites post-(C)RT. No significant changes in immune parameters were found between the pre-(C)RT and locally recurrent tissues. An increased density of CD8+ tumor-infiltrating lymphocytes (TILs) showed a significantly positive correlation with PD-L expression on tumor cells (TC-PD-L1). Patients with increased TC-PD-L1 expression and CD8+TIL density showed favourable prognosis, and one of them showed a favourable response to nivolumab therapy. Our study shows a positive association between TC-PD-L1 upregulation and increased CD8+TIL density, and demonstrates that patients with these changes have a favourable survival outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-68938-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371733PMC
July 2020

Sleep-related deglutition and respiratory phase patterns in the aged with obstructive sleep apnea under CPAP therapy.

Acta Otolaryngol 2020 Oct 13;140(10):861-868. Epub 2020 Jun 13.

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

Respiratory phase patterns associated with deglutition and clearance of pharynx by deglutition are important in protecting airways and lungs against aspiration. Sleep-related deglutition and respiratory phase patterns in the aged with obstructive sleep apnea (OSA) before and under CPAP therapy were investigated. Ten aged adults with severe OSA under CPAP therapy were examined by polysomnography and surface electromyography of the muscles related to swallowing and compared with the same patients before CPAP therapy. Under CPAP therapy, swallowing was also infrequent and absent for long periods. The deeper the sleep stage, the lower the deglutition frequency. The median number of swallows per hour during total sleep time was 1.5 and the median longest deglutition-free period was 74.5 min. Swallows following and/or followed by inspiration, which were observed a great deal before CPAP therapy, were markedly reduced. On the other hand, swallows following and/or followed by expiration markedly increased. Approximately, 73.5% of swallows occurred after expiration and approximately 66.8% were followed by expiration. Respiratory phase patterns associated with sleep-related deglutition improved under CPAP. CPAP therapy improved sleep-related deglutition and respiratory phase patterns in the aged with OSA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00016489.2020.1772504DOI Listing
October 2020

Histopathology of maxillary sinus mucosa with odontogenic maxillary sinusitis.

Laryngoscope Investig Otolaryngol 2020 Apr 17;5(2):205-209. Epub 2020 Mar 17.

Department of Otolaryngology-Head and Neck Surgery Kurume University School of Medicine Kurume Japan.

Objective: Histopathology of the maxillary sinus mucosa with intractable odontogenic maxillary sinusitis (OMS) was investigated and the role endoscopic sinus surgery (ESS) plays in its pathophysiology was clarified.

Study Design: Histopathological analysis of the OMS mucosa.

Methods: Surgical specimens were obtained from 20 patients who underwent ESS for intractable OMS. For rigid endoscopic observation of the mucosae, a 70° rigid endoscope 4 mm in diameter with an attached high definition surgical camera was used. Histopathological analyses of the maxillary sinus mucosa were conducted by light and scanning electron microscopy.

Results: All the maxillary sinuses were filled, not with viscous, but with purulent secretions. The high-definition camera showed that the maxillary sinus mucosa had gyrus-like appearance. Light microscopic histopathological studies revealed that the surface of the maxillary sinus mucosa was convoluted. Light and scanning electron microscopic histopathological studies revealed that the ciliated cells of the epithelium had not decreased and their goblet cells were not hypertrophic, indicating that the damage of the ciliated columnar epithelium was not severe and they were not injured irreversibly.

Conclusion: The ciliated columnar epithelium with intractable OMS was not severely damaged and not irreversibly injured. Hence, the pathophysiology of intractable OMS is one of the reasons why ESS is highly indicated for maxillary sinusitis requiring surgery and the treatment results are exceptionally good when the ventilation and drainage of the maxillary sinus is successfully restored after surgery.

Level Of Evidence: NA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lio2.376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178440PMC
April 2020

Organ preservation following radiation therapy and concurrent intra-arterial low dose cisplatin infusion for advanced T2 and T3 laryngeal cancer: Long-term clinical results from a pilot study.

Laryngoscope Investig Otolaryngol 2020 Feb 8;5(1):55-65. Epub 2020 Jan 8.

Department of Otolaryngology-Head and Neck Surgery Kurume University School of Medicine Kurume Japan.

Background: This pilot study evaluated the long-term outcomes of patients with advanced T2 or T3 squamous cell carcinoma of the larynx (SCC-L) who were treated with selective intra-arterial cisplatin and concomitant radiotherapy (RADPLAT).

Methods: We retrospectively investigated the data of 49 patients with advanced T2 or T3 SCC-L who received a RADPLAT regimen with low-dose cisplatin.

Results: The 5-year locoregional control, disease-specific survival, and overall survival rates were 83.3%, 88.1%, and 82.6%, respectively, while the 5-year freedom from laryngectomy, laryngectomy-free survival, and laryngo-esophageal dysfunction-free survival rates were 89.6%, 79.4%, and 77.1%, respectively. The incidences of grade 3-4 hematologic and nonhematologic toxicities were 18% and 6%, respectively. Although two patients (4%) developed late toxicities within 5 years following RADPLAT, no other events were noted beyond 5 years.

Conclusion: This pilot study demonstrated that RADPLAT is feasible and safe and yielded favorable survival outcomes and functional laryngeal preservation in patients with advanced T2 or T3 SCC-L.

Level Of Evidence: 3.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lio2.346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042651PMC
February 2020

Three-dimensional imaging of upper esophageal sphincter resting pressure.

Laryngoscope Investig Otolaryngol 2019 Dec 11;4(6):645-652. Epub 2019 Nov 11.

Department of Otolaryngology-Head and Neck Surgery Kurume University School of Medicine Kurume Japan.

Objective: High-resolution manometry (HRM) is used to analyze upper esophageal sphincter (UES) physiology. Conventional HRM can yield imprecise measurements of UES resting pressure given its unidirectional sensors and averaging of circumferential pressure. In contrast, three-dimensional (3D) measurements can yield precise UES resting pressure data over the entire length of the UES. This study conducted a detailed analysis of UES resting pressure as evaluated by 3D-HRM.

Methods: Seventeen young, healthy adult participants (7 females and 10 males) were recruited. The 3D-HRM system used includes a pressure sensor catheter (outer diameter, 4 mm) and eight-channel transducers arranged circumferentially to acquire pressure data at 45° intervals. The catheter was inserted transnasally into the esophagus and automatically retracted at a speed of 1 mm/s. Participants performed the following tasks: maintain resting breathing, perform breath holding, and perform the Valsalva maneuver. Data were obtained and compared per millimeter over the longitudinal UES length.

Results: Clear 3D waveforms were identified, with greater mean UES pressures in anterior-posterior directions than in lateral directions ( < .05). The anterior distribution was located superior to the posterior portion. Significant differences were observed in mean UES pressures and UES resting integrals between resting breathing and the Valsalva maneuver ( < 0.05). No differences in functional UES length were observed.

Conclusions: The normal UES resting pressure was not directionally uniform in the luminal structure. 3D-HRM imaging of UES resting pressure can help deepen our understanding of UES physiology.

Level Of Evidence: 4.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lio2.324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929582PMC
December 2019

Endoscopic Sealing With a Polyglycolic Acid Sheet for Restoration of Vocal Fold Mucosa in Dogs.

Laryngoscope 2020 07 6;130(7):E436-E443. Epub 2019 Nov 6.

Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan.

Objectives/hypothesis: Voice outcomes of cordectomy for early glottic cancer are often poor due to vocal fold scarring and tissue defects. Improvements in this aspect could make cordectomy a more acceptable treatment option than radiotherapy. We hypothesized that a polyglycolic acid (PGA) sheet could be used to cover vocal fold defects. The present study aimed to prevent vocal fold scarring after cordectomy using the PGA sheet.

Study Design: Animal experiment.

Methods: Nine male beagles were divided into three groups including a control group (n = 3). Following cordectomy, the vocal fold defect was covered with the PGA sheet plus fibrin glue (PGA group; n = 3) or with the PGA sheet plus fibrin glue containing basic fibroblast growth factor (bFGF; the PGA-bFGF group, n = 3). Vocal folds were chronologically observed, and larynges were removed 6 months after surgery. Mucosal amplitude was measured using a high-speed camera, and histological analysis was performed.

Results: The re-epithelialization process was delayed in the PGA and PGA-bFGF groups compared with the control group. The mucosal amplitude was significantly more normalized and the thickness ratio significantly higher in the PGA and PGA-bFGF groups compared with the control group. The PGA-bFGF group had the highest elastic fiber density, followed by the PGA group and then the control group, with a significant difference between the PGA-bFGF and control groups.

Conclusions: The PGA sheet plus fibrin glue could serve as an effective regenerative scaffold for reconstructing vocal fold morphology and function after cordectomy, with the potential benefit of establishing an endoscopic sealing method for vocal fold defects.

Level Of Evidence: NA Laryngoscope, 130:E436-E443, 2020.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lary.28357DOI Listing
July 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anl.2019.09.004DOI Listing
February 2020

Cytoskeleton of cells in vocal fold macula flava unphonated for a long period.

Auris Nasus Larynx 2020 Dec 29;47(6):1033-1037. Epub 2019 Sep 29.

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

Cells in the maculae flavae (MFe) are inferred to be involved in the metabolism of extracellular matrices of the human vocal fold mucosa. The latest research has supported the hypothesis that the tension caused by phonation (vocal fold vibration) regulates the behavior of these cells in the MFe of the human vocal fold. Tensile and compressive strains have direct effects on cell morphology and structure including changes in cytoskeletal structure and organization. Cytoskeletons are one of the structures which play a role as mechanoreceptors for the cells. The microstructure of the intermediate filaments and the expression of their proteins were investigated regarding the cells in the MFe of the human vocal fold unphonated over a decade. The adult vocal fold mucosa of a 64-year-old male with cerebral hemorrhage unphonated for 11 years was investigated by immunohistochemistry and electron microscopy. The intermediate filaments in the cytoplasm of the cells had become fewer in number. And the expression of their characteristic proteins (vimentin, desmin, GFAP) was also reduced. The results of this study are consistent with the hypothesis that mechanotransduction caused by vocal fold vibration could possibly be a factor in regulating the function and fate of the cells in the MFe.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anl.2019.09.002DOI Listing
December 2020

Lateral pharyngeal flap with a double pedicle for repair of unilateral velopharyngeal insufficiency.

Auris Nasus Larynx 2020 Apr 28;47(2):245-249. Epub 2019 Aug 28.

Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan.

Objectives: Conventional pharyngeal flap surgery, which closes the median portion of the velopharynx, has been performed for dysarthria patients with velopharyngeal insufficiency (VPI). However, for VPI due to unilateral pharyngeal paralysis, median closing disrupts pharyngeal contraction of the unaffected side and allows pharyngeal pressure to escape through the nose at the lateral portion of the affected side during speech and swallowing. The purpose of this study was to evaluate the effectiveness of lateral pharyngeal flap (LPF) surgery for unilateral VPI.

Methods: Seven patients with unilateral VPI (five males and two females with an average age of 54 years) underwent LPF surgery combined with other transoral surgeries for dysphagia. The LPF surgical technique was as follows: after the laterocaudal-based pedicle flap of the soft palate and cranial-based pedicle flap of the posterior pharyngeal wall on the affected side were transorally elevated, each mucosal pedicle flap was sutured together. Functional oral intake scale (FOIS) scores and swallowing pressure before and after surgery were compared.

Results: Unilateral velopharyngeal closure preserved nasal breathing after LPF surgery in all patients. Rhinolalia aperta improved postoperatively in all patients except one. The mean FOIS scores were 2.3 preoperatively and 3.7, 5.3, and 5.9 at 2 weeks, 1 month, and 6 months postoperatively, respectively. The mean pressures significantly increased at the velopharynx (from 49±30mmHg to 92±45mmHg) and oropharynx (from 48±18mmHg to 66±15mmHg) six months after the surgery.

Conclusion: LPF surgery leaving the unaffected side intact can be an effective surgical procedure for patients with unilateral VPI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anl.2019.08.003DOI Listing
April 2020

Metabolic activity of cells in the macula flava of the human vocal fold from the aspect of mitochondrial microstructure.

Laryngoscope Investig Otolaryngol 2019 Aug 21;4(4):405-409. Epub 2019 Jun 21.

Department of Otolaryngology-Head and Neck Surgery Kurume University School of Medicine Kurume Japan.

Objectives: There is growing evidence to suggest that the cells in the maculae flavae of the vocal fold mucosa are tissue stem cells of the human vocal fold. This study investigated the metabolic activity of the cells in the maculae flavae of the human vocal fold from the aspect of mitochondrial microstructure.

Study Design: Histologic analysis of the human vocal folds.

Methods: Five normal human adult vocal folds obtained from autopsy cases were investigated under transmission electron microscopy.

Results: Mitochondria were randomly distributed in the cytoplasm of the cells. The morphological features of the mitochondria consisted of a double-membrane-bounded body containing matrices and a system of cristae. In each mitochondria, the lamellar cristae were sparse. The intercristal space was occupied by a mitochondrial matrix which contained electron-dense matrix granules, mitochondrial DNA, and ribonucleoprotein granules. Some mitochondria spread out over or fused to the surface of a lipid droplet in the cytoplasm. In addition, both the mitochondrial outer and inner membranes and the membranes of the lipid droplets had disappeared. Some close association between mitochondria and rough endoplasmic reticulum was present.

Conclusions: The features of the mitochondria of the cells in the maculae flavae of the human vocal fold suggested that their metabolic activity and oxidative phosphorylation were low and that they may have shifted to the utilization of lipids to some extent for their metabolic needs.

Level Of Evidence: NA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lio2.285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6703107PMC
August 2019

Different responses to nivolumab therapy between primary and metastatic tumors in a patient with recurrent hypopharyngeal squamous cell carcinoma.

Oral Oncol 2020 02 9;101:104366. Epub 2019 Jul 9.

Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan.

We report the case of a 70-year-old man with primary and metastatic tumors, showing clinically progressive disease and complete response to nivolumab therapy, respectively. He underwent total pharyngo-laryngectomy, bilateral neck dissection, and reconstruction with free-jejunum after nivolumab therapy failure, and had no recurrent or newly arising lesions 8 months after the surgery. Immunohistochemistry analysis revealed that metastatic neck tumor with the clinical complete response to nivolumab showed higher PD-L1 expression with higher CD8+ TIL density, while primary lesion with progressive disease showed lower PD-L1 expression with lower CD8+ TIL density. This represents the first case reported on head and neck squamous cell carcinoma treated with salvage surgery after nivolumab therapy failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.oraloncology.2019.07.009DOI Listing
February 2020

Prognostic impact of p16 and PD-L1 expression in patients with oropharyngeal squamous cell carcinoma receiving a definitive treatment.

J Clin Pathol 2019 Aug 21;72(8):542-549. Epub 2019 May 21.

Department of Pathology, Kurume University School of Medicine, Kurume, Japan.

Aims: Limited information is available regarding the precise differences in the tumour immune microenvironment (TIM) of patients with human papilloma virus (HPV)-associated and non-HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Here, we retrospectively reviewed 137 patients with OPSCC treated with a definitive treatment to identify molecular relationships in the TIM.

Materials And Methods: We used immunohistochemical analysis to assess p16 status, programmed death ligand 1 (PD-L1) level, and/or CD8 tumour-infiltrating lymphocyte (TIL) density, followed by prognostic evaluation of these immune-related parameters.

Results: Multivariate analyses demonstrated that PD-L1 level on immune cells but not on tumour cells or CD8 TIL density was a significant predictive factor of disease-free survival (DFS) and overall survival (OS). Additionally, subgroup analyses demonstrated that patients positive for p16 and PD-L1 expression on immune cells had favourable DFS and OS, whereas patients negative for p16 and PD-L1 expression on immune cells showed worse DFS and OS.

Conclusions: We demonstrated that PD-L1 expression on immune cells but not tumour cells might represent a useful prognostic biomarker in patients with OPSCC receiving a definitive treatment. We propose that a co-assessment of p16 and PD-L1 expression on immune cells would have greater prognostic potential compared with evaluation of each factor alone in patients with OPSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jclinpath-2019-205818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678043PMC
August 2019

Stable Tracheal Regeneration Using Organotypically Cultured Tissue Composed of Autologous Chondrocytes and Epithelial Cells in Beagles.

Ann Otol Rhinol Laryngol 2019 Jul 4;128(7):585-594. Epub 2019 Mar 4.

1 Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan.

Objectives: In tracheal regeneration, the slow process of epithelialization is often a barrier to the stability and safety of the transplanted trachea. The aim of this study was to examine a new tracheal regeneration technique using organotypically cultured tissue composed of autologous cells.

Methods: Nine beagles were prepared. Chondrocytes from auricular cartilage and epithelial cells from buccal mucosa were isolated and cultured. Tissue-engineered cartilages were fabricated with chondrocytes at a density of 1 × 10 cells/mL (high-density group) and 1 × 10 cells/mL (low-density group). A fabricated epithelial cell sheet was laid on a poly(lactic-co-glycolic acid) block in atelocollagen gel containing the chondrocytes, and the organotypically cultured tissues were transplanted into a partially resected trachea. The control group had only the block transplanted.

Results: The tissue-engineered cartilages in the high-density group contained many viable chondrocytes and many cartilage matrices. The low-density group had abundant collagen fibers and no chondrocytes. Tracheal endoscopy revealed no deformation or atrophy at the transplant site in the high-density group. Histologically, partially hyaline cartilages covered with epithelium and lamina propria were found in the high-density group but not in the low-density and control groups.

Conclusions: Stable tracheal regeneration was achieved using organotypically cultured tissue fabricated with autologous high-density chondrocytes and epithelial cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0003489419834313DOI Listing
July 2019

Pathological mechanisms of laryngeal papillomatosis based on laryngeal epithelial characteristics.

Laryngoscope Investig Otolaryngol 2019 Feb 7;4(1):89-94. Epub 2019 Jan 7.

Department of Otolaryngology-Head and Neck Surgery Kurume University School of Medicine Kurume Japan.

Objectives: Human papillomavirus (HPV) infects basal cells of the stratified squamous epithelium through micro epithelial trauma. However, laryngeal papillomatosis commonly appears in any site on the laryngeal mucosa not covered by stratified squamous epithelium. The purpose of this study is to clarify pathological mechanisms of laryngeal papillomatosis based on the characteristics of the laryngeal epithelium.

Study Design: Morphological and immunohistochemical study.

Methods: Larynges from one newborn and two adults were used. Morphological differences in the laryngeal squamo-ciliary junction (lSCJ) were compared to those in the cervical squamo-columnar junction (cSCJ) in a resected cervix uterus. Morphological characteristics of laryngeal epithelial distribution were also compared between the newborn and adult larynges. Immunohistochemical evaluations were performed using p63 (an epithelial stem-cell marker) and integrin-α6 (a cellular HPV receptor).

Results: Morphological differences were noted between the lSCJ and the cSCJ. The lSCJ was present in the adult, but not the newborn supraglottis. Goblet cells in the pseudostratified ciliated columnar epithelium were also found in the adult but not the newborn larynx. In addition, basal cells of the stratified squamous epithelium as well as the pseudostratified ciliated columnar epithelium expressed p63 and integrin-α6 in both newborn and adult larynges.

Conclusions: HPV can infect any immature laryngeal epithelium with or without the lSCJ. Squamous metaplasia of pseudostratified ciliated columnar epithelium with a latent HPV infection can also cause tumorigenesis.

Level Of Evidence: N/A.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lio2.242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383308PMC
February 2019

Distribution of label-retaining cells and their properties in the vocal fold mucosa.

Laryngoscope Investig Otolaryngol 2019 Feb 28;4(1):76-82. Epub 2018 Nov 28.

Department of Pathology Kurume University School of Medicine Kurume Japan.

Objective: The latest research suggests cells in the maculae flavae (MFe) are putative stem cells of the vocal fold mucosa and the MFe are a candidate for a stem cell niche. Distribution and properties of label-retaining cells (LRCs) in the vocal fold mucosa were investigated.

Study Design: Histologic analysis of the rat vocal folds.

Methods: Oral administration of bromodeoxyuridine (BrdU) was given to rats and the LRCs in the vocal fold mucosa were observed by immunohistochemistry. Immunoreactivity to antibodies directed to BrdU, Ki67, cytokeratin, vimentin, glial fibrillary acidic protein, desmin, Sox17, CD34, CD45, Type I collagen, and CD44 was studied. Extracellular matrices around LRCs were observed by Alcian blue staining and hyaluronidase digestion study.

Results: LRCs were present in the MFe and were resting cells (G0-phase). They expressed epithelium, muscle, neural, and mesenchymal cell-associated intermediate filament proteins, and an endodermal marker, indicating cells in the MFe are undifferentiated and express proteins of all three germ layers. They expressed hematopoietic markers (CD34, CD45) and Type I collagen, which are the major markers of bone marrow derived circulating fibrocytes. The hyaluronan concentration in the MFe was high and the cells in the MFe expressed the surface hyaluronan receptor CD44, indicating that the MFe were a hyaluronan-rich matrix.

Conclusion: LRCs reside in the MFe and MFe had a hyaluronan-rich matrix. The results of this study are consistent with the hypothesis that the cells in the MFe are putative stem cells and the MFe are a candidate for a stem cell niche.

Level Of Evidence: N/A.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lio2.219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383309PMC
February 2019

Deglutition and respiratory patterns during sleep in the aged with OSAS.

Laryngoscope Investig Otolaryngol 2018 Dec 15;3(6):500-506. Epub 2018 Nov 15.

Department of Otolaryngology-Head and Neck Surgery Kurume University School of Medicine Kurume Japan.

Objective: Clearance of the pharynx by deglutition, which removes matter that could be aspirated, is important in protecting the airways and lungs against aspiration. The deglutition and respiratory phase patterns during sleep in the aged with obstructive sleep apnea syndrome (OSAS) were investigated.

Study Design: Retrospective study with case groups.

Methods: Ten aged adults with severe OSAS (average age 75, average apnea-hypopnea index 43.8) were examined via time-matched digital recordings of polysomnography and surface electromyography of the muscles (thyrohyoid and suprahyoid) related to swallowing and compared with aged adults without OSAS previously reported on.

Results: During sleep, swallowing was infrequent and absent for long periods. The median number of swallows per hour during total sleep time was 4.1 and the median longest deglutition-free period was 70.5 minutes. Three-fourths of deglutition occurred in association with respiratory electroencephalographic arousal. Deglutition was related to the sleep stage. The deeper the sleep stage, the lower the mean deglutition frequency. The median number of swallows per hour was 5.7 during stage N1 sleep and 2.8 during stage N2 sleep. There was no deglutition during stage N3 (deep) sleep. The median number of swallows per hour was 0.6 during REM sleep. Approximately 40% of swallows occurred after inspiration and approximately 42% were followed by inspiration.

Conclusion: Deglutition was infrequent and respiratory phase patterns were unique during sleep in the aged with OSAS. Sleep-related deglutition and respiratory phase patterns may adversely influence aspiration-related diseases (aspiration pneumonia, etc) in the aged with sleep-related breathing disorders.

Level Of Evidence: 4.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lio2.213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302710PMC
December 2018