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Laryngopharyngeal reflux disease (LPRD) is caused by pharyngeal mucosal damage due to the reflux of gastric contents, including acid, pepsin, and bile juice. Our previous study has demonstrated that LPRD is associated with the cleavage of E-cadherin, which is facilitated by the acid-activated matrix metalloproteinase-7 (MMP-7); however, the mechanism by which the acid activates MMP-7 remains unclear. The purpose of this study was to investigate the mechanism by which MMP-7 is activated in the pharyngeal epithelial cells that are exposed to acid. The levels of reactive oxygen species (ROS) were measured in the epithelial cells exposed to acid. To investigate the signaling mechanism of ROS in the expression of MMP-7, the mechanism of action of the mitogen-activated protein kinase was examined. The expression of various signaling factors was determined, according to the presence or absence of each inhibitor in the acid-exposed pharyngeal epithelial cells. To identify changes in the cleavage of E-cadherin, the integrity of the mucosal membrane was assessed using a transepithelial permeability test. We found that acid exposure increased the levels of ROS, phosphorylated-extracellular signal-regulated kinase (p-ERK) 1/2, and phosphorylated-c-Jun (p–c-Jun) in pharyngeal epithelial cells. The ROS inhibitor reduced the expression of p-ERK and MMP-7, while the ERK inhibitor reduced the expression of p–c-Jun and MMP-7. Moreover, the c-Jun inhibitor reduced the expression of MMP-7 and blocked the degradation of E-cadherin. In addition, decrease in the levels of immunostained E-cadherin and increase in transepithelial permeability after acid exposure were collectively alleviated by the inhibitors of ROS, ERK, and c-Jun. The degradation of E-cadherin that occurs after human mucosal cells are exposed to acid appears to be caused by an increase in the expression of MMP-7 via the ROS/ERK/c-Jun pathway, which is thought to be an important mechanism associated with the development of LPRD. Key messages: • ROS is triggered when reflux occurs. • ROS regulates the transcription factor c-Jun via the ERK pathway. • The increase in MMP-7 that induces LPRD is induced via the ROS/ERK/c-Jun pathway. • This study revealed for the first time the expression mechanism of MMP-7, which is one of the causes of LPRD. [ABSTRACT FROM AUTHOR]

Several diagnostic methods are currently being used to diagnose LPRD (laryngopharyngeal reflux disease), but have the disadvantage of being invasive, subjective, or expensive. Our purpose in this study was to investigate the correlation between pepsin and MMP-7 (Matrix Metalloproteinase-7) in pharyngeal secretions of subjects according to RSI (Reflux Symptom Index) score to find out the diagnostic value of MMP-7. We recruited 173 subjects aged between 19 and 85 years who completed the RSI scale. All samples were taken after waking up, and the amount of the pepsin and MMP-7 in saliva were measured by means of an enzyme activity assay. There was a significant increase of pepsin and MMP-7 activity in the study group with an RSI score of 13 or higher. The sensitivity and specificity of MMP-7 for predicting the possibility of an RSI of 13 or more was higher than that of pepsin. When MMP-7 and pepsin were combined, this sensitivity and specificity increased. An enzyme assay of MMP-7 in saliva may be a noninvasive and easy technique for diagnosing LPRD. [ABSTRACT FROM AUTHOR]

Backgrounds and purpose: Radiation therapy is an important mode of treatment for patients with head and neck cancers, but some associated complications can reduce the quality of life. We investigated whether N-acetylcysteine inhalation therapy improved the quality of life of such patients. Materials and methods: We designed a prospective, non-randomized controlled multi-center study involving 10 institutions. We enrolled 120 patients (80 in the experimental group and 40 in the control group). Patients in the experimental group inhaled nebulized liquid N-acetylcysteine (2400 mg daily) for 8 weeks from the start of radiation therapy. Quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire H&N 35. Results: N-acetylcysteine inhalation was not associated with any side effect or discomfort. The reduction in painkiller use from the end of N-acetylcysteine inhalation therapy to the 1-month follow-up was greater in the experimental group than in the control group (P = 0.014). Dry mouth symptoms also improved significantly in the experimental group (P = 0.019). Conclusion: N-acetylcysteine inhalation improves the quality of life of patients with head and neck cancers who are receiving radiation therapy, without any specific side effect. [ABSTRACT FROM AUTHOR]

Swallowing discomfort is a common postoperative complaint in patients undergoing thyroidectomy. Contraction of the strap muscles might cause resistance to elevation of the laryngotracheal unit, and downward movement of the laryngotracheal unit may lead to swallowing discomfort. However, few studies have evaluated the mechanism related to limited laryngotracheal elevation after thyroidectomy. We aimed to objectively verify the presence of postoperative impaired laryngotracheal elevation through ultrasound evaluation in patients undergoing thyroidectomy and evaluate its relationship with limitation of laryngotracheal elevation. This is a prospective clinical study. Among patients undergoing hemithyroidectomy and total thyroidectomy, the patients who were followed up for ≥ 6 months were selected (N = 40). Ultrasound evaluation was done preoperatively and at 1, 3, and 6 months postoperatively. Laryngotracheal movement was recorded and the length of elevation was measured. Symptom after thyroidectomy was evaluated through swallowing-related items of thyroidectomy-related voice questionnaire. Ultrasound evaluation verified the presence of limited laryngotracheal elevation postoperatively in patients undergoing thyroidectomy. After thyroidectomy, the swallowing-related score was significantly increased, and was recovered time-dependently at 1 month. Laryngotracheal elevation showed significant decrease after thyroidectomy. The symptom score of swallowing was significantly correlated with the length of laryngotracheal elevation. Post-thyroidectomy ultrasound evaluation verified that laryngotracheal elevation was significantly impaired. Presence of adhesion between the laryngotracheal unit and the superficial soft tissue was the probable cause of the limitation at 6 months after thyroidectomy. The length of laryngotracheal elevation was related to the symptom score of swallowing after thyroid surgery. [ABSTRACT FROM AUTHOR]

Purpose: Most tumors have obvious biologically active fibroblasts known variously as myofibroblasts or cancer-associated fibroblasts (CAFs) in the stroma. CAFs have been known as an important factor of cancer invasion and metastasis. This study aimed to investigate the presence of CAFs in patients with papillary thyroid carcinoma (PTC) and evaluate the correlation between CAFs and cervical lymph node (LN) metastasis in PTC through immunohistochemistry.Methods: The medical records of 128 patients who were diagnosed with PTC from January 1, 2010 to December 31, 2010 were reviewed, and 78 patients who underwent total thyroidectomy with or without neck dissection, were included in this study. A retrospective pathological evaluation was performed to verify the presence of CAFs. CD34 and α-smooth muscle actin (SMA) were used as markers of CAFs.Results: Among 78 patients with PTC, 65 had desmoplastic stromal reaction around the PTC. Through immunohistochemical study of anti-CD34 and α-SMA antibodies, CAFs were found in 42 (64.6%) cases with desmoplastic stroma around the PTC. Univariate analysis showed that tumor size and CAFs were the risk factors of LN metastasis in patients with PTC, while multivariate analysis revealed that CAFs were the only independent risk factor of LN metastasis in patients with PTC.Conclusion: This study revealed the presence of CAFs in PTC. Furthermore, CAFs were found to be a risk factor of LN metastasis in PTC. Therefore, CAFs may be used as a predictive marker for LN metastasis in patients with PTC. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate and compare learning curves for the retroauricular (RA) and transaxillary (TA) approaches in endoscopic hemithyroidectomy. Methods: The medical records of 290 patients who underwent hemithyroidectomy by either the RA or TA approach from November 2007 through December 2015 were retrospectively reviewed (113 patients with RA and 177 with TA). The two groups were compared with regard to patient characteristics, perioperative clinical results, and complications. Learning curves for the two approaches were compared based on the number of cases required to reach a consistent operation time and drainage amount. Results: Age at diagnosis, tumor size and location, and thyroid size were not significantly different between the two approach groups. Multiplicity and extrathyroid extension were more prevalent in the RA approach ( p = 0.048 and 0.020, respectively). Operation time and hospital day were significantly shorter in the RA approach ( p < 0.001 and p = 0.030), while postoperative bleeding was less common in the TA approach ( p = 0.021). Operation time and drainage amount stabilized after 50 cases for RA and 90 cases for TA. Additionally, operation time, amount of drainage, hospital stay, and complication rates significantly decreased after stabilization of the learning curve. When comparing the two approaches before stabilization, postoperative bleeding was more frequent in the RA approach ( p = 0.044), while no difference was observed after stabilization. Conclusions: The RA approach seems to be beneficial for reducing operation time and hospital stay, and for stabilization of the learning curve. Postoperative bleeding should be considered during the period of early experience for the RA approach. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate postoperative voice outcomes and functional parameters in total thyroidectomy via a transaxillary (TA) approach.Methods: Seventy-six patients who underwent total thyroidectomy via a TA approach (TA group) were included. A total of 204 patients who underwent conventional open total thyroidectomy (conventional group) in the same time period were analyzed as a control group. All patients underwent prospective functional evaluations before surgery and at 1 week and 1, 3, 6, and 12 months postoperatively using a comprehensive battery of functional assessments.Results: There was no conversion to conventional open thyroidectomy in the TA group. Operation time and the amount of drainage were significantly higher in the TA group than in the conventional group (p < 0.001 and p = 0.033, respectively), while vocal cord paralysis, hypoparathyroidism, and hematoma were not different among two groups (p = 0.215, 0.290, and 0.385, respectively). Regarding GRBAS, the TA group showed a more aggravated tendency postoperatively, although statistical significance was attained only at postoperative 6 months (p = 0.043). The voice handicap index abruptly increased postoperatively in the TA group, showing significant differences with the conventional group at postoperative 1 week and 1 month (p < 0.001 and p = 0.001, respectively). Fundamental frequency and maximal vocal pitch did not significantly change postoperatively in either group. The conventional group showed a more rapid decline in pain than the TA group, and paresthesias on the neck and chest were more aggravated in the TA group during the early postoperative period. The dysphagia handicap index was higher in the TA group, while cosmesis was better in the TA group at all postoperative periods.Conclusions: Although cosmetic outcome was better with the TA approach, the longer operation time, aggravated subjective voice outcomes, paresthesia, and swallowing function need to be considered in selecting the operative approach. [ABSTRACT FROM AUTHOR]

The original article can be found online at https://doi.org/10.1007/s00109-021-02166-z. Correction to: Matrix metalloproteinase-7 induces E-cadherin cleavage in acid-exposed primary human pharyngeal epithelial cells via the ROS/ERK/c-Jun pathway Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. [Extracted from the article]

Objective: The objective of this study was to evaluate the feasibility and safety of performing an endoscopic thyroidectomy (ETE) via a retroauricular approach. Methods: Forty-seven patients who underwent ETE via a retroauricular approach were included, and a total of 47 patients who underwent conventional open thyroid lobectomy in the same period were analyzed as a control group. All patients underwent prospective functional evaluations before the operation and 1 week, and 1, 3, 6, and 12 months postoperatively using a comprehensive battery of functional assessments. Results: The mean total operative time was 152 ± 48 min, with a mean endoscopic procedure time of 58 ± 18 min. One patient developed temporary vocal fold paralysis. Although most of the parameters for the functional outcome were worse in the ETE group, these differences were transient. Subjective worsening on the voice handicap index and dysphagia handicap index normalized by 3 months postoperatively. The average pain score on a visual analog scale at 1 week after surgery was 2.84, representing a tolerable range of discomfort. The mean paresthesia/hyperesthesia score was worse in the ETE group than the open surgery group by postoperative month 6; however, these differences eventually disappeared. Thirty-six of the 47 patients in the ETE group were satisfied or extremely satisfied with the retroauricular incision by 6 months after surgery. Conclusions: ETE via a retroauricular approach is a safe, feasible, and cosmetically desirable treatment option, with outcomes comparable to conventional open thyroidectomy in the longer term. [ABSTRACT FROM AUTHOR]

Site-specific delivery of nanoparticles poses a significant challenge, especially in the brain where the blood-brain barrier prevents the entry of most therapeutic compounds including nanoparticle-based anti-cancer agents. In this context, the use of macrophages as vectors for the delivery of gold-silica nanoshells to infiltrating gliomas will be reviewed in this article. Gold-silica nanoshells are readily phagocytosed by macrophages without any apparent toxic effects, and the results of in vitro studies have demonstrated the migratory potential of nanoshell-loaded macrophages in human glioma spheroids. Of particular interest is the observation that, after near-infrared exposure of spheroids containing nanoshell-loaded macrophages, sufficient heat was generated to suppress spheroid growth. Collectively, these findings demonstrate the potential of macrophages as nanoshell delivery vectors for photothermal therapy of gliomas, and they certainly provide the basis for future animal studies. [ABSTRACT FROM AUTHOR]

One of the major factors that limits the treatment effectiveness for gliomas is the presence of the blood-brain barrier (BBB) which protects infiltrating glioma cells from the effects of anti-cancer agents. Circulating monocytes/macrophages (Ma) have a natural ability to traverse the intact and compromised BBB and loaded with anti cancer agents could be used as vectors to target tumors and surrounding tumor infiltrated tissue. Nanoshells (NS) are composed of a dielectric core (silica) coated with an ultrathin gold layer which converts absorbed near-infrared light (NIR) to heat with an extremely high efficacy and stability. We have investigated the effects of exposure to laser NIR on multicell human glioma spheroids infiltrated with empty (containing no nanoshells) or nanoshell loaded macrophages. Our results demonstrated that; (1) macrophages could efficiently take up bare or coated (PEGylated) gold NS: (2) NS loaded macrophages infiltrated into glioma spheroids to the same or, in some cases, to a greater degree than empty Ma; (3) NIR laser irradiation of spheroids incorporating NS loaded macrophages resulted in complete growth inhibition in an irradiance dependent manner, and (4) spheroids infiltrated with empty macrophages had growth curves identical to untreated control cultures. The results of this study provide proof of concept for the use of macrophages as a delivery vector of NS into gliomas for photothermal ablation and open the possibility of developing such regimens for patient treatment. [ABSTRACT FROM AUTHOR]