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Objective: Voice dysfunction is frequently reported after thyroidectomy even in absence of vocal fold paralysis. The energy-based devices such as Harmonic scalpel (HS) or LigaSure (LS) are commonly used in conventional thyroidectomy. The objective of this study was to investigate the long-term voice outcome after total thyroidectomy using energy based devices.Methods: Patients who underwent total thyroidectomy with or without central neck dissection for papillary thyroid carcinoma using HS or LS from April 2012 to March 2013 were involved. The videolaryngostroboscopy, acoustic analysis, voice range profile, voice perceptual evaluation, and voice handicap index-30 were obtained preoperatively, 1 week, 1 month, 3 months, 6 months, and 1year after thyroidectomy.Results: Total 92 patients (HS group: 58 cases; LS group: 34 cases) were enrolled in this study. Demographics, tumor stage, and extent of operation were not significantly different between the HS and LS group. None of the patients evidenced any abnormalities at the pre- or postoperative videolaryngostroboscopic examination. The voice range profile (highest frequency), voice perceptual evaluation (grade, rough, and breathy), and voice handicap index-30 (total, functional, physical, and emotional) showed significantly worse scores in early postoperative period (<1month), but gradually returned to preoperative values. The all parameters of acoustic analysis, voice range profile, voice perceptual evaluation, and voice handicap index-30 were not significantly different between the HS and LS group.Conclusion: The long-term voice change after thyroidectomy shows similar results regardless of the type of energy-based devices. [ABSTRACT FROM AUTHOR]

Objective: Voice disturbance is an important problem after thyroidectomy. The aim of this study was to evaluate the efficiency of intraoperative neuromonitoring (IONM) in reducing early phonation change by comparing postoperative voice outcomes.Methods: The study retrospectively enrolled 68 consecutive female patients who had undergone IONM thyroidectomy for papillary thyroid carcinoma occurring between January 2014 and November 2014. A historical group of 117 similar female patients not receiving IONM thyroidectomy was used as an external control. Voice analyses were performed preoperatively and at 1 week, 1 month, and 3 months postoperatively. Voice outcomes between the IONM group and no IONM group were compared in patients who underwent hemithyroidectomy and total thyroidectomy.Results: In patients who underwent IONM, there were significantly smaller changes in the fundamental frequency at postoperative 1 month and in the maximum voice pitch of the voice range profile at postoperative 1 week irrespective of the extent of thyroid surgery.Conclusion: IONM during thyroid surgery resulted in better outcomes regarding fundamental frequency and high-pitch voice in the early postoperative period. IONM appears to be an effective method to reduce temporary phonation alteration after thyroid surgery. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the feasibility and efficacy of solo-surgeon retroauricular thyroidectomy.Materials and Methods: For solo-surgery, we used an Endoeye Flex Laparo-Thoraco Videoscope (Olympus America, Inc.). A Vitom Karl Storz holding system (Karl Storz GmbH & Co.) composed of several bars connected by a ball-joint system was used for fixation of endoscope. A snake retractor and a brain-spoon retractor were used on the sternocleidomastoid.Results: Endoscopic thyroidectomy using the solo-surgeon technique was performed in 10 patients having papillary thyroid carcinoma. The mean patient age was 36.0 ± 11.1 years, and all patients were female. There were no postoperative complications such as vocal cord paralysis and hematoma. When compared with the operating times and volume of drainage of a control group of 100 patients who underwent surgery through the conventional retroauricular approach between May 2013 and December 2015, the operating times and volume of drainage were not significantly different (P = .781 and .541, respectively).Conclusion: Solo-surgeon retroauricular thyroidectomy is safe and feasible when performed by a surgeon competent in endoscopic thyroidectomy. [ABSTRACT FROM AUTHOR]

Introduction: Allergic diseases are mediated by T helper cell type 2 (Th2) cells, which are differentiated by dendritic cells (DCs). Recently, it was reported that cAMP concentration in DCs is important for inducing allergic responses. However, the regulatory function of cAMP in DCs in Th2 immune responses is unclear. It was hypothesized that the regulation of G protein-coupled receptors (GPCRs) to increase cAMP levels in DCs would reduce Th2 immune responses. Methods: Human DCs from patients with allergic rhinitis (AR) and from healthy controls were subjected to next-generation sequencing (NGS) to identify potential GPCR. To investigate the functions of GPCR agonists, the in vitro co-culture experiment that THP-1 cells were differentiated into DCs and cultured with human CD4+ T-cells and an AR animal in vivo model were used. Results: Among the GPCRs, the beta-2 adrenergic receptor (ADRB2) of allergic DCs was significantly increased by NGS analysis. The expression of ADRB2 was also increased in Der p 1-treated DCs, which was reduced by treatment with the ADRB2 agonist salbutamol. Salbutamol treatment induced cAMP production in THP-1 derived DCs. In an in vitro co-culture experiment, salbutamol-treated DCs reduced the secretion of Th2 cytokine. In an in vivo AR animal experiment, salbutamol-administered mice showed reduced allergic behavior and Th2 cytokine expression in the nasal mucosa. Conclusions: The regulation of ADRB2 with salbutamol alleviated the allergic response in vitro DC-T cell co-culture and in vivo AR animal models, suggesting that ADRB2 is a therapeutic target for AR and that ADRB2 agonists may be a promising medication for AR. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the role of adjuvant radiation therapy in locoregional control in patients with locoregionally advanced papillary thyroid carcinoma (pT4 or pN1b) based on a comparison of a group that received radiation therapy and a group that did not receive radiation therapy. Methods: A retrospective analysis was performed on 165 patients with locoregionally advanced papillary thyroid carcinoma who underwent treatment between 2002 and 2011. Of these, 32 patients received adjuvant radiation therapy, and 133 patients did not receive radiation therapy. Results: The median follow-up period was 7.2 years (range, 3.4-13.6) for the overall study population. The 10-year locoregional recurrence-free survival rates for patients in the radiation therapy and no radiation therapy groups were 83.9 and 60.8%, respectively (p = 0.037). The overall survival rate and distant recurrence-free survival rate were not different between the two groups (p = 0.076 and p = 0.813, respectively). Multivariate analysis showed that adjuvant radiation therapy was an independent prognostic factor for locoregional recurrence-free survival (p = 0.040). Conclusions: Adjuvant radiation therapy for patients with either pT4 or pN1b disease improved locoregional recurrence-free survival and might be of benefit for patients with these high-risk features by reducing the need for additional salvage treatment after locoregional recurrence. [ABSTRACT FROM AUTHOR]

Objective: The preservation of periaural sensation is one of the most important things to improve the postoperative quality of life after performing the surgical procedures via retroauricular approach. The aim of this study is to describe the surgical technique of endoscopic submandibular gland (SMG) resection through the potential plane between great auricular nerve (GAN) and sternocleidomastoid muscle (sub-GAN dissection) and to evaluate its technical feasibility and advantage.Methods: The present study enrolled 22 patients who underwent endoscopic SMG resection through linear hairline incision and sub-GAN dissection. The assessment was performed on the following: the cosmetic satisfaction after surgery and surgery-related variables.Results: There was one case of a postoperative hematoma, which resolved with conservative management via a compression dressing, and one case of transient numbness at the surgical site, which spontaneously resolved within two months. In all other patients, no complications, such as seroma, skin necrosis, or marginal mandibular nerve palsy, occurred. The mean scores of pain and paresthesia evaluated with the graded scale approximated 0 (no pain or paresthesia). The cosmetic result score was as low as 1.5 ("extremely satisfied" or "satisfied").Conclusion: Linear hairline incision and sub-GAN dissection were feasible to acquire the sufficient working space for endoscopic SMG resection without sensory deterioration of GAN. This procedure may be useful to apply the surgery of other upper neck masses or thyroidectomy via retroauricular approach. [ABSTRACT FROM AUTHOR]

Objectives: In this study, we aimed to determine the relationship between oral health status and thyroid dysfunction. Methods: A population‐based cross‐sectional analysis using data from the Korean National Health and Nutrition Examination Survey (KNHNES) was performed. We investigated the association between oral health‐related parameters and the prevalence of thyroid diseases. In addition, the relationship between oral health status and thyroid function test (TFT) results was analyzed. One‐way analysis of variances or chi‐square test was used for comparisons between oral health‐related parameters and presence of thyroid diseases. Univariable and multivariable logistic regression analyses were conducted to evaluate the associations between participants' characteristics including oral health‐related parameters and the abnormal results of TFTs. Results: A total of 18,034 adults were surveyed. Histories of thyroid diseases were found to be more common in people who brushed their teeth frequently or used oral hygiene products. However, histories of periodontitis and community periodontal index (CPI) did not show significant associations with histories of thyroid diseases. Among 14,860 participants without history of thyroid disorders, people having higher CPI values demonstrated higher probabilities of abnormal TFTs (OR 1.381, 95% CI 1.241‒1.537, p <.0001); however, statistical significance was not found after adjusting for the other variables. Conclusions: Our study demonstrated that good oral health‐related behavior was associated with more frequent thyroid disease history. High CPI showed a significant association with TFT abnormalities; however, the significance of this association became lower when other variables such as age and sex were adjusted. Further studies will be needed to determine how the control of oral health‐related conditions actually has a causal relationship with thyroid disease/dysfunction through prospective cohort studies. [ABSTRACT FROM AUTHOR]

Objective: Head and neck cancer often accompany a synchronous secondary primary lesion in the digestive tract. The aim of this study was to compare detection rates between positron emission tomography–computed tomography (PET-CT) and esophagogastroduodenoscopy (G-fiber) or colonoscopy (C-fiber) in the initial staging and to analyze risk factors for premalignant, malignant, and total synchronous secondary primary lesions. Methods: A total of 739 patients with head and neck cancer who underwent PET-CT, G-fiber, or C-fiber were analyzed retrospectively. Results: Positron emission tomography–CT did not definitely detect any premalignant synchronous secondary primary lesions (0 [0%] of 739) but definitely detected 10 malignant synchronous secondary primary lesions (10 [1.35%] of 739). Esophagogastroduodenoscopy or C-fiber detected all 20 premalignant synchronous secondary primary lesions (20 [2.71%] of 739) and all 37 malignant synchronous secondary primary lesions (37 [5.00%] of 739). The patients with nasopharynx cancer tended to have premalignant synchronous secondary primary lesions (odds ratio [OR]: 3.793; 95% CI: 1.414-10.171; P =.008). Those with distant metastasis tended to have premalignant (OR: 4.743; 95% CI: 1.508-14.916; P =.009), malignant (OR: 3.803; 95% CI: 1.486-9.731; P =.005), and total synchronous secondary primary lesions (OR: 2.753; 95% CI: 1.159-6.538; P =.022). Conclusions: Premalignant or malignant synchronous secondary primary lesions that were not definitely detected by PET-CT could be found in the endoscopic examination. [ABSTRACT FROM AUTHOR]

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]

[Display omitted] To enhance photothermal treatment (PTT) efficiency, a delivery method that uses cell vector for nanoparticles (NPs) delivery has drawn attention and studied widely in recent years. In this study, we demonstrated the feasibility of M1 activated macrophage as a live vector for delivering NPs and investigated the effect of NPs loaded M1 stimulated by Lipopolysaccharide on PTT efficiency in vivo. M1 was used as a live vector for delivering NPs and further to investigate the effect of NPs loaded M1 on PTT efficiency. Non-activated macrophage (MФ) was stimulated by lipopolysaccharide (LPS) into M1 and assessed for tumor cell phagocytic capacity towards NPs We found M1 exhibited a 20-fold higher uptake capacity of NPs per cell volume and 2.9-fold more active infiltration into the tumor site, compared with non-activated macrophage M Ф. We injected M1 cells peritumorally and observed that these cells penetrated into the tumor mass within 12 h. Then, we conducted PTT using irradiation of a near-infrared laser for 1 min at 1 W/cm2. As a result, we confirmed that using M1 as an active live vector led to a more rapid reduction in tumor size within 1 day indicating that the efficacy of PTT with NPs-loaded M1 is higher than that with NPs-loaded M Ф. Our study demonstrated the potential role of M1 as a live vector for enhancing the feasibility of PTT in cancer treatment. [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]

Background: The advance in microsurgical technique has facilitated a proper approach for reconstruction of extensive head and neck defects. For the success of free tissue reconstruction, selection of the recipient vessel is one of the most important factors. However, the vascular anatomy of this region is very complex, and a clear guideline about this subject is still lacking. In this study, we present our 30 years of experiences of free tissue reconstruction for head and neck defects. Methods: In this retrospective study, we analyzed a total of 138 flaps in 127 patients who underwent head and neck reconstruction using free tissue transfer following tumor resection between October 1986 to August 2019. Patients who underwent facial palsy reconstruction were excluded. Medical records including patient's demographics, detailed operation notes, follow-up records, and photographs were collected and analyzed. Results: Among a total of 127 patients, 10 patients underwent a secondary operation due to cancer recurrence. The most commonly used type of flap was radial forearm flap (n= 107), followed by the anterolateral thigh flap (n= 18) and fibula flap (n= 10). With regard to recipient vessels, superior thyroid artery was most commonly used in arterial anastomosis (58.7%), and internal jugular vein (51.3%) was the first choice for venous anastomosis. The flap survival rate was 100%. Four cases of venous thrombosis were resolved with thrombectomy and re-anastomosis. Conclusion: Superior thyroid artery and internal jugular vein were reliable choices as recipient vessels. Proper recipient vessel selection could improve the result of head and neck reconstruction. [ABSTRACT FROM AUTHOR]

CCL2 mitigates cyclic AMP-suppressed Th2 immune response in human dendritic cells Keywords: allergic rhinitis; cAMP; CCL2; dendritic cells; Gnas CD11c mice EN allergic rhinitis cAMP CCL2 dendritic cells Gnas CD11c mice 1 4 4 07/29/20 20200801 NES 200801 Allergic rhinitis (AR) is a Th2-type chronic inflammatory disease of the nasal mucosa, characterized by symptoms including rhinorrhea, obstruction, and sneezing. However, CCL7 mRNA in AR MDDCs was not different from that in control MDDCs (Figure S4), suggesting that decreased cAMP levels in AR DCs induce the Th2 immune response through upregulation of CCL2. [Extracted from the article]

Objective: The radial forearm free flap (RFFF) is a commonly used free flap for tongue cancer. Postoperative changes in the volume of free flap are known to influence the functional restoration of the resected tongue. This study aimed to estimate chronological volume changes in RFFFs for tongue cancer and to determine the clinical factors affecting these changes.Methods: Clinical data for 19 patients who underwent RFFF reconstruction for tongue cancer between May 2004 and September 2013 were retrospectively reviewed. The flap volume was measured 3, 6, 12, 24, and 36 months after surgery using CT and the Picture Archiving and Communication System software.Results: Relative to volumes at 3 months, median flap volumes decreased to 98.55, 70.16, 62.86, and 58.84% at 6, 12, 24, and 36 months, respectively. None of the evaluated parameters were correlated with volume changes.Conclusions: Over time, the volume of RFFF in the tongue decreased. Considering this, free flap reconstruction should be carried out in tongue cancer surgery. [ABSTRACT FROM AUTHOR]

Objective: The incidence of pediatric thyroid cancer is relatively low compared to the disease in adults. This study aims to present the data in our institution on pediatric thyroid cancer patients, with particular emphasis on the risk factors of recurrence together with treatment outcomes. Subjects and Methods: Between January 2000 and July 2018, patients <20 years who were diagnosed with thyroid carcinoma and primarily treated with surgery at a major large-volume tertiary medical center specializing in thyroid cancer were enrolled. A total of 83 patients were eligible for this study. Results: The majority of the studied patients were girls and adolescents (age ≥13 years). Papillary thyroid carcinoma (PTC) was the most common pathology (n = 74). PTC tumors >1 cm showed higher rate of lymph node metastasis and extrathyroidal extension than tumors ≤1 cm. All patients survived with nine PTC patients who displayed treatment failure. Age, tumor size, multifocality, lateral lymph node metastasis, and postoperative thyroglobulin levels were significant prognosticators for disease recurrence. Conclusion: Pediatric thyroid cancer is relatively rare and should be considered a specific disease entity with respect to the thyroid cancer in adults, since there are several distinctive characteristics. [ABSTRACT FROM AUTHOR]

Anaplastic thyroid carcinoma (ATC) is a rare malignancy with very poor prognosis. The exact cause underlying its strong aggressive nature is not clear. Here, we discovered the elevated expression of anoctamin-1 (ANO1; Ca2+-activated Cl− channels) in advanced-stage ATC tissue. Using different ATC cell lines, the degree of expression of ANO1 was found to be related to the degree of ATC cell invasion by quantitative reverse transcription polymerase chain reaction and western blotting. Suppression of ANO1 activity either by selective inhibitor (T16Ainh-A01) or by siRNA significantly attenuated the migration and invasion of ATC cells. In conclusion, ANO1 appears to increase the ability of ATC cells to invade and migrate. Our results also suggest that the expression of ANO1 in patients with ATC may be helpful in predicting the prognosis of ATC. [ABSTRACT FROM AUTHOR]

Objective: In this study, we analyzed clinicopathological characteristics and survival outcomes according to extranodal involvement of diffuse large B-cell lymphoma (DLBCL) in the head and neck.Methods: A retrospective analysis was conducted on 110 patients from 2004 to 2014 with CD20-positive DLBCL involving the head and neck area. Patients were categorized into two groups, extranodal and nodal, according to involvement of extranodal sites in the head and neck. Outcome measurements for the groups included clinical response to treatment and recurrence rates.Results: Palatine tonsils were the most frequently involved extranodal site in the head and neck (29.1%). Among clinicopathological parameters, proportion of patients with lactate dehydrogenase over 350 IU/L (p=0.033), cell of origin (p<0.001), and treatment outcomes (p=0.007) were significantly different between the two groups. Among cell origin markers CD10, Bcl6, and MUM1, MUM1 was significantly correlated with extranodal involvement (p=0.029). Recurrence rates were similar between groups, while disease-specific survival was significantly higher in the extranodal group (p=0.011). Disease-specific survival of the extranodal group was also higher than the nodal group with extranodal involvement of other body sites (p=0.010). Among patients with negative expression of CD10 (p=0.015), Bcl6 (p=0.018), and MUM1 (p=0.005), survival was longer in the extranodal than the nodal group.Conclusions: DLBCL patients with extranodal involvement of the head and neck may have longer survival outcomes than patients with solely nodal involvement. Increased survival may be more prominent in patients with negative expression of CD10, Bcl6, and MUM1. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate differences in functional outcomes of postoperative complications and hypoparathyroidism between patients who underwent completion thyroidectomy (CT) after thyroid lobectomy or total thyroidectomy (TT) as an initial treatment.Materials and Methods: We retrospectively analyzed the differences of functional outcomes after completion thyroidectomy and total thyroidectomy without lymph node dissection. We reviewed the medical records of 396 patients who underwent CT or TT for thyroid disease at Korea University Guro Hospital from March 2002 to August 2016.Results: Of the 396 patients, 32 underwent CT and 364 underwent TT. There were 72 male patients and 324 female patients. Transient hypoparathyroidism was observed in 4 (9.4%) of the CT patients and 97 (26.6%) of the TT patients, with a statistically significant difference (p=0.031). Permanent hypoparathyroidism was observed in 1 patient (3.1%) in the CT group and in 13 patients (3.6%) in the TT group, which was not significantly different. There were no significant differences in the postoperative complication of temporary recurrent laryngeal nerve injury, wound infection, and hematoma between two patients group.Conclusion: The incidence of transient hypoparathyroidism in CT patients was significantly lower than in TT patients. These safety and functional superiority of CT should be considered when determining the scope and extent of operation in patients requiring surgery for thyroid disease. [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]

Background: In airway epithelium, thymus and activation-regulated chemokine (CCL17) and macrophage-derived chemokine (CCL22) are induced by defective epithelial barriers such as E-cadherin and attract the effector cells of Th2 immunity. However, the association between the epithelial barrier and CCL17 expression has not been studied in chronic rhinosinusitis with nasal polyp (CRSwNP). Thus, we aimed to evaluate the expression of CCL17 and its regulation by Th cytokines in nasal polyp (NP) epithelial cells. Methods: The expression and distribution of CCL17, CCL22, E-cadherin and/or epidermal growth factor receptor (EGFR) were measured using real-time PCR, western blot, and immunohistochemistry and compared between normal ethmoid sinus epithelium and NP epithelium. In addition, the expression level of CCL17 was determined in cultured epithelial cells treated with IL-4, IL-5, IL-13, TNF-α, and IFN-γ. Results: The expression of CCL17 was decreased in the NP epithelium compared to the epithelium of normal ethmoid sinus, whereas the expression of CCL22 was not decreased. E-cadherin was differentially distributed between the epithelium of normal ethmoid sinus and NP epithelium. EGFR was also decreased in NPs. Interestingly, the stimulation of cultured epithelial cells with Th2 cytokines, IL-4 and IL-5, resulted in an upregulation of CCL17 expression only in NP epithelial cells whereas the expression of CCL17 was increased in both normal epithelial cells and NP epithelial cells by Th1 cytokines. Conclusion: Our results suggest that the decreased expression of CCL17 in defective NP epithelium may be closely connected to NP pathogenesis and can be differentially regulated by cytokines in the NP epithelium of patients with CRSwNP. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the effectiveness of a scoring system based on the lymphocyte-to-monocyte ratio, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio for predicting disease-specific survival of oral cancer patients treated by surgery. Methods: From January 2007 to December 2016, we retrospectively analyzed data from 69 oral cancer patients who received surgery. Results: Lymphocyte-to-monocyte ratio was significantly associated with T classification, N classification, and pathologic stage. Neutrophil-to-lymphocyte ratio was significantly associated with T classification and pathologic stage. Platelet-to-lymphocyte ratio was significantly associated with N classification and pathologic stage. In multivariate analysis, only a higher score on this scoring system was significantly associated with poorer disease-specific survival. Conclusions: We found that the prognostic score system based on these three values was significantly associated with disease-specific survival of oral cancer patients who received surgery, indicating that the prognostic scoring system was effective in indirectly predicting systemic inflammatory response. [ABSTRACT FROM AUTHOR]

Objective: We analyzed the changes in voice- and swallowing-related symptoms that occurred over time in patients who underwent thyroidectomy and identified any associated risk factors. Methods: One hundred and three patients who underwent thyroidectomy were enrolled. Results: The mean thyroidectomy voice-related questionnaire (TVQ) score before surgery was 12.41 ± 12.19; it significantly increased to 28.24 ± 18.01 (P < .001) 1 month postoperatively, decreased to 24.02 ± 17.30 (P = .014) and 20.66 ± 15.29 (P = .023) 3 and 6 months postoperatively, respectively. It was continuously decreased to 18.83 ± 14.63 twelve months postoperatively. The temporal changes in TVQ scores between patients who underwent total thyroidectomy or lobectomy were significantly different. There was a statistically significant difference in the temporal changes in TVQ according to whether neck dissection was performed. The temporal changes in TVQ in patients with and without extrathyroidal extension were significantly different. Conclusions: Voice- and swallowing-related discomfort in patients who received thyroidectomy showed dynamic changes over time. There was a significant difference in the degree of change according to clinicopathological factors. Patients with these risk factors may benefit from appropriate patient education and various rehabilitation programs for symptom relief. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the clinical and prognostic significance of pathologic factors by analyzing the treatment results of patients who underwent thyroid lobectomy.Materials and Methods: We retrospectively analyzed data from 734 patients diagnosed with papillary thyroid cancer who underwent thyroid lobectomy at Korea University Hospital from January 2004 to December 2016.Results: A total of 734 patients were included in the study and their mean age was 44.5 years (range, 15-83). On univariate analysis, tumor size and recurrence-free survival were significantly related. The 10-year recurrence-free survival was 98.3% for tumors ≤1cm, 77.8% for >1cm and ≤2cm, and 66.7% for >2cm (p = 0.014). Recurrence-free survival was significantly different between patients with and without microscopic extrathyroidal extension (p=0.002). The 10-year recurrence-free survival rate was 99.2% for patients without extrathyroidal extension and 92.2% for patients with microscopic extrathyroidal extension. Multivariate analysis showed only microscopic extrathyroidal extension was significantly correlated with recurrence-free survival (p=0.029).Conclusion: In patients undergoing thyroid lobectomy for low-risk papillary thyroid cancer, microscopic extrathyroidal extension was an important prognostic factor associated with recurrence-free survival. However, in cases with microscopic extrathyroidal extension findings on postoperative pathologic examination, appropriate ultrasonographic follow-up of the contralateral thyroid lobe and cervical lymph node to facilitate early detection and prompt treatment of recurrence can control the disease without a deterioration of survival rate. [ABSTRACT FROM AUTHOR]

Objective: The invasiveness of papillary thyroid carcinoma (PTC), including the occurrence of cervical lymph node metastasis, is the main determining factors contributing to recurrence and poor prognosis. Laminin 332 is a glycoprotein involved in cell migration and cancer cell invasion into surrounding tissues and is therefore related to poor prognosis in many cancers. Here, we investigated the expression and role of laminin 332 in PTC and examine the possibility that laminin 332 could be involved in the invasiveness of PTC.Methods: Laminin 332 expression was determined by immunohistochemical staining in all 40 patients. The correlations between laminin 332 expression and clinical factors were investigated. We examined the expression of the laminin 332 γ2 chain using reverse transcription polymerase chain reaction and western blotting in PTC cells and determined the relationship between the expression of laminin 332 and the invasiveness of these cell lines using cell invasion assays.Results: Laminin 332 was expressed specifically within tumor tissue. The frequency of laminin 332 γ2 chain expression was significantly correlated with cervical lymph node metastasis (​p=0.003). Invasiveness increased as the expression of laminin 332 γ2 increased in the tested PTC cell lines.Conclusion: Laminin 332 expression may be a useful marker for predicting lymph node metastasis in papillary thyroid carcinoma, and could increase the ability of cancer cells to invade, which would influence the prognosis of patients with PTC. [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]

Objectives. This study evaluated the benefits of performing prophylactic central neck dissection (CND) with total thyroidectomy (TT) in management of papillary thyroid carcinoma (PTC) patients who were clinically node-negative at presentation. Methods. A total of 257 patients with stage T1 or T2 PTC and without preoperative evidence of lymph node involvement (N0) were enrolled in this prospective study. The patients were randomly assigned to two groups: (1) a total thyroidectomy (TT) group (n=104) or (2) a TT plus CND group (n=153). The two groups were compared for their perioperative data, complication rates, disease recurrence rates, and clinical outcomes. Results. The two groups of patients were similar in age, sex ratio, follow-up duration, and tumor size (P=0.227, 0.359, 0.214, and 0.878, resp.). The two groups showed similar rates of disease recurrence (3.9% in the TT group versus 3.3% in the TT plus CND group); however, complications occurred more frequently in the TT plus CND group; especially transient hypocalcemia (P=0.043). Conclusions. Patients treated with TT plus CND had a higher rate of complications with similar recurrence rate. We believe that CND may not be routinely recommended when treating patients with PTC. [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]

Background: Exposure to air particulate matter (PM) is associated with various diseases in the human respiratory system. To date, most in vitro studies showing cellular responses to PM have been performed in cell culture using a single cell type. There are few studies considering how multicellular networks communicate in a tissue microenvironment when responding to the presence of PM. Here, an in vitro three-dimensional (3D) respiratory mucosa-on-a-chip, composed of human nasal epithelial cells, fibroblasts, and endothelial cells, is used to recapitulate and better understand the effects of urban particulate matter (UPM) on human respiratory mucosa. Results: We hypothesized that the first cells to contact with UPM, the nasal epithelial cells, would respond similar to the tissue microenvironment, and the 3D respiratory mucosa model would be a suitable platform to capture these events. First, whole transcriptome analysis revealed that UPM induced gene expression alterations in inflammatory and adhesion-related genes in human nasal epithelial cells. Next, we developed an in vitro 3D respiratory mucosa model composed of human nasal epithelial cells, fibroblasts, and endothelial cells and demonstrated that the model is structurally and functionally compatible with the respiratory mucosa. Finally, we used our model to expose human nasal epithelial cells to UPM, which led to a disruption in the integrity of the respiratory mucosa by decreasing the expression of zonula occludens-1 in both the epithelium and endothelium, while also reducing vascular endothelial cadherin expression in the endothelium. Conclusions: We demonstrate the potential of the 3D respiratory mucosa model as a valuable tool for the simultaneous evaluation of multicellular responses caused by external stimuli in the human respiratory mucosa. We believe that the evaluation strategy proposed in the study will move us toward a better understanding of the detailed molecular mechanisms associated with pathological changes in the human respiratory system. [ABSTRACT FROM AUTHOR]

Cleavage of E-cadherin and the resultant weakness in the cell-cell links in the laryngeal epithelium lining is induced by exposure to acidic contents of the refluxate. Herein, we aimed to evaluate the role of matrix metalloproteinases (MMPs) in inducing E-cadherin level changes following acid exposure to the human pharyngeal mucosal cells. E-cadherin levels were inversely correlated with the duration of acid exposure. Treatment with actinonin, a broad MMP inhibitor, inhibited this change. Immunocytochemical staining and transepithelial permeability test revealed that the cell surface staining of E-cadherin decreased and transepithelial permeability increased after acid exposure, which was significantly inhibited by the MMP inhibitor. Among the various MMPs analyzed, the mRNA for MMP-7 in the cellular component was upregulated, and the secretion and enzymatic activity of MMP-7 in the culture media increased with the acid treatment. Consequently, MMP-7 plays a significant role in the degradation of E-cadherin after exposure to a relatively weak acidic condition that would be similar to the physiologic condition that occurs in Laryngopharyngeal reflux disease patients. [ABSTRACT FROM AUTHOR]

Objective: In the American Joint Committee on Cancer (AJCC) TNM staging of oropharyngeal cancer, T1-4a and N0-2c tumors are classified as the same stage (IVA), but their biological behaviors may be notably different. Our aim in this study was to identify clinical factors that can explain the differences in treatment outcome and to examine the value of HPV infection as a prognostic biomarker for stage IVA tonsillar carcinomas. Study design: Retrospective review. Methods: Seventy-four patients with tonsillar cancer classified as stage IVA were retrospectively analyzed with respect to survival outcomes according to various clinical factors. Among those analyzed, tissue from 24 patients was tested for HPV infection using a HPV DNA chip test and immunohistochemical staining of p16 and p53. Results: The disease-specific overall survival rate (OSR) between groups was not different according to various clinical factors. However, the disease-free survival rate (DFSR) was significantly lower according to the progression of local invasiveness and nodal status (p =0.01). Furthermore, although HPV positivity and p16 expression was more often found in locally advanced tonsillar carcinomas with advanced lymph node metastasis, the 5-year OSR was better in the HPV/p16-positive tumor patients. Conclusion: Even though AJCC staging system is a well-designed prognostic system showing the same OSR for all stage IVA tonsillar cancers, the DFSR may be different according to local invasiveness of the tumor and nodal status. In addition, HPV infection may be a useful biomarker for predicting treatment outcomes for stage VIA tumors. [Copyright &y& Elsevier]