Association between oral health and thyroid disorders: A population-based cross-sectional study.

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.

Objective Assessment of Postoperative Swallowing Difficulty Through Ultrasound in Patients Undergoing Thyroidectomy.

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.

Assessment of Chronological Volume Changes in Radial Forearm Free Flaps for Tongue Cancer.

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.

Role of Matrix Metalloproteinases 7 in the Pathogenesis of Laryngopharyngeal Reflux: Decreased E-cadherin in Acid exposed Primary Human Pharyngeal Epithelial Cells.

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.

Clinicopathological significance of cancer-associated fibroblasts in papillary thyroid carcinoma: a predictive marker of cervical lymph node metastasis.

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.

Recurrent laryngeal nerve injury with incomplete loss of electromyography signal during monitored thyroidectomy-evaluation and outcome.

PURPOSE: During monitored thyroidectomy, a partially or completely disrupted point of nerve conduction on the exposed recurrent laryngeal nerve (RLN) indicates true electrophysiologic nerve injury. Complete loss of signal (LOS; absolute threshold value <100 µV) at the end of operation often indicates a postoperative vocal cord (VC) palsy. However, the evaluation for the injured RLN with incomplete LOS and its functional outcome has not been well described. METHODS: Three hundred twenty-three patients with 522 RLNs at risk who underwent standardized monitored thyroidectomy were enrolled. The RLN was routinely stimulated at the most proximal (R2p signal) and distal (R2d signal) ends of exposure after thyroid resection to determine if there was an injured point on the RLN. Pre- and postoperative VC function was routinely examined. RESULTS: Twenty-nine RLNs (5.6 %) were detected with an injury point. Five nerves had complete LOS and other 24 nerves had incomplete LOS where the R2p/R2d reduction (% of amplitude reduction compared with proximal to distal RLN stimulation) ranged from 22 to 79 %. Postoperative temporary VC palsy was noted in those five RLNs with complete LOS (final vagal signal, V2 < 100 µV) and four RLNs with incomplete LOS (R2p/R2d reduction 62-79 %; V2 181-490 µV). In the remaining 20 nerves with R2p/R2d reduction ≤53 % (V2 373-1623 µV), all showed normal VC mobility. Overall, false negative results were found in two RLNs (0.4 %) featuring unchanged V2 and R2p/R2d but developed VC palsy. CONCLUSIONS: Testing and comparing the R2p/R2d signal is a simple and useful procedure to evaluate RLN injury after its dissection and predict functional outcome. When the relative threshold value R2p/R2d reduction reaches over 60 %, surgeon should consider the possibility of postoperative VC palsy.

Comparison of Learning Curves for Retroauricular and Transaxillary Endoscopic Hemithyroidectomy.

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.

The Role of Adjuvant Radiation Therapy for Locoregionally Advanced Papillary Thyroid Carcinoma.

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.

A prospective 1-year comparative study of transaxillary total thyroidectomy regarding functional outcomes: Is it really promising?

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.

A Randomized, Multicenter, Phase II Study of Cetuximab With Docetaxel and Cisplatin as Induction Chemotherapy in Unresectable, Locally Advanced Head and Neck Cancer.

BACKGROUND: We investigated the efficacy of cetuximab when added to induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) in patients with locally advanced head and neck squamous cell carcinoma. METHODS: Patients were randomized to receive three cycles of docetaxel and cisplatin (TP regimen) with or without cetuximab (TP plus cetuximab [CTP] vs. TP) as induction chemotherapy. Patients in the CTP arm received CCRT with cetuximab and cisplatin, whereas patients in the TP arm received cisplatin alone. The primary endpoint was the objective response rate (ORR) after induction chemotherapy. RESULTS: Overall, 92 patients were enrolled. The ORRs for induction chemotherapy in the CTP and TP arms were not different (81% vs. 82%). Adding cetuximab lowered the completion rate of induction chemotherapy and CCRT and resulted in more frequent dose reductions of the induction chemotherapy, although this did not reach statistical significance. In the CTP and TP arms, respectively, the 3-year progression-free survival (PFS) rates were 70% and 56% (p = .359), and the overall survival (OS) rates were 88% and 74% (p = .313). When limited to patients who completed induction chemotherapy, 3-year PFS rates of 78% and 59% (p = .085) and OS rates of 94% and 73% (p = .045) were observed in the CTP and TP arms, respectively. CONCLUSION: Adding cetuximab to sequential treatment did not increase the treatment efficacy and resulted in greater toxicity. In the intent-to-treat population, neither PFS nor OS was improved by the addition of cetuximab to sequential treatment; however, a suggestion of improved survival outcomes was observed in patients completing cetuximab-containing induction chemotherapy.

A prospective 1-year comparative study of endoscopic thyroidectomy via a retroauricular approach versus conventional open thyroidectomy at a single institution.

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.

Analysis of the Outcomes of Immediate Recurrent Laryngeal Nerve Reconstruction During Thyroid Surgery for Prevention of Vocal Fold Paralysis.

BACKGROUND: Recurrent laryngeal nerve (RLN) injury and the resulting paralysis is the most common and known complication of thyroid surgery. Several surgical techniques, such as medialization thyroplasty with or without arytenoid adduction and injection laryngoplasty, have been developed to treat RLN injury, but these procedures have specific limitations and complications. In this study, we present the outcomes for our patients who underwent immediate RLN reconstruction during thyroid surgery by analyzing both subjective and objective outcomes. METHODS: A retrospective study was conducted for patients who underwent total or subtotal thyroidectomy between May 2012 and March 2020. Among them, patients who underwent immediate RLN reconstruction due to unilateral RLN injury were followed for at least 12 months. The voice perceptual evaluation, acoustic analysis, voice range profile, and Voice Handicap Index (VHI) scores were obtained preoperatively, 1 month, 6 months, and 12 months after surgery. RESULTS: Among the 11 patients, 6 patients (54.5%) underwent direct anastomosis, and 5 patients (45.5%) underwent nerve grafts using ansa cervicalis and great auricular nerve. The grade and breathiness in the GRBAS (grade, roughness, breathiness, asthenia, and strain) scale and jitter item showed significant improvement at 12 months postoperatively, and although not statistically significant, the rest of the items also tended to improve. The total, functional, and physical scores on VHI improved significantly at 12 months postoperatively. Moreover, when comparing the voice analysis of the direct anastomosis group and the nerve graft group, there was no significant difference between the groups in objective and subjective results. CONCLUSION: Immediate RLN reconstruction demonstrated significant voice improvement postoperatively, and reconstructing the nerve immediately and combining follow-up treatment in the event of RLN injury will greatly help patients improve their long-term voice outcomes.

A new histopathological location of parathyroid gland with high possibility of unintended parathyroidectomy.

Background: Unintended parathyroidectomy occasionally happens despite meticulous capsular dissection and the histopathological location of removed parathyroid glands were traditionally classified as extracapsular, subcapsular, and intrathyroidal location. This study aimed to investigate the new histopathological location of parathyroid gland with high possibility of unintended parathyroidectomy that was difficult to be found with naked eye despite capsular dissection. Methods: This study investigated unintended parathyroidectomy that occurred in 743 patients who received thyroid surgery by reviewing pathology reports and slides. The histopathological location of unintentionally removed parathyroid glands was classified as intracapsule and extracapsule, and the intracapsular glands were further classified as completely buried in the thyroid parenchyme, partially buried, and subcapsular locations. Results: The incidence of unintended parathyroidectomy was 12.8%. Among the 103 unintentionally removed parathyroid glands, 74 (71.8%) were found intracapsular and 29 were extracapsular. Among the intracapsular glands, 57 (55.4%) parathyroid glands were found in difficult locations such as completely buried (40.8%) and partially buried (14.6%). Conclusions: The partially buried parathyroid gland can act as a risk factor for unintended parathyroidectomy comparable to intrathyroidal parathyroid gland despite the surgeon's best effort with meticulous capsular dissection. However, continued advances in visualizing technique such as autofluorescence imaging may lower the chance of incidentally removed partially buried parathyroid glands in the future.

Matrix metalloproteinase-7 induces E-cadherin cleavage in acid-exposed primary human pharyngeal epithelial cells via the ROS/ERK/c-Jun pathway.

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.

Effectiveness of a combination therapy using non-ablative fractional laser and intralesional triamcinolone injection for thyroidectomy scar treatment: a prospective, randomized, blinded pilot study.

BACKGROUND: The occurrence of thyroid cancer has increased dramatically, and postoperative scars are placed at easily visible locations. Many patients show stronger desire for scar prevention. So far, numerous approaches have been discussed for the treatment of scars; this study is conducted to verify whether the early application of combined therapy contributes to minimal scar formation. METHODS: Between March 2019 and December 2019, total of 64 patients with thyroidectomy scars of a size greater than 4.5 cm located on the anterior neck were enrolled in this prospective pilot study. Subjective and objective evaluation were carried out using the Patient and Observer Scar Assessment Scale (POSAS) at one, two, and six months after operation. Results were compared between a treatment group and a non-treatment group. RESULTS: In PSAS score, the mean values of pain, itching sensation, pliability, thickness, and relief were significantly higher in the laser and steroid treatment group (p = 0.009, p = 0.000, p = 0.013, p = 0.002, and p = 0.007). The value of color of the scars showed no significant differences (p = 0.504). In OSAS score, parameter of thickness, relief, and surface area score was significantly higher score in the combination group (p = 0.029, 0.035, and 0.020), while vascularity, pigmentation, and pliability were not significantly different between two groups (p = 0.548, p = 0.983, and p = 0.128). CONCLUSION: This study demonstrates that early combination therapy contributes to scar improvement to a meaningful extent based on POSAS. We believe that the combined therapy has a synergy effect on scar management, which improves the patients' quality of life in relation to their postoperative scars.

The Utility of Gastrointestinal Endoscopic Examination Versus Positron Emission Tomography-Computed Tomography in the Detection of Second Primary Lesions in Korean Patients With Head and Neck Cancer.

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.

Pretreatment serum level of 15-kDa granulysin might have a prognostic value in patients with diffuse large B cell lymphoma.

AIM: Granulysin (cytolytic molecules of cytotoxic T lymphocytes and natural killer cells) is synthesized as cytosolic 9-kDa and secretary 15-kDa isoforms. We evaluated the prognostic significance of the pretreatment serum level of 15-kDa granulysin in patients with diffuse large B cell lymphoma (DLBCL). PATIENTS AND METHODS: A retrospective analysis was conducted on 88 DLBCL patients treated homogeneously with standard chemotherapy. The granulysin level was quantified in pretreatment samples. RESULTS: The granulysin level in DLBCL patients was significantly lower than that in healthy controls (522 ± 496 vs. 1,945 ± 1,696 pg/ml; p < 0.0001), and the level in patients who experienced recurrence within 3 years was significantly lower than that of patients without recurrence (305 ± 337 vs. 720 ± 607 pg/ml; p = 0.001). Patients with granulysin levels higher than the median level showed significantly longer progression-free and overall survival according to univariate analysis (p = 0.031 and p = 0.014, respectively). In multivariate analysis, the granulysin level was an independently significant prognostic factor of overall survival (p = 0.018; hazard ratio, 0.521; 95% confidence interval, 0.188-0.841). CONCLUSIONS: Pretreatment serum level of 15-kDa granulysin may be a valuable prognostic marker in DLBCL patients treated with standard chemotherapy.

Interaction effect between the receptor for advanced glycation end products (RAGE) and high-mobility group box-1 (HMGB-1) for the migration of a squamous cell carcinoma cell line.

AIMS AND BACKGROUND: The receptor for advanced glycation end products (RAGE) is a multiligand cell surface receptor of the immunoglobulin superfamily and a newly recognized invasion-related gene. High mobility group box-1 (HMGB-1) is a 30-kD protein binding to RAGE and acting as a transcription-factor-like protein that regulates the expression of several genes. In this study, the interaction effect between RAGE and HMGB-1 on the migration of SCC7 cells was investigated along with the inhibitory effect of the drug nifedipine on this interaction effect. METHODS AND STUDY DESIGN: Ten surgical specimens from patients with squamous cell carcinoma (SCC) of the head and neck and a SCC7 cell line were stained using immunohistochemical and immunocytochemical methods. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect RAGE expression in SCC7 cells; Western blot analysis was used to detect HMGB-1 expression in SCC7 cells. An in vitro migration assay (Boyden chamber migration assay) was used for evaluating the interaction effect between RAGE and HMGB-1 on the migration of SCC7 cells. HMGB-1 and various concentrations of nifedipine were tested for their effect on SCC7 cell migration with in vitro migration assays. RESULTS AND CONCLUSIONS: RAGE and HMGB-1 were expressed in almost all human head and neck SCC tissues and in SCC7 cells as detected by immunostaining. The migration assay showed that the interaction between RAGE and HMGB-1 increased SCC7 migration activity depending on the level of HMGB-1, and nifedipine inhibited the interaction effect between RAGE and HMGB-1 on SCC7 cells in a dose-dependent manner. The interaction between RAGE and HMGB-1 could be closely associated with metastasis of SCC of the head and neck. Nifedipine may have an inhibitory effect on tumor metastasis.

Usefulness of matrix metalloproteinase-7 in saliva as a diagnostic biomarker for laryngopharyngeal reflux disease.

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.

Non-surgical animal model of gastroesophageal reflux disease by overeating induced in mice.

Previous animal models of gastroesophageal reflux disease (GERD) were not physiological and required a variety of surgical procedures. Therefore, the animal model developed by conditions that are similar to the pathogenesis of GERD is necessary. The aim is to establish a non-surgical animal model with GERD caused by overeating induced in mice. To induce mice to overeat, we designed dietary control protocols including repetitive fasting and feeding. The esophageal tissues were evaluated with GERD markers to prove the establishment of a GERD animal model. Mice fasted every other day (group 2) showed more pronounced overeating feature and demonstrated evident changes similar to the macroscopic and microscopic findings of GERD, the expressions of inducible nitric oxide synthase and substance P were stronger. The higher frequency of fasting and overeating could cause GERD effectively. The dietary control can make mice overeat, which elicits the change of lower esophageal mucosa similar to GERD. Thus, the overeating-induced mouse may be used as a GERD mouse model.