Comparative Study of Gasless Transaxillary, Bilateral Axillo-Breast, Unilateral Axillo-Breast With Carbon Dioxide Insufflation, Retroauricular, and Transoral Vestibular Endoscopic Thyroidectomy Approaches at a Single Institution: A Retrospective Analysis and Lessons Learned.

OBJECTIVES: This study aimed to present our experiences with various approaches for endoscopic thyroidectomy (ET) and to offer lessons for choosing an approach. METHODS: The medical records of 701 patients who underwent ET via the transaxillary (TA), bilateral axillo-breast (BABA), unilateral axillo-breast with carbon dioxide insufflation (UABA), retroauricular (RA), or transoral vestibular (TO) approach between May 2008 and March 2020 were retrospectively reviewed. Postoperative pain and cosmetic outcomes were evaluated using visual analog scales. RESULTS: The mean operative time of UABA was the shortest among the five approaches (TA, 194.65±51.13 minutes; BABA, 189.11±61.53 minutes; UABA, 118.62±30.23 minutes; RA, 168.22±45.63 minutes; TO, 196.10±40.19 minutes; P=0.02). BABA was the most painful approach, while TO was the least painful on postoperative day 1 (TA, 3.09±0.96; BABA, 3.59±0.92; UABA, 2.39±0.54; RA, 3.49±0.93; TO, 2.01±0.37; P=0.04) and day 3 (TA, 2.10±0.77; BABA, 2.59±0.88; UABA, 1.84±0.37; RA, 3.01±0.67; TO, 1.49±0.45; P=0.04). The TO group had the best cosmetic outcomes at 3 months (TA, 3.91±1.21; BABA, 4.52±1.13; UABA, 4.49±0.74; RA, 4.28±0.74; TO, 4.81±0.48; P=0.04). CONCLUSION: We present a single-surgeon experience of five distinctive ET approaches and the lessons from each approach, together with a literature review. This data may aid endoscopic thyroid surgeons in choosing from various ET approaches.

Care and Management of Voice Change in Thyroid Surgery: Korean Society of Laryngology, Phoniatrics and Logopedics Clinical Practice Guideline.

Voice change is a common complaint after thyroid surgery and has a significant impact on quality of life. The Korean Society of Laryngology, Phoniatrics and Logopedics assembled a task force to establish guideline recommendations on education, care, and management related to thyroid surgery. The guideline recommendations encompass preoperative voice education, management of anticipated voice change during surgery, and comprehensive voice care after thyroid surgery, and include in-depth information and up-to-date knowledge based on validated literature. The committee constructed 14 key questions (KQs) in three categories-preoperative (KQ 1-2), intraoperative (KQ 3-8), and postoperative (KQ 9-14) management-and developed 18 evidence-based recommendations. The Delphi survey reached an agreement on each recommendation. A detailed evidence profile is presented for each recommendation. The level of evidence for each recommendation was classified as high-quality, moderate-quality, or low-quality. The strength of each recommendation was designated as strong or weak considering the level of evidence supporting the recommendation. The guidelines are primarily targeted toward physicians who treat thyroid surgery patients and speech-language pathologists participating in patient care. These guidelines will also help primary care physicians, nurses, healthcare policymakers, and patients improve their understanding of voice changes and voice care after thyroid surgery.

The Influence of Non-Linear Frequency Compression on the Perception of Speech and Music in Patients with High Frequency Hearing Loss.

BACKGROUND AND OBJECTIVES: Non-linear frequency compression (NLFC) technology compresses and shifts higher frequencies into a lower frequency area that has better residual hearing. Because consonants are uttered in the high-frequency area, NLFC could provide better speech understanding. The aim of this study was to investigate the clinical effectiveness of NLFC technology on the perception of speech and music in patients with high-frequency hearing loss. SUBJECTS AND METHODS: Twelve participants with high-frequency hearing loss were tested in a counter-balanced order, and had two weeks of daily experience with NLFC set on/off prior to testing. Performance was repeatedly evaluated with consonant tests in quiet and noise environments, speech perception in noise, music perception and acceptableness of sound quality rating tasks. Additionally, two questionnaires (the Abbreviated Profile of Hearing Aid Benefit and the Korean version of the International Outcome Inventory-Hearing Aids) were administered. RESULTS: Consonant and speech perception improved with hearing aids (NLFC on/off conditions), but there was no significant difference between NLFC on and off states. Music perception performances revealed no notable difference among unaided and NLFC on and off states. The benefits and satisfaction ratings between NLFC on and off conditions were also not significantly different, based on questionnaires, however great individual variability preferences were noted. CONCLUSIONS: Speech perception as well as music perception both in quiet and noise environments was similar between NLFC on and off states, indicating that real world benefits from NLFC technology may be limited in Korean adult hearing aid users.

Survival Benefits From Surgery for Stage IVa Head and Neck Squamous Cell Carcinoma: A Multi-institutional Analysis of 1,033 Cases.

OBJECTIVES: Head and neck squamous cell carcinomas (HNSCs) are frequently diagnosed at the locoregional advanced stage (stage IVa), but controversy remains regarding whether stage IVa HSNCs should be treated with upfront surgery or definitive chemoradiation therapy (CRT). The purpose of this study was to compare overall survival (OS) and disease-free survival (DFS) in patients with stage IVa HNSC treated primarily by surgery with curative intent with/without (neo)adjuvant treatment (surgery group) versus those treated primarily with CRT (CRT group). METHODS: We reviewed data of 1,033 patients with stage IVa HNSC treated with curative intent at 17 cancer centers between 2010 and 2016. RESULTS: Among 1,033 patients, 765 (74.1%) received upfront surgery and 268 (25.9%) received CRT. The 5-year OS and DFS rates were 64.4% and 62.0% in the surgery group and 49.5% and 45.4% in the CRT group, respectively. In multivariate analyses, OS and DFS were better in the surgery group than in the CRT group (odds ratio [OR] for death, 0.762; 95% confidence interval [CI], 0.592-0.981; OR for recurrence, 0.628; 95% CI, 0.492-0.802). In subgroup analyses, the OS and DFS of patients with oropharyngeal cancer were better in the surgery group (OR for death, 0.548; 95% CI, 0.341-0.879; OR for recurrence, 0.598; 95% CI, 0.377-0.948). In the surgery group, patients with laryngeal cancer showed better OS (OR for death, 0.432; 95% CI, 0.211-0.882), while those with hypopharyngeal cancer DFS was improved (OR for recurrence, 0.506; 95% CI, 0.328-0.780). CONCLUSION: A survival benefit from surgery may be achieved even in patients with stage IVa HNSC, particularly those with oropharyngeal and laryngeal cancer. Surgery led to a reduction in the recurrence rate in patients with hypopharyngeal cancer.

Ultrasonographic Thyroid Nodule Classification Using a Deep Convolutional Neural Network with Surgical Pathology.

Ultrasonography with fine-needle aspiration biopsy is commonly used to detect thyroid cancer. However, thyroid ultrasonography is prone to subjective interpretations and interobserver variabilities. The objective of this study was to develop a thyroid nodule classification system for ultrasonography using convolutional neural networks. Transverse and longitudinal ultrasonographic thyroid images of 762 patients were used to create a deep learning model. After surgical biopsy, 325 cases were confirmed to be benign and 437 cases were confirmed to be papillary thyroid carcinoma. Image annotation marks were removed, and missing regions were recovered using neighboring parenchyme. To reduce overfitting of the deep learning model, we applied data augmentation, global average pooling. And 4-fold cross-validation was performed to detect overfitting. We employed a transfer learning method with the pretrained deep learning model VGG16. The average area under the curve of the model was 0.916, and its specificity and sensitivity were 0.70 and 0.92, respectively. Positive and negative predictive values were 0.90 and 0.75, respectively. We introduced a new fine-tuned deep learning model for classifying thyroid nodules in ultrasonography. We expect that this model will help physicians diagnose thyroid nodules with ultrasonography.

Immuno-PET imaging based radioimmunotherapy in head and neck squamous cell carcinoma model.

The epidermal growth factor receptor (EGFR) is one of the most comprehensively studied molecular targets in head and neck squamous cell carcinoma (HNSCC). However, inherent and acquired resistance are serious problems and are responsible for limited clinical efficacy and tumor recurrence. In this study, we evaluated the feasibility of immuno-positron emission tomography (PET) imaging and radioimmunotherapy (RIT) with 64Cu-/177Lu-PCTA-cetuximab in cetuximab-resistant SNU-1066 HNSCC xenografted model. The cellular uptake of 64Cu/177Lu-3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca-1(15),11,13-triene-3,6,9,-triacetic acid (PCTA)-cetuximab showed good correlation with western blot and flow cytometry analysis in EGFR expression level of various HNSCC cells. 177Lu-PCTA-cetuximab selectively killed cetuximab-resistant SNU-1066 cells in vitro. 64Cu-/177Lu-PCTA-cetuximab specifically accumulated in SNU-1066 tumor and those uptakes were peaked at 48 h and 7 day, respectively in biodistribution, PET and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging. RIT with single dose of 177Lu-PCTA-cetuximab exhibited significant tumor regression and markedly reduced 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) uptake, compared to other groups. Proliferation index were dramatically decreased and apoptotic index increased in RIT group. These results suggest that a diagnostic and therapeutic convergence radiopharmaceutical, 64Cu-/177Lu-PCTA-cetuximab has the potential of target selection using immuno-PET imaging and targeted therapy by RIT in EGFR expressing cetuximab-resistant HNSCC tumors.

Guidelines for the Surgical Management of Laryngeal Cancer: Korean Society of Thyroid-Head and Neck Surgery.

Korean Society of Thyroid-Head and Neck Surgery appointed a Task Force to develop clinical practice guidelines for the surgical treatment of laryngeal cancer. This Task Force conducted a systematic search of the EMBASE, MEDLINE, Cochrane Library, and KoreaMed databases to identify relevant articles, using search terms selected according to the key questions. Evidence-based recommendations were then created on the basis of these articles. An external expert review and Delphi questionnaire were applied to reach consensus regarding the recommendations. The resulting guidelines focus on the surgical treatment of laryngeal cancer with the assumption that surgery is the selected treatment modality after a multidisciplinary discussion in any context. These guidelines do not, therefore, address non-surgical treatment such as radiation therapy or chemotherapy. The committee developed 62 evidence-based recommendations in 32 categories intended to assist clinicians during management of patients with laryngeal cancer and patients with laryngeal cancer, and counselors and health policy-makers.

Expression of activated Notch1 and Hey1 in papillary thyroid carcinoma.

AIMS: The Notch signalling pathway is involved in normal development as well as tumorigenesis. However, it is unclear whether Notch activation is related to diverse clinicopathological factors in papillary thyroid carcinoma (PTC). METHODS AND RESULTS: We examined the relationship between clinicopathological factors and the expression of activated Notch1 and Hey1, which are indicators of Notch signalling pathway activation, in 109 PTC cases. Activated Notch1 showed strong, moderate and weak expression in 23, 48 and 36 cases, respectively. Its expression was related significantly to histopathological variants (P = 0.007), lymph node metastasis (P = 0.016), BRAF mutation (P = 0.036) and extent of surgery (P = 0.014). Hey1 immunostaining could be divided into two groups: positive and negative, with 26 and 83 cases, respectively. Its expression was related significantly to histopathological variants (P = 0.026), extrathyroidal extension (P = 0.005), BRAF mutation (P = 0.048) and recurrence or soft tissue metastasis (P = 0.000). Multivariate analysis revealed that tumour size (>1 cm), Hey1 immunoreactivity and the presence of lymph node metastasis were associated significantly with recurrence or soft tissue metastasis (odds ratio = 7.38, 4.28 and 12.00, respectively). CONCLUSIONS: Thus, we found that activation of Notch signalling was correlated significantly with clinicopathological parameters. Therefore, Notch signalling could be a useful prognostic marker in patients with PTC.

Fbxw7ß, E3 ubiquitin ligase, negative regulation of primary myoblast differentiation, proliferation and migration.

Satellite cells attached to skeletal muscle fibers play a crucial role in skeletal muscle regeneration. During regeneration, the satellite cells proliferate, migrate to the damaged region, and fuse to each other. Although it is important to determine the cellular mechanisms controlling myoblast behavior, their regulators are not well understood. In this study, we evaluated the roles of Fbxw7 in primary myoblasts and determined its potential as a therapeutic target for muscle disease. We originally found that Fbxw7ß, one of the E3 ubiquitin ligase Fbxw7 subtypes, negatively regulates differentiation, proliferation and migration of myoblasts and satellite cells on muscle fiber. However, these phenomena were not observed in myoblasts expressing a dominant-negative, F-box deleted Fbxw7ß, mutant. Our results suggest that myoblast differentiation potential and muscle regeneration can be regulated by Fbxw7ß.

Comparison of quality of life between open and endoscopic thyroidectomy for papillary thyroid cancer.

BACKGROUND: Recently, various endoscopic thyroidectomy techniques have been introduced for cosmetic purposes. However, few reports have compared the quality of life (QOL) between post-endoscopic thyroidectomy and post-conventional open thyroidectomy. In this study, we investigated whether endoscopic thyroidectomy was comparable to conventional open thyroidectomy with respect to QOL. METHODS: Between January 2010 and September 2011, 75 patients underwent endoscopic thyroid lobectomy and 233 patients underwent conventional open thyroid lobectomy. The QOL was assessed preoperatively and at 1, 3, and 6 months postoperatively by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30-question (EORTC-QLQ-C30) instruments. RESULTS: Both groups showed similar changes over time in most of the QOL scales. However, patients who underwent endoscopic thyroidectomy showed significantly greater improvement in emotional function at 1 month (p = .039) and physical function at 3 months (p = .032). However, the pain increased more in the patients who underwent endoscopic thyroidectomy at 1 month (p = .042). CONCLUSION: Current findings suggest that endoscopic thyroidectomy may offer more rapid recovery of emotional and physical function than open thyroidectomy. © 2015 Wiley Periodicals, Inc. Head Neck 38: E827-E831, 2016.

Expression of cancer stem cell markers and epithelial-mesenchymal transition-related factors in anaplastic thyroid carcinoma.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is an undifferentiated tumor of the thyroid that has poor prognosis owing to its aggressive behavior and resistance to current treatments. We hypothesized that the stem cell properties induced by the epithelial-mesenchymal transition (EMT) was one of reasons for the dismal outcome of ATC. MATERIALS AND METHODS: Paraffin blocks and slides of 17 ATC cases were retrieved. We also collected 60 cases of papillary thyroid carcinoma (PTC) for comparison. We used immunohistochemistry to examine the expression of multiple markers of cancer stem cells and EMT-activating transcriptional factors. RESULTS: Majority of ATC cases showed loss of epithelial (E)-cadherin expression (15/17); however, all PTC cases (60/60) retained E-cadherin expression. EMT-activating transcription factors, such as snail and slug, were more frequently expressed in ATC than PTC cases (35.3% versus 6.7%, 76.5% versus 5%, respectively). Cancer stem cell markers such as CD133 and nestin were more highly expressed in ATC than PTC (52.9% versus 5%, 52.9% versus 0%, respectively). CONCLUSION: We found that the expression of EMT-related factors and stem cell markers was higher in ATC than PTC. We therefore conclude that stemness induced by EMT plays an important role in the pathogenesis of ATC.

CXCR4 antagonist inhibits perineural invasion of adenoid cystic carcinoma.

AIM: Perineural invasion and expression of CXCR4 is characteristic of adenoid cystic carcinoma (ACC). Herein, we aimed to demonstrate CXCR4 expression in ACC, identify its association with perineural invasion and investigate the impact of CXCR4 inhibitor in vitro and in a murine perineural invasion model. METHODS: Expression of CXCR4 was assessed in ACC cell lines and in human tissue. The effects of gene knockdown using siRNA and specific blocker of CXCR4 (AMD3100) were evaluated in vitro. A preclinical perineural invasion model was developed using BALB/c nude mouse. The effect of AMD3100 was evaluated in vivo. RESULTS: CXCR4 was highly expressed in aggressive strains of ACC in vitro, in the tumour in the animal model and in the tumour of human tissue. SDF-1 expression was also demonstrated in the nerve of murine and human tissue. Gene knockdown by siRNA and inhibition by a CXCR4-specific inhibitor AMD3100 effectively abrogated invasion but not proliferation of ACC in vitro. The rate of perineural invasion was significantly decreased with AMD3100 treatment in the animal model. CONCLUSIONS: CXCR4 is associated with perineural invasion in ACC. AMD3100, which can effectively diminish perineural invasion of ACC, may have an adjuvant role in the management of ACC.

Comparative study of a gasless transaxillary approach versus a bilateral axillo-breast approach for endoscopic thyroidectomy in a single institute.

BACKGROUND: Gasless transaxillary approach (TA) and the bilateral axillo-breast approach (BABA) are 2 distinctive approaches for endoscopic thyroidectomy. The purpose of this study was to evaluate and compare these 2 procedures. METHODS: From May 2008 to July 2011, we performed endoscopic hemithyroidectomy via gasless TA (83 cases) and BABA (45 cases). The following variables were evaluated: operation time, postoperative pain score, drainage amount, drainage day, postoperative complications, and cosmetic satisfaction score. RESULTS: There were no significant differences between the 2 approaches in terms of clinicopathologic characteristics and surgical outcomes, except for postoperative pain and cosmetic satisfaction. As for postoperative pain and cosmetic satisfaction, the gasless TA group complained of less pain and the BABA group had a better cosmetic outcome. CONCLUSION: These findings will contribute to providing guidelines for the choice of surgeons between gasless TA and BABA techniques for endoscopic thyroidectomy.

Human salivary gland stem cells ameliorate hyposalivation of radiation-damaged rat salivary glands.

Salivary function in mammals may be defective for various reasons, such as aging, Sjogren's syndrome or radiation therapy in head and neck cancer patients. Recently, tissue-specific stem cell therapy has attracted public attention as a next-generation therapeutic reagent. In the present study, we isolated tissue-specific stem cells from the human submandibular salivary gland (hSGSCs). To efficiently isolate and amplify hSGSCs in large amounts, we developed a culture system (lasting 4-5 weeks) without any selection. After five passages, we obtained adherent cells that expressed mesenchymal stem cell surface antigen markers, such as CD44, CD49f, CD90 and CD105, but not the hematopoietic stem cell markers, CD34 and CD45, and that were able to undergo adipogenic, osteogenic and chondrogenic differentiation. In addition, hSGSCs were differentiated into amylase-expressing cells by using a two-step differentiation method. Transplantation of hSGSCs to radiation-damaged rat salivary glands rescued hyposalivation and body weight loss, restored acinar and duct cell structure, and decreased the amount of apoptotic cells. These data suggest that the isolated hSGSCs, which may have characteristics of mesenchymal-like stem cells, could be used as a cell therapy agent for the damaged salivary gland.

Effect of allergic rhinitis on the expression of human ß-defensin 2 in tonsils.

BACKGROUND: Human ß-defensins (HBDs) are a newly identified family of antimicrobial peptides that are expressed by epithelia on mucosal surfaces. Exposure of airway epithelial cells to TH2-type cytokines results in a significant decrease in the antimicrobial activity of the cells. OBJECTIVE: To investigate the effect of allergic rhinitis on the expression of HBD-2 in tonsils and adenoids. METHODS: Palatine tonsils and adenoids were obtained from 30 patients with no history of recurrent tonsillitis. The patients were divided into 2 groups: allergic rhinitis and nonallergic rhinitis groups. Real-time polymerase chain reaction analysis was used to measure messenger RNA (mRNA) levels of HBD-2 mRNA in tonsil and adenoid tissue samples from the 2 patient groups. Immunofluorescent staining and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the expression of HBD-2 protein in tonsil and adenoid tissues. The concentration of the cytokines interleukin (IL) 4, IL-5, and interferon γ (IFN-γ) in tissue homogenates was measured by ELISA. RESULTS: Immunofluorescent staining data demonstrated the expression of HBD-2 protein in the surface epithelia of tonsils, and a marked difference in the staining intensity was observed the between 2 groups. HBD-2 mRNA and protein levels in the tonsils were significantly lower in the allergic rhinitis group than that in the nonallergic rhinitis group (P = .03 and P = .04, respectively). IL-5 and IFN-γ were not detected, and no significant difference was found in IL-4 concentrations in tonsil homogenates between the 2 groups. CONCLUSION: Allergic rhinitis suppresses HBD-2, an epithelial antimicrobial peptide, in the tonsils.

New endoscopic thyroidectomy via a unilateral axillo-breast approach with gas insufflation: Preliminary report.

BACKGROUND: Invasiveness of endoscopic thyroidectomy has been in debate. The purpose of this study was to introduce new endoscopic thyroidectomy via a unilateral axillo-breast approach (UABA) with gas insufflation to lessen invasiveness. METHODS: We performed 68 cases of hemithyroidectomy via a UABA with gas insufflation from January to July 2011. The following variables were studied: operation time, pain score, drainage amount, drainage day, perioperative complications, pathological outcomes, and cosmetic satisfaction. RESULTS: Mean postoperative pain visual analogue scale (VAS) scores were 2.75 ± 0.93 and 2.07 ± 0.79 at 1 and 3 days after surgery. The mean amount of drainage over the first 3 postoperative days was 144.35 ± 51.64 mL, and the mean time to drain removal was 3.75 ± 0.81 days. Two cases (2.9%) of transient vocal cord palsy and 2 cases (2.9%) of seroma were identified. All patients were satisfied with the cosmetic results. CONCLUSION: Endoscopic thyroidectomy via a UABA with gas insufflation is a feasible and less invasive option for selected patients.

Predictive markers for neoadjuvant chemotherapy in advanced squamous cell carcinoma of maxillary sinus: Preliminary report.

CONCLUSION: ERCC 1 seems to be promising as a predictive marker for response to neoadjuvant chemotherapy (NAC) and early decision for surgery in advanced squamous cell carcinoma (SCC) of the maxillary sinus. OBJECTIVES: This study aimed to find a possible relation of ERCC1 or XRCC1 expression with response to NAC and prognosis in advanced SCC of the maxillary sinus. METHODS: From 1998 to 2006, 17 patients with advanced SCC of the maxillary sinus received NAC at the Seoul National University Hospital. The expression of ERCC1 and XRCC1 was assessed by immunohistochemistry. Complete and partial remissions were categorized as the chemo-sensitive group. On the other hand, stable and progressive diseases were categorized as the chemo-resistant group. RESULTS: Of these 17 patients, 1 had complete remission, 6 had partial remission, 4 had stable disease, and 6 had progression of disease. The 5-year survival rate was 40% for all 17 patients. The expression of ERCC1 and XRCC1 was not correlated with nodal or distant metastasis. With a cut-off value of 65%, patients with higher ERCC1 scores showed chemo-resistance and survival disadvantage over those with lower ERCC1 scores. However, XRCC1 did not show a significant effect on the response to NAC.

Sunitinib inhibits papillary thyroid carcinoma with RET/PTC rearrangement but not BRAF mutation.

Sunitinib, a multi-targeted tyrosine kinase inhibitor, is frequently incorporated into the management of papillary thyroid carcinoma refractory to standard therapies. Although clinical trials are in progress, the mechanism of action in papillary thyroid carcinomas is not clear, especially regarding the effect on BRAF mutation. We investigated the effect of sunitinib on papillary thyroid carcinoma cells harboring RET/PTC rearrangement and BRAF mutation using TPC-1M, SNU-790, and B-cPAP cell lines. Cell growth of papillary thyroid cancer cells with RET/PTC rearrangement was effectively inhibited at low doses of sunitinib (IC50=0.658 µM), whereas that of BRAF mutated cells required higher doses. Immunoblotting revealed effective blocking of MEK/ERK pathway in RET/PTC rearrangement cells, but not in BRAF mutated cells. Cell cycle analysis showed G1 arrest in RET/PTC rearrangement cells. In vivo orthotopic thyroid cancer mouse model demonstrated statistically significant tumor growth inhibition by sunitinib in RET/PTC rearrangement cancer cells. We conclude that sunitinib effectively inhibits RET/PTC rearrangement cells but not BRAF mutated cells. These data suggest that sunitinib exerts its effect by inhibiting the upstream MAPK signaling cascade. These findings support the unsatisfactory treatment outcomes of sunitinib in many already ongoing clinical trials compared to other tyrosine kinase inhibitors. Clinical application of sunitinib should be directed accordingly.

Prognostic factors in oral cavity cancer with skull base recurrence.

OBJECTIVE: Recurred oral cavity cancer at the skull base is complicated to treat due to difficult surgical approach and possible dural invasion. Therefore, initial curative treatment is of most importance and it would be helpful to know cases that would likely recur before treatment. We tried to identify prognostic factors that can predict skull base recurrence after initial treatment, to find out cases that need more aggressive initial treatment. METHODS: This retrospective study was performed on 51 patients diagnosed as squamous cell carcinoma in the oral cavity, and they underwent surgery and adjuvant radiotherapy. Variables associated with clinical findings, imaging studies, and pathologic results were analyzed to identify factors related to skull base recurrence. RESULTS: Recurrences occurred in 21% (11) cases, and skull base invasion in 5 of these recurred cases. Tumor location, clinical T stage, retromolar trigone (RMT) invasion, bone invasion, perineural invasion, positive resection margin, endolymphatic tumor emboli, and medial and lateral pterygoid muscle invasion were found to be significant prognostic factors by univariate analyses. Among those factors, medial pterygoid muscle invasion and positive resection margin remained independent predictors of skull base recurrence with multivariate analyses by Cox regression. CONCLUSION: Patients with medial pterygoid muscle invasion or a positive resection margin have a high risk of skull base invasion during tumor recurrence. Therefore, careful evaluation and aggressive management are needed to prevent skull base invasion in cases that recur.