Yoon Se Lee

Lateral cervical lymph node metastases from papillary thyroid carcinoma: predictive factors of nodal metastasis.

BACKGROUND Papillary thyroid carcinoma (PTC) frequently metastasizes to the regional neck; skip metastasis (metastasis to the lateral compartment in the absence of central disease) is uncommon. This prospective study was to evaluate the incidence of occult lateral neck metastasis (LNM) and elucidated the factors that predict LNM in PTC with central neck metastasis (CNM) by performing prophylactic selective lateral neck dissection (SND). METHODS Sixty-two patients with PTC without clinical LNM underwent total thyroidectomy with central compartment neck dissection and prophylactic SND consecutively after ipsilateral CNM was confirmed by intraoperative frozen biopsy. RESULTS The incidence of occult LNM in PTC was 55%. Patients with LNM had a larger primary tumor and more positive ipsilateral and bilateral central lymph nodes than patients without LNM. There were no differences between patients with and without LNM with regard to age and extrathyroidal extension. The incidence of occult LNM increased significantly as the number of metastatic ipsilateral and bilateral lymph nodes increased. Independent risk factors for occult LNM were tumor size and the number of positive bilateral lymph nodes (odds ratio [OR] = 1.449; OR = 1.110, respectively). The most common metastatic site was level III (68%: 23/34), followed by level IV (59%: 20/34) and level II (21%: 7/34). CONCLUSION The important risk factors for LNM in PTC are primary tumor size and the number of positive bilateral central lymph nodes. Prophylactic SND may be considered in selected patients with a large number of positive central lymph nodes and large tumors.

Knockdown of β-catenin controls both apoptotic and autophagic cell death through LKB1/AMPK signaling in head and neck squamous cell carcinoma cell lines.

The Wnt/β-catenin pathway regulates the viability and radiosensitivity of head and neck squamous cancer cells (HNSCC). Increased β-catenin predisposes HNSCC patients to poor prognosis and survival. This study was conducted to determine the mechanism by which β-catenin regulates the viability of HNSCC. AMC-HN-3, -HN-8, UM-SCC-38, and -SCC-47 cells, which were established from human head and neck cancer specimens, and underwent cell death following β-catenin silencing. β-Catenin silencing significantly induced G1 arrest and increased the expression of Bax and active caspase-3, which demonstrates the sequential activation of apoptotic cascades following treatment of HNSCC with targeted siRNA. Intriguingly, β-catenin silencing also induced autophagy. Here, we confirm that the number of autophagic vacuoles and the expression of type II light chain 3 were increased in cells that were treated with β-catenin siRNA. These cell death modes are most likely due to the activation of LKB1-dependent AMPK following β-catenin silencing. The activated LKB1/AMPK pathway in AMC-HN-3 cells caused G1 arrest by phosphorylating p53 and suppressing mTOR signaling. In addition, treating AMC-HN-3 cells with LKB1 siRNA preserved cell viability against β-catenin silencing-induced cytotoxicity. Taken together, these results imply that following β-catenin silencing, HNSCC undergo both apoptotic and autophagic cell death that are under the control of LKB1/AMPK. To the best of our knowledge, these results suggest for the first time that novel crosstalk between β-catenin and the LKB1/AMPK pathway regulates the viability of HNSCC. This study thus presents new insights into our understanding of the cellular and molecular mechanisms involved in β-catenin silencing-induced cell death.

Tumor location–dependent skip lateral cervical lymph node metastasis in papillary thyroid cancer

Lateral cervical lymph node metastasis without central lymph node (CLN) metastasis is not infrequent in papillary thyroid cancer (PTC). This study was designed to investigate the frequency and pattern of skip metastasis in PTC.

Prognostic value of expression of molecular markers in adenoid cystic cancer of the salivary glands compared with lymph node metastasis: a retrospective study

BackgroundAdenoid cystic cancer arising in the salivary glands has distinctive features such as perineural invasion, distant metastasis, and a variable prognosis. In salivary gland cancer, c-kit, EGFR, and VEGF are representative molecular markers that may predict remnant and recurrent tumors. In this study, the expression of c-kit, EGFR, and VEGF in adenoid cystic cancer was evaluated, and the relationships between the expression of these markers and the clinical findings were investigated.MethodsThe medical records of 48 patients who were treated for parotid adenoid cystic cancer from January 1990 to January 2006 were reviewed. The tumor location, size, histological subtypes, perineural invasion, the resected margin status, and lymph node metastasis were assessed. Immunohistochemical staining and semiquantitative analysis of c-kit, EGFR and VEGF were performed. The relationship between the expression of each marker and the clinicopathological factors were analyzed.ResultsPositive c-kit immunostaining was present in 45 patients (94%), with weak positivity (+1) in 23, moderate positivity (+2) in 19 and strong positivity (+3) in three. Positive EGFR immunostaining was observed in 27 (56%), with weak positivity (+1) in 19 and moderate positivity (+2) in eight with no strong positive staining. Positive VEGF immunostaining was present in 42 patients (88%) with weak positivity (+1) in 12, moderate positivity (+2) in 17, and strong positivity (+3) in 13. Only the expression of VEGF was significantly higher in parotid gland tumors than in any other gland (P = 0.032). Marginal involvement was associated with strong VEGF expression (P = 0.02). No marker was significantly correlated with recurrence or the survival rate. Lymph node status was related to the survival rate.ConclusionsThe expression of c-kit, EGRF, and VEGF had no predictive value for recurrence or the prognosis of adenoid cystic cancer. Only the lymph node status was related to the prognosis.

Nodal status of central lymph nodes as a negative prognostic factor for papillary thyroid carcinoma

The status of metastatic lymph nodes, including the size and extracapsular spread (ECS), in papillary thyroid cancer (PTC) has not been well established. This study evaluated the correlation between the specific status of central lymph node metastases (CLNM) and negative prognostic factors.

Frozen biopsy of central compartment in papillary thyroid cancer: Quantitative nodal analysis

Nodal metastasis in papillary thyroid cancer (PTC) usually occurs in the central compartment of the ipsilateral neck and spreads laterally. The purpose of this study was to evaluate the diagnostic accuracy of frozen biopsy for quantitative nodal evaluation of central neck metastasis in PTC.

Isolation of Mesenchymal Stromal Cells (MSCs) from Human Adenoid Tissue

Background: Mesenchymal stromal cells (MSCs) are multipotent progenitor cells that originally derived from bone marrow. Clinical use of bone marrow-derived MSC is difficult due to morbidity and low MSC abundance and isolation efficiency. Recently, MSCs have been isolated from various adult tissues. Here we report the isolation of adenoid tissue-derived MSCs (A-MSCs) and their characteristics. Methods: We compared the surface markers, morphologies, and differentiation and proliferation capacities of previously established tonsil-derived MSCs (T-MSCs) and bone marrow-derived MSCs (BM-MSCs) with cells isolated from adenoid tissue. The immunophenotype of A-MSCs was investigated upon interferon (IFN)-γ stimulation. Results: A-MSCs, T-MSCs, and BM-MSCs showed negative CD45, CD31 HLA-DR, CD34, CD14, CD19 and positive CD 90, CD44, CD73, CD105 expression. A-MSCs were fibroblast-like, spindle-shaped non-adherent cells, similar to T-MSCs and BM-MSCs. Adipogenesis was observed in A-MSCs by the formation of lipid droplets after Oil Red O staining. Osteogenesis was observed by the formation of the matrix mineralization in Alizarin Red staining. Chondrogenesis was observed by the accumulation of sulfated glycosaminoglycan-rich matrix in collagen type II staining. These data were similar to those of T-MSCs and BM-MSCs. Expression of marker genes (i.e., adipogenesis; lipoprotein lipase, proliferator-activator receptor-gamma, osteogenesis; osteocalcin, alkaline phasphatase, chondrogenesis; aggrecan, collagen type II α1) in A-MSCs were not different from those in T-MSCs and BM-MSCs. Conclusions: A-MSCs possess the characteristics of MSCs in terms of morphology, multipotent differentiation capacity, cell surface markers, and immunogeneity. Therefore, A-MSCs fulfill the definition of MSCs and represent an alternate source of MSCs.

Growth Inhibitory Effect of Palatine Tonsil-derived Mesenchymal Stem Cells on Head and Neck Squamous Cell Carcinoma Cells

Objectives Mesenchymal stem cells (MSCs) play an important role in the development and growth of tumor cells. However, the effect of human MSCs on the growth of human tumors is not well understood. The purpose of this study is to confirm the growth effect of palatine tonsil-derived MSCs (TD-MSCs) on head and neck squamous cell carcinoma (HNSCC) cell lines and to elucidate the mechanism of their action. Methods TD-MSCs were isolated from patient with chronic tonsillitis and tonsillar hypertrophy. Two human HNSCC cell lines (PNUH-12 and SNU-899) were studied and cocultured with isolated palatine tonsil-derived MSC. The growth inhibitory effect of MSCs on HNSCC cell lines was tested through methylthiazolyldiphenyl-tetrazolium (MTT) assay. The apoptosis induction effect of MSCs on cell lines was assessed with flow cytometry and reverse transcriptase (RT)-PCR. Results Palatine tonsil-derived MSCs exhibited a growth inhibitory effect on both cell lines. Cell cycle analysis showed an accumulation of tumor cells predominantly in G0/G1 phase with an increase in concentration of TD-MSCs, which was confirmed by increased mRNA expression of cell cycle negative regulator p21. Apoptosis of tumor cells increased significantly as concentration of cocultured TD-MSCs increased. Additionally, mRNA expression of caspase 3 was upregulated with increased concentration of TD-MSCs. Conclusion TD-MSCs have a potential growth inhibitory effect on HNSCC cell lines in vitro by inducing apoptotic cell death and G1 phase arrest of cell lines.

Intracordal auricular cartilage injection for unilateral vocal fold paralysis

We evaluated the efficacy and outcome of intracordal auricular cartilage injection in patients with unilateral vocal fold paralysis. Our interest developed from findings of a canine model study that reported that histologic characteristics of cartilage were preserved 2 and 3 years after intracordal autologous cartilage injection. Between May 2002 and July 2010, 29 patients with breathy dysphonia caused by unilateral vocal fold paralysis underwent intracordal auricular cartilage injection. Each subject underwent preoperative and postoperative perceptual assessments, acoustical voice analysis, and videostroboscopy. Fourteen patients were male, and the mean age was 52-years old. Patients were tracked for a mean duration of 257 days. Injections were performed through a transoral approach under general anesthesia. Perceptual assessments by GRBAS scale, acoustic parameters of jitter, shimmer, noise-to-harmonic ratio, and maximum phonation time significantly improved at 3, 6, and 12 months after cartilage injection (p < 0.005). No major complications were observed after injection. Initial clinical results with intracordal auricular cartilage injection are promising for patients with unilateral vocal fold paralysis. Autologous auricular cartilage can be a safe, effective, and alternative material for vocal fold medialization, and can be a long lasting one.

Multidisciplinary approach to lethal bleeding from an arteriovenous malformation in the external auditory canal.

Arteriovenous malformations (AVMs) are composed of abnormally connecting feeding arteries as well as draining veins and lack a regulatory system. Frequent recurrences and unpredictable behavior are their main problems. Potential mortality and morbidity associated with therapeutic procedures must be considered with these patients. Improper treatment often aggravates the condition, potentially rendering therapy more complex. A multidisciplinary approach, including an endovascular approach, surgical excision, and flap reconstruction, is considered to completely eradicate an AVM. This study introduces a complicated case of AVM with massive bleeding through the external auditory canal that was treated with a multidisciplinary approach.