• Korean Journal of Head & Neck Oncology
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• v.18 no.2
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• pp.157-162
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• 2002

Background and Objectives: Adenoid cystic carcinoma (ACC) is a unique tumor characterized by frequent and delayed distant metastasis (DM) with uncommon regional lymph node metastasis. We evaluated the factors affecting DM of ACC and survival after appearance of DM. Materials and Methods: Medical records, radiographs and pathologic slides were reviewed for 94 patients from 1979 through 2001. Results: DM of ACC occurred in 46 patients, and developed more frequently in patients with tumors of the solid histologic subtype than in patients with tubular or cribriform subtypes. DM occurred less frequently in the sinonasal tract, and development of DM was not affected by tumor stage. Disease-specific 5- and 10-year survival rates were 88% and 72% for patients without DM, respectively and 76% and 48% for those with DM(p=0.02). Regarding the site of DM and its impact on outcomes, 30 patients had lung metastasis alone, 5 patients bone metastasis alone and 6 patients developed both lung and bone metastasis. Median survivals after appearance of DM among patients with isolated lung metastases and those with bone metastases with or without lung involvement were 54 and 21 months, respectively (p=0.04). Conclusions: Development of DM in ACC is predicted by solid histologic subtype, and major salivary gland or oral/pharyngeal rather than sinonasal primary site. Those patients with bone involvement with our without lung metastases had worse outcomes than those with pulmonary metastasis only.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.32 no.2
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• pp.118-125
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• 2010

Background and Purpose: Bone metastases rarely occur in patients with oral squamous cell carcinoma (OSCC), so the molecular mechanisms of bone metastasis of OSCC remains unclear. Studies with animal models allow progresses in understanding the molecular events for bone metastasis and provide new targets for therapy. So we tried to establish a murine model for bone metastasis of oral squamous cell carcinoma. Materials and Methods: Human OSCC cells (KB cell line) were xenografted to nude mice via direct inoculation into the tibial marrow. Mice with tibial tumors were sacrificed once a week, until seven weeks after the injection of human tumor cells. Growth of tibial tumors were observed by histology. Expression of TGF-$\beta$ and CXCR-4 in bone OSCC (experimental) and subcutaneous tumor (control) was also evaluated by immunohistochemical staining. Results: Bone OSCC was successfully induced by intra-tibial injection of KB cells. Tumor mass was developed in the marrow tissues of tibia and finally invade the endosteum of tibia. Immunohistochemical staining showed higher expression of TGF-$\beta$ in bone tumors than in subcutaneous tumors. Conclusion: A murine model of bone metastasis of OSCC was suggested that imitated the clinical findings of distant vascular metastasis. This bone tumor model should facilitate understanding of the molecular pathogenesis of OSCC bone metastasis, and aid in the developement of treatment strategies against OSCC bone metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4045-4050
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• 2012

Objective: The impact of ablative oral cancer surgery was studied, with particular reference to recurrence and nodal metastasis, to assess survival probability and prognostic indicators and to elucidate if ethnicity influences the survival of patients. Methods: Patients who underwent major ablative surgery of the head and neck region with neck dissection were identified and clinical records were assessed. Inclusion criteria were stage I-IV oral and oropharyngeal malignancies necessitating resection with or without radiotherapy from 2004 to 2009. All individuals had a pre-operative assessment prior to the surgery. The post operative assessment period ranged from 1 year to 5 years. Survival distributions were analyzed using Kaplan-Meier curves. Results: 87 patients (males:38%; females:62%) were included in this study, with an age range of 21-85 years. Some 78% underwent neck dissections while 63% had surgery and radiotherapy. Nodal recurrence was detected in 5.7% while 20.5% had primary site recurrence within the study period. Kaplan-Meier survival analysis revealed that the median survival time was 57 months. One year overall survival (OS) rate was 72.7% and three year overall survival rate dropped to 61.5%. On OS analysis, the log-rank test showed a significant difference of survival between Malay and Chinese patients (Bonferroni correction p=0.033). Recurrence-free survival (RFS) analysis revealed that 25% of the patients have reached the event of recurrence at 46 months. One year RFS rate was 85.2% and the three year survival rate was 76.1%. In the RFS analysis, the log-rank test showed a significant difference in the event of recurrence and nodal metastasis (p<0.001). Conclusion: Conservative neck is effective, in conjunction with postoperative radiotherapy, for control of neck metastases. Ethnicity appears to influence the survival of the patients, but a prospective trial is required to validate this.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.37 no.1
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• pp.54-61
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• 2011

Introduction: Bisphosphonates is used widely for the treatment of the Paget's disease, multiple myeloma, bone metastases of malignant tumors with the prevention of pain and their pathological fracture. However, it was recently suggested that bisphosphonates related osteonecrosis of the jaw (BRONJ) is a side effect of bisphosphonate use. Materials and Methods: Twenty-four individuals, who were referred to the Department of Oral and Maxillofacial surgery, Dankook University Dental Hospital, were selected from those who had exposed bone associated with bisphosphonates from January, 2005 to December, 2009 according to the criteria of American Association of Oral and Maxillofacial Surgeons (AAOMS) for BRONJ. The patients group consisted of 7 males and 17 females between the age of 46 to 78 years (average 61.8 years). Each patient had panoramic imaging, computed tomography (CT), whole body bone scanning performed for a diagnosis and biopsy sampling from the necrotizing tissue. C-terminal cross-linking telopeptide of type I collagen (CTX) level of patients who had undergone surgical intervention was measured 7 days before surgery. Results: The main cause of bone exposure was post-extraction (15), chronic periodontitis (4), persistent irritation of the denture (3). Twenty people had undergone BRONJ treatment for two to eight months except for 4 people who had to maintain the bisphosphonates treatment to prevent a metastasis and bone trabecular pain with medical treatment. When the bisphosphonate treatment was suspended at least for 3 months and followed up according to the AAOMS protocols, the exposed necrotizing bones were found to be covered by soft tissue. Conclusion: Prevention therapy, interruption of bisphophonates for at least 3 months and cooperation with the physician for conservative treatment are the essential for treating BRONJ patient with high risk factors. The CTX level of BRONJ patients should be checked before undergoing surgical intervention. Surgical treatments should be delayed in the case of a CTX level <150 pg/mL.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.3
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• pp.199-203
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• 2007

Several matrix metalloproteinases (MMPs) have been shown to play an important role in the invasion and metastasis of oral squamous cell carcinoma (OSCC). The members of the TGF-$\beta$ signaling pathway are being considered as predictive biomarkers for progressive tumorigenesis and molecular targets for the prevention and the treatment of cancer and metastasis. The aim of the present study was to find the clinical significance of the expression of TGF-${\beta}1$ and MMP-2 related to the regional lymph node metastasis in OSCC. This study included 76 cases of primary OSCC, of which 42 cases showed regional lymph node metastases. Immunohistochemistry was used for the localization of protein. The relation between the expression of each protein and clinical variables was statistically evaluated. In results, the expression of TGF-${\beta}1$ both main mass with lymph node metastasis and without lymph node metastasis was found not to be statistically significant (p>0.05). The expression of MMP-2 was found to be statistically significant related to regional lymph node metastasis (p<0.05). When compared the expression in the metastatic lymph node, TGF-${\beta}1$ was significantly highly expressed than MMP-2 (p<0.05). In conclusion, the expression of MMP-2 was significantly elevated in patients with lymph node metastasis as compared to the patients without lymph node metastasis, which could be useful in predicting the risk of lymph node metastasis in OSCC.

• Tuberculosis and Respiratory Diseases
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• v.51 no.1
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• pp.65-69
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• 2001

The incidence of lung cancer and its mortality rate are increasing in Korea. At the time of diagnosis, 40% patients of lung cancer patients had metastatic lesions. The common metastatic sites are the contralateral lung, bone, liver, adrenal gland and the brain. Metastasis to oral mucosa is rarely encountered in lung cancer and metastasis to the gingiva is more uncommon. Approximately 1% of malignant carcinomas in the oral cavity are the result of metastases, and 10-25% of metastatic cancers originate from lung cancer. Clinically metastatic gingival lesions are benign including hemangioma, pyogenic granuloma, giant-cell granuloma or a peripheral fibroma. Often metastases to the gingiva are diagnosed too late and by the time they are detected, they have metastases to other organs. Here we report a case of small cell lung carcinoma that had metastased to the gingiva with review of relevant literature.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.43 no.2
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• pp.120-124
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• 2017

Osteonecrosis of the jaw (ONJ) is commonly described as an adverse effect of the use of bisphosphonates. A few cases of ONJ associated with tyrosine kinase inhibitors (sunitinib, imatinib) have been reported in the literature and usually they occurred in patients simultaneously treated with bisphosphonates. We report an atypical case of ONJ related only to imatinib. A 72-year-old male patient was treated with imatinib for metastases from gastrointestinal stromal tumors (GISTs). The patient developed ONJ after 22 months of imatinib only therapy. During his whole life, the patient had never been treated with bisphosphonates or radiotherapy. Microscope examination of the tissues confirmed the clinical diagnosis of diffuse osteonecrosis and showed absence of neoplastic cells. Thus, secondary localisations from GISTs were ruled out. Osteonecrosis of the lower jaw appeared 22 months after initial and exclusive therapy with imatinib. Therefore, imatinib monotherapy can induce ONJ in patients that have never been treated with bisphosphonates or radiotherapy.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.37 no.1
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• pp.72-76
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• 2011

Polymorphous low-grade adenocarcinomas (PLGA) are distinctive salivary gland neoplasms with a propensity to arise from the minor salivary glands. The most frequent location of PLGA is the palate, even though other locations have been described. Previously used terms for PLGA include lobular carcinoma and terminal duct carcinoma. Although the frequency of the tumor is unknown, the recognition of PLGA as an individual tumor has increased with the establishment of specific histopathological criteria characterizing the PLGA. The first choice of treatment is a wide surgical excision including the subjacent bone if necessary. The prognosis is generally good and the recurrence rate ranges from 17% and 22%. Distant metastases is unusual (9%) but occur mainly in the regional lymph nodes. This is a case report of a 67 year old female patient with PLGA who was treated with a wide excision by layers (2 stage) of the lesion including the surrounding bone. We present this case with a review of the relevant literature.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.6
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• pp.490-496
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• 2010

Introduction: This study examined the effect of a conservative neck dissection in patients with head and neck cancer. Materials and Methods: A total of 24 patients, who underwent a conservative neck dissection for the treatment of oral cancer from January 2002 to December 2007, were included. All procedures were performed by one oral and maxillofacial surgeon. The mean age was 58.2 years (range, 19 to 79 years). The medical recordings, pathologic findings, and radiographic findings were evaluated. The mean follow up period was 41.1 months (range, 4 to 88 months). Results: 1. Oral cancer was more common in men than women with a 3:1 ratio. 2. Histopathologically, squamous cell carcinoma(83%) was the most prevalent oral cancer in this study. 3. The most common primary site was the tongue(6 cases, 25%) followed by the mouth floor (5 cases, 21%), buccal mucosa (3 cases, 13%), lower lip, mandible, palate (2 cases, respectively) and salivary gland, retromolar area, oropharynx, alveolus (1 case, each). 4. Three out of the 24 (13%) subjects had a recurrence at the primary sites. 5. Two out of 24 (8%) subjects had a distant metastasis. 6. All 24 patients survived and there were eleven patients who passed 5 years postoperatively. Conclusion: A conservative neck dissection is a reliable and effective method for controlling neck node metastases in patients with oral cancer of the N0 or N1 neck node without serious complications.

• Korean Journal of Head & Neck Oncology
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• v.30 no.2
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• pp.90-94
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• 2014

Salivary duct carcinoma(SDC) is rare malignancy, accounting for approximately 1-3% of all malignant salivary gland tumors. Systemic chemotherapy has been used for stage IV SDC, but there is no consensus on the standard treatment. SDC is histologically similar to ductal carcinoma of breast and often overexpress HER2/neu, hence HER2/neu targeted therapy could be one of treatment options. A 75-year-old Arabian man was diagnosed as SDC of right parotid gland with extensive metastases. He received oral 5-FU as palliative chemotherapy, but he was intolerable to oral chemotherapy due to severe oral mucositis. Considering immunohistochemical stain of tumor tissue showing strong positive for HER2/neu, we decided to administer an anti-HER2/neu antibody, trastuzumab. Follow-up CT scans before the third dose of trastuzumab demonstrated remarkable regression of multiple metastases as well as primary tumor. This case suggests that HER2/neu targeted therapy may be a potential therapeutic option for the SDC patient with overexpression of HER2/neu.