Analysis of prognostic factors through survival rate analysis of oral squamous cell carcinoma patients treated at the National Cancer Center: 20 years of experience.

Objectives: This study aimed to analyze the clinicopathological prognostic factors affecting the survival of patients with oral squamous cell carcinoma (OSCC). Materials and Methods: A retrospective study was conducted on patients with OSCC who received treatment at the Oral Oncology Clinic of the National Cancer Center (NCC) from June 2001 to December 2020. The patients' sex, age, primary site, T stage, node metastasis, TNM staging, perineural invasion (PNI), lymphovascular invasion (LVI), differentiation, surgical resection margin, smoking, and drinking habits were investigated to analyze risk factors. For the univariate analysis, a Kaplan-Meier survival analysis and log-rank test were used. Additionally, for the multivariable analysis, a Cox proportional hazard model analysis was used. For both analyses, statistical significance was considered when P<0.05. Results: During the investigation period, 407 patients were received surgical treatment at the NCC. Their overall survival rate (OS) for five years was 70.7%, and the disease-free survival rate (DFS) was 60.6%. The multivariable analysis revealed that node metastasis, PNI, and differentiation were significantly associated with poor OS. For DFS, PNI and differentiation were associated with poor survival rates. Conclusion: In patients with OSCC, cervical node metastasis, PNI, and differentiation should be considered important prognostic factors for postoperative survival.

Treatment outcomes and prognostic factors in oral tongue cancer: a 20-year retrospective study at the National Cancer Center, South Korea.

Objectives: This study aimed to analyze the treatment outcomes and to evaluate the clinicopathological prognostic factors of oral tongue cancer. Patients and. Methods: We retrospectively analyzed treatment results and prognostic factors in 205 patients with oral tongue squamous cell carcinoma who were admitted to the National Cancer Center, South Korea, between January 2001 and December 2020. The patients were treated with surgery and postoperative, definitive radiotherapy (RT) or chemoradiotherapy (CRT). Results: Eighteen patients (8.8%) were treated with curative RT or CRT, while the rest (91.2%) were treated with surgery with or without postoperative RT or CRT. The median follow-up period was 30 months (range, 0-234 months). The 5-year overall survival (OS) and 5-year disease-free survival (DFS) were 72% and 63%, respectively. Multivariate analysis revealed that a positive neck nodal status (N1, N2-3) was significantly associated with poorer 5-year OS and DFS, while perineural invasion was associated with poorer 5-year DFS. Conclusion: Cervical metastasis and perineural invasion are significant prognostic predictors, and combination treatments are necessary for improving OS and DFS in patients with these factors.

Measurement of hepatitis B virus DNA in fresh versus processed dentin from chronically infected patients.

BACKGROUND: Demineralized dentin matrix (DDM) is commonly used as a bone-graft substitute. This study measured and compared human hepatitis B viruses (HBV) DNA in fresh dentin to that of dentin processed into DDM extracted during dental treatment from HBV-infected patients. The hypothesis was that the processing procedure for DDM would inactivate or eliminate HBV in the dentin matrix obtained from infected patients. METHODS: Dentin from eighteen HBV-infected patients was collected and each dentin specimen was divided into two fragments. One fragment was used before processing as fresh dentin (control group) and the other was processed into DDM (experimental group). DNA was extracted and purified from each fresh and processed dentin specimen and the HBV DNA copy number quantitated by real time polymerase chain reaction. The HBV DNA copy number in the fresh dentin specimens were compared relative to serologic test results. The second parameter was to evaluate the effectiveness of the processing procedure (defatting, demineralization, freeze-drying, and sterilization) to inactivate or eliminate HBV by comparing the DNA copy number in the processed DDM with that in the matched fresh dentin specimens. All results were analyzed using Mann-Whitney U test to compare numerical measurements between groups and differences were considered statistically significant at P-values less than 0.05. RESULTS: The presence of HBV DNA was detected in 55.56% (10/18) of the fresh dentin specimens. For the ten HBV DNA-positive fresh dentin specimens, HBV DNA was detected in two (20%) of the matched processed dentin specimens. The copy number of HBV DNA in the two positive processed dentin specimens was 1.79 and 4.03, which were statistically lower than that of the fresh dentin specimens (P = 0.0167). CONCLUSIONS: The results from this study suggested that fresh dentin may be a carrier of HBV and that the procedure used to generate DDM extensively reduced the levels of HBV DNA. Further studies are needed to evaluate the infectivity of HBV in processed dentin.

Novel PTCH1 Gene Mutation in Nevoid Basal Cell Carcinoma Syndrome.

The purpose of this study was to report clinical characteristics, surgical results, and new PTCH1 gene mutations in nevoid basal cell carcinoma syndrome (NBCCS). Five patients were referred to the Department of Oral and Maxillofacial Surgery from local dental clinics between 2006 and 2016 to treat multiple keratocystic odontogenic tumors (KOTs). The cystic lesions were enucleated and peripheral ostectomy was performed to obtain safety margin. Recurrence and/or de novo development of KOT were assessed. Gene analysis using peripheral blood was performed in all patients to identify the mutation of PTCH1 gene. Three patients showed familial history of first-degree relatives. Of the major criteria, all patients presented KOT but only 1 patient had basal cell carcinoma. Of the minor criteria, 4 of the 5 patients presented macrocephaly and hypertelorism. During follow-up periods, all patients showed recurrence and/or de novo development of KOT in the jaw bone. Mutation analysis of PTCH1 gene showed 3 frameshifts (c.817_818ins(T), c.1226_1227ins(A), and c.2748del(C)), 1 splicing (c.1504-2A>T), and 1 missense (c.385T>C) mutation. Mutations were found in exon 1, 6, 9, 17, and intron 10. Regular follow-up is necessary because recurrence rate of KOT was very high. To help early diagnosis, it is essential to routinely perform genetic testing to detect PTCH1 gene mutations among patients with NBCCS.

A single cervical lymph node metastasis of malignant ameloblastoma.

INTRODUCTION: Cervical node metastasis of malignant ameloblastoma is extremely rare. Because of its rarity, there is no standard treatment modality in a single lymph node metastasis in malignant ameloblastoma. MATERIALS AND METHODS: Eleven patients of malignant ameloblastoma involving a single cervical lymph node metastasis and one new case were reviewed. Neck treatment was classified into neck dissection and simple excision. Local nodal recurrence, distant metastasis and follow-up periods were investigated. RESULTS: Eight patients were treated with neck dissection (group A) and four patients underwent a simple node excision (group B). Two patients in group A experienced multiple organ metastases such as liver and lung seven months and 13 years after neck dissection respectively. The other patients showed no recurrence and metastasis. In group B, there was no report of a regional neck recurrence and distant metastasis during follow-up of 1-7 years. CONCLUSION: Multiple nodes metastasis requires a radical neck dissection; however, simple excision with close follow-up may be used in a single node metastasis in malignant ameloblastoma.

The chemopreventive properties and therapeutic modulation of green tea polyphenols in oral squamous cell carcinoma.

Chemoprevention is a relatively novel and promising approach for controlling cancer that uses specific natural products or synthetic agents to suppress, reverse, or prevent premalignancy before transformation into invasive cancer. Oral cavity squamous cell carcinoma (OCSCC) represents a large, worldwide health burden with approximately 274,000 cases diagnosed annually worldwide. Smoking and alcohol consumption are major inducers of OCSCC. Recently, the human papilloma virus was also shown to potentially be an etiologic factor. Due to its easily identifiable risk factors and the presence of premalignant regions, oral cancer makes a good candidate for chemoprevention. Green tea is the most widely consumed beverage in the world, and it has received considerable attention because of its abundant, scientifically proven, beneficial effects on human health. In this review, we discuss the role of green tea in oral cancer chemoprevention with regard to the multiple molecular mechanisms proposed in various in vitro, in vivo, and clinical trials.

The effect of combination anti-endothelial growth factor receptor and anti-vascular endothelial growth factor receptor 2 targeted therapy on lymph node metastasis: a study in an orthotopic nude mouse model of squamous cell carcinoma of the oral tongue.

OBJECTIVE: To evaluate the therapeutic effect of treatment with a combination of the monoclonal antibodies to the vascular endothelial growth factor receptor (DC101) and the epidermal growth factor receptor (cetuximab) in an orthotopic nude mouse model of metastatic squamous cell carcinoma of the oral tongue (SCCOT). DESIGN: In vivo study. SETTING: A translational research laboratory at a comprehensive cancer center. SUBJECTS: Male athymic nude mice aged 8 to 12 weeks. INTERVENTION: To develop orthotopic nude mouse models of SCCOT, OSC-19 cells or luciferase (Luc)-expressing OSC-19-Luc and JMAR-Luc cells were injected into the tongues of nude mice. Animals were randomly divided into 4 groups: DC101 alone, cetuximab alone, DC101 plus cetuximab, or placebo, and all treatments were administered twice per week for 4 weeks. The in vivo antitumor activity was monitored noninvasively by bioluminescence imaging. Tumors were resected at necropsy, and immunohistochemical and immunofluorescent staining were performed. MAIN OUTCOME MEASURES: Tumor size, bioluminescence, animal survival, and percentage of animals with lymph node metastasis. RESULTS: At the conclusion of the treatment period, the mean tumor volumes in the cetuximab alone and the DC101 plus cetuximab groups had decreased significantly compared with those that received the placebo control (68% [P = .002] and 84% [P < .001], respectively). Significant effects of the treatment were also observed in bioluminescence imaging. Mice treated with DC101 plus cetuximab also lived longer and had a lower incidence of neck lymph node metastases compared with the control group (P = .003). CONCLUSIONS: Treatment with DC101 plus cetuximab inhibited the growth of SCCOT and decreased the incidence of the neck lymph node metastases in vivo. These results suggest that this combination treatment may be an effective strategy against metastatic SCCOT and warrants further preclinical trials.

Vandetanib inhibits growth of adenoid cystic carcinoma in an orthotopic nude mouse model.

PURPOSE: Adenoid cystic carcinoma (ACC) can often be controlled with surgery and postoperative adjuvant radiotherapy but is also characterized by late local recurrence and distant metastasis. No effective systemic therapeutic agents have been found to alter the natural history of ACC. Therefore, new therapeutic approaches are needed. In this study, we evaluated whether vandetanib (Zactima), a potent inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR) tyrosine kinases, had antitumor efficacy in vitro and in an orthotopic nude mouse model of human ACC. EXPERIMENTAL DESIGN: The in vitro effects of vandetanib were assessed in three ACC cell lines on cell growth, apoptosis, and VEGFR-2 and EGFR phosphorylation levels. The in vivo antitumor activity of vandetanib was examined in nude mice bearing parotid gland ACC tumors. The mice were treated for 4 weeks with vandetanib (50 mg/kg/d) or placebo (control). Tumors were resected at necropsy, and immunohistochemical and immunofluorescence staining were done. RESULTS: In vitro, vandetanib caused dose-dependent inhibition of VEGFR-2 and EGFR phosphorylation in ACC cells. Vandetanib also inhibited the cell proliferation and induced their dose-dependent apoptosis. In vivo, mice in the vandetanib group had tumor volumes significantly lower than those in the control group (P < 0.01). In addition, immunohistochemical staining showed a decrease in microvessel density and an increase in apoptosis of both tumor cells and endothelial cells within the tumor xenografts. CONCLUSION: These results suggest that vandetanib inhibits the growth of ACC in vitro and in vivo, making it a promising novel agent for the treatment of ACC.

Expression of carbonic anhydrase IX is associated with postoperative recurrence and poor prognosis in surgically treated oral squamous cell carcinoma.

Carbonic anhydrase IX (CA9) is reportedly overexpressed in several types of carcinomas, but little is known about the expression pattern of CA9 in oral cavity cancer and the corresponding normal tissues. We aimed to assess the prevalence of CA9 expression and its prognostic implications in patients with oral cavity squamous cell carcinoma (SCC). Immunohistochemical staining with anti-CA9 antibody was performed in 117 oral SCC samples. Clinicopathologic factors were correlated with the results of CA9 expression. CA9 expression was restricted to tumor cells and did not appear in the corresponding normal tissue. Among 117 samples, 68 (58.1%) tumors displayed CA9 overexpression. CA9 expression was significantly associated with postoperative recurrence (P = .05) and poor overall survival (P = .02). CA9 expression was also associated with male sex, lymph node metastasis, and smoking history, but these correlations did not reach statistical significance. In conclusion, CA9 expression was a frequent and tumor-specific event in oral SCC. CA9 demonstrated significant associations with disease recurrence and poor clinical outcome and shows potential as a prognostic factor for oral SCC.

An anatomic assessment on perforators of the lateral circumflex femoral artery for anterolateral thigh flap.

The anterolateral thigh flap was originally described in 1984 as a septocutaneous flap based on the descending branch of the lateral femoral circumflex artery (LCFA). This flap has many advantages for head and neck reconstruction. However, it is not widely used as a result of the broad range of anatomic variation of the cutaneous perforators and because dissection of these perforators is tedious when they are small. The purposes of this study are to classify the vascular anatomy of the LCFA and to assess the suitability of the anterolateral thigh flap for head and neck reconstruction in Koreans. From 38 thigh dissections of Korean cadavers, the LCFA commonly arose from the deep femoral artery and divided into ascending, transverse, and descending branches. In five cases, the LCFA arose directly from the femoral artery. The cutaneous perforators were present in 37 cases except one and the septocutaneous perforators were found in 17 of the 38 cases. Of the 160 perforators, 28 (17.5%) were the septocutaneous perforators and 132 (82.5%) were the musculocutaneous perforators. The average number of cutaneous perforators for the anterolateral thigh flap was 4.2 (range, 0-8), and these perforators were concentrated in the middle third of the anterolateral thigh. The septocutaneous perforators were located more proximally than the musculocutaneous perforators. The average length of the vascular pedicle derived from the descending branch or the transverse branch was 83.3 mm (range, 53.4-124.3 mm). The results of this study suggest that the vascular anatomy of the anterolateral thigh flap was reliable and well suited for head and neck reconstruction in Koreans.

Clinical significance of metabotropic glutamate receptor 5 expression in oral squamous cell carcinoma.

The multifunctional G-protein-coupled metabotropic glutamate receptor (mGluR) family comprises eight subtypes, some of which participate in tumorigenesis. The purpose of this study was to evaluate mGluR5 expression in oral squamous cell carcinoma (SCC) tissues and oral cancer cell lines. We also investigated the prognostic significance of mGluR5 and its functional importance in the migration, invasion, and adhesion of oral cancer cells. We evaluated the expression of mGluR5 in samples from 131 oral SCC patients and in several oral cancer cell lines by immunohistochemistry and RT-PCR. We observed varying levels of mGluR5 in human oral SCC tissues and cancer cell lines. There was a significant association between strong mGluR5 immunoreactivity and overall survival (P=0.0109). The functional significance of the expression of mGluR5 in oral cancer cells was then investigated in HSC3 oral tongue cancer cells. An mGluR5 agonist, DHPG increased tumor cell migration, invasion, and adhesion in HSC3 cells (P<0.05). This was reversed by the mGluR5 antagonist MPEP. Our results strongly suggest that mGluR5 is a new prognostic marker and contributes to tumor cell migration and invasion in oral cancer.

Synovial chondromatosis of the temporomandibular joint with condylar extension.

Synovial chondromatosis is a benign disease that rarely affects the temporomandibular joint (TMJ). It can be seen commonly in the superior joint space and presents with various signs and symptoms according to the stage of progression. Sometimes it presents as a large swelling in the preauricular area with or without cranial extension, and the clinical and radiographic findings may be misdiagnosed as other benign or malignant diseases of TMJ. Therefore, we report an uncommon case of synovial chondromatosis presenting as a large preauricular mass arising from the inferior joint space of the TMJ with bony resorption of the mandibular condyle, which mimicked osteochondroma.

Initial presentation of lung sarcomatoid carcinoma as a metastatic lesion in the mandibular gingiva.

BACKGROUND: Sarcomatoid carcinoma of the lung is a very rare type of tumor characterized by distant metastasis. However, metastasis to the gingiva is an uncommon event. Occasionally, an oral metastatic lesion may be the preliminary clinical feature observed before the diagnosis of the primary tumor. METHODS: The clinical features of gingival metastasis as an initial presentation of lung sarcomatoid carcinoma are discussed. A 55-year-old male patient presented with a rapidly growing pedunculated exophytic mass on the gingiva at the left side of the lower jaw. Incisional biopsy was performed. RESULTS: The histologic and immunohistochemical diagnosis was metastatic carcinoma. To locate the primary tumor, we analyzed the lung lesion by chest computerized tomography (CT) scans and biopsy. The patient was ultimately diagnosed with sarcomatoid carcinoma of the lung with gingival metastasis. Palliative chemotherapy for lung cancer was administered. The gingival lesion disappeared after chemotherapy. CONCLUSION: Although this case is unusual, periodontists should recognize that gingival masses similar to benign or inflammatory lesions may represent an initial sign of underlying malignant tumors.