Prognostic value of a mandibular canal staging system for primary lesions in patients with lower gingival squamous cell carcinoma: a multicenter, retrospective study.

BACKGROUND: The Union for International Cancer Control and American Joint Committee on Cancer tumor staging system is used globally for treatment planning. As it may be insufficient for tumor staging of lower gingival carcinomas, we proposed the mandibular canal tumor staging system. In this study, we aimed to compare the two systems for such tumor staging and to identify prognostic markers. METHODS: This multicenter, retrospective study included patients with lower gingival squamous cell carcinoma who underwent radical surgery during 2001-2018. We compared survival rates (Kaplan-Meier estimator) and patient stratification according to the two systems. RESULTS: The proposed system yielded more balanced patient stratification than the existing system. Progression in the tumor grade according to the proposed system was associated with a poorer prognosis. The 5-year overall and disease-specific survival rates for the entire cohort were 74.9% and 81.8%, respectively. Independent factors affecting overall survival were tumor stage according to the proposed system, excision margins, and number of positive nodes, whereas those affecting disease-specific survival were excision margins and number of positive nodes. CONCLUSIONS: Subsite-specific tumor classification should be used for patients with oral cancer, and our results suggest that mandibular canal tumor classification may be effective for patients with lower gingival carcinoma.

Targeting CD36-Mediated Lipid Metabolism by Selective Inhibitor-Augmented Antitumor Immune Responses in Oral Cancer.

The fatty acid receptor CD36 is expressed on various malignant cells and is suggested to contribute to tumor progression. CD36 is also expressed by several immune cells and involved in immune responses and may be a potential target in cancer immunotherapy. In this study, we investigated whether the selective inhibition of CD36 can inhibit tumor progression and facilitate an antitumor immune response in oral squamous carcinoma cells (OSCCs). We assessed the effects of sulfosuccinimidyl oleate sodium (SSO), a CD36 inhibitor, on the proliferation apoptosis and alteration in tumor cell surface expression levels of immune accessory molecules in vitro. We also assessed whether SSO-treated OSCCs could promote a T cell response via a Mixed Lymphocyte Reaction (MLR) assay. We also investigated the direct antitumor effects and immunomodulatory effects of SSO using a mouse oral cancer OSCC model. SSO treatment significantly inhibited OSCC proliferation, increased apoptotic cell death, and upregulated the cell surface expression of several immune accessory molecules, including CD83, MHC-Class II, and PD-L1. SSO-treated OSCCs augmented T cell proliferation following MLR. In vivo SSO administration significantly attenuated mouse tumor growth with an increased proportion of immune cells, including CD4+ T, CD8+ T, and dendritic cells; it also decreased the proportion of immune suppressive cells, such as myeloid-derived suppressor and regulatory T cells. These results suggest that the selective inhibition of CD36 can induce direct and indirect antitumor effects by facilitating host antitumor immune responses in OSCCs.

A Multicenter Study on the Effect of Margin Distance on Survival and Local Control in Stage 1-2 Squamous Cell Carcinoma of the Tongue.

BACKGROUND: Pathological close margins are considered a significant factor for local recurrence in patients with oral cancer. However, the oral cavity has complicated anatomical features, and the appropriate margin distance for each site is unknown. This multicenter, retrospective study aimed to determine the appropriate resection margin for early tongue cancer and investigate the need for additional treatment for close margins and stump dysplasia. PATIENTS AND METHODS: In total, 564 patients from ten hospitals were enrolled in this study. Sex, age, performance status, T stage, tumor length diameter, depth of invasion, elective neck dissection, iodine staining, horizontal margin distance, vertical margin distance, pathological differentiation, invasion pattern, lymphatic invasion, perineural invasion, dysplasia in the resection edge, additional treatment for close margins, local recurrence, neck metastasis, distant metastasis, and outcomes were investigated. RESULTS: Receiver operating characteristic analysis for local recurrence revealed cut-off values of 3.3 mm for horizontal distance and 3.1 mm for vertical distance. Patients with close horizontal or vertical margins showed significantly higher local recurrence rates, but these were not associated with overall or disease-specific survival. Furthermore, there was no effect of additional treatment in patients with dysplasia at the surgical margin. CONCLUSION: For early tongue cancer, a horizontal margin of 3.3 mm was defined as a close margin. Close margins were significantly correlated with local recurrence but did not affect survival. In the future, we would like to examine the concept of "quality margins," including the surrounding anatomical features.

The Impact of Pretreatment Low Body Mass Index on Cause-Specific Mortality in Patients with Squamous Cell Carcinoma of the Oral Cavity.

The association between the pretreatment body mass index (BMI) and oral squamous cell carcinoma (SCC) outcomes is controversial. We aimed to examine the association between BMI and cause-specific mortality due to cancer of the oral cavity and patterns of failure that correlate with increased mortality. We enrolled 2,023 East Asian patients in this multicenter cohort study. We used the cumulative incidence competing risks method and the Fine-Gray model to analyze factors associated with cause-specific mortality, local recurrence, regional metastasis, and distant metastasis as first events. The median follow-up period was 62 mo. The 5-year cause-specific mortality for patients with underweight was 25.7%, which was significantly higher than that for patients with normal weight (12.7%, P < 0.0001). The multivariate model revealed that underweight was an independent risk factor for cause-specific mortality and regional metastasis (P < 0.05). Moreover, patients with underweight displayed a 51% and 55% increased risk of cause-specific mortality and regional metastasis, respectively, compared with their normal weight counterparts. Local recurrence was not associated with the BMI categories; however, the incidence of distant metastasis inversely decreased with BMI value. In summary, being underweight at diagnosis should be considered a high-risk mortality factor for oral SCC.

Is withdrawal of antiresorptive agents necessary before and after tooth extraction? A systematic review.

OBJECTIVES: The need for prevention and management of medication-related osteonecrosis of the jaw (MRONJ) has increased with the growing number of patients using antiresorptive agents. The scope of this systematic review (SR) was to determine whether the withdrawal of antiresorptive agents is necessary for tooth extractions in patients receiving each of the antiresorptive medications. MATERIALS AND METHODS: The searches were performed using the MEDLINE databases. We selected SRs, randomized controlled trials (RCTs), prospective and retrospective non-randomized clinical (observational) studies, and case reports/case series in this order of preference. RESULTS: We included one SR, one RCT, five observational studies, and three case reports. Meta-analyses were not conducted because the RCT had an extremely small sample size and the observational studies had different definitions of intervention and comparison that could not be integrated across studies. In this SR, no studies showed a benefit (i.e., a reduction in the incidence of osteonecrosis of the jaw) of short-term withdrawal of antiresorptive agents for tooth extraction. Additionally, no studies examined the harm (i.e., an increase in femoral and vertebral fractures and skeletal-related events during bone metastasis) of withdrawal for tooth extraction. CONCLUSIONS: We were unable to determine whether withdrawal before and after tooth extraction is necessary with a high certainty of evidence. Future systematic reviews including RCTs with larger samples are expected to provide such evidence. CLINICAL RELEVANCE: This systematic review provides evidence-based information for multidisciplinary collaborations related to patients receiving antiresorptive agents.

Association between dental extraction after radiotherapy and osteoradionecrosis: A multi-centre retrospective study.

OBJECTIVE: Radiotherapy (RT) carries a substantial risk for the development of osteoradionecrosis (ORN) of the jaw. This study was performed to investigate the relationship between dental extractions after RT and the development of ORN. MATERIAL AND METHODS: Thirty-two patients with head and neck cancer who underwent tooth extraction after RT were investigated for correlations between the development of ORN and various factors. RESULTS: Postextraction ORN was diagnosed in 12 (12.1%) teeth of 9 patients. The RT dose against the site of tooth extraction was 62.0 and 37.4 Gy in the ORN and Non-ORN groups, respectively (p < .001). The duration from RT to tooth extraction was 41.2 and 28.2 months in the ORN and Non-ORN groups, respectively (p = .025). Tooth extraction was significantly associated with ORN in patients with a high RT dose against the site (odds ratio = 1.231) and a longer duration of time from RT (odds ratio = 1.084). CONCLUSIONS: Extraction of non-restorable teeth and those with a poor prognosis should not necessarily be postponed even when patients are undergoing RT. However, clinicians should pay special attention to postoperative management after tooth extraction in patients with a high RT dose and longer time from RT.

Oral melanoma: a multicenter study of 69 patients from Japan.

OBJECTIVES: The purpose of this multicenter retrospective study was to investigate the demographic characteristics and treatment outcomes of patients with mucosal malignant melanoma (MM) of the oral cavity. MATERIALS AND METHODS: This was a multicenter study involving 8 Japanese universities. The medical records of 69 patients who were diagnosed with primary oral MM between January 2000 and December 2020 were retrospectively analyzed. Overall survival (OS) and prognostic factors for OS were analyzed statistically. RESULTS: There were 40 (58.0%) males and 29 (42.0%) females, and their mean (range) age was 69.8 ± 14.6 (22-96) years old. The most common primary site was the palate (30 patients, 43.5%). Stage IVA was the most common disease stage (36 patients, 52.2%). Radical therapy was performed in 55 patients (79.7%). The 2-year and 5-year OS rates of the 69 patients were 64.6% and 42.5%, respectively. The 2-year and 5-year OS rates of the stage III patients were 85.9% and 72.5%, respectively, and those of the stage IVA patients were 56.3% and 26.0%, respectively. The 1-year OS rate of the stage IVB/IVC patients was 26.7%. The 2-year and 5-year OS rates of the radical therapy group were 74.1% and 50.5%, respectively, whereas the 2-year OS rate of the non-radical therapy group was 26.0%. An advanced T classification was the only identified prognostic factor for OS (hazard ratio: 6.312, 95% confidence interval: 1.133-38.522, p < 0.05). CONCLUSIONS: Early detection and radical treatment are essential for improving the prognosis of oral MM patients. CLINICAL RELEVANCE: Early detection and adequate radical therapy leads to the better prognosis of oral MM patients.

Awareness of Complications of Dental Treatment in Patients Treated with Drugs Affecting the Immune System : A Nationwide Questionnaire Survey of Dental Practitioners in Japan.

The aim of this study was to investigate the awareness and experience, among dental practitioners, of adverse events resulting from dental treatment of patients undergoing therapy with drugs that affect the immune system [angiogenesis inhibitors, biological agents, immunosuppressants, and disease-modifying anti-rheumatic drugs (DMARDs)]. For this purpose, a nationwide questionnaire survey was conducted. Questionnaires were sent to 2,050 dentists, of which 206 (10.1%) were completed and returned. The results showed that most dentists were aware of complications associated with dental treatment of patients treated with drugs that affect the immune system, and about half had actually experienced such complications. Delayed wound healing, osteonecrosis of the jaw (ONJ), and postoperative infections were reported. Whereas approximately 50% of dentists did not discontinue the drugs during dental treatment, about 18% did. During temporary drug discontinuation, some patients experienced aggravation of the primary disease, such as worsening of rheumatism, growth of tumors, and rejection reactions of transplanted organs. As for medical cooperation, only less than half of the dentists were asked for oral hygiene management by a physician prior to starting the drug treatment. Prospective studies are needed because evidence for dental treatments in patients treated with these drugs remains limited.

Relationship between dry mouth and hypertension.

OBJECTIVES: Salivary dysfunction, such as reduced salivary flow and an altered salivary composition, is caused by several diseases, medical conditions, and medications. The purpose of the present study was to clarify the relationship between hypertension and morphological changes in the submandibular glands. MATERIALS AND METHODS: An epidemiological study was conducted to elucidate the relationship between hypertension and dry mouth. The effects of hypertension on morphological changes and the intima thickness of arteries in the submandibular glands were histopathologically investigated. RESULTS: Among 1933 subjects in the epidemiological study, 155 (8.0%) had dry mouth. A multivariate analysis revealed that dry mouth correlated with age (p < 0.001), sex (p < 0.001), and hypertension (p < 0.05). No significant differences were observed in the size of the submandibular glands between patients with or without hypertension. The average area of acinar cells was smaller in patients with than in those without hypertension (0.366 ± 0.153 vs. 0.465 ± 0.178, p < 0.05). The arteriosclerotic index was significantly higher in patients with than in those without hypertension (0.304 ± 0.034 vs 0.475 ± 0.053, p < 0.05). CONCLUSIONS: Hypertension may contribute to the degeneration of the submandibular glands by decreasing the number of acinar cells and promoting fatty infiltration and stenosis of the arteries. CLINICAL RELEVANCE: There may be a correlation between hypertension and the degeneration of the submandibular glands by decreasing the number of acinar cells and promoting fatty infiltration and stenosis of the arteries.

Clinical significance of the G8 screening tool in elderly patients with oral squamous cell carcinoma.

OBJECTIVES: The present study investigated the clinical significance of the G8 screening tool in elderly oral squamous cell carcinoma (OSCC) patients using a multicenter analysis. MATERIALS AND METHODS: The medical records of 438 primary OSCC patients aged 75 years and older were retrospectively reviewed. To examine the clinical significance of the G8 screening tool in elderly OSCC patients, self-reliance (SR) rates and prognostic factors were statistically analyzed. RESULTS: The mean score of the G8 screening tool was 10.9 ± 2.93. The SR cut-off value of the G8 score was 9.5 in a receiver operating characteristic curve analysis. Five-year overall survival rates were 40.1% in patients with a G8 score < 9.5 and 58.4% in those with a G8 score ≥ 9.5 (p < 0.01). Five-year cancer-specific rates were 34.3% in patients with a G8 score < 9.5 and 55.7% in those with a G8 score ≥ 9.5 (p < 0.01). Five-year SR rates were 40.7% in patients with a G8 score < 9.5 and 55.3% in those with a G8 score ≥ 9.5 (p < 0.05). A multivariate analysis identified an advanced age (≥ 80 vs < 80; HR, 1.437; 95%CI, 1.181-1.843; p < 0.01), poorer ECOG-PS (2-4 vs 0-1; HR, 1.560; 95%CI, 1.14-2.106; p < 0.01), and standard treatment (non-standard therapy vs standard therapy; HR, 0.598; 95%CI, 0.405-0.910; p < 0.05) as significant independent prognostic factors for SR. A lower G8 score was associated with poorer SR (≥ 9.5 vs < 9.5; HR, 0.765; 95%CI, 0.575-1.034; p = 0.081). CONCLUSION: The clinical significance of the G8 score for elderly OSCC patients was demonstrated and its combination with ECOG-PS may be useful for assessing their prognoses.

Oral Candida Mannan Concentrations Correlate with Symptoms/Signs of Ill Health and the Immune Status.

BACKGROUND: A relationship has been proposed between increases in oral Candida concentrations and host immunity. Therefore, the present study was conducted to investigate the relationship between oral Candida mannan concentrations and symptoms/signs of ill health and the immune status and also to examine whether health/the immune status may be evaluated based on oral Candida mannan concentrations. PATIENTS AND METHODS: The health conditions of 25 healthy individuals and 10 cancer patients receiving cytotoxic chemotherapy were assessed using a questionnaire and oral rinse solutions collected on consecutive days. Candida mannan concentrations in oral rinse solutions were measured using a commercial sandwich ELISA kit. RESULTS: The use of dentures was identified as a significant independent factor increasing Candida mannan concentrations. In a stratified analysis based on the use of dentures, significantly increased Candida mannan concentrations were detected in healthy volunteers with chills and in cancer patients with slight/moderate fever (37.5-38.4 °C) (multivariate analysis, p < 0.01) who were non-denture users. These symptoms/signs may be associated with (pre-)infection, during which the immune system is activated and needs to function well. CONCLUSIONS: The present results suggest that oral Candida mannan concentrations are a predictive marker for health/the immune status.

On-lay grafting of a calcium hydroxyapatite bone substitute: A preliminary animal experimental study.

BACKGROUND: Bone substitutes are widely accepted for various clinical applications. However, the usage is predominantly intraosseous implantation, whereas extraosseous on-lay grafting is rare and lacks scientific evidence. The purpose of this study is to elucidate whether osteoconduction occurs in on-lay grafted bone substitute. METHODS: Custom-made interconnected porous calcium hydroxyapatite ceramic (IPCHA) was on-lay grafted with screw or anchor fixation (S- and A-groups, respectively) at the anterior aspect of the femur of skeletally mature Japanese white rabbits. At 3, 6 and 12 weeks postoperatively, 4 samples for each time point and each group were evaluated by microfocus computed tomography (micro-CT) and histology. RESULTS: Volume-rendered three-dimensional micro-CT images showed a high-density calcified area infiltrating IPCHA from the femoral cortex as of 6 weeks. When quantified, the calcified volume per unit volume first showed no difference between the two groups at 3 weeks but increased over time, and became significantly greater in the S-group than in the A-group (p = 0.012 and 0.004 at 6 and 12 weeks, respectively). Histologically, IPCHA pores were first occupied by fibrous tissue at 3 weeks; then, the pores adjacent to the femoral cortex were gradually replaced by bony tissue as of 6 weeks for both fixations. CONCLUSIONS: IPCHA allowed new bone formation inside the material even though it was implanted in an on-lay fashion on the cortical bone. Our results suggested that on-lay grafted IPCHA exerted its osteoconductivity well, with more new bone forming in screw-fixated samples than in anchor-fixated samples.

Treatment outcomes of adjunctive teriparatide therapy for medication-related osteonecrosis of the jaw (MRONJ): A multicenter retrospective analysis in Japan.

BACKGROUND: Therapeutic strategies for patients with medication-related osteonecrosis of the jaw (MRONJ) remain controversial. The aim of the present study was to clarify the effectiveness and safety of teriparatide therapy in Japanese MRONJ patients based on a large number of case series with a multicenter retrospective analysis. PATIENTS AND METHODS: Between January 2012 and December 2016, 29 patients who were diagnosed with MRONJ at 10 hospitals were treated with teriparatide. The medical records of these patients were retrospectively reviewed to assess the efficacy and safety of teriparatide therapy for MRONJ patients. RESULTS: Adverse events occurred in 17.2% of patients (5/29). One patient developed severe arthralgia and discontinued teriparatide therapy after 12 days, while others continued the treatment. Among 29 patients, the median period of administration of teriparatide was 14.0 months (range, 0.3-26 months), and treatment outcomes were evaluated as effective in 75.9% of patients with complete resolution in 65.5%. Among patients treated with oral bisphosphonates (BPs), 83.3% were effectively treated with teriparatide and 40% with intravenous BPs. The oral administration of BPs was associated with successful treatment outcomes with teriparatide (p = 0.062). CONCLUSIONS: Teriparatide therapy has potential as an effective treatment option for MRONJ.

Prevalence of and risk factors for postoperative hemorrhage after lower third molar extraction on warfarin therapy: a multicenter retrospective study in Japan.

Postoperative hemorrhage after tooth extraction is a critical and clinically important issue for clinicians and patients receiving anticoagulants. The purpose of the present study was to investigate the prevalence of and risk factors for postoperative hemorrhage after lower third molar extraction in Japanese patients receiving warfarin therapy. A total of 142 patients who underwent lower third molar extraction between January 2010 and December 2016 were included, and their medical records were retrospectively reviewed. The prevalence of and risk factors for postoperative hemorrhage were investigated. The prevalence of postoperative hemorrhage after lower third molar extraction was significantly higher in patients receiving warfarin than in healthy subjects (21.8% vs 0.7%, P < 0.001). The cutoff value for PT-INR was 2.11 based on a receiver-operating characteristic analysis. A multivariate analysis indicated that an elevated PT-INR value [hazard ratio (HR) 3.798, 95% confidence interval (CI) 1.400-10.467, P < 0.01], preoperative antibiotic administration (HR 4.434, 95% CI 1.591-14.775, P < 0.01), difficulties with intraoperative hemostasis (HR 16.298, 95% CI 2.986-110.677, P < 0.01), and higher serum creatinine levels (HR 7.465, 95% CI 1.616-39.576, P < 0.05) are significant predictors of postoperative hemorrhage after lower third molar extraction. Multivariate correlations were observed between risk factors including an elevated PT-INR value, preoperative antibiotic administration, and higher serum creatinine levels, and postoperative hemorrhage after lower third molar extraction in patients receiving warfarin therapy. Clinicians need to consider these risk factors for postoperative hemorrhage after the lower third molar extraction and monitor PT-INR in patients receiving warfarin therapy.

Tumor budding and adjacent tissue at the invasive front correlate with delayed neck metastasis in clinical early-stage tongue squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: Some patients with early-stage oral cancer have a poor prognosis owing to the delayed neck metastasis (DNM). Tumor budding is reportedly a promising prognostic marker in many cancers. Moreover, the tissue surrounding a tumor is also considered to play a prognostic role. In this study, we evaluated whether tumor budding and adjacent tissue at the invasive front can be potential novel predictors of DNM in early tongue cancer. METHODS: In total, 337 patients with early-stage tongue squamous cell carcinoma were retrospectively reviewed. The patient characteristics and histopathological factors were evaluated for association with DNM. DNM rates were calculated; items which were significant in the univariate analysis were used as explanatory variables, and independent factors for DNM were identified by the multivariate analysis. RESULTS: The univariate analysis identified T classification, depth of invasion, tumor budding, vascular invasion, and adjacent tissue at the invasive front as significant predictors of DNM; the multivariate analysis using these factors revealed all the above variables except vascular invasion, which are independent predictors of DNM. CONCLUSION: In addition to conventional predictors, high grade tumor budding and adjacent tissue at the invasive front can serve as useful predictors of DNM in early tongue cancer.

Treatment outcomes and prognostic factors of medication-related osteonecrosis of the jaw: a case- and literature-based review.

OBJECTIVES: The purpose of this study was to investigate the treatment outcomes and prognostic factors of medication-related osteonecrosis of the jaw (MRONJ) in Japanese patients. PATIENTS AND METHODS: Among 409 cases, treatment outcomes and prognostic factors were investigated in 275 patients. In statistical analyses, the 1-year cumulative curative rate was calculated with the Kaplan-Meier method, and significance was examined with the Wilcoxon test. Cox's proportional hazards regression analysis was used for the multivariate analysis. RESULTS: Resolution of the disease was achieved in 137 out of 275 MRONJ patients (49.8%). One-year cumulative curative rates were 39.8% in stage 1 patients, 26.3% in stage 2, and 19.0% in stage 3. The 1-year cumulative curative rates of treatment interventions were 17.2% for conservative treatment, 34.5% for sequestrectomy, and 40.7% for extended surgery including bone resection and segmental resection. As the prognostic factors of treatment outcomes, the type of medication, stage of MRONJ, and type of surgical intervention were identified as independent factors in a multivariate analysis. CONCLUSION: These results suggest that surgical interventions may lead to a good prognosis in MRONJ patients. CLINICAL RELEVANCE: This study indicated that surgical intervention for MRONJ might lead to improvement of prognosis and quality of life in MRONJ patients.

Relationship Between the Quantity of Oral Candida and Systemic Condition/Diseases of the Host: Oral Candida Increases with Advancing Age and Anemia.

BACKGROUND: The impact of host systemic conditions/diseases on the prosperity of oral Candida colonies remains unclear. The aim of the present study was to investigate whether a relationship exists between the quantity of oral Candida and the systemic condition/diseases of the host. PATIENTS AND METHODS: The cross-sectional relationship between Candida mannan concentrations and health check-up results was analyzed in consideration of local conditions that influence the prevalence of oral Candida. RESULTS: Candida mannan concentrations correlated with age, the number of untreated decayed teeth, number of prosthetic teeth, salivary pH, HbA1c, and the red blood cell count in a univariate analysis. In a multivariate analysis, Candida mannan concentrations correlated with age, the number of untreated decayed teeth, number of prosthetic teeth, salivary pH, and the red blood cell count. Candida mannan concentrations were higher in subjects older than 80 years, with a higher number of either untreated or prosthetic teeth, with a lower salivary pH, and with a decreased red blood cell count. Mannan concentrations were slightly higher in subjects with elevated HbA1c. CONCLUSIONS: The present results suggest a close relationship between the quantity of oral Candida and the systemic condition/diseases of the host. Oral Candida may increase in immunocompromised hosts.

Multi-center retrospective study of the prognosis and treatment outcomes of Japanese oral squamous cell carcinoma patients with single lymph node metastasis and extra nodal extension.

BACKGROUND: Oral squamous cell carcinoma (OSCC) containing single lymph node metastasis (pN1) with extra nodal extension (ENE) is a rare clinical situation. Therefore, it is unclear whether pN1 with ENE is at high risk of recurrence among the OSCC population, or whether postoperative radiotherapy (RT)/concomitant chemoradiotherapy (CCRT) is effective in these cases. OBJECTIVES: The purpose of this retrospective study was to investigate the prognosis and compare between no postoperative therapy and postoperative RT/CCRT in pN1 with ENE OSCC patients. METHODS: Clinicopathological data and treatment modalities were investigated. The evaluated endpoints were overall survival (OS) and type of recurrence. RESULTS: The 3-year cumulative OS rates for the pN1 only, multiple lymph node metastasis (MLM) only, ENE + MLM, and ENE + pN1 groups were 77.2%, 66.8%, 43.3%, and 66.6%, respectively. In the ENE + pN1 group, the most common cause of death in the surgery only group was from regional failure. The surgery + RT/CCRT group was associated with better disease-specific survival and OS rates than the surgery only groups (P < 0.05). CONCLUSIONS: The prognosis of ENE + pN1 was not as poor as that of ENE + MLM, although both these groups feature ENE. Adjuvant therapy (RT/CCRT) after surgery is recommend for cases of ENE + pN1.

Progression level of extracapsular spread and tumor budding for cervical lymph node metastasis of OSCC.

OBJECTIVES: The progression level of extracapsular spread (ECS) for cervical lymph node metastasis of oral squamous cell carcinoma (OSCC) was previously divided into three types, and their relationships with the prognosis of patients were re-examined. PATIENTS AND METHODS: The Kaplan-Meier method was used to examine overall survival (OS) and relapse-free survival (RFS) curves. Prognosis factor for recurrence was analyzed with univariate and multivariate analysis. RESULTS: ECS was detected in 216 cases of OSCC and analyzed. The 5-year overall survival and RFS rates of patients with type C, which was microscopically defined as tumor invasion to perinodal fat or muscle tissue, were significantly poor at 40.6 and 37.8%, respectively. The results of a univariate analysis suggested that the prognosis of ECS in OSCC patients is associated with its progression level, particularly type C. The 5-year RFS rate of type C with tumor budding was significantly poor at 31.5%. Type C with tumor budding correlated with local and regional recurrence as well as distant metastasis. In a multivariate analysis, tumor budding was identified as an independent prognostic factor. CONCLUSIONS: These results suggest that the progression level of ECS and tumor budding are useful prognostic factors in OSCC patients. CLINICAL RELEVANCE: This study indicated that the progression level and tumor budding of ECS for cervical lymph node metastasis were useful prognostic factors in OSCC patients.