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Introduction: Benign submandibular gland tumors pose challenges in balancing treatment effectiveness and preserving gland function. This study aimed to compare gland-preserving surgery, extracapsular dissection (ECD), with total excision in managing these tumors, focusing on function preservation and recurrence rate., Methods: Fifty consecutive patients with treatment-naïve benign submandibular gland tumors were alternatively allocated to receive ECD (n = 25) or total excision (n = 25) without randomization procedures. Intraoperative findings, postsurgical complications, subjective satisfaction, and gland function were assessed. Follow-up data were collected for a median duration of 55 months (24-80 months) to monitor recurrences., Results: ECD demonstrated significant advantages, including shorter operation time, reduced bleeding, and preservation of the facial artery and vein (P < 0.05). Both groups exhibited acceptable postsurgical pain and taste sensations. Complications were minimal and similar between the two groups. ECD resulted in superior facial contour satisfaction (P = 0.030) and preserved gland function, as evidenced by salivary scintigraphy. No recurrences were observed in either group during the follow-up period., Conclusions: ECD is a practical approach for benign submandibular gland tumors, offering favorable functional outcomes, reduced surgical morbidity, shorter operation times, and improved cosmetic results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Gland-preserving surgery has gained popularity for treating benign parotid tumors, offering potential benefits by preserving facial nerve function and salivary secretion while reducing complications. This study aims to evaluate the functional, cosmetic, and disease control outcomes of gland-preserving surgery via a postauricular sulcus incision., Methods: An observational longitudinal investigation encompassed 46 patients undergoing gland-preserving surgery for benign parotid tumors via the postauricular sulcus incision approach. Patient assessments included cosmetic contentment, functional repercussions, and disease management throughout the follow-up., Results: Predominantly, tumors were situated in the superficial lobe, with successful application observed in 8 instances (17%) within the deep lobe. Notably, no tumor recurrences were detected during the follow-up period. Postoperative pain remained minimal, accentuated by high patient satisfaction regarding the incision scar and facial symmetry. Furthermore, preservation of facial nerve functionality and salivary secretion was observed., Conclusion: Gland-preserving surgery via the postauricular sulcus incision technique exemplifies advantageous functional and cosmetic outcomes when addressing benign parotid tumors. This approach presents a secure and efficient alternative, facilitating effective local management., Competing Interests: Declaration of Competing Interest The author declares no conflict of interest., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Ferroptosis is a newly discovered form of programmed cell death caused by redox-active iron-mediated lipid peroxidation. Ferroptosis exhibits a unique morphological phenotype resulting from oxidative damage to membrane lipids. Ferroptosis induction has been shown to be effective in treating human cancers that rely on lipid peroxidation repair pathways. Nuclear factor erythroid 2-related factor 2 (Nrf2) can control the regulatory pathways of ferroptosis, which involve genes associated with glutathione biosynthesis, antioxidant responses, and lipid and iron metabolism. Resistant cancer cells often utilize Nrf2 stabilization by Keap1 inactivation or other somatic alterations in the genes from the Nrf2 pathway, which can confer resistance to ferroptosis induction and other therapies. However, pharmacological inactivation of the Nrf2 pathway can sensitize cancer cells to ferroptosis induction. Inducing lipid peroxidation and ferroptosis through regulating the Nrf2 pathway is a promising strategy for enhancing the anticancer effects of chemotherapy and radiation therapy in therapy-resistant human cancers. Despite promising preliminary studies, clinical trials in human cancer therapy have not yet been realized. A deeper understanding of their exact processes and efficacies in various cancers remains unsolved. Therefore, this article aims to summarize the regulatory mechanisms of ferroptosis, their modulation by Nrf2, and the potential of targeting Nrf2 for ferroptosis-based cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Frey syndrome (FS) is a typical late complication following parotidectomy. Parotid surgery without proper coverage or reconstruction of exposed parotid parenchyma may contribute to the development of FS. Therefore, this study compared the closure versus the non-closure of exposed parotid parenchyma in the occurrence of FS., Methods: This study included 195 patients with parotid lesions who underwent partial or superficial parotidectomy plus closure or non-closure of exposed parotid parenchyma, both with the application of fibrin glue. Two surgical methods of closure and non-closure were allocated to patients without randomization and blinding processes. The primary outcome was FS, and the second outcome was other complication rates., Results: The closure and non-closure of exposed parotid parenchyma were performed in 102 and 93 patients, respectively. Early postoperative complications occurred with temporary events: transient facial weakness, 32 (16.4%); hematoma, 13 (6.7%); and wound infection, 2 (1.0%), without statistical difference between the two groups (P > 0.1). However, sialocele occurred in the non-closure group (n = 19) more than in the closure group (n = 7) (P = 0.005). In the first postoperative year, decreased sensation and local pain were found in 16 patients (8.2%) and 9 patients (4.6%), respectively, with no statistical difference between the two groups (P > 0.1). FS was found more in the non-closure group (n = 19, 20.4%) than in the closure group (n = 4, 3.9%) (P < 0.001)., Conclusion: The closure of exposed parotid parenchyma and covering fascia is preferred over the non-closure to prevent FS., Competing Interests: Declaration of Competing Interest The author declares no conflict of interest., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Ferroptosis is a recently identified type of regulated cell death characterized by lipid peroxidation and redox-active iron accumulation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial regulator of genes involved in glutathione biosynthesis, antioxidant responses, lipid metabolism, and iron metabolism, contributing to the evasion of ferroptosis. Inhibiting the Nrf2 pathway has been shown to sensitize cancer cells to ferroptosis. In head and neck cancer cells, we found that activation of the Nrf2-antioxidant responsive element pathway leads to ferroptosis resistance, and inhibiting this pathway reverses ferroptosis evasion. Our study suggests that modulating the Nrf2 pathway could be a promising strategy to overcome resistance in cancer therapy for head and neck cancer. Further research is required to investigate the potential of ferroptosis induction in therapy-resistant head and neck cancer. Targeting Nrf2 through ferroptosis-based cancer therapy may be a novel and effective approach to reverse the resistance of head and neck cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Gland-preserving surgery is often used for benign tumours in the parotid gland. Partial superficial parotidectomy via a periauricular incision may bring satisfactory cosmetic outcomes but the disease control outcome remains unrevealed. This study evaluated functional and disease control outcomes after gland-preserving surgery via periauricular incision for pleomorphic adenoma of the parotid gland., Methods: This longitudinal study included 248 consecutive patients with parotid pleomorphic adenoma who underwent the preservation of most normal parotid tissues and the facial nerve combined with the en-bloc resection of tumours via periauricular incision. Postoperative complications, subjective satisfaction, salivary function, and tumour recurrence were assessed in each patient. The secretory function of the salivary gland was measured using salivary scintigraphy at 6 months after surgery, and ultrasonography was regularly followed., Results: Median tumour size was 2.5 cm (range, 0.8-5.2 cm) and median operation time was 55 min (range, 39-88 min). All tumours were safely removed by gland-preserving surgery via periauricular incision without extension to Blair or hairline incision and tumour spillage. Temporary and permanent paralysis of the facial nerve was 14 (5.6%) and none of the study patients, respectively. Postoperative complications were minor and Frey's syndrome was found in 6 (2.4%) patients. The Secretary function of the affected gland was equal to that of the unaffected gland. No patients had a recurrence for a median follow-up of 78 months (range, 24-126 months)., Conclusions: Functional gland-preserving surgery via periauricular incision can treat pleomorphic adenoma in the parotid gland with satisfactory functional, cosmetic, and disease control outcomes., Competing Interests: Declaration of competing interest The author declares no conflict of interest., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: Sarcopenia may result in negative outcomes in patients with cancer, but its impact on surgical and oncological outcomes in older adult patients with head and neck squamous cell carcinoma (HNSCC) has not been systematically studied. This study evaluated the clinical impact of sarcopenia on postsurgical and oncological outcomes in older adult patients with HNSCC., Methods: This is a prospective study of 190 consecutive HNSCC patients aged ≥65 years who underwent curative surgery at a tertiary referral hospital. Sarcopenia was determined from measurement of the cross-sectional area of skeletal muscles at the level of the third lumbar vertebra on pretreatment images of whole body 18 F-fluorodeoxyglucose positron emission tomography/computed tomography. Primary outcomes were early complications and overall survival. Factors of early complications and readmission were identified using binary logistic regression analyses, and factors of overall survival and disease-free survival were identified using univariate and multivariate Cox proportional hazards regression analyses., Results: Pretreatment sarcopenia were found in 64 (33.7%) patients. In multivariate analysis, sarcopenia and N classification were significantly associated with early complications, while sarcopenia and T classification were associated with readmission. Independent factors of overall survival outcomes were age, sarcopenia, and extranodal extension (all P < .005). Sarcopenia was also an independent factor predictive of disease-free survival outcome (P < .001). Sarcopenia was associated with a 3.2-fold increase in the early complication rate and 4.5-fold increase in mortality in older adult surgical patients with HNSCC., Conclusion: Sarcopenia may predict early complications and survival after curative surgery in older adult patients with HNSCC., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Pre- and post-treatment 18 F-FDG PET/CT may have a prognostic role in human cancers. 18 F-FDG PET/CT after primary surgery for head and neck cancer might also predict survival. Therefore, we evaluated the prognostic value of post-treatment 18 F-FDG PET/CT in primary surgical patients with advanced-stage head and neck squamous cell carcinoma (HNSCC)., Materials and Methods: This prospective study involved 225 patients with previously untreated advanced-stage HNSCC who underwent primary surgery with or without postoperative radiotherapy or chemoradiotherapy. The patients also had 18 F-FDG PET/CT scanning at a median 6 months after surgery. Post-treatment 18 F-FDG PET/CT was considered positive, based on interpretation by experienced nuclear medicine physicians with integrating clinical information. Positive and negative predictive values (PPV and NPV) for positive 18 F-FDG PET/CT in association with recurrence were calculated. Predictors for positive post-treatment 18 F-FDG PET/CT were evaluated using binary logistic regression. Survival analysis was performed using Cox proportional hazard regression analysis., Results: PPV and NPV for post-treatment PET/CT for overall recurrence were 75.8% and 98.7%, respectively. A positive post-treatment PET/CT was an independent predictive factor for overall and disease-free survival (both P < 0.001). Five-year overall survival rates for patients with positive and negative PET/CT were 48.1% and 92.3%, respectively. Corresponding 5-year disease-free survival rates were 22.5% and 82.4%, respectively. Perineural invasion, positive resection margin, positive pathological node, and extranodal extension were the independent predictors of positive 18 F-FDG PET/CT (all P < 0.05)., Conclusions: Post-treatment 18 F-FDG PET/CT predicts survival and recurrence in patients undergoing curative surgery for advanced-stage HNSCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Soft tissue sarcomas of the head and neck (HNSTS) show various histological types and clinical behaviour. Recently, the 8th edition of the American Joint Committee on Cancer (AJCC) proposed a staging system for HNSTS independent of other body soft tissue sarcomas, which requires validation. Therefore, we evaluated the prognostic factors for the survival of HNSTS patients through a comparison between previous and current AJCC staging systems., Materials and Methods: This study involved 135 consecutive HNSTS patients who underwent primary surgery, chemoradiotherapy or chemotherapy. Patients were grouped into staged (S) and not staged (NS) cancer according to the AJCC 8th edition staging. Cox proportional-hazard regression analyses were used to identify factors associated with overall survival (OS), and progression-free survival (PFS) in all, S or NS patients., Results: Median follow-up period was 75 months and the 5-year OS and PFS rates of all patients were 67.8% and 53.4%, respectively, which was similar between S and NS groups. Age, tumour size and grade, overall stage (7th edition) and resection margin were the significant prognostic factors for OS and PFS in all patients and NS group (all P < 0.05), whereas positive resection margin was the only significant factor for OS and PFS in the S group (P < 0.001). While OS was poorly discriminated among different 8th edition T-categories, different 7th edition showed good discrimination among overall stages in all patients and the NS group., Conclusion: The revised staging system may not provide an improved risk stratification for survival of HNSTS patients., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Neutrophil-to-lymphocyte ratio (NLR), may predict treatment response and outcomes in some human malignancies. However, NLR has rarely been examined in older patients with head and neck squamous cell carcinoma (HNSCC). This study evaluated factors, including pre-treatment evaluation tests, predictive of mortality in older patients with HNSCC., Methods: This study prospectively enrolled 233 consecutive HNSCC patients aged 65 years or older. Pre-treatment evaluations included patient demographics, comorbidity, body weight loss, voice handicap index, dysphagia, Beck's depression inventory, comprehensive geriatric assessment, and circulating biomarkers. Cumulative incidence and cause-specific hazard functions were used to analyse the risk factors for overall mortality (OM), cancer mortality (CM), and non-cancer mortality (NCM)., Results: Multivariate analyses showed that age, performance scale, NLR, and nodal stage were independent predictors of OM and CM (all P < .05). Age, body weight loss, frailty, and NLR were independent predictors of NCM (all P < .05). Older age ≥ 75 years and NLR showed strong association with all OM, CM, and NCM (all P < .05). NLR >2.5 was related to a higher risk of OM (hazard ratio [HR] = 1.77, 95% confidence interval [CI]: 1.05-2.97, P = .031), CM (HR = 1.89, 95% CI: 1.09-3.29, P = .023), and NCM (HR = 6.29, 95% CI: 2.16-18.37, P = .001)., Conclusion: Cancer and non-cancer mortalities among older patients with HNSCC may be predicted by several clinical and haematological data. NLR might be used as a circulating prognostic marker for mortality in older patients with HNSCC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Diminished skeletal muscle mass (SMM) is a reliable marker of poor survival outcomes in patients with cancer. SMM or body composition is generally assessed at the third lumbar vertebra (L3) by abdominal computed tomography (CT) scans, not routinely evaluated in patients with head and neck squamous cell carcinoma (HNSCC). Therefore, we evaluated the effectiveness of head and neck CT images to assess SMM in patients with HNSCC for predicting their overall survival., Materials and Methods: SMM was assessed in 305 consecutive patients with stage III-IV HNSCC by measuring the cross-sectional area (CSA) at the third lumbar and cervical (C3) vertebrae levels. A formula for predicting the L3 SMM was established using linear regression analysis obtained from C3 CSA and other clinical factors. The actual SMM CSAs measured at L3 level and those obtained from the prediction model were compared using correlation analysis. The predictive power of our formula for estimating overall survival was compared using C-index., Results: Median SMM CSAs at the L3 and C3 levels were 174.5 cm 2 and 56.3 cm 2 , respectively, and were not strongly correlated (adjusted R 2  = 0.421). Prediction model 2 included the strongest predictive factors including sex, age, weight, and C3 SMM CSA, and significantly increased the L3 SMM correlation power (adjusted R 2  = 0.721). The C-index of the prediction model was 0.713 (95% confidence interval 0.692-0.747)., Conclusions: Head and neck CT imaging might be useful to estimate L3 SMM and predict overall survival in HNSCC patients., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: Tumor multifocality or bilaterality is associated with increased risk of papillary thyroid carcinoma (PTC) recurrence. However, its prognostic value in clinical outcomes remains controversial. This study aimed to evaluate the association of multifocality or bilaterality with recurrence and survival after total thyroidectomy., Methods: This was a retrospective study of 2390 consecutive patients with pathologically confirmed PTC who underwent total thyroidectomy. Multifocality and bilaterality were decided based on the final pathology results, that is, if there were two or more tumor foci and bilateral location, respectively. Primary outcomes were recurrence-free survival (RFS). Cox proportional hazards regression analyses were used to assess the associations of multifocality, bilaterality, and other clinicopathological factors with RFS., Results: Multifocal and bilateral PTC were found in 892 (37.3%) and 593 (24.8%) patients, respectively. Multivariate analyses showed that multifocality, lymphovascular invasion, N category, and number of positive lymph node (>5) were significant independent variables predictive of RFS (all P < 0.05). Multifocality was associated with adjusted hazard ratios for RFS of 1.93 (95% confidence interval = 1.33-2.80; P = 0.001). In a subset analysis, the prognostic value of multifocality was found to be significant in those patients with PTC > 1 cm, but not in papillary thyroid microcarcinoma., Conclusions: Tumor multifocality is an independent risk factor of PTC recurrence after total thyroidectomy. This indicate a more progressive state of disease, being included in risk stratification., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: Current guidelines recommend chest computed tomography (CT) with locoregional CT/magnetic resonance imaging for patients with head and neck squamous cell carcinoma (HNSCC), and 18 F-fluorodeoxyglucose (FDG) positron-emission tomography (PET)/CT is suggested for stage III-IV patients. However, whole body screening with 18 F-FDG PET/CT may provide better detection of distant metastases and synchronous cancer than conventional imaging. We evaluated the utility of 18 F-FDG PET/CT in detecting distant metastasis and synchronous cancer., Methods: This prospective study enrolled 740 consecutive patients with previously untreated HNSCC diagnosed between September 2010 and December 2015. Synchronous cancer was histologically confirmed and distant metastases were confirmed by biopsy or serial imaging follow-ups. McNemar test was used to compare the true-positive detection rates of chest radiography (CXR) + head and neck CT (hnCT) (A) versus 18 F-FDG PET/CT (C) and chest CT + hnCT (B) versus 18 F-FDG PET/CT., Results: Distant metastases and synchronous cancer were found in 23 (3.1%) and 55 (7.4%) patients, respectively. A, B, and C detected distant metastases in 10 (1.3%), 19 (2.6%), and 21 (2.8%) patients, respectively. The absolute differences were 1.5% (A versus C, P = 0.003) and 0.3% (B versus C, P = 0.687). A, B, and C detected synchronous cancer in 15 (2.0%), 22 (2.9%), and 36 (4.9%) patients, respectively. The absolute differences were 2.8% (A versus C, P < 0.001) and 1.4% (B versus C, P = 0.013)., Conclusions: 18 F-FDG PET/CT detected more distant metastases and synchronous cancer than CXR + hnCT and more synchronous cancer than chest CT + hnCT., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: The recently published 8th edition of the American Joint Committee on Cancer (AJCC) tumour-node-metastasis (TNM) staging system was significantly updated following the thyroid cancer-related guidelines to provide better predictability of survival but not focus on recurrence. Therefore, we compared the predictive values of the 7th and 8th editions of the AJCC staging systems for recurrence-free survival (RFS) and overall survival (OS) after thyroidectomy for papillary thyroid carcinoma (PTC)., Methods: This retrospective study included 2930 patients who underwent thyroidectomy and neck dissection for previously untreated PTC between 2006 and 2014. TNM stage was defined according to 7th and 8th editions. Univariate and multivariate Cox proportional hazard regression analyses were used to identify associations between variables and RFS or OS. Multivariate models for the AJCC TNM stages were adjusted for clinical and pathological variables., Results: A significant number of patients classified as T3 with overall TNM stages II-IV in the AJCC 7th edition were down-staged in the 8th edition. Unadjusted T classification and overall TNM staging in both the 7th and 8th editions were significantly associated with RFS and OS rates (P < 0.001). After adjustment for clinicopathological factors, the overall TNM stage according to the AJCC 8th edition, but not the 7th edition, remained significantly associated with RFS and OS (P < 0.05), with better predictability of recurrence and survival, in patients with PTC., Conclusions: The 8th edition AJCC staging system down-staged a large proportion of PTC patients, resulting in better predictability of recurrence and survival compared to the previous staging system., Condensed Abstract: This study compared the abilities of the 7th and 8th edition AJCC staging systems to predict recurrence and overall survival in 2930 patients with papillary thyroid carcinoma. The updated guidelines down-staged a large proportion of patients, resulting in better prediction of recurrence and survival than the previous staging system., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: Adenoid cystic carcinoma (AdCC) in the salivary gland shows a high rate of distant metastasis, which is related to the resulting poor prognosis. We therefore examined the role of pretreatment 18 F-FDG PET/CT for prediction of distant metastasis, recurrence/progression, and survival in AdCC., Methods: This study included 52 patients who underwent pretreatment 18 F-FDG PET/CT scanning and subsequent treatments for AdCC. Maximum, mean, and peak standardized uptake value (SUV max , SUV mean , and SUV peak ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured on 18 F-FDG PET/CT. Univariate and multivariate Cox proportional hazards regression analyses were used to identify associations between the quantitative measurements of 18 F-FDG PET, and progression-free survival (PFS), distant metastasis-free survival (DMFS), and disease-specific survival (DSS)., Results: Distant metastases were found in 20 (39%) patients: 6 (12%) at initial diagnosis and 14 (27%) during the median follow-up of 72 months after treatment. Univariate analyses showed that all the 18 F-FDG PET parameters of SUV max , SUV mean , SUV peak , MTV, and TLG were significantly associated with overall PFS, DMFS, and OS (all P < .05). After controlling for clinicopathological variables, SUV max remained an independent factor predictive of PFS (P = .001), while MTV and TLG were independent predictors of DMFS (P = .009) and DSS (P = .017). Patients with MTV > 14.8 mL showed a 5.9-fold higher risk of distant metastasis and a 4.2-fold higher risk of disease-specific death than those with a lower MTV., Conclusions: Quantitative measurements using 18 F-FDG PET/CT are useful for predicting tumor progression, distant metastasis, and survival in patients with AdCC., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: Wound healing is generally faster and associated with less scarring in the oral mucosa than in the skin. Although rarely studied, oral mucosa equivalents may contribute to rapid, scarless cutaneous wound healing. Therefore, we examined the potential utility of our newly developed oral mucosal cell sheet in skin wound healing., Materials and Methods: Oral mucosa and skin samples were obtained from surgical patients and Sprague-Dawley rats. Keratinocytes and fibroblasts were primarily cultured for in vitro cell expansion. Mucosa and skin equivalents were produced with a mixture of cultured fibroblasts and autologous fibrin from plasma and seeding keratinocytes. Mucosal and skin cell sheets were transplanted in full-thickness excisional wounds of rat skin with control wounds. Gross, histological, and molecular characteristics of wound healing according to different postsurgical days were compared in control and cell sheet-covered wounds., Results: Keratinocytes and fibroblasts derived from the oral mucosa were cultured faster than those derived from the skin. The in vitro-engineered oral mucosa and skin equivalents were successfully produced using complete autologous mucosa or skin and plasma fibrin, showing similarity to the histological characteristics of the skin or mucosa. In the in vivo rat model, the oral mucosal and skin cell sheet promoted wound healing with early wound closure and less scarring. The cell sheet-treated wounds showed lower TGF-β1, α-smooth muscle actin, and fibronectin mRNA expression than the control wounds., Conclusions: The oral mucosal cell sheet demonstrated in vivo tissue plasticity through good adaptation to skin wounds, contributing to accelerated and scarless healing., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: Severe oral mucosal and tissue defects can lead to pain, infection, and later undesirable healing of scarring and adhesion, resulting in a poor quality of life. In vitro-engineered oral mucosal equivalents for covering such defects are an alternative to avoiding the donor site morbidity of conventional skin or tissue grafts. We examined the efficacy of our newly developed three-dimensional mucosal cell sheets in an in vivo tongue wound model mimicking the surgical extirpation of tongue cancer., Materials and Methods: Small oral mucosal and autologous fibrin samples were obtained from surgical patients and Sprague-Dawley rats. The fibrin was mixed with fibroblasts and seeded with keratinocytes that had been primarily cultured for in vitro cell expansion. The three-dimensional autologous cell sheets, cultured in air-lift interface inserts, were transplanted into deep wounds of the rat ventral tongue. Gross and microscopic findings of the postsurgical wounds were compared between wound control and cell sheet groups., Results: The cell sheets were flexible, expandable, and easy to transfer, and had histological characteristics similar to that of the normal oral mucosa, with high p63 positivity. They promoted oral wound healing with earlier re-epithelialization and less fibrosis than that in the wound control. The cell sheet-healed tongue had similar histology to that of a normal tongue., Conclusions: Our engineered cell sheets have potential applicability for the rapid healing of oral mucosal and soft tissue defects, without scarring, adhesion, and functional deficits., Condensed Abstract: The efficacy of in vitro-engineered mucosal equivalents, using completely autologous mucosa and plasma, was examined. Transplantation of the autologous cell sheets into deep wounds of the rat ventral tongue promoted oral wound healing with earlier re-epithelialization and less fibrosis than that in controls. Healed and normal tongues showed similar histology., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Human papillomavirus (HPV) (+) tonsil squamous cell carcinoma (TSCC) responds well to concurrent chemoradiation therapy (CCRT) and demonstrates a favorable prognosis. However, cases of HPV (+) TSCC-related death remain unresolved. We evaluated the distribution and prognostic value of inflammatory cells in HPV (+) TSCC., Methods: We reviewed the medical records of 53 patients who were diagnosed with TSCC. HPV (+) TSCC was confirmed using HPV DNA PCR and immunohistochemical p16 overexpression. The numbers of CD4 (+), CD8 (+), and CD68 (+) stained cells were used to evaluate peritumoral lymphocyte infiltration. Patients were divided into two groups according to the mean numbers of stained cells and the mean ratios of each cell type., Results: HPV (+) was noted in 39 patients. During the follow-up period, 27 patients had no evidence of disease, 2 patients showed disease, and 10 patients died of disease. In this group, advanced T and N stages were not related to overall or disease-specific survival outcomes. The overall survival rate was affected by a high CD68 (+) (HR=19.8; P=0.040) and low CD8/CD4 ratio (HR=7.7, P=0.025). The disease-specific survival rate was affected by a high number of CD68 (+) cells (HR=15.2; P=0.03) and low CD8 (+)/CD4 (+) ratio (HR=3.3; P=0.04)., Conclusions: The number of CD68 (+) cells and the distribution of cytotoxic or immunosuppressive T lymphocytes could be determining factors for CCRT outcomes in HPV (+) TSCC patients., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: We examined the effect of extranodal extension (ENE) and its thickness (ENET) of metastatic lymph node (LN) on the disease course of patients with head and neck squamous cell carcinoma., Methods: Data from 438 patients who were initially treated surgically at our center was retrospectively analyzed. ENE presence and ENET were examined in metastatic LN from each patient. Clinicopathologic characteristics, recurrence, and survival were then compared., Results: Of 438 patients, 219 (50%) showed positive nodal status, and ENE was identified in 84 (19.6%). Forty-five of 219 (20.5%) node-positive patients were classified with ENET ≥ 2 mm, which was associated with an increase in both the size and number of positive LN, bilateral cervical involvement, and a higher LN ratio. ENE-positive patients had a higher risk of recurrence and a lower overall survival rate; however, multivariate analysis failed to identify a significant difference in cancer-specific survival (CSS) between those with and those without ENE. On the contrary, ENET ≥ 2 mm was significantly associated with a poor CSS, even in multivariate analysis., Conclusion: ENET ≥ 2 mm might be a complementary prognostic marker in CSS estimation for ENE positivity., (Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: This study examined prognostic factors in patients with head and neck squamous cell carcinoma with advanced neck disease., Study Design: The records of 191 patients with previously untreated head and neck squamous cell carcinoma and metastatic cervical lymph node (LN) >6 cm (cN, n = 70) and 3.01 to 6 cm (control, n = 121) in the greatest dimension were reviewed. Univariate and multivariate analyses were used to identify factors associated with disease-free survival (DFS) and locoregional control (LRC)., Results: In the cN3 group, independent variables for DFS were age, active drinking, LN size, and extranodal extension (P < .05), and that for LRC was age (P = .025). In the control group, independent variables for DFS were tumor location and differentiation and LN bilaterality (P < .05), and that for LRC was LN bilaterality (P = .011)., Conclusions: The survival of cN3 patients is affected by host and nodal characteristics including age, drinking, nodal size, and extranodal extension., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Central compartment lymph node metastasis (CLNM) in patients with laryngeal, hypopharyngeal, or cervical esophageal squamous cell carcinoma is associated with unfavorable clinical outcomes, but cannot be reliably detected using computed tomography (CT)/magnetic resonance imaging (MRI). Therefore, we assessed the clinical utility of using (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT to identify CLNM in these patients., Patients and Methods: A total of 62 patients were preoperatively evaluated using (18)F-FDG PET/CT and CT/MRI. Histopathologic analysis of the dissected neck tissues was used as the gold standard for assessing these imaging techniques. The diagnostic value of (18)F-FDG PET/CT for detecting CLNM was calculated and compared with CT/MRI. Univariate and multivariate analyses were utilized to determine the factors predictive of CLNM., Results: Of the 62 patients in the study cohort, 12 (19%) had CLNM. Compared with histology, both (18)F-FDG PET/CT and CT/MRI demonstrated low sensitivity for detecting CLNM (58% vs 42%, respectively, P = 0.625). The specificities of (18)F-FDG PET/CT and CT/MRI for the detection of CLNM were 88% and 90%, respectively (P = 1.000). Univariate and multivariate analyses showed that clinical metastasis to any cervical lymph node was significantly associated with CLNM (P = 0.018)., Conclusions: Neither (18)F-FDG PET/CT nor CT/MRI is a sensitive diagnostic imaging modality for detecting CLNM. Routine elective central compartment dissection or radiotherapy should be advocated for the treatment of these patients., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: Human papillomavirus (HPV), a causative agent of oropharyngeal squamous cell carcinoma (SCC), may be detected in metastatic cervical lymph nodes (MCNs). We investigated whether HPV and p16 expression in MCNs can help identify oropharyngeal primaries in patients with cervical lymph node metastases from an unknown primary tumor (CUP) and predict their survival outcomes., Materials and Methods: SCC MCNs of 58 patients with CUP were assayed for HPV by in situ hybridization and for p16 and p53 expression by immunohistochemistry. The presence of HPV and p16 in MCN was correlated with oropharyngeal tumor location and prognosis., Results: Oropharyngeal primaries were found in 20 patients. The sensitivity and negative predictive value (NPV) of HPV for oropharyngeal localization were 90.0% and 92.6%, respectively, and the sensitivity and NPV of p16 were 80.0% and 86.2%, respectively. Multivariate analyses showed that the location of the largest MCN (P=0.035) and HPV (P=0.004) were independent predictors of oropharyngeal tumors. Multivariate analyses showed that p16 expression was an independent predictor of disease-free survival (P=0.030; hazard ratio (HR)=0.286; 95% CI, 0.092-0.887) and that p53 expression (P=0.017; HR=3.154, 95% CI=1.288-8.103) and extracapsular extension of MCN (P=0.010; HR=3.924, 95% CI=1.387-11.097) were independent predictors of overall survival., Conclusion: Detection of HPV and p16 may help identify hidden oropharyngeal primaries in CUP patients and predict their survival outcomes., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: Significant laryngeal edema (SLE) after radiotherapy for squamous cell carcinoma of the larynx and hypopharynx may be associated with upper airway obstruction or tumor recurrence. We assessed the risk factors predictive of SLE and those differentiating tumor recurrence from SLE., Patients and Methods: We evaluated 127 patients with laryngohypopharyngeal squamous cell carcinomas who were primarily treated with radiotherapy with/without chemotherapy, had no previous major head and neck surgery, and underwent laryngoscopic examinations after radiotherapy. SLE was defined as RTOG grades ≥ 2 and patient characteristics and imaging, treatment and survival results were compared in patients with and without SLE., Results: Of the 127 patients, 56 (44%) had SLE. Univariate analyses showed that tumor location, T and N classifications, overall stage, pathologic differentiation, and chemotherapy were significantly predictive of SLE (P<0.05). Multivariate analysis revealed that T classification remained an independent predictor of SLE (T1 vs. T2-4; odds ratio=5.070, 95% confidence interval=1.999-12.857; P=0.001). Twenty-seven (21%) patients had tumor recurrences, diagnosed by PET/CT (sensitivity 88%; specificity 92%) and CT (sensitivity 68%; specificity 88%). Twenty-seven patients with severe SLE were treated but only 9 (33%) had improvement. Tumor recurrence rate was higher (39% vs. 7%, P<0.001) and 3-year overall survival rate lower (54% vs. 87%, P<0.001) in patients with than without SLE., Conclusion: Patients with T2-4 laryngohypopharyngeal cancers are at higher risk of SLE development and tumor recurrence after radiotherapy that can be properly detected by (18)F-FDG PET/CT., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The issue of whether aberrant expression of β1-integrin is associated with cancer progression and development of resistance to cytotoxic therapy is of considerable interest. Studies to date have shown that the anchorage-independent survival of cancer is attributed, in part, to epithelial-to-mesenchymal transition (EMT). Here, we have reported a novel alternative mechanism of anchorage-independent survival of cancer cells. Cell lines derived from head and neck cancer patients (AMC-HN-3 and AMC-HN-9) and the well-known EMT cancer cell line, MDA-MB231, were examined. The EMT features of AMC-HN-9 cells were comparable to those of MDA-MB231, whereas AMC-HN-3 cells showed no EMT characteristics. Although the pattern and degree of β1-integrin expression were similar in all three cell lines, sensitivities of the cells to β1-integrin knockdown with small interfering RNA (siRNA) were different. Cancer cells with no EMT features underwent cell death to a more significant extent following β1-integrin silencing than those with EMT. Intriguingly, we observed reactive activation of the p53-p21 pathway after β1-integrin silencing in AMC-HN-9 cells lacking an apparent cell death response. Simultaneous knockdown of wild-type p53 and β1-integrin in this cell line promoted cell death. Our data collectively indicate that β1-integrin-related cell death is closely associated with EMT phenotypes and activation of the p53-p21 pathway is partly involved in the acquisition of resistance to apoptosis induced by β1-integrin silencing. Further clarification of the mechanisms underlying p53 integration with β1-integrin signaling may facilitate the development of novel anti-cancer strategies., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We assessed the risk factors associated with surgical site infection (SSI) in 697 patients who underwent major oncological surgery for head-and-neck cancer (HNC). SSIs within 30days were classified as incision, space, or leakage/fistula. Preoperative and operative risk factors for SSIs were assessed by univariate and multivariate analyses. Of these 697 patients, 128 (18.4%) had SSIs. Univariate analysis showed that SSIs were associated with tumor location, advanced tumor stage, smoking and alcohol habits, diabetes, history of prior radiotherapy or chemotherapy, anemia, hypoalbuminemia, mandible cutting, flap reconstruction, tracheotomy, clean-contaminated wounds, blood transfusion, and operation times. Multivariate analysis showed that independent risk factors for developing SSIs were oral cavity cancer (odds ratio [OR]: 6.06, 95% confidence interval [CI]: 1.209-30.378), history of prior radiotherapy (OR: 2.85, 95% CI: 1.172-6.931), tracheotomy (OR: 9.757, 95% CI: 2.609-36.491), and clean-contaminated wounds (OR: 13.953, 95% CI: 2.231-87.275). In contrast, thyroid malignancy was an independent predictor of not developing SSI (OR: 0.152, 95% CI: 0.035-0.658). High-risk patients of SSIs after major HNC surgery are predicted. Preventive measures or close monitoring in these patients may be required to reduce the likelihood of postoperative SSIs. Our data may help identify and properly manage high-risk patients., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We evaluated the clinical utility of combined [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT), as well as CT and magnetic resonance imaging (MRI) in identifying nodal metastases in the contralateral neck in patients with head and neck squamous cell carcinoma (HNSCC). A total of 114 patients were preoperatively evaluated with PET/CT and CT/MRI. Histopathologic analysis from bilateral neck dissection tissues was used as the gold standard in assessing these imaging techniques. Of the 114 patients, 63 (55%) had neck metastases and 26 (23%) had contralateral neck metastases. On a per-level basis, FDG PET/CT was significantly more sensitive and accurate than CT/MRI in the ipsilateral (88% vs. 70%, P<0.01 and 93% vs. 89%, P<0.01, respectively) and contralateral (52% vs. 36%, P<0.01 and 91% vs. 90%, P=0.039, respectively) neck. PET/CT and CT/MRI were less sensitive in detecting contralateral than ipsilateral neck metastases due to the lower incidence of metastases and smaller nodes on the contralateral side. Combined PET/CT is superior to CT/MRI in detecting metastatic neck nodes in HNSCC patients. However, PET/CT may not abrogate the need for contralateral neck surgery or radiotherapy in these patients., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We evaluate whether p53-reactivating (p53RA) small molecules induce p53-dependent apoptosis in head and neck squamous cell carcinoma (HNSCC), a question that has not been previously addressed in head and neck cancer. PRIMA-1, CP-31398, RITA, and nutlin-3 were tested in four human HNSCC cell lines differing in TP53 status. Cell growth, viability, cell cycle progression, and apoptosis after treatment with p53RA small molecules individually or in combination with chemotherapeutic agents were assessed. Prominent p53 reactivation was observed in mutant TP53-bearing tumor cell lines treated with PRIMA-1 or CP-31398, and in wild-type TP53-bearing cell lines treated with nutlin-3. Cell-cycle arrest and apoptosis induced by p53RA small molecules were associated with upregulation of p21 and BAX, and cleavage of caspase-3. Nutlin-3 showed maximal growth suppression in tumor cells showing MDM2-dependent p53 degradation. High-dose treatment with p53RA small molecules also induced apoptosis in cell lines independent of p53 or MDM2 expression. In combination therapy, p53RA small molecules enhanced the anti-tumor activity of cisplatin, 5-fluorouracil, paclitaxel, and erlotinib against HNSCC cells. The p53RA small molecules effectively restored p53 tumor-suppressive function in HNSCCs with mutant or wild-type TP53. The p53RA agents may be clinically useful against HNSCC, in combination with chemotherapeutic drugs., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Targeting hypoxia-inducible factor-1 (HIF-1) active cells in tumors may be an excellent strategy to improve the outcome of radiation therapy. On the basis of the reported role of YC-1 as a HIF-1 inhibitor with anti-cancer activity, we tested the therapeutic efficacy of YC-1 against radioresistance in vitro. The AMC-HN3 cancer cell line, developed from squamous cell carcinoma of the larynx, was cultured under hypoxic conditions or in the presence of cobalt chloride. Both treatments induced nuclear accumulation of HIF-1alpha protein. Cells cultured under normoxic or hypoxic conditions with and without YC-1 treatment were irradiated and analyzed using flow cytometry and clonogenic assays. In the absence of YC-1 treatment, irradiation induced a greater cytotoxic effect in normoxic cells than in cobalt-treated cells. Treatment of cobalt-treated cells with YC-1 effectively inhibited HIF-1alpha expression, and enhanced the sensitivity of cells to radiation, decreasing the surviving fraction to that of normoxic cells. Flow cytometry confirmed these results, showing that the sub-G1 fraction was increased in YC-1-treated hypoxic cells after irradiation. Our results suggest that YC-1 treatment may be an effective therapeutic strategy for overcoming the radioresistance of HIF-1alpha-expressing, hypoxic cancer cells.

The purpose of this study was to evaluate the effect of neuromuscular electrical stimulation (NMES) in patients suffering from dysphagia following treatment for head and neck cancer. In a prospective, double blinded, randomized case control study between January 2006 and December 2007, 14 patients were randomized to 30min of NMES and 30min of traditional swallowing training for 5 days per week for 2 weeks (experimental group), and 12 patients were randomized to sham stimulation plus traditional swallowing training (control group). Effects were assessed using the clinical dysphagia scale (CDS), the functional dysphagia scale (FDS), the American speech-language-hearing association national outcome measurement system (ASHA NOMS) and the M.D. Anderson dysphagia inventory (MADI). Pretreatment evaluation showed no significant differences between the two groups for all parameters. Average changes of FDS score were 11.4+/-8.1 for the experimental group and 3.3+/-14.0 for the control group (P=0.039). CDS, ASHA NOMS and MADI showed some difference with treatment, but the changes were not significant (P>0.05). NMES combined with traditional swallowing training is superior to traditional swallowing training alone in patients suffering from dysphagia following treatment for head and neck cancer.

(18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) has been reported to identify primary tumors in patients with cervical metastases from cancer of unknown primary (CUP). However, few reports have assessed the use of combined FDG-PET/computed tomography (CT) in this setting. We therefore examined the utility of combined FDG-PET/CT in the detection of primary tumors and unrecognized metastases in these patients. Patients with previously untreated CUPs underwent head and neck CT and whole-body FDG-PET/CT before panendoscopy and guided biopsy. The diagnostic accuracy of CT and FDG-PET/CT in detecting primary tumors and cervical metastases was compared with that of histopathology. The ability of FDG-PET/CT to detect distant metastases was also tested. Of the 44 eligible patients, 16 had occult primary tumors in the head and neck. FDG-PET/CT was significantly more sensitive than CT for detecting primary tumors (87.5% vs. 43.7%, P=.016), but their specificity did not differ (82.1% vs. 89.3%, P=.500). Thirty-four of 44 patients underwent neck dissection; 67 of 182 dissected cervical levels had metastatic nodal diseases. On a level-by-level basis, FDG-PET/CT was significantly more sensitive than CT (94.0% vs. 71.6%, P<.001), but the two methods were equally specific (94.8% vs. 96.5%). FDG-PET/CT correctly detected distant metastases in 6 of 6 patients. Combined FDG-PET/CT is a useful screening method for primary tumor detection, accurate nodal staging, and distant metastases in patients with CUPs.

Tumor hypoxia is associated with poorer outcome in patients with head and neck carcinomas, but little is known about hypoxia biomarkers in oral tongue cancer. We evaluated whether hypoxia biomarkers and clinicopathologic variables were prognostic predictors in patients with T2-staged squamous cell carcinoma (SCC) of the oral tongue. Tissue microarrays were constructed from formalin-fixed tumor blocks of 43 patients with T2-staged tongue SCCs treated by surgical resection and neck dissection. Tissue samples were stained with monoclonal antibodies to hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, carbonic anhydrase (CA)-9, glucose transporter (GLUT)-1, and erythropoietin receptor (EPOR). Locoregional control and survival rates were calculated by the Kaplan-Meier method, and prognostic factors were calculated from uni- and multivariate analyses. Tumor thickness was correlated with expression of CA-9 and GLUT-1 and nodal classification was correlated with GLUT-1 expression. The nodal metastasis rate was 51%, and the 5-year locoregional control and disease-specific survival (DSS) rates were 59% and 69%, respectively. Univariate analysis showed that HIF-1alpha and EPOR expression were significantly related to DSS. Multivariate analysis showed that EPOR expression was an independent predictor of DSS (P=0.030). EPOR expression may be an independent predictor for DSS in patients with T2-staged SCC of the oral tongue.

Nongastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma, although generally indolent in nature, has variable and heterogeneous clinical course and biologic behavior. We have evaluated the clinical features and follow-up of patients with MALT lymphomas involving the head and neck in our institution. Forty-four new patients with MALT lymphomas arising in ocular adnexa (24 patients, group A) and other head and neck sites (20 patients, group B) of the salivary gland (13), thyroid gland (3) and other regions (4) were retrospectively analyzed. At initial diagnosis, 21 patients had solitary lesions (16/24 in the group A vs. 5/20 in the group B, P=.008); 23 had disseminated disease at multiple sites (11 patients) and/or lymph node involvement (15 patients: 3/24 in the group A vs. 12/20 in the group B, P=.025). Treatment consisted of local therapy, consisting of surgical resection and/or radiotherapy, in 34 patients and systemic chemotherapy with/without local therapy in 10 patients. Eight patients experienced tumor recurrence: four patients died of disease, two were alive with disease, and two were disease-free at last follow-up. With a mean follow-up of 46 months, the 5-year overall survival and relapse-free rates were 83% and 74%, respectively, which did not differ between the two groups (P>.5). Patients with MALT lymphomas of the head and neck are at relatively high risk for multifocal or lymph node involvement. Recurrence at prolonged times after therapy indicates the need for close long-term monitoring, and for prospective trials to prevent recurrence.

Endovascular treatments for carotid blowout syndrome (CBS) have been advocated by interventional neuroradiologists. We therefore retrospectively evaluated the efficacy of endovascular treatments of CBS in 16 patients with head and neck cancers (HNC). The clinical, treatment and outcome data were evaluated in 16 HNC patients with CBS, all of whom underwent permanent embolization or covered stent graft of the affected carotid artery. All patients received multimodal treatments, including radiotherapy (mean total dose, 78.5 Gy). CBS was caused by tumor carotid invasion in 8 patients, pharyngocutaneous fistula in 7, and laryngeal chondroradionecrosis in 1, with the external and common carotid arteries being the most common rupture sites. CBS was occluded by embolization or revascularized by covered stent placement. Immediate hemostasis was achieved in all patients; however, 7 patients had recurrent CBS, all of whom were retreated effectively by endovascular management. Three patients had strokes and four had extrusion of intervention materials from the infected wounds. Most patients died of tumor progression, with a mean survival time of five months from initial CBS; only two patients survived. Endovascular therapy, by both permanent occlusion and stent grafts, is effective in hemostasis of CBS but its long-term efficacy may not be high in these HNC patients.

There are few controlled studies on surgical approaches for excision of the submandibular gland (SMG). This study evaluated the benefits of a submental approach, compared with a conventional submandibular approach, for SMG resection. Twenty patients with benign SMG disorders, 12 with pleomorphic adenoma and eight with chronic sialadenitis with sialolithiasis, were resected using a submental (10) or submandibular (10) approach. The submental approach consisted of a horizontal incision on the submental skin and flap elevation to the gland, and the submandibular approach consisted of an incision along the skin crease overlying the SMG. Operation time, complications, hospital stay, cosmetic appearance and subjective satisfaction with the incision scar were compared between groups. The two groups were well matched in age, gender, marital status, and SMG disorders. Mean operation time, hospital stay and complication rates were comparable in the 2 groups. Mean patient satisfaction score was higher in the submental than in the submandibular group (8.8 vs. 5.4, P=.01), and the incision scar in the submental group was usually less visible. Compared with the submandibular approach, the submental approach can provide better cosmetic outcomes with no increases in operation time and complication rates.

The role of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in identifying bone metastases in patients with head and neck cancer is not clear. We compared the ability of FDG-PET and bone scintigraphy (BS) to detect bone metastases in patients with upper aerodigestive tract (UADT) malignancies. Patients with histologically confirmed malignancies in the UADT underwent both FDG-PET and BS at initial staging or follow-up. The two methods were compared in patients and in seven skeletal regions. Maximum standard uptake value (SUVmax) on PET was calculated in each lesion and compared between true- and false-positive lesions. This study included 564 eligible patients, of whom 17 had bone metastases. The spine was the most frequently involved site, followed by the lungs and liver. Both FDG-PET and BS had high specificity, accuracy, and negative predictive values for detecting bone metastases (>95% each), and the two methods did not differ in sensitivity, specificity, and predictive values (P>0.05). Both FDG-PET (n=15) and BS (n=14) yielded a significant number of false-positive results, which could be corrected by further work-ups and follow-up imaging. Compared with true-positive lesions, the false-positive lesions on FDG-PET were usually single (86.7% vs. 12.5%, P<0.001) and had lower mean SUVmax (2.4 vs. 5.6, P<0.001). FDG-PET is not more accurate than BS for detecting bone metastasis in patients with UADT cancer. Positive findings on FDG-PET or BS require further confirmation.

The combination of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) has been reported to be more accurate than CT or PET alone in a preoperative setting. We compared the diagnostic utility of preoperative PET/CT, PET and CT/MRI in 167 patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), of whom 104 underwent FDG PET and 63 underwent combined PET/CT with all receiving CT/MRI. These preoperative PET, PET/CT, and CT/MRI results were reviewed and their accuracies were compared in patients in whom diagnosis was confirmed histopathologically. Age, sex, primary sites and stage, and nodal involvement were comparable between two groups. The accuracy of PET and PET/CT for detecting primary tumors and cervical metastases was comparable, but significantly higher than that of CT/MRI (98%-97% vs. 86-88% for primary; 92%-93% vs. 85%-86% for neck on a level-by-level basis; P<.05). PET and PET/CT gave false negative results: in 2 (2%) and 2 (3%) patients for primary tumors; in 6 (6%) and 3 (5%) patients for neck metastases, respectively. PET and PET/CT also gave false-positive results for cervical metastases in 5 (5%) and 4 (6%) patients, respectively. Compared with PET alone, preoperative FDG PET/CT may not yield significantly improved diagnostic accuracy in patients with HNSCC. Moreover, despite their high accuracy, PET and PET/CT may not abrogate the need for conventional imaging and pathologic staging based on primary resection and neck dissection.

Few studies have used positron emission tomography (PET) to identify metastases or simultaneous thoracic malignancies in patients with head and neck cancer (HNC). We retrospectively investigated the role of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in detecting thoracic malignancies in patients with previously untreated HNC. Patients (n=86) with HNC and intrathoracic lesions on PET were divided into those who had abnormal FDG uptake in the mediastinum (n=29), lungs (n=34), or both (n=23). Whole body PET and chest computed tomography (CT) results were blindly reviewed and scored by two observers. The accuracy of FDG PET and CT were drawn from patients in whom diagnosis was confirmed, by histopathology or follow-up imaging, and risk factors for thoracic malignancy were analyzed. Malignancy was suspected in 23 of 86 patients (27%) with FDG uptake. Most of the lesions (83%) with abnormal FDG uptake were benign, with thoracic malignancy confirmed in 15 patients (17%). The overall sensitivity, specificity, and accuracy of FDG PET for intrathoracic malignancy in these patients were 80%, 85%, and 84%, respectively. The likelihood of thoracic malignancy in the HNC patients was associated with high FDG uptake of thoracic lesions. FDG PET may reveal lung and mediastinal malignancies with high accuracy in patients with HNC. The thoracic staging by FDG PET may be helpful in therapeutic planning for these patients.

Although the practice of neck dissection has greatly advanced from radical to function-preserving surgery, the impact of the sensory nerve-preserving neck surgery on the pain and quality of life (QOL) of patients has received little study. We evaluated neck morbidity and its impact on QOL associated with selective or modified radical neck dissection with or without preservation of cervical root branches. We conducted a retrospective cohort study comparing 24 patients who had their cervical root branches preserved to 29 patients whose root branches were removed during neck dissection. The spinal accessory nerve was preserved and sex, age, pathologic status, side and extent of neck dissection, and radiotherapy were comparable between groups. The groups were compared based on sensory and motor functions of the neck and shoulder and questionnaires on depression and QOL at follow-up of mean 18.7 (range 12-34) months after surgery. The nerve-preserved patients showed a low incidence and severity of neck and shoulder pain compared to the nerve-removed subjects (p<.05). Loss of sensation was more frequently experienced in the nerve-removed group on the earlobe and the lateral neck of the operated side (p<.05). Depression and QOL scores were higher in the nerve-removed group and significantly correlated with pain intensity. Preservation of the cervical root branches reduces postoperative pain as well as permanent anesthetic areas of the neck. This may also improve the mental state and QOL of patients undergoing neck dissection.