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Background: Second branchial cleft cyst (2nd BCC) is treated by complete excision. Conventional transcervical skin incision on the lesion may leave a prominent scar in the cosmetically sensitive area. The retroauricular hairline incision (RAHI) approach may maintain neurological, mobility, and cosmetic functions of the neck and face after excision. This study evaluated the clinical outcomes and disease control of scarless surgery via RAHI in 57 consecutive patients with 2nd BCC. Methods: The patients received the prospective evaluation of postoperative neurological, subjective pain, swallowing, neck motion, and cosmetic functions. Postoperative complications, subjective satisfaction, and recurrence were also assessed in each patient. Results: Excision was performed in all cases without injury to the facial nerve or other neurological complications and conversion to other incisions or approaches with a median operation time of 44 min. Complications were minimal, without dysphagia, neurological deficits, or limited neck motion. Postoperative incision scars in the postauricular and hairline region were commonly invisible. Subjective satisfaction with the scar and facial deformity was high after surgery. No patients had a recurrence for a median follow-up of 66 months. Conclusion: The RAHI approach for 2nd BCC has excellent cosmetic, functional, and disease control outcomes. This can be safely applied to the treatment of 2nd BCC. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Supraglottic laryngectomy has evolved from open to transoral endoscopic approaches with advancements in surgical techniques and instruments such as lasers, endoscopes, ultrasonic devices, and robotics. Transoral laser‐assisted microsurgery has emerged as an effective treatment option, offering faster functional recovery and serving as an alternative to partial laryngectomy or non‐surgical therapies. Traditional endoscopic supraglottic laryngectomy involves resection of both suprahyoid and infrahyoid supraglottic structures. However, in cases where the tumor is limited to the infrahyoid epiglottis, a new technique known as transoral laser‐assisted infrahyoid supraglottic laryngectomy allows for tumor removal while preserving the suprahyoid epiglottis, aryepiglottic folds, and vallecula, ensuring optimal preservation of laryngopharyngeal function. This procedure enables patients to swiftly return to their daily routines with minimal complications. This article discusses the surgical technique, potential indications, and advantages and disadvantages of the new approach for infrahyoid epiglottic cancer. [ABSTRACT FROM AUTHOR]

Objectives: Surgical management of parotid pleomorphic adenoma ranges from total parotidectomy to extracapsular dissection (ECD). Minimalistic techniques aim to preserve function and minimize the rate of recurrence. This study assesses functional, aesthetic, and disease control outcomes post-ECD through a sole transverse cervical incision for parotid pleomorphic adenoma. Materials and methods: This longitudinal analysis enrolled 36 consecutive patients with pleomorphic adenoma who underwent ECD via a single cervical incision. Complications, satisfaction, salivary function, and tumor recurrence were evaluated. Salivary gland function was assessed using scintigraphy at 6 months post-surgery. Results: Tumors occurred in superficial (83%) or deep (17%) parotid inferior parts according to the European Salivary Gland Society level classification. The median tumor size was 2.8 cm (1.8–6.0 cm); the median operation time was 42 min (30–65 min). No tumor spillage or facial nerve injuries occurred. Facial nerve paralysis was only temporary in two (6%) patients, with minimal other complications. Operated parotid gland function matched the unoperated side. No recurrence was found during the median follow-up of 44 months (24–60 months). Conclusions: ECD via a single transverse cervical incision is a safe approach for benign parotid tumors, yielding excellent functional and disease control outcomes. Clinical relevance: These findings can provide clinically meaningful minimally invasive recommendations to treat pleomorphic adenoma with minimal complications. [ABSTRACT FROM AUTHOR]

Ferroptosis is a newly recognized form of oxidative-regulated cell death resulting from iron-mediated lipid peroxidation accumulation. Radical-trapping antioxidant systems can eliminate these oxidized lipids and prevent disrupting the integrity of cell membranes. Epigenetic modifications can regulate ferroptosis by altering gene expression or cell phenotype without permanent sequence changes. These mechanisms include DNA methylation, histone modifications, RNA modifications, and noncoding RNAs. Epigenetic alterations in cancer can control the expression of ferroptosis regulators or related pathways, leading to changes in cell sensitivity to ferroptosis inducers or cancer progression. Epigenetic alterations in cancer are influenced by a wide range of cancer hallmarks, contributing to therapeutic resistance. Targeting epigenetic alterations is a promising approach to overcoming cancer resilience. However, the exact mechanisms involved in different types of cancer remain unresolved. Discovering more ferroptosis-associated epigenetic targets and interventions can help overcome current barriers in anticancer therapy. Many papers on epigenetic modifications of ferroptosis have been continuously published, making it essential to summarize the current state-of-the-art in the epigenetic regulation of ferroptosis in human cancer. [ABSTRACT FROM AUTHOR]

Iron is a mineral micronutrient essential for survival and vital functions in many biological processes in living organisms. Iron plays a crucial role as a cofactor of iron-sulfur clusters in energy metabolism and biosynthesis by binding with enzymes and transferring electrons to targets. Iron can also impair cellular functions by damaging organelles and nucleic acids by producing free radicals from redox cycling. Iron-catalyzed reaction products can induce active-site mutations in tumorigenesis and cancer progression. However, the boosted pro-oxidant iron form may contribute to cytotoxicity by increasing soluble radicals and highly reactive oxygen species via the Fenton reaction. An increased redox-active labile iron pool is required for tumor growth and metastasis, but the increased cytotoxic lipid radicals also lead to regulated cell death, such as ferroptosis. Therefore, this may be a major target for selectively killing cancer cells. This review intends to understand altered iron metabolism in cancers and discuss iron-related molecular regulators highly associated with iron-induced cytotoxic radical production and ferroptosis induction, focusing on head and neck cancer. [ABSTRACT FROM AUTHOR]

Ferroptosis, a recently identified form of regulated cell death characterized by the iron-dependent accumulation of lethal lipid peroxidation, has gained increasing attention in cancer therapy. Ferroptosis suppressor protein 1 (FSP1), an NAD(P)H-ubiquinone oxidoreductase that reduces ubiquinone to ubiquinol, has emerged as a critical player in the regulation of ferroptosis. FSP1 operates independently of the canonical system xc–/glutathione peroxidase 4 pathway, making it a promising target for inducing ferroptosis in cancer cells and overcoming ferroptosis resistance. This review provides a comprehensive overview of FSP1 and ferroptosis, emphasizing the importance of FSP1 modulation and its potential as a therapeutic target in cancer treatment. We also discuss recent progress in developing FSP1 inhibitors and their implications for cancer therapy. Despite the challenges associated with targeting FSP1, advances in this field may provide a strong foundation for developing innovative and effective treatments for cancer and other diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Iron-sulfur clusters (ISCs) play a crucial role in cancer cell survival and growth, and their dysregulation is associated with the development and progression of cancer. This review highlights the link between ISC metabolism and ferroptosis, a new form of regulated cell death induced by iron-dependent accumulation of lethal lipid peroxidation. The review summarizes the current knowledge on the mechanisms of ISC biogenesis, the role of ISC modulation in ferroptosis, and the potential of targeting ISCs for cancer therapy. The review provides insight into new therapeutic strategies for cancer treatment based on regulating ISC metabolism. Iron dysregulation is a hallmark of cancer, characterized by an overexpression of genes involved in iron metabolism and iron-sulfur cluster (ISC) biogenesis. Dysregulated iron homeostasis increases intracellular labile iron, which may lead to the formation of excess cytotoxic radicals and make it vulnerable to various types of regulated cell death, including ferroptosis. The inhibition of ISC synthesis triggers the iron starvation response, increasing lipid peroxidation and ferroptosis in cancer cells treated with oxidative stress-inducing agents. Various methods, such as redox operations, iron chelation, and iron replacement with redox-inert metals, can destabilize or limit ISC formation and function, providing potential therapeutic strategies for cancer treatment. Targeting ISCs to induce ferroptosis represents a promising approach in cancer therapy. This review summarizes the state-of-the-art overview of iron metabolism and ferroptosis in cancer cells, the role of ISC modulation in ferroptosis, and the potential of targeting ISCs for ferroptosis induction in cancer therapy. Further research is necessary to develop and validate these strategies in clinical trials for various cancers, which may ultimately lead to the development of novel and effective treatments for cancer patients. [ABSTRACT FROM AUTHOR]

Background: This study compared the complete closure versus the exposure of remnant parotid parenchyma in sialocele formation. Methods: This study included 151 patients with benign parotid lesions who underwent partial parotidectomy plus the complete closure or exposure of remnant parotid parenchyma. Two surgical methods of closed or exposed parenchyma were alternatively allocated to consecutive patients without randomization and blinding processes. Results: Complete closure and exposure of the remnant parotid parenchyma were performed in 81 and 70 patients. Early postoperative complications occurred with temporary events: transient facial weakness, 24 (16%); hematoma, 9 (6%); wound infection, 1 (0.7%) without statistical difference between the two groups (p > 0.1). Postoperative sialocele was more frequently found in the exposure group (n = 15) than the closure group (n = 4; p = 0.003). Conclusions: The complete closure of remnant parotid parenchyma is preferred over the exposure of injured parenchymal parenchyma to prevent postparotidectomy sialocele. [ABSTRACT FROM AUTHOR]

Divalent metal transporter 1 (DMT1) inhibitors can selectively kill iron-addicted cancer stem cells by causing lysosomal iron overload, but their role in head and neck cancer (HNC) is unknown. We examined the role of DMT1 inhibition or salinomycin in promoting ferroptosis by lysosomal iron targeting in HNC cells. RNA interference was performed by transfection of siRNA targeting DMT1 or scrambled control siRNA in HNC cell lines. Cell death and viability, lipid peroxidation, iron contents, and molecular expression were compared between the DMT1 silencing or salinomycin group and the control. DMT1 silencing markedly accelerated cell death induced by the ferroptosis inducers. DMT1 silencing marked increases in the labile iron pool, intracellular ferrous and total iron contents, and lipid peroxidation. DMT1 silencing revealed molecular changes in iron starvation response, resulting in increases in TFRC, and decreases in FTH1. Salinomycin treatment also showed similar results to the above DMT1 silencing. DMT1 silencing or salinomycin can promote ferroptosis in HNC cells, suggesting a novel strategy for killing iron-avid cancer cells. [ABSTRACT FROM AUTHOR]

Dysphagia and feeding tube dependency commonly occur in patients with laryngeal or hypopharyngeal cancer (LHC) during and after treatment, often leading to poor functional outcomes. Therefore, we examined the factors related to feeding tube dependency among advanced-stage LHC patients undergoing curative surgery. This study included 69 consecutive patients who underwent conservative surgery for previously untreated, advanced-stage LHC (squamous cell carcinoma) between 2006 and 2016. Persistent feeding tube dependency was defined as 1 year or more after treatment completion. Binary logistic regression analysis was used to determine the factors associated with reactive prolonged and persistent feeding tube dependency. Cox proportional hazard regression analysis was used to determine the association between feeding tube dependency and survival. None of the study patients had a prophylactic feeding tube, but 15 (21.7%) patients had reactive feeding tube placement for 3 months or more. A total of 9 (13.0%) patients had persistent feeding tube dependency. Univariate analysis showed that age, tracheostomy, and common terminology criteria for adverse events (CTCAE) ≥ 3 were significantly associated with reactive prolonged and persistent feeding tube dependency (all P < 0.05). In the multivariate analysis, advanced age and CTCAE ≥ 3 remained the independent factors of reactive prolonged and persistent feeding tube dependency (all P < 0.05). Feeding tube dependency was not associated with overall survival or disease-free survival (P > 0.1). Feeding tube dependency might be related to clinical factors, such as age and severe adverse events, in the patients undergoing function-preserving surgery for advanced-stage LHC. [ABSTRACT FROM AUTHOR]

Objective: Deep lobe parotid tumour is commonly removed with the covering superficial lobe of parotid gland. Total or subtotal parotidectomy leads to an increase in surgical morbidity. This study evaluated recurrence and function after selective deep lobe parotidectomy via retroauricular hairline (Roh's) incision for pleomorphic adenoma. Materials and methods: Twenty‐eight patients with deep lobe parotid pleomorphic adenomas underwent selective deep lobe parotidectomy with preservation of the superficial lobe and the facial lobe via Roh's incision. Each patient was evaluated with any complications, cosmetic and salivary functions and local recurrence. Results: Superficial lobe‐preserving surgery via Roh's incision was successfully applied to all patients without injury to the facial nerve and the Stensen's duct for a median operation time of 65 min. Facial nerve paralysis was found only temporarily in 9 (32%) patients, and other complications were minimal. None of the patients had postoperative Frey's syndrome. Salivary secretory function in the operated side was well preserved. No recurrence was found in the patients for a median follow‐up of 94 months. Conclusions: Selective deep lobe parotidectomy via Roh's incision is a reliable option of treatment for deep lobe parotid pleomorphic adenoma. [ABSTRACT FROM AUTHOR]

SLC7A11 is a cell transmembrane protein composing the light chain of system xc−, transporting extracellular cystine into cells for cysteine production and GSH biosynthesis. SLC7A11 is a critical gateway for redox homeostasis by maintaining the cellular levels of GSH that counter cellular oxidative stress and suppress ferroptosis. SLC7A11 is overexpressed in various human cancers and regulates tumor development, proliferation, metastasis, microenvironment, and treatment resistance. Upregulation of SLC7A11 in cancers is needed to adapt to high oxidative stress microenvironments and maintain cellular redox homeostasis. High basal ROS levels and SLC7A11 dependences in cancer cells render them vulnerable to further oxidative stress. Therefore, cyst(e)ine depletion may be an effective new strategy for cancer treatment. However, the effectiveness of the SLC7A11 inhibitors or cyst(e)inase has been established in many preclinical studies but has not reached the stage of clinical trials for cancer patients. A better understanding of cysteine and SLC7A11 functions regulating and interacting with redox-active proteins and their substrates could be a promising strategy for cancer treatment. Therefore, this review intends to understand the role of cysteine in antioxidant and redox signaling, the regulators of cysteine bioavailability in cancer, the role of SLC7A11 linking cysteine redox signaling in cancer metabolism and targeting SLC7A11 for novel cancer therapeutics. [ABSTRACT FROM AUTHOR]

Purpose: Conventional surgery for submandibular gland tumour is total excision of the gland affected by the tumour. Gland-preserving surgery is commonly used for benign tumours arising in the parotid gland but not in the submandibular gland. This study evaluated long-term oncological and functional outcomes after gland-preserving surgery in patients with pleomorphic adenoma of the submandibular gland via the submental approach. Methods: This longitudinal study included 105 consecutive patients with submandibular gland pleomorphic adenoma who underwent the gland-preserving surgery combined with the en-bloc resection of tumours via the submental approach. Salivary scintigraphy was performed 6 months after surgery, and ultrasonography was regularly followed. Intraoperative findings, postoperative complications, cosmetic and salivary functions, and tumour recurrence were assessed in these patients. Results: Median tumour size and submental incision length were 2.0 and 3.3 cm, respectively. Median operation time and amount of blood loss were 25 min and 18.5 mL, respectively. None had marginal or lingual nerve paralysis and most patients were satisfied with incision scar and facial contour. The salivary function of the affected gland was equal to that of the unaffected gland. One patient (0.9%) had single nodular recurrence 54 months after surgery and others had no recurrence for follow-up of median 96 months. Conclusions: Pleomorphic adenoma of the submandibular gland can be safely removed by the gland-preserving surgery via the submental approach which has operation time, cosmetic and functional benefits with compromising oncological outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Plunging ranula is a pseudocyst of saliva extravasated from the sublingual gland (SLG) to the submandibular space. This is treated by transoral excision of the SLG or transcervical cyst excision that might differently affect surgical morbidity and recurrence. This study compared the clinical outcomes of complete vs partial excision of the SLG for plunging ranula. Study Design: A nonrandomized comparative study. Setting: Academic medical center. Methods: This study included 42 patients with plunging ranula who underwent complete or partial excision of the SLG with the evacuation of cystic content. Two surgical methods of complete or partial SLG resection were alternatively allocated to consecutive patients without randomization. The primary outcome was a postoperative recurrence. Secondary outcomes were operation time and complications. Results: Complete and partial excision of the SLG was performed in 22 and 20 patients, respectively, without injury to the Wharton's duct or the lingual nerve. Postoperative complications in 42 patients were minor with temporary events: hematoma, 1 (5%); tongue numbness, 2 (5%); dysgeusia, 4 (9%); and dysphagia, 2 (5%), which did not differ between patients with complete and partial excision of the SLG (P >.1). However, recurrence occurred in only 5 of 20 patients with partial SLG excision but none of 22 patients with complete SLG excision for a median follow-up of 36 months. Conclusions: Complete SLG excision is preferred over partial SLG excision to treat plunging ranula for reducing postsurgical risks of complications and recurrence. [ABSTRACT FROM AUTHOR]

Background: Thyroglossal duct cyst (TGDC) is the most common congenital cyst in the neck and is removed by the Sistrunk procedure. This surgery involves a horizontal skin incision over the cyst that may leave a noticeable scar on the front of the neck. Therefore, this study examined the clinical outcomes and cosmetic benefits of the Sistrunk procedure by an incision in the submental area that is not easily visible from the front. Materials and methods: This observational study was performed on 152 patients who underwent the Sistrunk procedure by a submental approach to remove TGDC at a university medical center. Intraoperative findings, postoperative complications, subjective pain levels, and satisfaction with incision scars and neck and facial deformities, and recurrence were prospectively evaluated. Results: The length of the submental incision was about 3 cm and the median total operation time was 36 min. Postoperative complications were minimal. Hematoma occurred in two cases (1.3%), surgical site infection in 1 case (0.7%), and dysphagia for more than 1 week occurred in 1 case (0.7%). On a 0–10 visual analogue scale, the pain had a median value of 2 on the first day after surgery, and satisfaction with incision scars and neck and facial deformities showed median values of 8 and 10 at 6 months after surgery, respectively. Recurrence occurred in one patient (0.7%) during the median follow-up period of 68 months. Conclusions: The submental approach for TGDC excision may be a reliable new surgical method that is safe and has cosmetic advantages. This observational study evaluated the clinical outcomes and cosmetic benefits of the Sistrunk procedure by a submental incision for thyroglossal duct cyst in 152 patients. The surgical procedure showed no increased operation time, no need for wide flap elevation, easy suprahyoid dissection, and an invisible scar in a natural position of the neck. [ABSTRACT FROM AUTHOR]

Background: Thyroid lobectomy is recommended as the primary treatment for low-risk thyroid cancer. However, recurrence and hypothyroidism may develop after lobectomy, necessitating thyroid hormone supplementation. The 2015 American Thyroid Association (ATA) guidelines recommended post-lobectomy thyroid-stimulating hormone (TSH) suppression. This study examined the need for TSH suppression and recurrence after lobectomy for unilateral papillary thyroid carcinoma (PTC). Methods: This study involved 369 patients who underwent thyroid lobectomy and ipsilateral central neck dissection for PTC between 2007 and 2015. Thyroid function tests were performed before and regularly after lobectomy. Binary logistic regression analyses were used to find factors predictive of the post-lobectomy need for TSH suppression that was defined by the 2015 ATA guidelines. Results: Serum TSH concentrations gradually increased after lobectomy: proportions with TSH >2 mIU/L at post-lobectomy 1, 3–6, 12, and 24 months were found in 77.0%, 82.3%, 66.7%, and 59.9%, respectively. After lobectomy, 168 (45.5%) patients received levothyroxine (T4) supplementation. Multivariate logistic regression analyses showed that pre-TSH level >2 mIU/L was the sole independent variable predictive of the need for post-lobectomy TSH suppression (P = 0.003). During the median follow-up of 72 months, recurrence was found in 4 (1.1%) patients who never received T4 supplementation and had post-lobectomy TSH levels >2 mIU/L. Conclusions: Our data show that thyroid lobectomy for unilateral PTC is associated with a low recurrence rate, but a significant risk of hypothyroidism. Preoperative TSH level can predict the need for post-lobectomy TSH suppression compliant with the 2015 ATA guidelines. [ABSTRACT FROM AUTHOR]

Background: Progesterone receptor membrane component 1 (PGRMC1) is a heme-binding protein inducing dimerization with cytochrome P450, which mediates chemoresistance. Increased PGRMC1 expression is found in multiple types of resistant cancers, but the role of PGRMC1 in the ferroptosis of cancer cells remains unrevealed. Therefore, we examined the role of PGRMC1 in promoting ferroptosis in paclitaxel-tolerant persister cancer cells (PCC). Methods: The effects of ferroptosis inducers and PGRMC1 gene silencing/overexpression were tested on head and neck cancer (HNC) cell lines and mouse tumor xenograft models. The results were analyzed about cell viability, death, lipid ROS and iron production, mRNA/protein expression and interaction, and lipid assays. Results: PCC had more free fatty acids, lipid droplets, and fatty acid oxidation (FAO) than their parental cells. PCC was highly sensitive to inhibitors of system xc− cystine/glutamate antiporter (xCT), such as erastin, sulfasalazine, and cyst(e)ine deprivation, but less sensitive to (1S,3R)-RSL3. PGRMC1 silencing in PCC reduced ferroptosis sensitivity by xCT inhibitors, and PGRMC1 overexpression in parental cells increased ferroptosis by xCT inhibitors. Lipid droplets were degraded along with autophagy induction and autophagosome formation by erastin treatment in PCC. Lipophagy was accompanied by increased tubulin detyrosination, which was increased by SIRT1 activation but decreased by SIRT1 inhibition. FAO and lipophagy were also promoted by the interaction between lipid droplets and mitochondria. Conclusion: PGRMC1 expression increased FAO and ferroptosis sensitivity from in vivo mice experiments. Our data suggest that PGRMC1 promotes ferroptosis by xCT inhibition in PCC. Paclitaxel-tolerant persister cancer cells (PCC) had PGRMC1 upregulation related to increased free fatty acids, lipid droplets, and fatty acid oxidation. PGRMC1 expression substantially increased ferroptosis by xCT inhibition via lipophagy and tubulin detyrosination, whereas PGRMC1 silencing decreased ferroptosis: this suggests that PGRMC1 expression promotes ferroptosis in PCC. [ABSTRACT FROM AUTHOR]

Purpose: Oral cavity squamous cell carcinoma (OCC) can spread to the neck without apparent lymphadenopathy. Pretreatment detection or prediction of occult metastasis might contribute to proper management of clinically node-negative (cN0) OCC. We examined the role of tumour quantitative 18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) measurements for predicting OCC occult metastasis and survival. Methods: This study included 130 cN0 OCC patients who underwent 18F-FDG PET/CT scanning and subsequent curative surgery and neck dissection. Maximum, peak, and mean standardized uptake value (SUVmax, SUVpeak, and SUVmean), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were measured on pretreatment 18F-FDG PET/CT. Binary logistic regression was used to identify factors predicting occult cervical metastasis. Univariate and multivariate Cox proportional hazard regression were used to find factors associated with overall survival (OS). Results: Pathological cervical metastasis (pN +) was found in 29 (22.3%) patients. Age, tumour differentiation, lymphovascular invasion, and T classification were significantly associated with pN + (all P < 0.05). After adjustment for these factors, MTV and TLG independently predicted pN + (P < 0.05). Invasion depth, lymphovascular invasion, T and N classifications, and overall TNM stage were significantly associated with OS. After adjustment for these factors, SUVmax and TLG independently predicted OS (all P < 0.05). Patients with TLG > 9.3 g had a 5.7-fold increased risk of overall mortality. Conclusions: Tumour 18F-FDG PET/CT parameters might predict occult metastasis and survival in cN0 OCC patients. [ABSTRACT FROM AUTHOR]

Purpose: Tumor explant culture systems can mimic the in vivo tumor microenvironment, proposing as a substitute for preclinical studies for prediction of individual treatment response. Therefore, our study evaluated the potential usefulness of ex vivo tumor explants culture assembled into the cell sheets by anticancer drug screening in patients with head and neck squamous cell carcinoma (HNSCC). Methods: Our model included tumor explants incorporated into cell sheet composing of epithelium and subepithelial stroma using tumor and mucosal samples obtained from the HNSCC patients who underwent surgery. Cell growth, viability, and hypoxia were measured by cell counting kit-8, live/dead assay, propidium iodide, and LOX-1 staining, and were compared among the different treatment groups with vehicle, cisplatin or docetaxel. Results: Tumor explants stably survived in the cell sheet over 10 days after explantation, whereas most of the explants in non-matrix culture became nonviable within 5–8 days with the significant daily decrease of viability. The live tissue areas of tumor explants in the cell sheet maintained over 30 days without significant changes although hypoxic cell areas gradually increased up to 5 days. Tissue viability and live cancer tissue areas significantly decreased after the treatment of cisplatin or docetaxel in the dose and time-dependent manners. Conclusion: Our cell sheet-based tumor explants model might be applied to the reliable ex vivo screening for anticancer chemotherapeutics for HNSCC. [ABSTRACT FROM AUTHOR]

Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of the salivary gland. However, reports of high grade transformation in MEC are extremely rare, and only two cases have so far been described. Recent development of salivary gland pathology revealed recurrent gene rearrangements in many kinds of tumors, including MAML2 fusion of MEC. To date, the MAML2 status of high grade transformed MEC has not been studied. Here we report the first case of minor salivary gland origin high grade transformation in MEC with a MAML2 break apart FISH study. A 73-year-old woman presented with a 1-month history of left mandibular area swelling, and computed tomography and magnetic resonance imaging revealed a mass in the hard palate with various-sized lymphadenopathy of the neck. The resected tumor histologically consisted of two carcinomatous components. Approximately 30% of the tumor showed a conventional MEC feature, while 70% was comprised of a high grade transformed component. In the conventional MEC component, FISH revealed MAML2 rearrangement. High grade transformed cells showed multiple split signals, and the results were interpreted as rearrangement and polyploidy after comparison with 1p/19q FISH as validation. The patient received adjuvant radiation therapy after wide resection with neck dissection and retropharyngeal dissection. Nevertheless, as the remaining tumor grew up rapidly and metastatic lymph nodes were newly revealed, the patient expired 7 months after the diagnosis. We first report regarding a high grade transformation in MEC with polyploidy of the rearranged MAML2 gene and aggressive biological behavior. [ABSTRACT FROM AUTHOR]

Background: This study compared our proposed N classification including the addition of the number of positive lymph node (LN+) and extranodal extension (ENE) with the current and previous American Joint Committee on Cancer (AJCC) N classifications in salivary gland cancer (SGC). Methods: This study involved 172 SGC patients who underwent surgery. Cox proportional hazard regression analyses were used to identify factors associated with overall survival (OS) and disease‐free survival (DFS). Results: In multivariate analyses, LN+ number, LN ratio, and ENE were associated with OS and DFS outcomes (all P <.05). Our new N classification proposed three categories: N0 (0 LN+), N1 (1 LN+), and N2 (≥2 LN+ or ENE). The C‐index of our N classification showed improvement in OS prediction (0.768) compared with the AJCC seventh (0.743) and eighth (0.756) edition N classifications. Conclusions: Our proposed N classification incorporating LN+ number and ENE may improve prediction of post‐treatment survival and recurrence in patients with SGC. [ABSTRACT FROM AUTHOR]

Purpose: Adenoid cystic carcinoma (AdCC) is generally slow growing but has highly metastatic potential to distant organs. Several factors and biomarkers are associated with metastasis and treatment outcomes, although further definition is needed. Therefore, this study aimed to evaluate the risk factors for survival and distant metastasis in patients with head and neck AdCC. Methods: This study included 125 patients with previously untreated AdCC who underwent primary surgery with or without radiotherapy in our tertiary referral centre. Univariate and multivariate Cox proportional hazard regression analyses were used to identify risk factors associated with overall survival (OS), cause-specific survival (CSS), disease-free survival (DFS), and distant metastasis-free survival (DMFS). Factors associated with OS in patients with distant metastasis were separately analysed. Results: During a median follow-up of 9.8 years (range 3.0–22.6 years), 58 patients (46.4%) had distant metastasis and 29 (23.2%) died of disease. Multivariate analyses showed that lymphovascular invasion, lymph node metastasis, and distant metastasis were independent factors of OS and CSS outcomes (all P < 0.05). The T classification and extranodal extension were independent factors of DFS and DMFS outcomes (P < 0.05). After patients presented with distant metastasis, the median survival was 5.8 years. Multivariate analyses showed that extranodal extension and regional recurrence were independent factors of survival after occurrence of distant metastasis (P < 0.05). Conclusion: Several clinicopathological factors can predict distant metastasis and survival of patients with AdCC treated with primary surgery. This may promote post-treatment surveillance in patients with AdCC. [ABSTRACT FROM AUTHOR]

Objectives: Immediate facial nerve substitution or graft technique has been used for the repair of facial nerve defects occurring as a result of tumour dissection. However, some patients report unsatisfactory outcomes, such as difficulty in maintaining resting or smiling symmetry, due to persistent flaccid facial palsy. Here we evaluated the functional outcomes of transferring the masseteric branch of the trigeminal nerve to the facial nerve adjunct to facial nerve graft. Methods: We reviewed the medical records of seven patients who underwent facial reanimation surgery between 2014 and 2016. The patients were divided into two groups according to the type of facial reanimation surgery: group A, masseteric nerve innervation with interposition graft; group B, interposition graft only. The postoperative resting symmetry and dynamic movement were compared. Results: Facial contraction was first observed in group A at 4 months and in group B at 7.3 months. Most of the patients achieved reliable resting symmetry; however, one patient in group B exhibited unsatisfactory facial weakness on the affected side. Group A patients showed better dynamic movement than group B patients. Eye closure, oral excursion and oral continence were better in group A than in group B patients. Smile symmetry in both groups was similar due to hyperkinetic movement in group A patients and flaccidity in group B patients. Conclusions: Dual innervation of the masseteric branch of the trigeminal nerve improves the dynamic movement of paralysed facial muscles and shortens the recovery period in patients with iatrogenic facial palsy. [ABSTRACT FROM AUTHOR]

Purpose: Cervical metastasis from unknown primary (CUP) is commonly classified as an advanced overall stage. P16 or human papillomavirus (HPV) positivity in metastatic lymph nodes (LN) might be associated with a favorable survival outcome of CUP. Therefore, we evaluated the prognostic values of p16 immuno-positivity in LN and other clinicopathological factors in patients with squamous cell carcinoma CUP (SCCUP). Methods: This study involved 83 patients who underwent therapeutic neck dissection and panendoscopic examination and biopsy for suspected CUP. P16 immunostaining and HPV typing in LN were performed in 56 patients. Cox proportional hazard regression analyses were used to identify factors associated with overall survival (OS) and disease-free survival (DFS). Results: Postoperatively, primary tumors (PT) were found in 32 (38.6%) patients, mainly (90.6%) in the oropharynx, and not found in 51 (61.4%) patients. The clinicopathological data (except for histological grade) and 5-year OS and DFS rates did not significantly differ between patients with and without PT identification (all P > 0.05). P16 positivity was associated with favorable OS and DFS outcomes in the patients with PT (P < 0.05) but not in those without PT (P > 0.1). Multivariate analyses showed that age (> 60 years) and LN ratio (≥ 0.1) were the independent predictors of OS and DFS outcomes (all P < 0.05). P16 positivity or other factors were not independent factors. Conclusion: Age and LN ratio are significant risk factors of survival and recurrence after primary surgery for SCCUP. Prognostic significance of LN p16 positivity should be further studied. [ABSTRACT FROM AUTHOR]

Objective: Conservative parotidectomy is known to reduce morbidity, but has been rarely examined in patients with clinically node-negative (cN0) parotid cancers. We evaluated the clinicopathological variables influencing the outcomes of these patients and the efficacy of conservative parotidectomy. Methods: We reviewed the clinical and pathological data of 256 patients with cN0 parotid carcinomas who underwent curative surgery at our institution. Of these, 110 and 146 underwent conservative and total parotidectomy, respectively, with 83 undergoing elective neck dissection and 135 receiving postoperative radiotherapy. Univariate and multivariate analyses of variables predicting recurrence-free survival (RFS) and overall survival (OS) were performed. Morbidity, survival, and recurrence rates were compared between the conservative and total parotidectomy groups. Results: The 5-year RFS and OS rates in all patients were 85.7 and 91.4%, respectively. Multivariate analysis showed that advanced T classification, positive resection margin, and high-histologic grade were independent prognostic factors for both RFS and OS. Among the 201 patients with low- or intermediate-grade parotid cancers, those who underwent total parotidectomy had a greater chance of facial nerve paralysis than those who underwent conservative parotidectomy (p < 0.001). The 5-year RFS and OS after conservative parotidectomy (93.7 and 100%, respectively) were not worse than those after total parotidectomy (85.5 and 90.9%, respectively). Conclusion: Patients with cN0 parotid cancers may be stratified by histological grade and T classification. Conservative parotidectomy may be suitable for early T1–2 low- or intermediate-grade tumors if a resection margin is secured. [ABSTRACT FROM AUTHOR]

Purpose: Subclinical lymph node (LN) metastasis is associated with poor survival outcome in oral cavity squamous cell carcinoma (OCC), which alleges elective neck LN dissection. Preoperative detection of metastatic LNs may improve prognosis and proper management of OCC. We examined the clinical usefulness of fluorine 18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) for the detection of occult neck LN metastasis in OCC patients in comparison with conventional CT/magnetic resonance (MR) imaging. Methods: A total of 178 OCC patients with negative neck palpation findings were assessed prospectively with 18F-FDG PET/CT and CT/MR imaging. Histopathological analyses of neck dissection samples served as reference. Diagnostic values of 18F-FDG PET/CT versus CT/MR imaging were compared with the McNemar test and logistic regression with generalized estimating equations. Results: Forty-two patients (23.6%) had metastasis in 44 sides and 58 levels of the neck. The sensitivity for detection of occult metastasis was higher for 18F-FDG PET/CT than that for CT/MR imaging on a per-patient (69.1% vs 35.7%), per-side (70.5% vs 36.4%), and per-level (62.1% vs 29.3%) basis (all P ≤ 0.001). However, the specificity for metastatic detection was higher for CT/MR imaging than that for 18F-FDG PET/CT (all P < 0.005). 18F-FDG PET/CT improved detection of occult metastasis up to 33.4% in these patients compared to CT/MR imaging. Conclusions: 18F-FDG PET/CT can better detect occult neck metastasis than CT/MR imaging, which may potentially impact the clinical management of OCC patients. [ABSTRACT FROM AUTHOR]

Purpose: Metastatic lymph node (LN) burden is one of the most important prognosticators in human solid cancers, but has rarely been examined in laryngeal and hypopharyngeal cancers (LHC). We evaluated the nodal factors predictive of recurrence and survival in patients with LHC. Methods: This study included 141 consecutive patients who underwent primary surgery and neck dissection for previously untreated LHC at our tertiary referral centre. Nodal factors included the presence of pathological LN metastasis, number of positive LNs, LN ratio, and extra-nodal extension (ENE). Our proposed N classification was analysed by recursive partitioning analysis and compared with the AJCC and other N classifications using the c-index. Univariate and multivariate Cox proportional hazard regression analyses were used to define significant predictors of post-treatment disease-free survival (DFS) and overall survival (OS). Results: Of the 141 patients, 66 (46.8%) had positive LNs, and 27 (19.1%) had ENE. In multivariate analyses, the number of positive LNs was strongly associated with DFS and OS outcomes (P < 0.01). Our new N classification was proposed with four categories, such as N0 (0 LN +), N1 (1 LN +), N2 (2–4 LN + or ENE) and N3 (≥ 5 LN +). The C-index of our new N classification improved the OS prediction (0.718) compared with the AJCC and the other N classifications (0.704–0.713). Conclusion: Metastatic LN burden is an important predictor of survival in patients with LHC. A proposed N classification using the number of positive LNs and ENE might improve the LHC survival prediction. [ABSTRACT FROM AUTHOR]

Background: This study examined the risk factors of pharyngocutaneous fistula development and poor survival after salvage laryngectomy. Methods: Binary logistic regression analyses were carried out to analyze the relationship between post‐salvage fistula development and variables. Univariate and multivariate Cox proportional hazard regression analyses were performed to evaluate prognostic factors associated with disease‐free survival (DFS) and overall survival (OS) after salvage laryngectomy. Results: Multivariate analyses showed that previous radiotherapy and pre‐salvage tracheostomy were the independent variables predictive of post‐salvage fistula development (all P < .05). The 5‐year DFS and OS rates were 58.8% and 45.9%, respectively. Multivariate analyses showed that nodal positivity at salvage remained the independent factor predictive of both DFS (hazard ratio [HR] 2.83, P = .002) and OS (HR 2.22, P = .006). Conclusions: Fistula development after salvage laryngectomy might be predicted by a history of radiotherapy or tracheostomy. Post‐salvage survival is associated with nodal positivity at salvage. This study examined the risk factors of pharyngocutaneous fistula development and survival in 103 patients who underwent salvage laryngectomy. Previous radiotherapy and tracheostomy were the independent variables predictive of post‐salvage fistula development, and nodal positivity at salvage was the independent factor predictive of both disease‐free survival and overall survival. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prognostic values of tumor‐related leukocytosis (TRL) as a reliable biomarker predictive of recurrence and survival after definitive surgery for oral cavity squamous cell carcinoma (OSCC). Materials and methods: This retrospective study involved 322 patients who underwent tumor extirpation combined with neck dissection for treatment‐naïve OSCC between 2006 and 2014. Multivariate binary logistic regression analyses were used to analyze the relationship between TRL and pathological variables. Cox proportional hazard regression analyses were used to find associations between factors and disease‐free survival (DFS) or overall survival (OS). Results: TRL was significantly related to advanced disease status, tumor size, invasion depth, poor differentiation, and T and N classifications, resulting in increased post‐treatment recurrence rate, particularly in the distant site. Multivariate logistic regression analyses showed that only the T classification was significantly associated with baseline TRL (p = 0.018). Multivariate analyses also showed that the tumor depth of invasion, pathological N classification, extranodal extension, and TRL remained the independent variables predictive of DFS and OS (all p < 0.05). TRL was related to a more than twofold increased risk of post‐treatment recurrence and mortality. Conclusions: TRL is associated with advanced tumor disease and increased recurrence and mortality in OSCC patients. [ABSTRACT FROM AUTHOR]

Copyright of Acta Oto-Laryngologica is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The current use of steroids or pharmacological immunomodulators for the treatment of intractable oral ulceration is ineffective, necessitating newer cell‐based therapeutic approaches. We examined the potential efficacy of an oral mucosa equivalent developed in this study in an in vivo model of repeat major oral ulceration mimicking the intractable oral ulceration observed clinically. Oral mucosal samples and plasma fibrin were obtained from Sprague–Dawley rats. The oral mucosa equivalents were prepared with cultured mucosal keratinocytes and plasma fibrin mixed with cultured fibroblasts. Ulcers were chemically induced on the rat buccal mucosa thrice in 3 weeks and covered with or without mucosa equivalents. Gross and microscopic findings and mRNA expression levels were compared between the ulcer control and mucosa equivalent groups. Oral mucosal keratinocytes and fibroblasts were cultured in vitro to achieve high viability and colony‐forming efficiency. The equivalents showed epithelial and subepithelial structures similar to those of oral mucosa and exhibited high p63 positivity. In the in vivo study, ulceration was resolved earlier without significant granulation or scarring in the equivalent group than in control group (p < 0.05). Microscopic examinations revealed rapid re‐epithelialization and less fibrosis in the equivalent group than in the control group (p < 0.05). Mucosa equivalent‐covered ulcers showed histological characteristics similar to those of the normal buccal mucosa and exhibited lower expression of TGFB1, ACTA2, and FN1 mRNAs than the control group. The in vitro‐engineered oral mucosa equivalent promotes ulcer healing without scarring and functional deficits. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1779–1785, 2019. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the prognostic role of Fluorine 18‐fluorodeoxyglucose positron emission tomography/CT (18F‐FDG PET/CT) parameters quantitatively measured in patients with recurrent oral cavity cancer. Methods: Cox proportional hazards regression analyses were used to assess the associations between quantitative 18F‐FDG PET/CT parameters and other clinicopathological factors and progression‐free survival (PFS) and overall survival (OS). Results: All of the 18F‐FDG PET parameters (SUVmax, SUVmean, SUVpeak, metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) were significantly associated with poor PFS and OS outcomes after salvage treatment (P < .01). In multivariate analyses, Karnofsky performance score, recurrence site, MTV, and TLG were independent variables predictive of both PFS and OS (P < .05). High MTV (>8.8 mL) or TLG (>29.4 g) values at recurrent lesions were associated with >5‐fold increased risk for tumor progression and mortality after salvage surgery. Conclusions: The PET parameters of MTV and TLG measured at recurrent lesions may predict tumor progression and survival after salvage treatment. This study examined the role of 18F‐FDG PET/CT at recurrent staging for predicting tumor progression and survival in 71 consecutive patients with recurrent oral cavity squamous cell carcinomas. Of 18F‐FDG parameters, metabolic tumor volume and total lesion glycolysis were independent factors predictive of tumor progression and survival after salvage treatment. [ABSTRACT FROM AUTHOR]

Purpose: Submandibular gland (SMG) carcinoma has an unfavorable clinical course and a low survival rate. Specific tumor and nodal findings might help predict posttreatment recurrence and survival in SMG carcinoma patients. This study evaluated factors predictive of posttreatment recurrence and survival in SMG carcinoma patients. Methods: This study enrolled 99 consecutive patients with previously untreated SMG carcinoma. All patients underwent tumor and metastatic lymph node resection along with or without radiation/chemo-radiation. The predictive clinical and pathological factors for disease-free survival (DFS), distant metastasis–free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were determined using univariate and multivariate Cox proportional hazards regression analyses. Results: The median tumor size was 2.7 cm and 53 patients (53.5%) had high-grade tumors. The rates of initial nodal and distant metastasis at initial presentation or follow-up were 45.5% and 42.4%, respectively. The actuarial 5-year DFS, DMFS, DSS, and OS rates were 46.4%, 55.9%, 61.5%, and 59.7%, respectively. The independent factors associated with poor DFS, DMFS, DSS, and OS outcomes (all p < 0.05) were T3–T4 classification and lymph node ratio. A histological high-grade tumor was an independent prognostic factor predictive of poor DMFS, DSS, and OS outcomes (all p < 0.05). Conclusions: A high rate of distant site failure is associated with SMG carcinoma, resulting in a poor survival rate. Lymph node ratio might help predict recurrence, distant metastasis, and death due to SMG carcinoma. [ABSTRACT FROM AUTHOR]

Background: This study examined the potential use of our newly developed prevascularized oral mucosal cell sheet for the treatment of skin wounds. Methods: Mucosal cell sheets containing cultured keratinocytes and plasma fibrin without (K sheet) or with a mixture of fibroblasts and endothelial progenitor cells (PV sheet) were transplanted into full‐thickness skin excisional wounds of nude mice. Results: This technique was successful for in vitro culture; expanding keratinocytes, fibroblasts, and endothelial progenitor cells; and generating prevascularized mucosal cell sheets. Cell sheets promoted in vivo wound healing with rapid wound closure and less scarring compared to controls. This result was more apparent in the PV than the K sheet (P < .05). Wounds covered with cell sheets showed less expression of TGFB1, ACTA2, and FN1 mRNAs than the controls (P < .05). Conclusion: The prevascularized mucosal cell sheet showed in vivo efficacy and tissue plasticity in cutaneous wounds by promoting accelerated healing. [ABSTRACT FROM AUTHOR]

Purpose: High-grade salivary gland carcinoma (SGC) shows a high rate of metastasis and post-treatment recurrence, resulting in poor patient survival. Therefore, we evaluated the utility of pre-treatment 18F-FDG PET/CT parameters in predicting metastasis, tumor progression, and survival of high-grade SGC patients.Methods: This observational study included 75 patients with previously untreated high-grade SGC who underwent pre-treatment 18F-FDG PET/CT scanning and subsequent treatment. Standardized uptake values (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured on pre-treatment 18F-FDG PET/CT. Logistic regression analysis was used to identify the relationship of these factors with metastasis. Cox proportional hazard regression analyses were used to identify associations between PET parameters and both progression-free survival (PFS) and overall survival (OS).Results: A total of 36 (48%) patients had neck or distant metastases at initial staging. After controlling for clinical factors, MTV (> 8.8 mL) was an independent factor for initial metastasis (adjusted odds ratio 4.80, 95% confidence interval 1.09-21.20; P = 0.039). All PET parameters of SUVmax (> 4.3), SUVmean (> 3.0), SUVpeak (3.9), MTV (> 8.8 mL), and TLG (> 31.1 g) were significant variables for PFS (all P < 0.05), while MTV and TLG were significant factors for OS. After controlling for clinicopathological factors, MTV (adjusted hazard ratio 4.36, 95% confidence interval 1.69-11.26; P = 0.002) and TLG (3.41, 1.47-7.91; P = 0.004) were significantly associated with PFS, but not OS.Conclusions: MTV is useful among quantitative PET measurements for predicting initial metastasis and PFS in patients with high-grade SGC. [ABSTRACT FROM AUTHOR]

Background: This study analyzed the expression of CD44 and cystine‐glutamate transporter SLC7A11 (xCT) in primary oral cavity squamous cell carcinoma (SCC) and the relationships of expression to tumor recurrence and patient survival. Methods: Associations between CD44 and xCT expression and clinicopathologic results were analyzed in 231 patients with oral cavity SCC. Cox proportional hazard analyses were used to identify factors associated with recurrence‐free survival (RFS), disease‐specific survival (DSS), and overall survival (OS). Results: Overexpression of CD44 and/or xCT was associated with advanced T classification, perineural invasion, and lymphovascular invasion (P <.05 each). High expression of xCT was also associated with nodal metastasis and depth of invasion (P <.01 each). Multivariate analysis indicated that high expression of xCT and both xCT and CD44 were independent predictors of poor RFS, DSS, and OS (P <.05 each). Conclusion: Overexpression of xCT or xCT plus CD44 may predict posttreatment recurrence and survival in patients with oral cavity SCC. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to compare the characteristics of idiopathic unilateral vocal fold paralysis (IUVFP) in elderly versus younger patients, including the diagnostic yield of computed tomography (CT) scans for identifying the structural causes of IUVFP. Methods: We retrospectively analyzed medical records of the patients initially diagnosed with IUVFP in a single referral tertiary hospital. We compared patients’ baseline characteristics, initial symptoms, laryngoscopic findings, and prevalence of structural causes on CT scans with respect to age (younger, <65 years vs older, ⩾65 years). Results: One hundred forty-two patients were enrolled (90 younger, 52 older). Evident structural causes were more frequently found on CT in older patients than younger patients (40.4% vs 22.2%, P = .034). Among truly idiopathic cases (70 younger, 31 older), recovered vocal fold mobility was identified in 48.6% younger and 41.9% older patients (P = .666). There was no statistically significant difference in the characteristics between unrecovered and recovered subjects of the older patients with true IUVFP (all P > .05). Conclusions: The CT scans provided significantly higher diagnostic yields in older patients than younger patients. The degrees of symptoms and complications and likelihood of natural recovery did not significantly differ between younger and older patients with IUVFP. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Patients with head and neck cancer (HNC) can die of index tumor progression and second tumor or non‐cancer causes. Here, we investigated the risk factors for competing non‐cancer mortality (NCM) in a prospective cohort of patients with advanced‐stage HNC. Materials and Methods: A prospective observational study was conducted with 604 patients who underwent definitive treatment for advanced‐stage HNC between 2010 and 2015. Main outcomes were NCM and cancer mortality (CM) defined as death from non‐cancer causes and HNC or second cancers, respectively. Cumulative incidence and cause‐specific hazard functions were used to analyze the risk factors of NCM and CM. Results: Age, smoking, Charlson comorbidity index (CCI), performance status, body mass index, rural residence, education and hemoglobin level at diagnosis, and chemotherapy were significantly associated with NCM (all p < 0.05). Multivariate analyses showed that age, CCI, and hemoglobin were independent factors of NCM. Age (≥65 years), CCI (≥2), and hemoglobin (<11 g/dl) were related to 4.5‐, 3.2‐, and 2.7‐fold increased adjusted risk of NCM, respectively. Conclusions: Old age, comorbidity, and hemoglobin at diagnosis were independent predictors of NCM. The risk factors could be used to predict non‐cancer death after definitive treatment for advanced‐stage HNC. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To compare the diagnostic accuracy of 18F‐FDG PET/CT and conventional contrast‐enhanced CT for the re‐staging of recurrent salivary gland carcinoma (SGC). Materials and Methods: This study included 58 consecutive patients who underwent recurrent SGCs after definitive treatment. The recurrences were evaluated by 18F‐FDG PET/CT and contrast‐enhanced CT of the neck and chest. McNemar's test was used to compare the diagnostic accuracy of 18F‐FDG PET/CT with standard neck and chest CT imaging, and a Cox proportional hazards model was used to assess the prognostic value of PET/CT. Results: Of 58 patients with recurrent SGCs, 17 (29%) had a local recurrence, 17 (29%) had a regional recurrence, and 38 (66%) had a distant metastasis, with these classifications showing overlap. The sensitivity and accuracy of 18F‐FDG PET/CT for the detection of distant metastases were significantly higher than those of CT (p < 0.05), whereas, for detection of loco‐regional recurrences, they did not differ (p > 0.1). The 18F‐FDG PET/CT‐positive findings at distant sites were predictors of poor progression‐free and overall survival outcome (all p < 0.05). Conclusions: 18F‐FDG PET/CT is a more effective method than CT for detecting distant site recurrences of SGC. This may lead to prognostic prediction for recurrent SGCs. [ABSTRACT FROM AUTHOR]

Amplification of fibroblast growth factor receptor 1 (FGFR1) has been reported in many squamous cell carcinomas, and human papillomavirus (HPV)–related oropharyngeal squamous cell carcinoma has been characterized as a distinct subset with favorable prognosis. Here, we investigated the FGFR1 amplification and HPV status in tonsillar squamous cell carcinoma (TSCC) and analyzed the clinical characteristics. HPV in situ hybridization (HPV ISH) and FGFR1 fluorescence in situ hybridization (FISH) were performed using tissue microarray from 89 cases of TSCC. Fourteen of 89 (15.7%) TSCC cases had FGFR1 amplification, and HPV was detected in 59 of 89 (66.3%) cases. FGFR1 amplification status was not associated with HPV positivity (p =0.765). Outcomes were not significantly different between FGFR1 amplified and non-amplified patients. Although FGFR1 amplified patients (n =4) in the HPV ISH–negative group (n =30) had a tendency for poorer overall survival, no statistical significance was identified (p =0.150, log-rank). FGFR1 protein overexpression showed better disease-free survival (p =0.031, log-rank) in HPV-negative TSCC. This study suggests FGFR1 amplification may be important in the pathogenesis of TSCC regardless of HPV status. [ABSTRACT FROM AUTHOR]

Copyright of Acta Oto-Laryngologica is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Background: Surgical site infection is a complication of surgery for patients with head and neck cancer. We examined the risk factors for surgical site infection in patients undergoing surgery for head and neck cancer. Methods: The study involved 369 patients who underwent surgery for head and neck cancer. Hematological and nutritional parameters were measured preoperatively and postoperatively. Univariate and multivariate analyses were used to determine the risk factors for surgical site infection. Results: Of the 369 patients, 104 (28.2%) had surgical site infections: 45 (12.2%) superficial incisional; 6 (1.6%) deep incisional; and 53 (14.4%) organ/space infections. Multivariate analyses showed that history of radiotherapy, weight loss at diagnosis (>5%), preoperative hypoalbuminemia, neutrophil/lymphocyte ratio (NLR), reconstructive surgery, and tracheostomy were the independent factors predictive of surgical site infection. Patients with preoperative low serum albumin levels (<3.3 g/L) had a 3‐fold higher risk of surgical site infection. Conclusion: Our study shows that patient nutritional and hematological markers are associated with the risk of surgical site infection after major surgery for head and neck cancer. [ABSTRACT FROM AUTHOR]

Objective: Histological grade is the most important factor for defining treatment strategies and predicting prognosis for salivary gland carcinoma (SGC). We examined factors affecting long-term recurrence and survival among intermediate-grade SGC (IGSGC) patients to define optimal treatment modalities and outcomes. Methods: We reviewed the clinical and pathological data on 108 IGSGC patients who underwent definitive surgery with or without postoperative radiotherapy. We compared treatment outcomes by treatment strategies such as surgical extent for the primary tumor, neck dissection, or postoperative radiotherapy. Results: During a 103-month median follow-up, local, regional, and distant recurrences were detected in 14 (13.0%), 3 (2.8%), and 21 (19.4%) patients, respectively. The 10-year locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) rates were 83.1, 76.0, and 80.1%, respectively. Multivariate analyses identified a nonparotid primary site as an independent prognostic factor for LRC (p = 0.018). Adenoid cystic carcinoma and a positive pN classification were significantly unfavorable prognostic factors for DMFS (p = 0.025 and p = 0.030, respectively); overall advanced stage was an independent prognostic factor for OS (p = 0.020). Surgical extent, elective neck dissection, and postoperative adjuvant radiotherapy did not significantly affect treatment outcomes. Conclusion: Patients with early-stage IGSGC of parotid origin can achieve favorable treatment outcomes with conservative surgery alone. [ABSTRACT FROM AUTHOR]

Abstract: Background: We developed a highly efficient in vitro‐engineered mucosa equivalent using completely autologous mucosa and blood and investigated its feasibility and efficacy for oral surgical wound healing. Methods: Small oral mucosa samples were obtained from surgical patients, and keratinocytes and fibroblasts were primarily grown in media without animal products for generating 3D cell sheets. Results: Morphological characteristics of the cell sheets were comparable to those of human mucosa, although p63‐positive cells were more numerous in cell sheets. In addition, cell sheets were flexible, expandable, and easy to handle or transfer. In further in vivo rat experiments with deep wounding of the buccal mucosa and soft tissues, controls had significantly thinner epithelium and thicker collagen densities than those with cell sheets. Conclusion: Autologous cell sheets can be engineered in vitro from oral keratinocytes, fibroblasts, and fibrin, and can be used clinically to accelerate healing of oral soft tissue defects. [ABSTRACT FROM AUTHOR]

Background: Lymph node (LN) yield and ratio are considered important predictors of post-treatment outcomes for several human cancers. This study examined the association between nodal factors, including the LN yield and ratio, with recurrence after thyroidectomy plus central compartment neck dissection (ND) for papillary thyroid carcinoma (PTC). Materials and Methods: This retrospective study involved 2384 consecutive patients who underwent a thyroidectomy plus central compartment ND combined with ( n = 440) or without lateral compartment ND at the authors' tertiary referral center between 2006 and 2012. The number of harvested LNs, as well as other tumor and nodal findings, were carefully reviewed. Univariable and multivariable Cox proportional hazards regression models were conducted to predict recurrence and its association with clinicopathologic variables. Results: All nodal factors, including the positive number of LNs, ratio, and extranodal extension, were significantly associated with nodal and any-site recurrence after thyroidectomy, as well as the tumor size and multifocality ( p < 0.01). The multivariable analysis showed that tumor size, multifocality, LN ratio, and extranodal extension were independent factors predictive of post-treatment recurrence ( p < 0.05). The LN yield was higher in patients with nodal recurrence but did not significantly affect the nodal recurrence. Patients with a LN ratio >0.3 exhibited a 1.7-fold higher risk of post-treatment nodal recurrence than their counterparts ( p < 0.01). Conclusions: LN ratio is an independent determinant predictive of nodal and any-site recurrence following thyroidectomy for PTC. [ABSTRACT FROM AUTHOR]

Objectives: Despite the excellent prognosis of early glottic cancer (T1-T2), the significance of preoperatively measured tumor thickness has not been elucidated. We evaluated the role of tumor thickness measured using computed tomography (CT) as a predictive factor for recurrence of early glottic cancer after transoral laser microsurgery (TLM). Methods: The medical records of 134 patients who were diagnosed with early glottic squamous cell carcinoma and underwent TLM were reviewed. Age, sex, clinical stage, preoperative biopsy, anterior commissure involvement, CT findings, recurrence, and overall survival were evaluated. Results: Seventy-three patients (54 T1a, 2 T1b, and 17 T2) were enrolled. Tumor thickness on pathology increased proportionally with increased tumor thickness on CT. The recurrence-free survival (RFS) and overall survival rates were 82.2 and 91.2%, respectively. Upon univariate analysis, RFS was affected by the type of cordectomy, tumor differentiation, margin involvement, anterior commissure involvement, impaired vocal fold mobility, and tumor thickness (> 4 mm) on CT scan (all p < 0.01). Among the relevant covariates, an involved or close resection margin [hazard ratio (HR) 19.2; 95% confidence interval (CI) 3.5-105.6; p < 0.01], impaired vocal cord mobility (HR 8.5; 95% CI 1.45-49.2; p = 0.02), and pathological tumor thickness (> 4 mm) (HR 6.0; p = 0.02) were predictive of RFS. Conclusion: Tumor thickness may be another predictive factor for recurrence in early glottic cancer. Before TLM, reviewing the extent of tumor thickness will help to improve local control in cases of early glottic cancer. [ABSTRACT FROM AUTHOR]