Search

(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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Chronic sclerosing sialadenitis, known as Küttner's tumor (KT), is a chronic inflammatory disease of the salivary gland characterized by progressive periductal fibrosis, dilated ducts with a dense lymphocyte infiltration and lymphoid follicle formation, and acinar atropy. We report a unique case of KT in a 30-year-old female who presented with time-serial involvement of the bilateral lacrimal and submandibular glands with reactive follicular hyperplasia of bilateral upper cervical lymph nodes. All tissue samples of the submandibular and lacrimal glands were typical of KT on pathologic examination. There was no evidence of lymphoepithelial lesions or intraepithelial lymphocytes. This is the first case of KT involving both lacrimal and submandibular glands, suggesting that KT is closely related to an active local immune process. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Ferroptosis, a novel form of regulated cell death characterized by iron-mediated lipid peroxidation, holds immense potential in cancer therapeutics due to its role in tumor progression and resistance. This review predominantly explores the intricate relationship between ferroptosis and cholesterol metabolism pathways, mainly focusing on the cholesterol biosynthesis pathway. This review highlights the therapeutic implications of targeting cholesterol metabolism pathways for cancer treatment by delving into the mechanisms underlying ferroptosis regulation. Strategies such as inhibiting HMG-CoA reductase and suppressing squalene synthesis offer promising avenues for inducing ferroptosis in cancer cells. Moreover, insights into targeting the 7-dehydrocholesterol pathway provide novel perspectives on modulating ferroptosis susceptibility and managing ferroptosis-associated diseases. Understanding the interplay between ferroptosis and cholesterol metabolism pathways underscores the potential of lipid metabolism modulation as an innovative therapeutic approach in cancer treatment., 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 © 2024 Elsevier B.V. All rights reserved.)

The diverse functions of ferroptosis suppressor protein 1 (FSP1/AIFM2) in cancer have positioned it as a promising therapeutic target across various malignancies, including head and neck cancer (HNC). Initially characterized as a potential tumor suppressor due to its involvement in apoptosis and ferroptosis, recent studies have revealed its complex role in tumor growth, metabolism, and therapy resistance. Pharmacological inhibition of FSP1 shows potential in sensitizing cancer cells to ferroptosis and overcoming resistance to conventional therapies, offering new avenues for precision medicine approaches. Identifying novel FSP1 inhibitors and their synergistic effects with existing therapies presents exciting opportunities for therapeutic development. However, translating preclinical findings into clinical practice requires the refinement of FSP1 inhibitors, robust biomarkers for patient stratification, and further investigations into the molecular mechanisms underlying FSP1-mediated therapy resistance. Integrating FSP1-targeted therapies into comprehensive treatment regimens holds promise for improving outcomes in cancer patients and advancing the field of precision oncology., 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 © 2024 Elsevier B.V. All rights reserved.)

Macroautophagy/autophagy is a complex degradation process with a dual role in cell death that is influenced by the cell types that are involved and the stressors they are exposed to. Ferroptosis is an iron-dependent oxidative form of cell death characterized by unrestricted lipid peroxidation in the context of heterogeneous and plastic mechanisms. Recent studies have shed light on the involvement of specific types of autophagy (e.g. ferritinophagy, lipophagy, and clockophagy) in initiating or executing ferroptotic cell death through the selective degradation of anti-injury proteins or organelles. Conversely, other forms of selective autophagy (e.g. reticulophagy and lysophagy) enhance the cellular defense against ferroptotic damage. Dysregulated autophagy-dependent ferroptosis has implications for a diverse range of pathological conditions. This review aims to present an updated definition of autophagy-dependent ferroptosis, discuss influential substrates and receptors, outline experimental methods, and propose guidelines for interpreting the results. Abbreviation : 3-MA:3-methyladenine; 4HNE: 4-hydroxynonenal; ACD: accidentalcell death; ADF: autophagy-dependentferroptosis; ARE: antioxidant response element; BH2:dihydrobiopterin; BH4: tetrahydrobiopterin; BMDMs: bonemarrow-derived macrophages; CMA: chaperone-mediated autophagy; CQ:chloroquine; DAMPs: danger/damage-associated molecular patterns; EMT,epithelial-mesenchymal transition; EPR: electronparamagnetic resonance; ER, endoplasmic reticulum; FRET: Försterresonance energy transfer; GFP: green fluorescent protein;GSH: glutathione;IF: immunofluorescence; IHC: immunohistochemistry; IOP, intraocularpressure; IRI: ischemia-reperfusion injury; LAA: linoleamide alkyne;MDA: malondialdehyde; PGSK: Phen Green™ SK;RCD: regulatedcell death; PUFAs: polyunsaturated fatty acids; RFP: red fluorescentprotein;ROS: reactive oxygen species; TBA: thiobarbituricacid; TBARS: thiobarbituric acid reactive substances; TEM:transmission electron microscopy.

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 ., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

The TP53 gene, encoding the p53 protein, has been a focal point of research since its 1979 discovery, playing a crucial role in tumor suppression. Ferroptosis, a distinct form of cell death characterized by lipid peroxide accumulation, has gained prominence since its recognition in 2012. Recent studies have unveiled an intriguing connection between p53 and ferroptosis, with implications for cancer therapy. Recent research underscores p53 as a novel target for cancer therapy, influencing key metabolic processes in ferroptosis. Notably, p53 represses the expression of the cystine-glutamate antiporter SLC7A11, supporting p53-mediated tumor growth suppression. Furthermore, under metabolic stress, p53 mitigates ferroptosis sensitivity, aiding cancer cells in coping and delaying cell death. This dynamic interplay between p53 and ferroptosis has far-reaching implications for various diseases, particularly cancer. This review provides a comprehensive overview of ferroptosis in cancer cells, elucidating p53's role in regulating ferroptosis, and explores the potential of targeting p53 to induce ferroptosis for cancer therapy. Understanding this complex relationship between p53 and ferroptosis offers a promising avenue for developing innovative cancer treatments., 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 © 2024 Elsevier B.V. All rights reserved.)

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.)

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., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2023. Springer Nature Switzerland AG.)

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.)

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., (© 2023. Springer Nature Switzerland AG.)

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.

Background: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours., Methods: In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186., Findings: Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039)., Interpretation: Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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.

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., (© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.)

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., (© 2023 Wiley Periodicals LLC.)

Cancers polarized to a mesenchymal or poorly differentiated state can often evade cell death induced by conventional therapies. The epithelial-mesenchymal transition is involved in lipid metabolism and increases polyunsaturated fatty acid levels in cancer cells, contributing to chemo- and radio-resistance. Altered metabolism in cancer enables invasion and metastasis but is prone to lipid peroxidation under oxidative stress. Cancers with mesenchymal rather than epithelial signatures are highly vulnerable to ferroptosis. Therapy-resistant persister cancer cells show a high mesenchymal cell state and dependence on the lipid peroxidase pathway, which can respond more sensitively to ferroptosis inducers. Cancer cells may survive under specific metabolic and oxidative stress conditions, and targeting this unique defense system can selectively kill only cancer cells. Therefore, this article summarizes the core regulatory mechanisms of ferroptosis in cancer, the relationship between ferroptosis and epithelial-mesenchymal plasticity, and the implications of epithelial-mesenchymal transition 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.)

Cancer metabolic alterations have been emphasized to protect cancer cells from cell death. The metabolic reprogramming toward a mesenchymal state makes cancer cells resistant to therapy but vulnerable to ferroptosis induction. Ferroptosis is a new form of regulated cell death based on the iron-dependent accumulation of excessive lipid peroxidation. Glutathione peroxidase 4 (GPX4) is the core regulator of ferroptosis by detoxifying cellular lipid peroxidation using glutathione as a cofactor. GPX4 synthesis requires selenium incorporation into the selenoprotein through isopentenylation and selenocysteine tRNA maturation. GPX4 synthesis and expression can be regulated by multiple levels of its transcription, translation, posttranslational modifications, and epigenetic modifications. Targeting GPX4 in cancer may be a promising strategy for effectively inducing ferroptosis and killing therapy-resistant cancer. Several pharmacological therapeutics targeting GPX4 have been developed constantly to activate ferroptosis induction in cancer. The potential therapeutic index of GPX4 inhibitors remains to be tested with thorough examinations of their safety and adverse effects in vivo and clinical trials. Many papers have been published continuously in recent years, requiring state-of-the-art updates in targeting GPX4 in cancer. Herein, we summarize targeting the GPX4 pathway in human cancer, which leads to implications of ferroptosis induction for tackling cancer resilience., 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.)

Cancer often perturbs lipid metabolism, which leads to the alteration of metabolism intermediates, contributing to their deregulated growth and metastasis. Alteration of lipid metabolism shifting to contain more polyunsaturated fatty acids (PUFAs) in membrane phospholipids (PLs) also leads to cancer therapy resistance. High amounts of PL-PUFAs render cancer cells more vulnerable to lipid peroxidation (LPO), predisposing them towards ferroptosis, a new form of iron-dependent oxidative regulated cell death. The commitment of cancer undergoing ferroptotic cell death depends on the adaptive lipidome remodeling, LPO patterns, and LPO scavenging ability in heterogeneous cancer cells. Ferroptosis is receiving attention in cancer research as treating cancers, altering membrane lipid homeostasis, and refractory from conventional therapies. Therefore, a better understanding of the molecular underpinning of lipid metabolism alterations may provide new opportunities for solving cancer resistance. This review intends to understand altered lipid metabolism in cancers and discuss lipid composition and metabolic processes associated with ferroptosis induction in cancers., 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.)

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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2021 Wiley Periodicals LLC.)

Ferroptosis is a newly regulated cell death induced by the accumulation of iron-mediated lipid peroxidation. The alteration of cancer metabolism may contribute to proliferation, metastasis, and treatment resistance in human cancers, implicating the sensitivity to ferroptosis induction. Altered metabolism in cancer cells regulates oxidative stresses and changes metabolism intermediates, contributing to their deregulated growth and proliferation. Cancer metabolic changes toward the elevation of cellular free iron and polyunsaturated fatty acids sensitize cancer cells to lipid peroxidation toxicity tightly linked to ferroptosis. The altered metabolism in cancers can be served as a promising target to reverse cancer therapeutic resistance by ferroptosis induction to selectively kill cancer cells while sparing normal cells. The role of mitochondria and lipid metabolism in inducing ferroptosis in head and neck cancer (HNC) has been elucidated in previous studies. Ferroptosis is receiving attention in cancer research as treating cancers altering cellular metabolism and refractory from conventional therapies. More in-depth studies are needed to develop highly therapeutic drugs and practical methods to induce ferroptosis in diverse cancer cells and tumor microenvironments effectively. Therefore, this review intends to understand the altered metabolism and find new therapeutic possibilities using ferroptosis in HNC., 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 © 2022 Elsevier B.V. All rights reserved.)

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.

Most head and neck cancers (HNCs) originate from mucosal epithelial cells and show epithelial traits. It often changes to a mesenchymal or poorly differentiated state as cancer progresses, leading to invasion, metastasis, and resistance to treatment. The loss of epithelial traits by the epithelial-mesenchymal transition may render resilient cancers vulnerable to a novel non-apoptotic regulated cell death ferroptosis by the iron-dependent accumulation of excessive lipid peroxidation. By regulating mitochondrial or iron metabolism, intracellular ferrous iron and lipid peroxidation accumulation can be boosted, making resistant cancer cells more susceptible to ferroptosis. This article discusses the potential effect of ferroptosis induction as a novel treatment for resilient HNCs., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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.

Background: This study evaluated functional and disease control outcomes after gland-preserving surgery via a single transverse cervical incision for Warthin's tumor of the parotid gland., Methods: One-hundred eleven patients with Warthin's tumor underwent the preservation of most normal parotid tissues and the facial nerve combined with the en-bloc resection of tumors. Postoperative complications, subjective satisfaction, salivary function, and metachronous tumor were assessed in each patient., Results: No patients had an extension to modified Blair or periauricular incision with the median operation time of 32 min. Temporary and permanent paralysis of the facial nerve was 5 (4.0%) and none of 125 tumor resection sides, respectively. Postoperative complications were minimal. The secretory functions between the affected and unaffected glands did not differ. One patient had metachronous tumor for a median follow-up of 72 months., Conclusion: Functional gland-preserving surgery via single transverse cervical incision can safely treat Warthin's tumor in the parotid gland., (© 2022 Wiley Periodicals LLC.)

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., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Introduction: Cervical schwannomas are rare diseases treated by complete resection, leading to potential neurological deficits. Intracapsular enucleation is an acceptable alternative to preserve the involved nerve function, but the clinical outcomes by an aesthetically pleasing approach remain unrevealed. This study evaluated functional and oncological outcomes after intracapsular enucleation of cervical schwannomas via retroauricular hairline (Roh's) incision., Materials and Methods: This prospective observational study included 17 patients with cervical schwannomas who underwent intracapsular enucleation to preserve the involved nerve and capsule via Roh's incision. Each patient was evaluated with any complications, nerve function, subjective satisfaction, voice and swallowing questionnaires, and local recurrence., Results: Intracapsular enucleation via the Roh's incision was successfully applied to all patients for a median operation time of 48 min. Tumours of 4.5-cm median size were removed with the minimization of injury to the nerve and sheath deflected on the surface of the tumour. Temporary and permanent paralysis of the unilateral vocal fold was found in 3 (33%) and none of 9 patients with vagal schwannomas, respectively. Horner's syndrome occurred temporarily in two of 5 (40%) patients with sympathetic chain schwannomas. Postoperative complications were minor. Subjective satisfaction of scar and facial deformity was high, and subjective voice and swallowing difficulties were minimal one year after surgery. No recurrence was found in the patients for a median follow-up of 82 months., Conclusion: Intracapsular enucleation via Roh's incision is a viable treatment for cervical schwannomas with the highest functional, cosmetic, and oncological outcomes., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A cytosolic iron chaperone poly(rC)-binding protein 1 (PCBP1) is a multifunctional RNA-binding protein involving gene transcription, RNA regulation, and iron loading to ferritins. PCBP1 is also known to repress autophagy, but the role of PCBP1 in ferritinophagy and ferroptosis remains unrevealed. Therefore, we examined the role of PCBP1 in ferritinophagy-mediated ferroptosis in head and neck cancer (HNC) cells. The effects of system xc - cystine/glutamate antiporter (xCT) inhibitors and PCBP1 gene silencing/overexpression were tested on HNC cell lines and mouse tumor xenograft models. These effects were analyzed by assessing cell viability and death, lipid reactive oxygen species and iron production, lipid, malondialdehyde, mRNA/protein expression, and autophagy flux assays. Interaction between PCBP1 and BECN1 mRNA was also examined by luciferase and RNA-protein pull-down assays. PCBP1 gene silencing increased autophagosome generation and autophagic flux. Conversely, PCBP1 upregulation inhibited autophagy activation via direct binding to the CU-rich elements on the 3'-untranslated region (3'-UTR) of BECN1 mRNA. The internal deletion or mutation of the 3'-UTR F2 region recovered BECN1 mRNA stability repressed by PCBP1, resulting in enhanced ferritinophagy-mediated ferroptosis. Besides, PCBP1 knockdown promoted polyunsaturated fatty acid peroxidation by increasing ALOX15 expression. Further, excess iron accumulation caused mitochondrial dysfunction in PCBP1-suppressed cells. A ferroptosis inducer sulfasalazine significantly suppressed tumor growth in mice with the transplantation of PCBP1-silenced HNC. Our data suggest that the dual functions of PCBP1 repressing BECN1 and ALOX15 mRNAs contribute to attenuating cancer susceptibility to ferroptosis inducers., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.)

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., (© 2021. The Author(s).)