Otolaryngology & Head and Neck Surgery

The impact of diabetes in head and neck cancer Purpose of review A strong association between diabetes mellitus and carcinogenesis has been reported in different organs. The purpose of this review is to summarize the new evidences in relation to diabetes mellitus and its association with the development, prognosis, and therapeutic strategies of head and neck squamous cell carcinomas (HNSCC). Recent findings Recent publications suggest that glycemic metabolism is altered in HNSCC. Elevated blood glucose levels, before or around the time of diagnosis, have been reported to reduce survival rates in HNSCC. Also, the homeostasis model assessment-insulin resistance has been independently associated with disease-free survival, suggesting that improving the glycemic control may improve the prognosis in this group of patients. Epidemiological studies revealed that cancer patients with diabetes mellitus have less cancer-related mortality after antiglycemic treatment, opening the option to include antiglycolytic agents, such as metformin, in the therapeutic plan. This finding is in accordance with in-vitro studies that demonstrated a decrease in tumor-cell proliferation with antidiabetic medications. Summary Recent findings highlight the importance of glucose metabolism in the pathogenesis and progression of cancer cells. The knowledge of these altered pathways gives us an opportunity to design target treatments aimed to modulate glucose catabolism. Correspondence to Isabel Vilaseca, Otorhinolaryngology Department, Hospital Clinic, c/ Villarroel 170, 08036 Barcelona, Spain. Tel.: +34 932275442;. e-mail: ivila@clinic.cat Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Potential therapeutic implications of the new tumor, node, metastasis staging system for human papillomavirus-mediated oropharyngeal cancer Purpose of review The 8th edition tumor, node, metastasis (TNM) classification (TNM-8) introduced a new classification for human papillomavirus (HPV)-mediated oropharyngeal carcinoma (HPV+ OPC). This review summarizes its potential therapeutic implications focusing on literature published since 2018. Recent findings The following are active research areas involved in clinical care and therapy relevant to TNM-8: tumor HPV testing and its clinical implications; stage I disease: treatment selection and lessons learned from recent deintensification trials; emerging strategies addressing stage II and III disease. Summary The TNM-8 classification depicts prognosis of HPV+ OPC much more reliably compared with TNM-7. Among the advantages in outcome comparison and stratification for clinical trial entry and conduct, it also enables more satisfactory individual patient consultation to adequately estimate prognosis, and facilitates clinical and translational research. However, clinicians must remain mindful that the TNM classification is not a guideline for treatment but, instead, provides a framework for clinical research and treatment decision-making. The TNM-8 has potential to improve risk-tailored treatment algorithms for HPV+ OPC including selection of treatment modality (primary trans-oral surgery vs. radiotherapy, addition of chemotherapy) and adjusting the intensity of approaches. To realize these goals fully, it is apparent that the TNM-8 needs to evolve further. Correspondence to Brian O'Sullivan, MD, FRCPC, FRCPI, FFRRCSI (Hon), FASTRO, Department of Radiation Oncology, Department of Otolaryngology, Head and Neck Surgery, The Princess Margaret Cancer Centre, University of Toronto, Room 7-323, 700 University Avenue, Toronto, ON, Canada M5G 1Z5. E-mail: Brian.OSullivan@rmp.uhn.ca Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Airway management, symptom relief and best supportive care in anaplastic thyroid cancer Purpose of review Anaplastic thyroid cancer (ATC) is a rare but aggressive form of thyroid cancer that is associated with significant morbidity and mortality. Because ATC is locally invasive, airway management is a critical component of treating these patients. Timely decisions regarding airway interventions can contribute to symptom relief and supportive care for patients. Over the last decade, there has been a paradigm shift in our recommendations for airway management. The purpose of this review is to summarize airway management, symptom relief and best supportive care for patients with ATC. Recent findings More recent literature discusses the morbidities associated with tracheostomy and instead focuses on the benefits of supportive care and surgical resection. The multidisciplinary treating team should initiate early discussions for airway management, end-of-life care and palliative goals for patients with ATC. Tracheostomy should be offered to patients with careful thought and preoperative planning. Summary Our goal in symptom relief and airway management is to improve the quality of life of patients with ATC and avoid the unnecessary morbidity of tracheostomy until clinically indicated. Correspondence to Ashok R. Shaha, MD, FACS, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Room C-1061, New York, NY 10065, USA. Tel: +1 212 639 7649; e-mail: shahaa@mskcc.org Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Infratemporal fossa surgical approaches to primary/recurrent malignancies of salivary origin: paradigm surgical shift, patient selection, and oncologic outcomes Purpose of review To review, the surgical approaches available on diagnosing a patient with salivary gland malignancy in the infratemporal fossa (ITF). To comment on patient evaluation and method of treatment selection. To identify and report on patient outcome data and make recommendations on future needs. Recent findings There is a need to define the anatomic boundaries contents of the ITF, masticator space, parapharyngeal space (PPS), pterygopalatine fossa, ventral skull base, and paramedian skull base, as evidence from publications. The pathological subtypes identified mainly include adenoid cystic and mucoepidermoid carcinomas. The source of these tumours originates from primary disease in the sinonasal tract and nasopharynx superiorly, and the PPS/deep lobe of parotid inferiorly. Current surgical options available, in suitable selected patient, available in tertiary head and neck cancer hospitals, which have available facilities and staffing is the endoscopic endonasal approach. This approach offers patients a ‘complete margin-free surgical excision’, minimal complications, shorter hospital stay, and no delay with commencement of any adjuvant treatment compared with the traditional ‘open transcutaneous’ approach. Summary The current evidence specifically to the surgical management of salivary gland malignancy involving the ITF is sparse, with great difficult identifying treated patients and their details among a heterogeneous group of patients with many lesions. There is a need for patient data that have specific pathologic conditions to be amalgamated from such centers and publish on outcome events. Correspondence to Patrick J. Bradley, MBA, FRCS, Department Otorhinolaryngology, Head and Neck Surgery, Nottingham University Hospitals, Queens Medical Centre Campus, Derby Road, 10 Chartwell Grove, Mapperley Plains, Nottingham NG3 5R, UK. Tel: +44 0 115 9201611; e-mail: pjbradley@zoo.co.uk Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Controversies in the surgical management of sporadic medullary thyroid carcinoma Purpose of review Medullary thyroid carcinoma (MTC) represents a wide spectrum of tumours with differing biology, behaviour and natural history. The only current available curative treatment is surgery in the form of thyroidectomy with or without ipsilateral or bilateral neck dissection. There is a lack of consensus in the available published guidelines on the optimum extent of initial surgery, and there is significant variation in clinical practice. This review focuses on the most recently published evidence. Recent findings Many patients with limited disease do not receive total thyroidectomy and central neck compartment dissection as recommended by international guidelines. Despite this, 5-year disease-specific survival is over 90% in those without distant metastases at presentation. Over 20% of patients may harbour occult lateral compartment nodal metastases, and baseline calcitonin alone (>1000 pg/ml) is not a good predictor of nodal metastasis. Although delayed lateral neck compartment dissection results in similar survival outcomes to prophylactic neck dissection for clinically node-negative patients, there is an underappreciated psychological effect of having biochemical evidence of persistent disease following limited surgery. Summary No single currently available prognostic indicator is sufficient to predict disease behaviour and evidence of occult nodal metastases. In clinically ad radiologically node-negative patients, the extent of neck dissection at initial operation, therefore, needs to be planned and executed on an individual patient basis. Correspondence to Jonathan Mark Fussey, FRCS (ORL-HNS), Department of Head and Neck Surgery, Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, United Kingdom. Tel: +44 0 1392 411611; e-mail: jfussey@nhs.net Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Perineural invasion in head and neck squamous cell carcinoma: background, mechanisms, and prognostic implications Purpose of review Perineural invasion (PNI) is a pathological feature frequently observed in head and neck squamous cell carcinoma (HNSCC). The difficulties of pathological standardization and the lack of a simple validated experimental model to study PNI render its analysis complex. Here, we aim to summarize the recent advances in the understanding of the biology of PNI in HNSCC and their potential clinical implications. Recent findings PNI is a multistep process leading to a dialogue between cancer cells and nerve fibers in HNSCC. Recent studies have identified some of the active molecular mechanisms involved in PNI. Comprehensive studies addressing the transcriptional regulation of PNI bring interesting perspectives for a standardized molecular diagnosis of PNI and a better assessment of its contribution to the aggressiveness of HNSCC. Summary Perineural invasion is a complex process that reflects specific tumor biology. In addition to unveiling new fundamental concepts about the tumor microenvironment, research on PNI promises to identify new biomarkers, enabling progress in therapeutic development against HNSCC. Correspondence to Zuzana Saidak, PhD, Laboratoire d’Oncobiologie Moléculaire, Centre de Biologie Humaine (CBH), CHU Amiens Sud, Avenue Laennec, 80054 Amiens Cedex, France. Tel: +33 322087074; e-mail: Saidak.Zuzana@chu-amiens.fr Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

From head and neck lipoma to liposarcoma: a wide spectrum of differential diagnoses and their therapeutic implications Purpose of review To overview the array of differential diagnoses among lipomatous tumours of the head and neck with special focus on their evaluation, three-dimensional assessment, and their available treatments. Recent findings The head and neck is an infrequent localization for lipomatous tumours, even though they represent the most common mesenchymal lesions. Lipoma, spindle cell/pleomorphic lipoma (SC/PL), atypical lipomatous tumour/well differentiated liposarcoma (ALT/WDLPS), de-differentiated liposarcoma (DDLPS), myxoid liposarcoma (MLPS), and pleomorphic liposarcoma (PLPS) are the most distinctive histotypes. Lipoma and SC/PL present alterations of chromosomes 12 and 13, ALT/WDLPS and DDLPS both show the Mouse Double Minute 2 amplification, whereas MLPS presents a CHOP gene fusion. Diagnosis of PLPS is purely morphological as there is no pathognomonic genetic alteration identified to date. Radiological assessment can be challenging for the presence of nonadipose components within the lesion. Surgery is the mainstay of treatment, even though achieving true radicality in terms of a large cuff of healthy tissue surrounding the tumour is not always realistic in the head and neck. Adjuvant radiation, eventually in combination with systemic chemotherapy, has been shown to improve overall survival in patients with positive margins, high-grade, deep, and more than 5 cm lesions. Further studies should be aimed at the evaluation of the role of hadron therapy, as well as targeted drugs against overexpressed proteins. Summary Adequate differential diagnosis of the histotypes collected under the umbrella term of head and neck lipomatous tumours plays a fundamental role in treatment and follow-up of these lesions and requires specific expertise with referral to high-volume centres. Correspondence to Lorenzo Giannini, MD, Department of Otorhinolaryngology, Maxillofacial and Thyroid Surgery, Fondazione IRCCS, National Cancer Institute of Milan, Via Giacomo Venezian 1, 20133 Milan, Italy. Tel: +39 223902158; e-mail: lorenzo.giannini@istitutotumori.mi.it Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

The transmanubrial osteomuscular-sparing approach: a valuable adjunct to the head and neck surgical armamentarium Purpose of review To describe and popularize the transmanubrial osteomuscular-sparing approach (TOSA) outside its original thoracic surgical field of application, based on the consideration that it could be of interest for the management of a number of head and neck cases in both elective and emergent scenarios. Recent findings The main advantages of TOSA compared with transclavicular techniques are its superb exposure of anatomic structures located at the level of the cervicothoracic junction, and superior postoperative aesthetic and functional outcomes. Recently, a number of studies have described the association of TOSA with other minimally invasive approaches, such as video-assisted thoracoscopic surgery and robotic hybrid approaches, with the aim of avoiding association of the transmanubrial route with anterior/posterior thoracotomies, or more extended surgeries, such as the trapdoor or hemiclamshell procedures. Summary TOSA, even though originally conceived to reduce the morbidity ensuing from classic transclavicular approaches for management of Pancoast tumors, may well play an important role in a number of head and neck surgical conditions, including those related to mediastinal goiter and thyroid cancer, management of stenosis and lesions of the thoracic trachea and esophagus, treatment of the junction between innominate, internal jugular, and subclavian veins, epiaortic arteries, thoracic duct, brachial plexus, and low sympathetic chain. Whenever comprehensive control of vascular and nonvascular structures of the upper mediastinal inlet is required, TOSA should be planned and performed by combining the expertise of cooperating professionals. Correspondence to Lorenzo Giannini, MD, Department of Otorhinolaryngology, Maxillofacial and Thyroid Surgery, Fondazione IRCCS, National Cancer Institute of Milan, Via Giacomo Venezian 1, 20133 Milan, Italy. E-mail: gianninilorenzo88@gmail.com Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.