Treatment of the neck in residual/recurrent disease after chemoradiotherapy for advanced primary laryngeal cancer.

Concomitant chemoradiotherapy (CRT) is extensively used as primary organ preservation treatment for selected advanced laryngeal squamous cell carcinomas (LSCC). The oncologic outcomes of such regimens are comparable to those of total laryngectomy followed by adjuvant radiotherapy. However, the management of loco-regional recurrences after CRT remains a challenge, with salvage total laryngectomy being the only curative option. Furthermore, the decision whether to perform an elective neck dissection (END) in patients with rN0 necks, and the extent of the neck dissection in patients with rN + necks is still, a matter of debate. For rN0 patients, meta-analyses have reported occult metastasis rates ranging from 0 to 31 %, but no survival advantage for END. In addition, meta-analyses also showed a higher incidence of complications in patients who received an END. Therefore, END is not routinely recommended in addition to salvage laryngectomy. Although some evidence suggests a potential role of END for supraglottic and locally advanced cases, the decision to perform END should weigh benefits against potential complications. In rN + patients, several studies suggested that selective neck dissection (SND) is oncologically safe for patients with specific conditions: when lymph node metastases are not fixed and are absent at level IV or V. Super-selective neck dissection (SSND) may be an option when nodes are confined to one level. In conclusion, current evidence suggests that in rN0 necks routine END is not necessary and that in rN + necks with limited nodal recurrences SND or a SSND could be sufficient.

Management of Older Patients with Head and Neck Cancer: A Comprehensive Review.

The projected increase in life expectancy over the next few decades is expected to result in a rise in age-related diseases, including cancer. Head and neck cancer (HNC) is a worldwide health problem with high rates of morbidity and mortality. In this report, we have critically reviewed the literature reporting the management of older patients with HNC. Older adults are more prone to complications and toxicities secondary to HNC treatment, especially those patients who are frail or have comorbidities. Thus, this population should be screened prior to treatment for such predispositions to maximize medical management of comorbidities. Chronologic age itself is not a reason for choosing less intensive treatment for older HNC patients. Whenever possible, also older patients should be treated according to the best standard of care, as nonstandard approaches may result in increased treatment failure rates and mortality. The treatment plan is best established by a multidisciplinary tumor board with shared decision-making with patients and family. Treatment modifications should be considered for those patients who have severe comorbidities, evidence of frailty (low performance status), or low performance status or those who refuse the recommendations of the tumor board.

Management of Recurrent Well-Differentiated Thyroid Carcinoma in the Neck: A Comprehensive Review.

Surgery has been historically the preferred primary treatment for patients with well-differentiated thyroid carcinoma and for selected locoregional recurrences. Adjuvant therapy with radioactive iodine is typically recommended for patients with an intermediate to high risk of recurrence. Despite these treatments, locally advanced disease and locoregional relapses are not infrequent. These patients have a prolonged overall survival that may result in long periods of active disease and the possibility of requiring subsequent treatments. Recently, many new options have emerged as salvage therapies. This review offers a comprehensive discussion and considerations regarding surgery, active surveillance, radioactive iodine therapy, ultrasonography-guided percutaneous ablation, external beam radiotherapy, and systemic therapy for well-differentiated thyroid cancer based on relevant publications and current reference guidelines. We feel that the surgical member of the thyroid cancer management team is empowered by being aware and facile with all management options.

Evaluating new treatments for anaplastic thyroid cancer.

INTRODUCTION: Anaplastic thyroid cancer (ATC) is one of the most lethal diseases known to humans with a median survival of 5 months. The American Thyroid Association (ATA) recently published guidelines for the treatment of this dreadful thyroid malignancy. AREAS COVERED: This review presents the current therapeutic landscape of this challenging disease. We also present the results from trials published over the last five years and summarize currently active clinical trials. EXPERT OPINION: Recent attempts to improve the prognosis of these tumors are moving toward personalized medicine, basing the treatment decision on the specific genetic profile of the individual tumor. The positive results of dabrafenib and trametinib for ATC harboring the BRAF V600E mutation have provided a useful treatment option. For the other genetic profiles, different drugs are available and can be used to individualize the treatment, likely using drug combinations. Combinations of drugs act on different molecular pathways and achieve inhibition at separate areas. With new targeted therapies, average survival has improved considerably and death from local disease progression or airway compromise is less likely with improvement in quality of life. Unfortunately, the results remain poor in terms of survival.

Primary hyperparathyroidism: Disease of diverse genetic, symptomatic, and biochemical phenotypes.

Genetic, symptomatic, and biochemical heterogeneity of patients with primary hyperparathyroidism (PHPT) has become apparent in recent years. An in-depth, evidence-based review of the phenotypes of PHPT was conducted. This review was intended to provide the resulting information to surgeons who operate on patients with hyperparathyroidism. This review revealed that the once relatively clear distinction between familial and sporadic PHPT has become more challenging by the finding of various germline mutations in patients with seemingly sporadic PHPT. On the one hand, the genetic and clinical characteristics of some syndromes in which PHPT is an important component are now better understood. On the other hand, knowledge is emerging about novel syndromes, such as the rare multiple endocrine neoplasia type IV (MEN4), in which PHPT occurs frequently. It also revealed that, currently, the classical array of symptoms of PHPT is seen rarely upon initial presentation for evaluation. More common are nonspecific, nonclassical symptoms and signs of PHPT. In areas of the world where serum calcium levels are checked routinely, most patients today are "asymptomatic" and they are diagnosed after an incidental finding of hypercalcemia; however, some of them have subclinical involvement of bones and kidneys, which is demonstrated on radiographs, ultrasound, and modern imaging techniques. Last, the review points out that there are three distinct biochemical phenotypes of PHPT. The classical phenotype in which calcium and parathyroid hormone levels are both elevated, and other disease presentations in which the serum levels of calcium or intact parathyroid hormone are normal. Today several, distinct phenotypes of the disease can be identified, and they have implications in the diagnostic evaluation and treatment of patients, as well as possible screening of relatives.

Hürthle Cell Carcinoma of the Thyroid Gland: Systematic Review and Meta-analysis.

INTRODUCTION: Hürthle cell carcinoma (HCC) comprises about 5% of thyroid carcinoma cases. Partly because of its rarity there is much we still need to know about HCC as compared to other histological cancer subtypes. METHODS: We conducted a systematic literature review following PRISMA guidelines and meta-analysis, from 2000 to 2020, to investigate the main characteristics of HCC and clarify information concerning tumor behavior and treatment. RESULTS: Our review included data from 9638 patients reported in 27 articles over the past 20 years. This tumor occurred more frequently in women (67.5%). The mean age was 57.6 years, and the mean size of the neoplasm at diagnosis was 30 mm. Extrathyroidal extension was common (24%) but lymph node metastasis was not (9%). Total thyroidectomy was the most common surgical approach, with neck dissection usually performed in cases with clinically apparent positive neck nodes. Radioiodine therapy was frequently applied (54%), although there is no consensus about its benefits. The mean 5- and 10-year overall survival was 91% and 76%, respectively. CONCLUSION: This review serves to further elucidate the main characteristics of this malignancy. HCC of the thyroid is rare and most often presents with a relatively large nodule, whereas lymph node metastases are rare. Given the rarity of HCC, a consensus on their treatment is needed, as doubts remain concerning the role of specific tumor findings and their influence on management.

Current Trends and Controversies in the Management of Warthin Tumor of the Parotid Gland.

PURPOSE: To review the current options in the management of Warthin tumors (WTs) and to propose a working management protocol. METHODS: A systematic literature search was conducted using PubMed and ScienceDirect database. A total of 141 publications were selected and have been included in this review. Publications were selected based on relevance, scientific evidence, and actuality. RESULTS: The importance of parotid WTs is increasing due to its rising incidence in many countries, becoming the most frequently encountered benign parotid tumor in certain parts of the world. In the past, all WTs were treated with surgery, but because of their slow growth rate, often minimal clinical symptoms, and the advanced age of many patients, active observation has gradually become more widely used. In order to decide on active surveillance, the diagnosis of WT must be reliable, and clinical, imaging, and cytological data should be concordant. There are four clear indications for upfront surgery: uncertain diagnosis; cosmetic problems; clinical complaints, such as pain, ulceration, or recurrent infection; and the patient's wish to have the tumor removed. In the remaining cases, surgery can be elective. Active surveillance is often suggested as the first approach, with surgery being considered if the tumor progresses and/or causes clinical complaints. The extent of surgery is another controversial topic, and the current trend is to minimize the resection using partial parotidectomies and extracapsular dissections when possible. Recently, non-surgical options such as microwave ablation, radiofrequency ablation, and ultrasound-guided ethanol sclerotherapy have been proposed for selected cases. CONCLUSIONS: The management of WT is gradually shifting from superficial or total parotidectomy to more conservative approaches, with more limited resections, and to active surveillance in an increasing number of patients. Additionally, non-surgical treatments are emerging, but their role needs to be defined in future studies.

Salvage surgery for residual or recurrent laryngeal squamous cell carcinoma after (Chemo)radiotherapy: Oncological outcomes and prognostic factors.

Nonsurgical primary treatment of early and advanced laryngeal squamous cell carcinoma, employing radiotherapy with or without chemotherapy, is considered a standard of care in many centers throughout the world. When patients have persistent or recurrent disease after non-surgical treatment, salvage surgery is frequently the only remaining potentially curative treatment. Depending on the extent of the residual/recurrent disease, different surgical salvage options are at the surgeon's disposal. In selected cases with limited local disease, salvage transoral laser microsurgery, transoral robotic surgery and open partial laryngectomies can be employed to achieve cure while preserving laryngeal function. For more advanced cases total laryngectomy is necessary. Identifying situations with unacceptable results from surgical salvage may guide future therapies.

Contemporary management of the neck in nasopharyngeal carcinoma.

Up to 85% of the patients with nasopharyngeal carcinoma present with regional nodal metastasis. Although excellent nodal control is achieved with radiotherapy, a thorough understanding of the current TNM staging criteria and pattern of nodal spread is essential to optimize target delineation and minimize unnecessary irradiation to adjacent normal tissue. Selective nodal irradiation with sparing of the lower neck and submandibular region according to individual nodal risk is now emerging as the preferred treatment option. There has also been continual refinement in staging classification by incorporating relevant adverse nodal features. As for the uncommon occurrence of recurrent nodal metastasis after radiotherapy, surgery remains the standard of care.

Incidence of Occult Lymph Node Metastasis in Primary Larynx Squamous Cell Carcinoma, by Subsite, T Classification and Neck Level: A Systematic Review.

BACKGROUND: Larynx cancer is a common site for tumors of the upper aerodigestive tract. In cases with a clinically negative neck, the indications for an elective neck treatment are still debated. The objective is to define the prevalence of occult metastasis based on the subsite of the primary tumor, T classification and neck node levels involved. METHODS: All studies included provided the rate of occult metastases in cN0 larynx squamous cell carcinoma patients. The main outcome was the incidence of occult metastasis. The pooled incidence was calculated with random effects analysis. RESULTS: 36 studies with 3803 patients fulfilled the criteria. The incidence of lymph node metastases for supraglottic and glottic tumors was 19.9% (95% CI 16.4-23.4) and 8.0% (95% CI 2.7-13.3), respectively. The incidence of occult metastasis for level I, level IV and level V was 2.4% (95% CI 0-6.1%), 2.0% (95% CI 0.9-3.1) and 0.4% (95% CI 0-1.0%), respectively. For all tumors, the incidence for sublevel IIB was 0.5% (95% CI 0-1.3). CONCLUSIONS: The incidence of occult lymph node metastasis is higher in supraglottic and T3-4 tumors. Level I and V and sublevel IIB should not be routinely included in the elective neck treatment of cN0 laryngeal cancer and, in addition, level IV should not be routinely included in cases of supraglottic tumors.

Facial nerve electrodiagnostics for patients with facial palsy: a clinical practice guideline.

PURPOSE: Facial nerve electrodiagnostics is a well-established and important tool for decision making in patients with facial nerve diseases. Nevertheless, many otorhinolaryngologist-head and neck surgeons do not routinely use facial nerve electrodiagnostics. This may be due to a current lack of agreement on methodology, interpretation, validity, and clinical application. Electrophysiological analyses of the facial nerve and the mimic muscles can assist in diagnosis, assess the lesion severity, and aid in decision making. With acute facial palsy, it is a valuable tool for predicting recovery. METHODS: This paper presents a guideline prepared by members of the International Head and Neck Scientific Group and of the Multidisciplinary Salivary Gland Society for use in cases of peripheral facial nerve disorders based on a systematic literature search. RESULTS: Required equipment, practical implementation, and interpretation of the results of facial nerve electrodiagnostics are presented. CONCLUSION: The aim of this guideline is to inform all involved parties (i.e. otorhinolaryngologist-head and neck surgeons and other medical specialists, therapeutic professionals and the affected persons) and to provide practical recommendations for the diagnostic use of facial nerve electrodiagnostics.

Parathyroid cancer: An update.

Parathyroid cancer (PC) is a rare malignant tumor which comprises 0.5-5% of patients with primary hyperparathyroidism (PHPT). Most of these cancers are sporadic, although it may also occur as a feature of various genetic syndromes including hyperparathyroidism-jaw tumor syndrome (HPT-JT) and multiple endocrine neoplasia (MEN) types 1 and 2A. Although PC is characterized by high levels of serum ionized calcium (Ca) and parathyroid hormone (PTH), the challenge to the clinician is to distinguish PC from the far more common entities of parathyroid adenoma (PA) or hyperplasia, as there are no specific clinical, biochemical, or radiological characteristic of PC. Complete surgical resection is the only known curative treatment for PC with the surgical approach during initial surgery strongly influencing the outcome. In order to avoid local recurrence, the lesion must be removed en-bloc with clear margins. PC has high recurrence rates of up to 50% but with favorable long-term survival rates (10-year overall survival of 60-70%) due to its slow-growing nature. Most patients die not from tumor burden directly but from uncontrolled severe hypercalcemia. In this article we have updated the information on PC by reviewing the literature over the past 10 years and summarizing the findings of the largest series published in this period.

Paraneoplastic Syndromes Associated with Laryngeal Cancer.

OBJECTIVES: Paraneoplastic syndromes occur rarely in association with laryngeal cancer. When present, the syndrome may be the first sign of the malignancy. The aim of the present study was to review and report on all published cases in the international literature. METHODS: A search of PubMed was conducted for "paraneoplastic syndromes in laryngeal cancer" without any restrictions on language or publication year. The full texts of all relevant articles were reviewed and all cases of paraneoplastic syndromes associated with any type of laryngeal cancer were extracted and analyzed. RESULTS: We identified 59 cases of paraneoplastic syndromes related to laryngeal cancer in the literature published from 1963 until recently. There were 46 squamous cell carcinomas and 10 neuroendocrine carcinomas. Twenty-two of the paraneoplastic syndromes involved the endocrine system, 21 were dermatologic or cutaneous, 8 neurologic, 5 osteoarticular or rheumatologic, 1 ocular, 1 muscular, and 1 hematologic. Treatment strategies included surgery, radiotherapy, chemotherapy, and often multimodal therapy, depending on the histology and stage of the laryngeal cancer. CONCLUSIONS: Because of their rarity, paraneoplastic syndromes associated with laryngeal cancer are difficult to diagnose. By presenting and systematically reviewing all published cases in the international literature, the present review may help clinicians to recognize them and to suspect the diagnosis of laryngeal cancer at an earlier stage than otherwise might be possible.

Thyroid Surgery: Whose Domain Is It?

In the United States of America (US), most departments of otorhinolaryngology head and neck surgery have been performing thyroid surgery for many years. In contrast to the US, thyroid surgery is still dominated by general surgeons in most European countries. In numerous university centers, there continues to be friction regarding thyroid surgery. The focus of this editorial is to demonstrate that there is objective data in the literature to suggest that otorhinolaryngologists with appropriate training in head and neck surgery are well suited to perform the entire spectrum of thyroid surgery. The question of who is qualified to perform thyroid surgery is not determined by the basic specialty certification of the surgeon-general or otolaryngology; rather it depends on the training, skill and experience in surgery of the neck, of post-surgical and post-irradiated necks, and of neighboring structures.

Transoral laser microsurgery for glottic cancer in the elderly: Efficacy and safety.

BACKGROUND: Data about the results of transoral laser microsurgery (TLM) in elderly patients are limited. METHODS: A retrospective study of 72 consecutive cases of glottic carcinoma (63 pT1 and 9 pT2 cases) in elderly patients (≥70 years old, mean 76 years) treated with TLM was made. A systematic review of the literature was performed. RESULTS: Six patients (8%) had postoperative complications, but no treatment-related deaths were observed. Local recurrences occurred in 12 patients (16.5%): nine with pT1 (14%) and three with pT2 (33%) tumors. Five-year disease-specific survival (DSS), overall survival, and laryngectomy-free survival were 95%, 68%, and 88%, respectively. The literature review indicated that TLM is safe and effective treatment for these patients, with few complications and good local control (>85%) and DSS (>90%) rates. CONCLUSIONS: Our results and the information from the literature show that TLM for glottic cancer in elderly patients can lead to satisfactory treatment results.

Surgical margins in head and neck cancer: Intra- and postoperative considerations.

OBJECTIVE: To provide a perspective on the significance of recent reports for optimizing cancer free surgical margins that have challenged standard practices. METHODS: We conducted a review of the recent literature (2012-2018) using the keywords surgical margin analysis, frozen and paraffin section techniques, head and neck cancer, spectroscopy and molecular markers. RESULTS: Of significance are the reports indicating superiority of tumor specimen directed sampling of margins compared to patient directed (tumor bed) sampling for frozen section control of oral cancers. With reference to optimal distance between tumor and the surgical margin, recent reports recommended cutoffs less than 5mm. Employment of new technologies such as light spectroscopy and molecular analysis of tissues, provide opportunities for a "real time" assessment of surgical margins. CONCLUSIONS: The commonly practiced method of patient directed margin sampling involving previous studies raises concern over conclusions made regarding the efficacy of frozen section margin control. The recent studies that challenge the optimal distance for clear surgical margins are retrospective and address patient cohorts with inherently confounding factors. The use of novel ancillary techniques require further refinements, clinical trial validation, and justification based on the additional resources.

Molecular and health effects in the upper respiratory tract associated with tobacco smoking other than cigarettes.

The objective of the review was to compare molecular and health effects of tobacco smoking using cigars, cigarillos, pipe and water pipe in relation to the effects of cigarette smoking. In this review we will focus on the upper respiratory tract. Mechanisms of interaction of tobacco smoke constituents after products other than cigarettes are similar to these associated with cigarette smoking. Carcinogenic activity was demonstrated for any type of tobacco smoking, although the risk of developing head and neck squamous cell carcinoma (HNSCC) remains lower in users of cigars, traditional pipe and water pipe as compared to cigarette smoking. Nevertheless, there is no way of safe tobacco smoking.

Carotid blowout syndrome: modern trends in management.

Carotid blowout syndrome (CBS) refers to rupture of the carotid artery and is an uncommon complication of head and neck cancer that can be rapidly fatal without prompt diagnosis and intervention. CBS develops when a damaged arterial wall cannot sustain its integrity against the patient's blood pressure, mainly in patients who have undergone surgical procedures and radiotherapy due to cancer of the head and neck, or have been reirradiated for a recurrent or second primary tumor in the neck. Among patients irradiated prior to surgery, CBS is usually a result of wound breakdown, pharyngocutaneous fistula and infection. This complication has often been fatal in the past, but at the present time, early diagnosis and modern technology applied to its management have decreased morbidity and mortality rates. In addition to analysis of the causes and consequences of CBS, the purpose of this paper is to critically review methods for early diagnosis of this complication and establish individualized treatment based on endovascular procedures for each patient.

Management of the facial nerve in parotid cancer: preservation or resection and reconstruction.

PURPOSE: Management of the facial nerve is instrumental in the surgical treatment of parotid cancer. METHODS: A literature search was conducted using PubMed and ScienceDirect database. A total of 195 articles were finally included into the analysis, based on relevance, scientific evidence and actuality. RESULTS: In the majority of cases the facial nerve is not involved by tumor. In these cases, identification and preservation of the nerve, in addition to complete tumor removal, are essential for successful surgery. When the nerve is infiltrated by tumor, the affected portion of the nerve must be resected as part of radical parotidectomy. Primary nerve reconstruction or other reanimation techniques give the best long-term functional and cosmetic results. A comprehensive diagnostic evaluation with current imaging and electrophysiological studies will provide the surgeon with the best knowledge of the relationship of the facial nerve to the tumor. Several standardized methods are helpful in finding, dissecting and preserving the nerve during parotid cancer surgery. When radical parotidectomy is indicated, the initial diagnostic work-up can assist in defining the need for adjuvant postoperative therapy and facial reanimation. The aim of rehabilitation is to restore tone, symmetry, and movement to the paralyzed face. CONCLUSIONS: The surgical management of facial paralysis has undergone many improvements in recent years. This review gives an overview of recent advances in the diagnostic work-up, surgical techniques and any necessary rehabilitation of the facial nerve in parotid cancer surgery.

Radiation-induced carotid artery lesions.

PURPOSE: To review the current aspects of knowledge related to the risk of cerebrovascular events in patients receiving head and neck radiotherapy. METHODS: A literature search was performed in PubMed. Papers meeting selection criteria were reviewed. RESULTS: We provide an update on the problem by identifying key studies that have contributed to our current understanding of the epidemiology, radiologic features, pathogenesis, and treatment of the disease. The incidence of carotid artery stenosis ranged from 18 to 38% in patients who underwent radiotherapy for head and neck cancer versus from 0 to 9.2% among the nonirradiated patients. Neck irradiation increases the intima-media thickness of the carotid artery wall. These changes are the earliest visible alteration in the carotid wall and are also detected with color Doppler ultrasonography. Endovascular treatment with a carotid angioplasty and stenting is the first-line treatment for most symptomatic patients. CONCLUSIONS: Radiation-induced atherosclerosis is a different and accelerated form of atherosclerosis, which implies a more aggressive disease with a different biologic behavior. The disease is characterized by a high rate of carotid artery stenosis compared to those observed in nonirradiated control group patients. To prevent the risk of stroke, surveillance and imaging with ultrasonography should enable detection of severe stenosis. Endovascular treatment with a carotid angioplasty and stenting has been proposed as an attractive and minimally invasive alternative for some radiation-induced stenoses.