Novel Immunotherapeutic Approaches to Treating HPV-Related Head and Neck Cancer.

Head and neck cancer (HNC) is the seventh most common malignancy, with oropharyngeal squamous cell carcinoma (OPSCC) accounting for a majority of cases in the western world. While HNC accounts for only 5% of all cancers in the United States, the incidence of a subset of OPSCC caused by human papillomavirus (HPV) is increasing rapidly. The treatment for OPSCC is multifaceted, with a recently emerging focus on immunotherapeutic approaches. With the increased incidence of HPV-related OPSCC and the approval of immunotherapy in the management of recurrent and metastatic HNC, there has been rising interest in exploring the role of immunotherapy in the treatment of HPV-related OPSCC specifically. The immune microenvironment in HPV-related disease is distinct from that in HPV-negative OPSCC, which has prompted further research into various immunotherapeutics. This review focuses on HPV-related OPSCC, its immune characteristics, and current challenges and future opportunities for immunotherapeutic applications in this virus-driven cancer.

Neck Surgery for Non-Well Differentiated Thyroid Malignancies: Variations in Strategy According to Histopathology.

Lymph node metastases in non-well differentiated thyroid cancer (non-WDTC) are common, both in the central compartment (levels VI and VII) and in the lateral neck (Levels II to V). Nodal metastases negatively affect prognosis and should be treated to maximize locoregional control while minimizing morbidity. In non-WDTC, the rate of nodal involvement is variable and depends on the histology of the tumor. For medullary thyroid carcinomas, poorly differentiated thyroid carcinomas, and anaplastic thyroid carcinomas, the high frequency of lymph node metastases makes central compartment dissection generally necessary. In mucoepidermoid carcinomas, malignant peripheral nerve sheath tumors, sarcomas, and malignant thyroid teratomas or thyroblastomas, central compartment dissection is less often necessary, as clinical lymphnode involvement is less common. We aim to summarize the medical literature and the opinions of several experts from different parts of the world on the current philosophy for managing the neck in less common types of thyroid cancer.

Review: Improving quality of life in patients with differentiated thyroid cancer.

Well differentiated thyroid cancer is a common malignancy diagnosed in young patients. The prognosis tends to be excellent, so years of survivorship is expected with low risk disease. When making treatment decisions, physicians should consider long-term quality of life outcomes when guiding patients. The implications for treating indolent, slow growing tumors are immense and warrant careful consideration for the functioning years ahead. Surgery is the standard of care for most patients, however for a subset of patients, active surveillance is appropriate. For those wishing to treat their cancer in a more active way, novel remote access approaches have emerged to avoid a cervical incision. In the era of "doing less", options have further expanded to include minimally invasive approaches, such as radiofrequency ablation that avoids an incision, time off work, a general anesthetic, and the possibility of post-treatment hypothyroidism. In this narrative review, we examine the health related quality of life effects that surgery has on patients with thyroid cancer, including some of the newer innovations that have been developed to address patient concerns. We also review the impact that less aggressive treatment has on patient care and overall wellbeing in terms of active surveillance, reduced doses of radioactive iodine (RAI) treatment, or minimally invasive techniques such as radiofrequency ablation (RFA) for low risk thyroid disease.

Surgical treatment of thyroid cancer: Established and novel approaches.

Thyroid surgery is one of the most common head and neck procedures. The thyroid can be accessed through an anterior cervical incision, or by remote access techniques such as the transoral endoscopic thyroidectomy vestibular approach (TOETVA) which is favored for its ease, safety and direct plane to the thyroid gland. Other novel approaches for targeting small-localized well-differentiated thyroid cancer are by thermal ablation, namely ultrasound guided radiofrequency ablation. These innovative techniques for minimizing a cutaneous scar or for targeting small cancers directly without removal of the gland have developed alongside our realization that low risk well-differentiated thyroid cancer tends to be slow growing and indolent. Up to date, the most robust data supports offering these therapies primarily to patients who would be eligible for active surveillance protocols. In this paper, we review the traditional surgical approaches for removing well-differentiated thyroid cancer, as well as innovative remote access techniques (namely TOETVA), and minimally invasive thermal ablation (namely RFA).

Epstein-Barr virus directed screening for nasopharyngeal carcinoma in individuals with positive family history: A systematic review.

OBJECTIVES: Evidence to support Epstein-Barr virus (EBV)-directed population nasopharyngeal carcinoma (NPC) screening has been growing. Familial aggregation is a well-recognized phenomenon in endemic regions. This systematic review summarizes the role of EBV-directed screening in individuals with a positive family history (FH+) of NPC. METHODS: We searched four electronic databases from their inception to October 2021. We included studies on individuals with FH+ of NPC who had undergone EBV-directed investigations, with no restriction in the testing methods or analytic techniques. The primary and secondary outcomes were EBV positivity rates and NPC incidence rates, respectively. Meta-analyses were performed using the random-effect model. RESULTS: Ten cross-sectional studies (n = 7436) and three cohort studies (n = 4306) were included. The pooled relative risk (RR) of EBV positivity between individuals with and without FH+ of NPC were 2.79 (95 % CI 1.37-5.68, p = 0.005) for viral capsid antigen (VCA) IgA, 3.09 (95 % CI 0.65-14.83, p = 0.16) for Epstein-Barr nuclear antigen (EBNA1) IgA, and 1.76 (95 % CI 1.04-2.96, p = 0.03) for combined EBNA1/VCA IgA. In the three cohort studies, the NPC incidence rates ranged from 90.2 to 266 per 100 000 person-years with high proportions of early-stage diseases. FH+ individuals who were EBV-positive had a 2.5 to 30.7-fold risk of NPC development compared to their EBV-negative counterparts. CONCLUSION: Family members of NPC patients had significantly higher EBV positivity rates than the general population. FH+ individuals who are EBV-positive had high risks of developing NPC. Familial screening using EBV serology may facilitate early NPC detection in endemic areas.

Improving Voice Outcomes after Thyroid Surgery and Ultrasound-Guided Ablation Procedures.

The field of endocrine surgery has expanded from the traditional open neck approach to include remote access techniques as well as minimally invasive approaches for benign and malignant thyroid nodules. In experienced hands and with careful patient selection, each approach is considered safe, however complications can and do exist. Post-operative dysphonia can have serious consequences to the patient by affecting quality of life and ability to function at work and in daily life. Given the significance of post-procedural dysphonia, we review the surgical and non-surgical techniques for minimizing and treating recurrent laryngeal nerve injury that can be utilized with the traditional open neck approach, remote access thyroidectomy, or minimally invasive thermal ablation.

The Treatment of Thyroid Cancer With Radiofrequency Ablation.

In the past decade, there has seen been a shift from treating all thyroid cancer surgically, to favoring less aggressive approaches for low-risk thyroid cancer. Surgery was historically the treatment of choice for most thyroid cancer. Active surveillance has emerged as an alternative for low-risk thyroid cancer in select patients. This approach has been accepted worldwide, and sound evidence supports its oncological safety in carefully selected patients. However, not all patients want to undergo lifelong monitoring, and some patients may wish to treat their cancer in a minimally invasive manner. Thermal ablation has developed as a minimally invasive alternative to surgery and active surveillance for well selected patients with thyroid malignancy. Herein, we review the role of thermally ablative techniques, specifically radiofrequency ablation, for the treatment of small primary thyroid cancers, recurrent thyroid cancer, and lymph node metastases.

Intraoperative Neuromonitoring: Evaluating the Role of Continuous IONM and IONM Techniques for Emerging Surgical and Percutaneous Procedures.

Continuous and intermittent intraoperative nerve monitoring (IONM) has become an important asset for endocrine surgeons over the past few decades. The ability to determine neurophysiologic integrity of the recurrent laryngeal nerve (RLN) and external branch of the superior laryngeal nerve (EBSLN) on top of identification and meticulous dissection of the nerve in the surgical field, has allowed for advances in technology and improved outcomes when it comes to prevention of vocal fold immobility. This article aims to compare in review continuous and intermittent nerve monitoring (CIONM, IIONM), as well as review the current paradigms of their use. This article will also discuss the future of intraoperative nerve monitoring technologies in scarless thyroid surgery and percutaneous approaches to thyroid pathology in form of radiofrequency ablation (RFA).

Revisiting the role of surgery in the treatment of Graves' disease.

Graves' disease (GD) can be managed by antithyroid drugs (ATD), radioactive iodine (RAI) and surgery. Thyroidectomy offers the highest success rates for both primary and persistent disease, yet it is the least recommended or utilized option reaching <1% for primary disease and <25% for persistent disease. Several surveys have found surgery to be the least recommended by endocrinologists worldwide. With the development of remote access thyroidectomies and intraoperative nerve monitoring of the recurrent laryngeal nerve, combined with current knowledge of possible risks associated with RAI or failure of ATDs, revaluation of the benefit to harm ratio of surgery in the treatment of GD is warranted. The aim of this review is to discuss possible reasons for the low proportion of surgery in the treatment of GD, emphasizing an evidence-based approach to the clinicians' preferences for surgical referrals, surgical indications and confronting traditional reasons and concerns relating to the low referral rate with up-to-date data.

Update of Radiofrequency Ablation for Treating Benign and Malignant Thyroid Nodules. The Future Is Now.

Thermal and chemical ablation are minimally invasive procedures that avoid removal of the thyroid gland and target symptomatic nodules directly. Internationally, Radiofrequency ablation (RFA) is among one of the most widely used thermal ablative techniques, and is gaining traction in North America. Surgery remains the standard of care for most thyroid cancer, and in the right clinical setting, Active Surveillance (AS) can be a reasonable option for low risk disease. Minimally invasive techniques have emerged as an alternative option for patients deemed high risk for surgery, or for those patients who wish to receive a more active treatment approach compared to AS. Herein, we review the literature on the safety and efficacy of RFA for treating benign non-functioning thyroid nodules, autonomously functioning thyroid nodules, primary small low risk thyroid cancer (namely papillary thyroid cancer) as well as recurrent thyroid cancer.

Transoral Thyroidectomy: Safety and Outcomes of 200 Consecutive North American Cases.

BACKGROUND: North American adoption of the transoral endoscopic thyroidectomy vestibular approach (TOETVA) has been limited due to concerns regarding the generalizability of published outcomes, as data are predominantly from Asian cohorts with a different body habitus. We describe our experience with TOETVA in a North American population in the context of the conventional transcervical approach thyroidectomy (TCA). STUDY DESIGN: Cases of TOETVA and TCA were reviewed from August 2017 to March 2020 at a tertiary care center. Outcomes included operative time, major (permanent recurrent laryngeal nerve (RLN) injury, permanent hypoparathyroidism, hematoma, conversion to open surgery), and minor complications. The TOETVA cohort was stratified into body mass index (BMI) classes of underweight/normal < 25 kg/m2, overweight 25-29.9 kg/m2, and obese ≥ 30 kg/m2 for comparative analysis. Multivariable logistic regression analyses were performed for odds of cumulative complication. RESULTS: Two hundred TOETVA and 333 TCA cases were included. There was no difference in incidence of major complications between the TOETVA and TCA cohorts (1.5% vs. 2.1%, p = 0.75). No difference was found in the rate of temporary RLN injury (4.5% vs. 2.1%, p = 0.124) or temporary hypoparathyroidism (18.2% vs. 12.5%, p = 0.163) for TOETVA and TCA, respectively. Surgical technique (TOETVA vs TCA) did not alter the odds of cumulative complication (OR 0.69 95% CI [0.26-1.85]) on logistic regression analysis. In the TOETVA cohort, higher BMI did not lead to a significantly greater odds of cumulative complication, 0.52 (95% CI [0.17-1.58]) and 1.69 (95% CI [0.74-3.88]) for the overweight and obese groups, respectively. CONCLUSION: TOETVA can be performed in a North American patient population without a difference in odds of complication compared to TCA. Higher BMI is not associated with greater likelihood of complication with TOETVA.

Novel Approaches for Treating Autonomously Functioning Thyroid Nodules.

Benign thyroid nodules are exceedingly common in the adult population. Only a small percentage of nodules are toxic or autonomously functioning thyroid nodules (AFTNs). The options clinicians have for treating the symptoms of hyperthyroidism include anti-thyroidal medications, radioactive iodine, or surgery. Depending on the patient population treated, these options may not be suitable or have inherent risks that are undesirable to the patient. On the other hand, untreated hyperthyroidism can lead to osteoporosis, atrial fibrillation, emotional lability, and neurological consequences. Thus, we present a review of two novel safe and effective approaches for treating AFTN; one surgical (transoral endoscopic thyroid surgery) and one non-surgical (radiofrequency ablation), as a means for expanding our treatment armamentarium.

Imaging and choosing the right patients for transoral endoscopic parathyroidectomy vestibular approach.

Advances in imaging for preoperative localization have propelled the widespread adoption of minimally invasive/focused parathyroidectomy in primary hyperparathyroidism. Though it is performed through a relatively small incision, studies have shown that the presence of a neck scar increases attentional bias towards the neck resulting in compromised quality of life. Transoral endoscopic parathyroidectomy vestibular approach (TOEPVA) eliminates a neck scar. While indications for TOEPVA are the same as that of minimally invasive open parathyroidectomy, confident preoperative localization of the parathyroid with a surgeon performed ultrasound along with concordant localization with SPECT CT is an essential prerequisite before offering patients this approach for parathyroidectomy. Early data has demonstrated the feasibility and safety of this approach.

Health care professionals' neckties as a source of transmission of bacteria to patients: a systematic review.

BACKGROUND: There is growing concern that neckties worn by health care professionals may contribute to infections contracted in health care settings. We evaluated the evidence for health-care-associated infections resulting from neckties and whether the evidence is sufficient to warrant a tieless policy in Canada. METHODS: We performed a systematic review to determine whether neckties worn by health care professionals colonize harmful pathogenic bacteria and whether they contribute to the spread of infection to patients in the inpatient or outpatient setting. We searched PubMed (1966 to 2017) and Embase (1974 to 2017). The level of evidence was appraised according to the Oxford Centre for Evidence-Based Medicine levels of evidence. We evaluated the quality of evidence and the risk of bias using the Jadad scale or the Newcastle-Ottawa Scale. RESULTS: We screened 1675 citations, of which 6 were ultimately included in the systematic review. Only 1 study gave level 1b evidence (randomized controlled trial). Neckties were more likely than shirt pockets to colonize bacteria. There is limited evidence that neckties may be contaminated with pathogenic bacteria (e.g., methicillin-resistant Staphylococcus aureus) and very limited evidence that contaminated neckties may transmit bacteria (in a controlled experimental setting to a mannequin). INTERPRETATION: There is no evidence of increased rates of health-care-associated infections related to the wearing of neckties by health care professionals. There is weak evidence that neckties are contaminated with pathogenic (and nonpathogenic) bacteria. The level of evidence was weak and the studies were heterogeneous. Evidence to support the need for a tieless dress code policy is lacking.

Randomized controlled trial: hybrid technique using balloon dilation of the frontal sinus drainage pathway.

BACKGROUND: The objectives of this study were as follows: (1) to evaluate frontal sinus ostial patency following balloon dilation with the Ventera Sinus Dilation System, compared with frontal sinusotomy (Draf 2a); and (2) to compare mean blood loss and mean surgical time for frontal sinusotomy using balloon dilation compared with traditional surgical methods. METHODS: A single blinded, randomized, controlled, prospective study was performed at St. Paul's Sinus Center, Vancouver, a tertiary referral rhinology center. Thirty patients undergoing functional endoscopic sinus surgery (FESS) for chronic rhinosinusitis (CRS) were randomized to a hybrid approach with exposure of the frontal recess using standard instrumentation and then balloon dilation of 1 frontal sinus drainage pathway and traditional frontal sinusotomy for the opposite side. Blood loss and surgical time for opening the frontal sinus drainage pathway was recorded for each side. Patients acted as their own controls. Ostial patency and size were assessed 5 weeks and 3 months postoperatively using endoscopy. Ostial patency was also recorded at 1 year following surgery. RESULTS: All frontal sinus ostia in both groups (n = 30) were successfully opened and were patent with both techniques 3 months postoperatively. All frontal sinus ostia assessed at 1 year (73%) remained patent and none required revision frontal surgery. Balloon dilation showed a mean surgical time of 655 seconds compared to 898 seconds for traditional FESS (p = 0.03). Mean blood loss was less with balloon dilation (58 mL vs 91 mL; p = 0.008). CONCLUSION: A hybrid balloon technique successfully dilates the frontal sinus drainage pathway with reduced blood loss. Also, short-term patency appears to be comparable to traditional frontal sinusotomy.

The rhinological manifestations of women's health.

OBJECTIVE: To systematically review the literature and appraise the evidence reporting the effects of women's health, including pregnancy, postpartum, menstruation, oral contraception, menopause, and hormone replacement therapy, on common rhinological pathologies and nasal physiology. DATA SOURCES: Systematic search strategy using MEDLINE (1966-2012) and EMBASE (1980-2012) databases. REVIEW METHODS: Title review, abstract screening, and then full paper analysis were undertaken by 2 authors independently. Level of evidence was graded according to the Oxford Centre of Evidence Based Medicine 2011 criteria and risk of bias assessment using the Jadad scale for randomized controlled trials and Newcastle-Ottawa Scale for cohort and case-controlled studies. RESULTS: Over the 46 years analyzed, the search strategy produced 2904 titles. In total, 314 abstracts were screened, from which 192 full-text articles were evaluated, and 145 research papers met all the criteria for inclusion in the study. Overall, the available evidence was of low quality. Seventy percent of studies (102 of 145) were case reports or case series from which only limited conclusions can be drawn. Only 3% of the included papers (4 of 145) were randomized controlled studies. The remaining data were mainly of a prospective cohort design. Study heterogeneity in design and measured outcomes resulted in data synthesis being limited to a descriptive/exploratory review. Study findings are presented by women's health category and then by rhinological manifestation with important clinical correlations highlighted. CONCLUSION: Physiological and hormonal changes occurring as a normal part of women's health have an important influence on rhinological function and disease.

Laryngeal candidiasis in the outpatient setting.

OBJECTIVES: We present the largest case series on laryngeal candidiasis and review the literature on the diagnosis and management of laryngeal candidiasis. SUBJECTS AND METHODS: Fifty-four patients were included in a retrospective chart review of all cases seen at the Pacific Voice Clinic, University of British Columbia, Vancouver, from 1995 to 2005. RESULTS: The most common presenting symptom was dysphonia (37 patients; 69%). Forty-eight patients (89%) were on steroid inhalers, and four patients (7%) were on oral prednisone. In terms of anatomic involvement, 18 patients (33%) showed Candida involvement in all three anatomic locations: the hypopharynx, the supraglottis, and the glottis. In 15 patients (28%), the Candida was isolated to the glottis. The remaining patients showed subglottic and glottic involvement. Fifty-two patients (96%) were successfully treated with a single course of an oral antifungal. CONCLUSION: The most common risk factor identified was inhaled steroids. Most often, laryngeal candidiasis is effectively treated with oral antifungal medications.

Case Series: raising awareness about Kikuchi-Fujimoto disease among otolaryngologists: is it linked to systemic lupus erythematosus?

OBJECTIVES: Kikuchi-Fujimoto disease (KFD) is a rare, benign, self-limiting condition occasionally associated with systemic lupus erythematosus (SLE). Although rising in incidence, nonspecific symptoms make diagnosis difficult. We present a small case series and review the literature to increase awareness of this condition among otolaryngologists. METHODS: Nine cases of KFD were diagnosed between 2003 and 2006 at the McGill University Health Care institution by either excisional or fine-needle biopsy. Clinical and histologic features were reviewed in the context of a comprehensive analysis of the KFD literature. RESULTS: Seven of nine cases are female, with a mean age of 27.2 years (range 18-35 years). Only one patient had systemic SLE predating KFD. Our results are comparable to those in the current literature regarding the association with SLE. CONCLUSIONS: We present the first Canadian small case series and extensive review of the literature to highlight the clinical and pathologic features of this disease and its association with SLE.

Cost savings of patients with a MACIS score lower than 6 when radioactive iodine is not given.

OBJECTIVE: To assess the cost savings if the current policy of treating patients with a MACIS (metastases, age, completeness of resection, invasion, and size) score lower than 6 using radioactive iodine (RAI) was changed to reflect the findings of recent studies. DESIGN: Retrospective medical record review. SETTING: Mount Sinai Hospital, Toronto, Ontario. PATIENTS: Between January 1, 2002, and July 1, 2005, 199 consecutive patients with a MACIS score lower than 6 who received RAI treatment after total thyroidectomy. MAIN OUTCOME MEASURES: Patient demographics were analyzed. Costs for the dose of RAI, hospital stay, and health insurance claims were included in the calculations. RESULTS: For 199 consecutive patients, the cost for sodium iodide 131 treatment totaled Can$161 588, and the required 2-day stay in isolation totaled Can$764 558. The overall cost to the health care system was Can$934 106, which translates into approximately Can$4694 per patient. CONCLUSIONS: By following the recommendations of recent evidence-based studies and by ceasing to treat patients with a MACIS score lower than 6 after total thyroidectomy using RAI, cost savings can be accrued for health care systems involved in the treatment of thyroid cancer. Alternate strategies, such as treating patients who need RAI therapy on an outpatient basis and reducing the dose of RAI, can lower costs as well.