Is 2045 the best we can do? Mitigating the HPV-related oropharyngeal cancer epidemic.

INTRODUCTION: Oropharyngeal cancer (OPC) will be among the most common cancers in men by 2045 due to a rapid rise in human papillomavirus (HPV)-related OPC. Those who survive their cancer often suffer life-long treatment effects and early death. HPV vaccination could prevent virtually all HPV-related cancers but is not an effective preventive strategy for those already exposed. Without a dramatic increase in vaccine uptake in the U.S., HPV vaccination will have a negligible effect on OPC incidence through 2045 and no substantial impact until 2060. Additionally, targeted screening for earlier diagnosis may soon be feasible for those inadequately protected by vaccination. AREAS COVERED: PubMed search for English-language articles related to incidence, screening, and prevention of HPV-related malignancies, focused on OPC in the U.S. EXPERT OPINION: HPV-related OPC incidence will continue to increase for the foreseeable future with prophylactic vaccination offering no substantial public health impact for decades. Consequently, we must rapidly increase vaccination rates and develop screening methods to identify high-risk individuals. Such individuals would be eligible for potential preventive treatments and screening to diagnose early-stage HPV-related OPC allowing less morbid treatments. These methods will bridge the population into an era of decreasing incidence after vaccination takes effect.

Thyroid nodules of indeterminate cytology in Hispanic/Latinx patients.

BACKGROUND: Behavior of differentiated thyroid cancer (DTC) varies among ethnic groups. Recommended management of thyroid nodules with indeterminate cytology (TN-IC) is based on molecular analysis from predominantly non-Hispanic white patients. We hypothesized that TN-IC in Hispanic/Latinx patients would have different features, management, and outcomes and that molecular testing might perform differently in Hispanic/Latinx patients. METHODS: Retrospective chart review was performed on 127 TN-IC analyzed with Afirma. Patient characteristics were compared using linear model ANOVA and Fisher's exact test. RESULTS: Out of 127 TN-IC, 71 (56%) were Hispanic/Latinx. Hispanic/Latinx had a greater prevalence of diabetes, but Afirma results (benign or suspicious) were similar between ethnic groups. Fourteen patients had malignant pathology. Their management and outcomes were similar across groups. The negative predictive value for our cohort (97.9%) was similar to published data. CONCLUSIONS: Data from our predominantly-Hispanic/Latinx cohort suggest that Afirma performs similarly in Hispanic/Latinx and non-Hispanic white patients with TN-IC.

Recurrent Neck Mass: A Case Report.

Fourth branchial cleft anomalies are an exceptionally rare cause of recurrent neck mass in pediatric and adult patients. In this report, we present a case of an infected fourth branchial cleft cyst in a 20-year-old woman that presented with recurrent throat pain and deep neck abscesses. After undergoing repeated incision and drainage procedures, the patient underwent definitive management with direct laryngoscopy, ablation of the left pyriform sinus tract, left hemithyroidectomy, and excision of the branchial anomaly without evidence of recurrence. In addition to diagnosis and management, this case report highlights the unique anatomical relationship between fourth branchial anomalies and the pyriform fossa as well as the superior and recurrent laryngeal nerves.

Perioperative pain management and opioid-reduction in head and neck endocrine surgery: An American Head and Neck Society Endocrine Surgery Section consensus statement.

BACKGROUND: This American Head and Neck Society (AHNS) consensus statement focuses on evidence-based comprehensive pain management practices for thyroid and parathyroid surgery. Overutilization of opioids for postoperative pain management is a major contributing factor to the opioid addiction epidemic however evidence-based guidelines for pain management after routine head and neck endocrine procedures are lacking. METHODS: An expert panel was convened from the membership of the AHNS, its Endocrine Surgical Section, and ThyCa. An extensive literature review was performed, and recommendations addressing several pain management subtopics were constructed based on best available evidence. A modified Delphi survey was then utilized to evaluate group consensus of these statements. CONCLUSIONS: This expert consensus provides evidence-based recommendations for effective postoperative pain management following head and neck endocrine procedures with a focus on limiting unnecessary use of opioid analgesics.

Postoperative Complications in Obese Patients After Tracheostomy.

OBJECTIVE: To determine the prevalence of varying classes of obesity in patients undergoing tracheostomy and the associated complication rates as compared with nonobese patients. STUDY DESIGN: A retrospective chart review was performed from 2012 to 2018 on all patients who underwent open tracheostomy by the Department of Otolaryngology-Head and Neck Surgery. SETTING: All tracheostomies were performed at a single tertiary care center. METHODS: Patients were classified by body mass index (BMI) according to the World Health Organization classification system: underweight (<18.5), normal-overweight (18.5-29.9), class I (30-34.9), class II (35-39.9), and class III (>40). Charts were reviewed for patient demographic information, Charlson Comorbidity Index score, surgical indication, operative time, tracheostomy tube type, and postoperative complications. RESULTS: A total of 387 patients (mean ± SD BMI, 31.3 ± 14.2) were identified per the inclusion/exclusion criteria. Of patients with BMI >30 (n=153), 34.6% were categorized as obesity class I, 29.4% as class II, and 35.9% as class III. The most common indication for tracheostomy was malignancy in nonobese patients (41.5%) and respiratory failure for obese patients (58.2%). Operative time was significantly longer in obese patients, and most of these patients required an extended-length tracheostomy tube. Patients with a BMI >40 had higher rates of multiple postoperative complications or death (P = .009). Underweight patients also had a higher rate of complication than normal-overweight patients (P = .016). CONCLUSION: Class III and underweight patients had higher rates of postoperative complications, which should be taken into consideration during perioperative counseling.

Evaluating contemporary pain management practices in thyroid and parathyroid surgery: A national survey of head and neck endocrine surgeons.

BACKGROUND: There is currently a lack of evidence-based guidelines regarding postoperative opioids after thyroid and parathyroid surgery. This study aimed to objectively characterize contemporary postoperative pain management practices via a national survey of head and neck endocrine surgeons. METHODS: A standardized electronic survey was distributed to the membership of the American Head and Neck Society's Endocrine section. RESULTS: A total of 102 surgeons completed the survey representing a 34% response rate. In all, 65.7% of respondents utilize opioids with wide variations in the total morphine equivalents prescribed. Practice environment (χ2 = 10.0; P = 0.04) and performing preoperative pain counseling (χ2 = 9.7; P = 0.002) were significantly associated with a decreased likelihood of prescribing postoperative opioids. Utilization of non-opioid pain management strategies was common and significantly associated with performing outpatient surgery (χ2 = 6.2; P = 0.013) and preoperative pain counseling (χ2 = 4.5; P = 0.034). CONCLUSIONS: Pain management practice patterns vary significantly among head and neck endocrine surgeons which further emphasize the need for evidence-based guidelines.

Contemporary treatment patterns and outcomes of salivary gland carcinoma: a National Cancer Database review.

PURPOSE: Salivary gland carcinomas (SGC) are rare malignancies and data regarding treatment outcomes stratified by histologic subtype are currently limited. This study aims to examine current, national treatment patterns and overall survival (OS) of patients with the major histologic subtypes of salivary gland carcinoma. SUBJECTS AND METHODS: A review was performed of the National Cancer Database (NCDB) of patients with confirmed diagnoses of mucoepidermoid carcinoma, acinic cell carcinoma, adenoid cystic carcinoma, adenocarcinoma, or carcinoma ex pleomorphic receiving curative treatment between 2004 and 2014. Univariate and multivariate regression modeling were performed to identify risk factors significantly associated with overall survival (OS). Adjusted survival analyses stratified by treatment and staging were performed with the primary outcome of overall survival (OS) and were further stratified based on histologic subtype. RESULTS: The final analysis included 7342 patients [3547 men (48.3%) and 3795 women (51.7%); mean age 58.3 years (range 18-90 years)]. Mucoepidermoid carcinoma was the most common histology encountered [n = 2669 (36.4%)]. Unadjusted and adjusted analysis demonstrated improved survival with surgery and radiation therapy (RT) for adenoid cystic (HR = 0.69; p = 0.029), adenocarcinoma (HR = 0.61; p < 0.001), high-grade mucoepidermoid carcinoma (HR = 0.70; p = 0.026), and carcinoma ex pleomorphic (HR = 0.64; p = 0.028), while surgery with chemoradiation therapy (CRT) was associated with worse OS regardless of histologic subtype. The impact of advanced stage on survival varied amongst the histologic subtypes but portended the worst prognosis for patients with adenocarcinoma and carcinoma ex pleomorphic. CONCLUSIONS: The results of this NCDB review demonstrate unique treatment patterns and survival outcomes for SGC based on major histologic subtype.

Use of a midline mandibular osteotomy to improve surgical access for transoral robotic resection of the base of tongue in a patient with trismus.

BACKGROUND: The utilization of transoral robotic surgery (TORS) in patients with trismus is limited because of poor surgical exposure. METHODS: This report is about a 46-year-old man with a recurrent right base of tongue cancer who had severe postradiation trismus. We performed a midline mandibular osteotomy without a lip split and this resulted in a markedly improved surgical exposure. He underwent a TORS resection of the right base of the tongue with no significant complications. RESULTS: The midline mandibular osteotomy significantly improved the surgical exposure and facilitated exposure for TORS in a patient who otherwise would not be able to undergo TORS. CONCLUSION: Utilization of a midline mandibular osteotomy allowed for increased exposure for TORS in a patient with limited mouth opening from postradiation trismus. Postoperative hemorrhage remains a significant concern and appropriate measures to mitigate the catastrophic consequences of this should be considered.

The effects of anesthesia on the morphoproteomic expression of head and neck squamous cell carcinoma: a pilot study.

The prognosis and disease-free survival rates for head and neck squamous cell carcinoma (HNSCC) have remained relatively stagnant for the last several decades. Moreover, as is the case with other malignancies, locoregional recurrence and distant metastasis are all too common even after seemingly successful oncologic surgery and adjuvant therapy. Recently, increased focus has been placed on understanding the influence of perioperative factors on tumor cell behavior and surgical outcomes. More specifically, emerging research suggests that anesthetic agents may play a role in cancer recurrence by interacting with prosurvival protein signaling pathways which harden tumor cells against oncologic treatments. In the present pilot study, we tested the hypothesis that inhalational anesthesia and total intravenous anesthesia (TIVA) exert differential effects on the proteomic expression of HNSCC. Ten patients with previously untreated oral cavity or oropharyngeal HNSCC were randomized to receive either sevoflurane and remifentanil or propofol and remifentanil for the duration of their respective surgeries. Morphoproteomic analysis using 10 pro-oncogenic protein markers was performed on both pre- and postanesthesia tumor samples to qualitatively grade changes in protein expression. The results of this analysis demonstrated differential expression of several protein markers. Specifically, the exposure to sevoflurane but not TIVA resulted in a statistically significant increase in the expression of cytoplasmic hypoxia-inducible factor-2alpha (P = 0.049) and nuclear p-p38 mitogenic-activated protein kinase (P = 0.041). This study represents one of the first to evaluate the effects of anesthesia on the molecular biology of HNSCC in vivo, and the results suggest that the exposure to sevoflurane may increase the expression of pro-oncogenic protein markers in HNSCC tumor cells.

Applications for transoral robotic surgery in the pediatric airway.

OBJECTIVES/HYPOTHESIS: To report preliminary experience in the utilization of transoral robotic surgical (TORS) techniques in pediatric airway surgery. STUDY DESIGN: Retrospective case series. METHODS: A retrospective chart review was performed on all pediatric patients undergoing robotic airway surgery at a university-based children's hospital between August 2010 and December 2012. RESULTS: Three pediatric patients underwent robotic repair of various airway anomalies between August 2010 and December 2012. Case 1 is a 15-year-old boy with posterior glottic stenosis for which a robotic-assisted posterior cricoid split with cartilage graft placement was attempted but ultimately required conversion to an open technique. Case 2 is a 6-year-old male with Trisomy 21 who had robotic-assisted endoscopic repair of a type II laryngeal cleft, with subsequent resolution of his chronic aspiration and successful initiation of oral feeding. Case 3 is a 3-year-old female who underwent robotic-assisted left posterior cordectomy and subtotal arytenoidectomy for idiopathic bilateral vocal cord paralysis, resulting in improved Passy-Muir valve tolerance. CONCLUSION: TORS is being increasingly utilized in the field of head and neck surgery as it is frequently less invasive and often demonstrates improved outcomes compared with traditional approaches. This study details our experience utilizing TORS in the management of pediatric airway anomalies and represents one of the earliest such series in the literature. Although TORS has the potential to improve the management of pediatric airway disorders, larger, prospective studies are needed to better elucidate its feasibility and efficacy. LEVEL OF EVIDENCE: 4.

Robotic surgery for primary head and neck squamous cell carcinoma of unknown site.

IMPORTANCE: Identification of the primary site in head and neck squamous cell carcinoma (HNSCC) is crucial because it improves the patient's prognosis and minimizes morbidity from treatment. OBJECTIVES: To determine the efficacy of transoral robotic surgery (TORS) in identifying unknown primary sites of head and neck squamous cell carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Retrospective, multi-institutional case series from January 1, 2010, to February 28, 2013, in which data were pooled from the following 6 institutions: University of Washington Medical Center, The University of Texas MD Anderson Cancer Center, University of Alabama-Birmingham Hospital, The University of Texas Medical School at Houston, Johns Hopkins Hospital, and Oregon Health Sciences University. All patients diagnosed as having HNSCC of an unknown primary site who underwent TORS to identify the primary site were included in the study. We excluded those with recurrent disease, a history of radiation therapy to the head and neck, or evidence of a primary tumor site based on previous biopsy results. MAIN OUTCOME AND MEASURE: Identification of the primary tumor site. RESULTS: Forty-seven patients were eligible for the study. The tumor site was identified by TORS in 34 of 47 patients (72.3%). The primary site was located in the base of tongue for 20 patients (58.8%) and the palatine tonsil for 13 patients (38.2%), with 1 patient having a primary site in both the base of tongue and the palatine tonsil. Suspicious physical examination findings were present in 23 of 47 patients (48.9%), with positive and negative predictive values of 56.5% and 25.0%, respectively. Of those who underwent any imaging, 16 patients had suspicious findings, with positive and negative predictive values of 50.0% and 16.7%, respectively. In 18 of 47 patients (38.3%), both preoperative radiographic and physical examination failed to suggest a primary site. Of these 18 patients, 13 (72.2%) were identified after undergoing TORS. CONCLUSIONS AND RELEVANCE: We demonstrate that TORS is a useful approach to identify and treat the primary site in patients with HNSCC who present with an unknown primary site.

14-3-3zeta mediates resistance of diffuse large B cell lymphoma to an anthracycline-based chemotherapeutic regimen.

Patients presenting with diffuse large B cell lymphoma (DLBCL) are treated with a standard anthracycline-based chemotherapeutic mixture consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Half of DLBCL patients will develop chemo-refractory tumors due to the emergence of CHOP-resistant DLBCL cells. We isolated DLBCL cells that were resistant to CHOP as a model system to investigate the molecular basis of CHOP resistance. Resistant cells emerged from CHOP-sensitive DLBCL populations after repeated cycles of on-off exposure to stepwise increased dosages of CHOP. A proteomic analysis of CHOP-sensitive and -resistant DLBCL cells identified the zeta isoform of the 14-3-3 family as a differentially expressed protein. CHOP-sensitive cells showed reduced expression of 14-3-3zeta protein in the presence of high-dose CHOP relative to control cells. In contrast, CHOP-resistant cells expressed markedly higher levels of 14-3-3zeta regardless the presence of high-dose CHOP. Because 14-3-3zeta is known to exert anti-apoptotic influences and chemoresistance in lung, colon, and prostate carcinoma, we hypothesized that 14-3-3zeta promotes survival of DLBCL cells in CHOP. In support of our hypothesis, knockdown of 14-3-3zeta by small interfering RNA restored the sensitivity of resistant DLBCL to CHOP-induce apoptosis. In addition, 14-3-3zeta expression was highly up-regulated in a resected DLBCL lymph node relative to a normal lymph node by Western blot analysis. Furthermore, more than half of 35 DLBCL tissues showed elevated 14-3-3zeta expression relative to normal lymph tissue by immunohistochemical analysis. Our study implicates 14-3-3zeta in the pathogenesis of DLBCL and suggests a promising combination strategy with a 14-3-3 inhibitor for the treatment of refractory DLBCL.