Human papillomavirus circulating tumor DNA: a diagnostic tool in squamous cell carcinoma of unknown primary-a pilot study.

Introduction: Neck mass is the most common presentation of human papillomavirus-related (HPV-related) oropharyngeal squamous cell carcinoma (OPSCC). Recently, circulating tumor HPV-DNA (ctHPVDNA) assays have been developed to detect active OPSCC. This pilot study investigates the diagnostic accuracy of ctHPVDNA in establishing HPV status for known vs. unknown OPSCC presenting as a neck mass. Methods: A single-institution pilot study was conducted on all patients with OPSCC presenting as a neck mass between 2021 and 2022. The diagnostic accuracy of ctHPVDNA was compared to that of standard diagnostic procedures used to obtain HPV status according to the American Society of Clinical Oncology (ASCO) guideline for squamous cell carcinoma of unknown primary (SCCUP). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ctHPVDNA were calculated. Results: A total of 27 patients were included; 70.4% were current or former smokers, 48.1% (N = 13) had identifiable primaries, and 51.9% (N = 14) had SCCUP. Four patients with known primaries required operative direct laryngoscopy with biopsy (DLB) to establish HPV status. Two patients with SCCUP underwent diagnostic transoral robotic surgery (TORS) to establish HPV status and localize the primary. Twelve patients underwent therapeutic TORS and neck dissection. The gold standard for HPV status was based on final histopathologic p16 or HPV in situ hybridization (ISH) staining during workup/treatment. ctHPVDNA had 95.8% sensitivity, 100% specificity, 100% PPV, and 75% NPV in predicting HPV-positive OPSCC in the whole sample. Binary logistic regression model using ctHPVDNA results to predict HPV-positive OPSCC was significant (-2 log likelihood = 5.55, χ2 = 8.70, p <.01, Nagelkerke's R squared = .67). Among patients with identifiable primaries, all patients had HPV-positive tumors on final pathology, and ctHPVDNA was positive in 100%. In the unknown primary patients, ctHPVDNA had 90.9% sensitivity, 100% specificity, 100% PPV, and 75% NPV. Discussion: ctHPVDNA demonstrated good diagnostic accuracy for both known and unknown primaries. Incorporation of ctHPVDNA into the diagnostic algorithm for SCCUP may reduce the need for multiple procedures to establish HPV status.

Effect of 2 Teams and Operative Time on Complications After Oral Cavity Free Flap Reconstruction.

OBJECTIVE: Evaluate the effects of operative time and 2 team approach on complications after soft tissue free flap reconstruction for oral tongue cancer. METHODS: Patients with oncologic glossectomy with myocutaneous or fasciocutaneous free flap reconstruction were included from the 2015 to 2018 American College of Surgery National Surgical Quality Improvement Program. The primary predictive variables assessed were operative time and 2 team approach; control variables included age, sex, body mass index (BMI), 5-question-modified frailty index (mFI-5), American Society of Anesthesiologists (ASA) class, and total work relative value units (wRVU). Outcomes assessed included 30-day mortality, 30-day reoperation, hospital length of stay beyond 30 days, readmission, medical and surgical complications, and non-home discharge. Multivariable logistic/linear regression models were used to predict surgical outcomes. RESULTS: Microvascular soft tissue free flap reconstruction of the oral cavity after glossectomy was performed on 839 patients. Operative time was independently associated with readmission, prolonged length of stay, surgical complications, medical complications, and non-home discharge. A 2-team approach was independently associated with prolonged length of stay and medical complications. The mean operative time of the 1-team and 2-team approach was 8.73 and 9.13 hours. The 1-team approach did not significantly increase operative time (P = .16). CONCLUSIONS: In the largest study to date of operative time on post-surgical outcomes after glossectomy and soft tissue free flap reconstruction, we found longer operative times increased rates of postoperative complications and non-home discharge. The 1-team approach is non-inferior to the 2-team approach with respect to operating time and complications.

Optimizing Reversal of Muscle Relaxation with Sugammadex to Accelerate Discharge Readiness in Operative Laryngoscopy: A Randomized Clinical Trial.

IMPORTANCE: Operative laryngoscopy is a commonly performed ambulatory procedure in patients with significant co-morbidity. Optimal anesthetics for surgical exposure with rapid return to baseline after the procedure enhances postoperative patient safety. OBJECTIVE: To determine whether sugammadex hastens recovery in patients undergoing operative laryngoscopy under general anesthesia with rocuronium-induced paralysis. DESIGN: Prospective clinical intervention randomized single-blinded, single-center study in an academic tertiary care center. Approved by the institutional review board and registered with ClinicalTrials.gov. SETTINGS: Single center tertiary care academic institution. PARTICIPANTS: 18 years or older, American Society of Anesthesiology physical status I-III with ability to give written informed consent undergoing operative laryngoscopy. INTERVENTION: Participants were randomized into two groups. Both groups received inhaled anesthetic: sevoflurane, remifentanil, and rocuronium at 0.6-1.2 mg/kg for intubation and anti-nausea prophylaxis. Group 1 received reversal with neostigmine (0.04 mg/kg) and glycopyrrolate (0.01 mg/kg). Group 2 received reversal with sugammadex (4 mg/kg). Vital signs were maintained at 20% of baseline in both groups. Post anesthesia care unit nurses were blinded to the reversal agent and were the evaluators of the discharge criteria and times. Primary end point was time to extubation after the procedures and secondary end points were: Subjective interpretation of surgical conditions by the surgeon, hemodynamic, respiratory parameters, anesthetics, and opioids used, operative time, and duration to achieve discharge readiness. RESULTS: A total of eighty-four participants, who were similar in age, sex, and weight in both groups. The primary end point and secondary end points were similar except time to meet discharge criteria in the two groups. 65% in the sugammadex versus 35% in the neostigmine group met Aldrete criteria of 18 or higher on arrival at the post anesthesia care unit. CONCLUSIONS: Optimizing the anesthetic regimen, along with stable intraoperative hemodynamics and reversal with sugammadex improves discharge readiness in patients undergoing operative laryngoscopy.

Preoperative low-molecular weight heparin chemoprophylaxis in head and neck free flap reconstruction.

BACKGROUND: The safety of presurgical thromboprophylaxis using low molecular weight heparin (LMWH) has not been well described in head and neck oncologic surgery with free tissue transfer (HNS-FTT). METHODS: Retrospective chart review of HNS-FTT patients receiving versus not receiving presurgical subcutaneous enoxaparin (Px-LMWH) was performed. Outcomes included estimated blood loss (EBL), hematoma, flap compromise, DVT or pulmonary embolus (PE). Fisher's exact test and Wilcoxon Rank Sum test were performed to compare groups. Odds ratios and associated 95 % confidence intervals were provided as appropriate. RESULTS: 43 of 128 patients (34 %) received Px-LMWH. There was no significant difference in EBL, hematoma, or flap complications between groups. Patients without Px-LMWH had higher rates of DVT and PE, although the difference did not reach statistical significance (p = 1.00, 0.095, respectively). CONCLUSION: Presurgical Px-LMWH can be used in major head and neck reconstructive surgery without increased intraoperative blood loss or postoperative complications. Larger studies will need to be done to determine the impact of Px-LMWH on DVT and PE in this patient population.

Distribution of the head and neck surgical oncology workforce in the United States.

BACKGROUND: The recent trends in education and geographic distribution of the head and neck surgery workforce have not been studied extensively. METHODS: We reviewed publicly available sources to locate all fellowship-trained head and neck surgeons and recent graduates. The number of surgeons in each state was compared against head and neck cancer incidence data from the Centers for Disease Control. RESULTS: The number of graduates increased annually by 1 per 100 000 000 people from 2011-2020. The average number of fellowship-trained surgeons per state was 10 (SD: 12). The average number of new head and neck cancer cases per surgeon was 247 (SD: 135). Ten states (20%) had cases >1 SD above the national average/surgeon, while 3 (6%) had cases >1 SD below the national average. CONCLUSION: Head and neck surgeons are located in most states, but not uniformly. Most states have approximately average density of surgeons; however, several states are outliers.

Factors Associated With a Prolonged Diagnosis-to-Treatment Interval in Laryngeal Squamous Cell Carcinoma.

OBJECTIVE: Evaluate factors associated with treatment delays and their effect on survival in laryngeal squamous cell carcinoma. STUDY DESIGN: Retrospective cohort study. SETTING: National Cancer Database. METHODS: Patients receiving primary radiation or surgery for laryngeal squamous cell carcinoma were included from 2004 to 2017. The primary outcomes were the diagnosis-to-treatment interval (DTI) and 5-year survival. Variables of prolonged DTI (>30 days) were assessed via logistic regression models. Survival was then assessed through Cox proportional hazards models. Candidate variables for both outcomes included age, sex, race, ethnicity, distance to treatment facility, insurance coverage, treatment facility type, TNM T stage, nodal status, and DTI (in models estimating survival). RESULTS: An overall 136,203 patients with laryngeal cancer were identified, from which 51,747 remained after exclusions were applied: 18,499 received primary surgery and 33,248 received primary radiation. Being a member of a racial or ethnic minority, advanced age, female sex, ≥30 miles from treatment facility, lack of insurance, treatment at an academic cancer center, and primary radiation were associated with a prolonged DTI. However, in spite of a faster DTI, treatment at a community cancer center was independently associated with higher mortality (hazard ratio, 1.2; P < .0001). CONCLUSIONS: Despite being associated with prolonged DTI, receiving treatment at a high-volume academic facility was associated with significantly improved survival. Our results indicate that improved referral pathways or outreach may help improve survival in laryngeal cancer, especially in high-risk populations.

Consensus of free flap complications: Using a nomenclature paradigm in microvascular head and neck reconstruction.

BACKGROUND: We aim to define a set of terms for common free flap complications with evidence-based descriptions. METHODS: Clinical consensus surveys were conducted among a panel of head and neck/reconstructive surgeons (N = 11). A content validity index for relevancy and clarity for each item was computed and adjusted for chance agreement (modified kappa, K). Items with K < 0.74 for relevancy (i.e., ratings of "good" or "fair") were eliminated. RESULTS: Five out of nineteen terms scored K < 0.74. Eliminated terms included "vascular compromise"; "cellulitis"; "surgical site abscess"; "malocclusion"; and "non- or mal-union." Terms that achieved consensus were "total/partial free flap failure"; "free flap takeback"; "arterial thrombosis"; "venous thrombosis"; "revision of microvascular anastomosis"; "fistula"; "wound dehiscence"; "hematoma"; "seroma"; "partial skin graft failure"; "total skin graft failure"; "exposed hardware or bone"; and "hardware failure." CONCLUSION: Standardized reporting would encourage multi-institutional research collaboration, larger scale quality improvement initiatives, the ability to set risk-adjusted benchmarks, and enhance education and communication.

Complications, Mortality, and Functional Decline in Patients 80 Years or Older Undergoing Major Head and Neck Ablation and Reconstruction.

Importance: Data regarding outcomes after major head and neck ablation and reconstruction in the growing geriatric population (specifically ≥80 years of age) are limited. Such information would be extremely valuable in preoperative discussions with elderly patients about their surgical risks and expected functional outcomes. Objectives: To identify patient and surgical factors associated with 30-day postoperative complications, 90-day mortality, and 90-day functional decline; to explore whether an association exists between the type of reconstructive procedure and outcome; and to create a preoperative risk stratification system for these outcomes. Design, Setting, and Participants: This retrospective, multi-institutional cohort study included patients 80 years or older undergoing pedicle or free-flap reconstruction after an ablative head and neck surgery from January 1, 2015, to December 31, 2017, at 17 academic centers. Data were analyzed from February 1 through April 20, 2019. Main Outcomes and Measures: Thirty-day serious complication rate, 90-day mortality, and 90-day decline in functional status. Preoperative comorbidity and frailty were assessed using the American Society of Anesthesiologists classification, Adult Comorbidity Evaluation-27 score, and Modified Frailty Index. Multivariable clustered logistic regressions were performed. Conjunctive consolidation was used to create a risk stratification system. Results: Among 376 patients included in the analysis (253 [67.3%] men), 281 (74.7%) underwent free-flap reconstruction. The median age was 83 years (range, 80-98 years). A total of 193 patients (51.3%) had 30-day serious complications, 30 (8.0%) died within 90 days, and 36 of those not dependent at baseline declined to dependent status (11.0%). Type of flap (free vs pedicle, bone vs no bone) was not associated with these outcomes. Variables associated with worse outcomes were age of at least 85 years (odds ratio [OR] for 90-day mortality, 1.19 [95% CI 1.14-1.26]), moderate or severe comorbidities (OR for 30-day complications, 1.80 [95% CI, 1.34-2.41]; OR for 90-day mortality, 3.33 [95% CI, 1.29-8.60]), body mass index (BMI) of less than 25 (OR for 30-day complications, 0.95 [95% CI, 0.91-0.99]), high frailty (OR for 30-day complications, 1.72 [95% CI, 1.10-2.67]), duration of surgery (OR for 90-day functional decline, 2.94 [95% CI, 1.81-4.79]), flap failure (OR for 90-day mortality, 3.56 [95% CI, 1.47-8.62]), additional operations (OR for 30-day complications, 5.40 [95% CI, 3.09-9.43]; OR for 90-day functional decline, 2.94 [95% CI, 1.81-4.79]), and surgery of the maxilla, oral cavity, or oropharynx (OR for 90-day functional decline, 2.51 [95% CI, 1.30-4.85]). Age, BMI, comorbidity, and frailty were consolidated into a novel 3-tier risk classification system. Conclusions and Relevance: Important demographic, clinical, and surgical characteristics were found to be associated with postoperative complications, mortality, and functional decline in patients 80 years or older undergoing major head and neck surgery. Free flap and bony reconstruction were not independently associated with worse outcomes. A novel risk stratification system is presented.

Metastatic Renal Cell Carcinoma of the Head and Neck: A Case Series.

Background: Renal cell carcinoma (RCC) accounts for over 80% of malignant tumors arising from the kidney. However, metastatic RCC to the head and neck is a relatively rare entity. Case Presentation: We describe three patients with metastatic RCC to the head and neck with the involvement of the parapharyngeal space, the level V region of the neck, and the maxillary sinus. Conclusion: Metastatic RCC in the head and neck is uncommon; however, it must be taken into consideration given a patient with a history of RCC. Multiple pathways allow for the spread of RCC to the head and neck region. Treatment options include mastectomy or local radiation and systemic chemotherapy.

Intraoperative neuronavigation for transoral surgical approach: use of frameless stereotaxy with 3D rotational C-arm for image acquisition.

The transoral route is a standard surgical approach to the anterior craniovertebral junction, where neuronavigation is difficult secondary to the mobility of the cervical spine in relation to the cranium. We describe the use of neuronavigation combined with intraoperative 3D C-arm to direct our approach and resection of two lesions of the craniovertebral junction. Neuronavigation was employed in planning of incision, bony resection, and assessment of lesion resection. Both patients underwent transoral approach without complication using this method. Frameless stereotaxy with BrainLab VectorVision and 3D C-arm is an effective method of neuronavigated approach to the anterior craniocervical junction, which may contribute to the safety of this approach.

Sorafenib and thyroid cancer.

The emergence of serine-threonine small molecule, multi-targeted kinase inhibitors over the past decade is greatly impacting the therapeutic armamentarium for numerous malignancies, especially thyroid carcinoma. Chief among them are a class of agents referred to as vascular endothelial growth factor signal pathway inhibitors. Sorafenib is a lead compound that has been recently approved by the US FDA for radioactive iodine-refractory differentiated thyroid cancer (DTC). Sorafenib clearly is altering the natural history of DTC. In the largest randomized Phase III study ever conducted in DTC, sorafenib significantly improved progression-free survival compared to placebo (10.8 vs 5.8 months) and had an acceptable and manageable safety profile, though commonly attributed side effects of hand-foot skin reaction, diarrhea and hypertension were more frequent than in other settings. This agent represents a new treatment option for patients with progressive radioactive iodine-refractory DTC.

Surgical anatomy of the thyroid and parathyroid glands.

This article describes the anatomy and embryology of the thyroid and parathyroid glands and the recurrent laryngeal nerve, discussing how the anatomy affects function and dysfunction of the glands.

Otitis media with effusion: a possible role for Helicobacter pylori?

OBJECTIVES: To compare Helicobacter pylori prevalence rates in the nasopharynx of pediatric patients with and without otitis media with effusion (OME). STUDY DESIGN: Prospective, controlled. METHODS: The study group consisted of patients undergoing adenoidectomy for persistent OME. A control group of patients with no history of OME undergoing adenoidectomy was simultaneously enrolled. As a substudy, middle ear effusion samples were also analyzed for Helicobacter pylori. Polymerase chain reaction assays were run by using primers against the Helicobacter pylori gene. RESULTS: Helicobacter pylori was detected in the adenoids of 10 of 45 study group patients, and 6 of 37 controls (P = 0.49). Thirty-two percent of middle ear aspirates were positive for Helicobacter pylori. CONCLUSION: The current study confirms the presence of Helicobacter pylori in the nasopharynx and middle ear space, but our results do not support a role for this bacterium in the pathogenesis of otitis media with effusion.