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.

Complications following salvage transoral robotic surgery with and without reconstruction: A systematic review of the literature.

BACKGROUND: Transoral robotic surgery (TORS) has been used in the salvage setting for head and neck cancers both with and without reconstruction. The complications of salvage TORS and the effect of reconstruction on complications has not been studied. OBJECTIVE: To study the complications of salvage TORS and examine the effect of reconstruction on complication rates. METHOD: An electronic search of the English- language literature using PubMed, Medline, and the Cochrane database was conducted and a systematic review performed in accordance with PRISMA guidelines (CRD42020181057). RESULTS: A total of 23 studies including 533 patients have been published on salvage TORS.The average patient age was 61.2 years.Prior treatment was described for 420 patients.205 (48.8%) underwent prior definitive radiotherapy (RT).160 (38.1%) underwent definitive chemoradiotherapy (CRT).Only 55 (13.1%) had prior surgery.Overall, there were 158 complications with a pooled rate of 33.6% (95%CI: 25.4-42.3%).77 were major complications requiring surgical intervention with a pooled rate of 18.9% (95% CI: 14.8-23.3%).The number of patients undergoing reconstruction among salvage cases in the literature is 59 (9.19%), with 24 local flaps and 25 microvascular free flaps.Reconstruction was associated with lower overall hemorrhage rates but had no impact on major hemorrhage rates. CONCLUSIONS: The pooled incidence rates of major complications, major POH and emergency tracheostomy following salvage TORS are 18.9%, 10.5%, and 4.4%.The rate of death following salvage TORS is 3.6%. Reconstruction was associated with lower overall hemorrhage rate after salvage TORS but had no impact on major postoperative hemorrhage rates.

Complications and Outcomes of Endovascular Embolization for Intractable Epistaxis: A Systematic Review and Meta-analysis.

OBJECTIVES: Endovascular embolization has emerged as an effective treatment for intractable epistaxis. This systematic review and meta-analysis aimed to calculate the rates of success, rebleeds, and complications and to identify the etiologies and complications of patients who undergo endovascular embolization. METHODS: This systematic review and meta-analysis was conducted per the guidelines set forth by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Articles were extracted from Scopus, PubMed, Web of Science, and Cochrane Central and were filtered by a systematic review process using Rayyan software. A random-effects model was used to quantify the rates success, rebleeds, and complications. RESULTS: Forty-two studies were included, totaling 1660 patients. The pooled success rate was 89% (95% confidence interval [CI] 86%-92%) and the pooled rebleed rate was 19% (95% CI 16%-22%). The pooled minor complication rate was 18% (95% CI 11%-27%). The most common major complication was soft tissue necrosis followed by stroke. The most common minor complication was facial pain. No minor complications were reported to be permanent. Of the patients who failed initial embolization, 42% underwent repeat embolization and 34% underwent surgical arterial ligation. CONCLUSIONS: Endovascular embolization is an effective treatment for intractable epistaxis. The decision to perform embolization should be carefully weighed given the rare but significant major complications.

Contralateral Transmaxillary Approach for Resection of Chondrosarcoma of the Petrous Apex: A Case Report.

BACKGROUND: Deep location and neurovascular structures make access to lesions of the petrous apex a significant challenge. A novel approach for these tumors is the contralateral transmaxillary approach. CLINICAL PRESENTATION: A 31-year-old male was evaluated for left abducens nerve palsy. Magnetic resonance imaging (MRI) and computed tomography revealed an enhancing, lytic lesion of the petrous apex with extension to the cavernous sinus and petroclival junction. The patient underwent a combined endoscopic contralateral transmaxillary and endoscopic endonasal transclival approach for resection of the lesion. No new or worsening neurologic deficits were noted following the procedure. Pathology revealed low-grade chondrosarcoma (grade I). Postoperative MRI revealed gross total resection of the lesion. Patient underwent adjuvant radiation therapy at the discretion of radiation oncology. CONCLUSION: The contralateral transmaxillary approach to the petrous apex allows for resection of lesions of the petrous apex with the ability to extend the dissection laterally. Excellent results achieved by institutions with advanced extended endoscopic endonasal experience can be reproduced in institutions with less experience. Further characterization of the risks and benefits of this approach is needed.

Botulinum toxin A for the treatment of first bite syndrome-a systematic review.

Background: First bite syndrome (FBS) is a rare post-surgical complication resulting in peri-parotid pain after the first bite of meals. Intra-parotid Botulinum toxin A may offer relief for these symptoms. There is no consensus on the optimal dosage, timing to symptom improvement, need for repeat injections, and safety of this treatment. The objective of this systematic review was to assess the efficacy and safety of intra-parotid Botulinum toxin A injection in treating FBS. Methods: The MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar were searched from the inception until July 2020. Case reports, case series, prospective and retrospective trials in which patients with post-surgical FBS were treated with intra-parotid botulinum toxin A injection were included. The primary outcome was improvement of FBS symptoms. Secondary outcomes were time to symptom improvement and complications. Risk of bias was assessed with National Institute of Health (NIH) Quality Assessment Tools. Results: Search results yielded 41 studies. Thirty-three articles were excluded after screening titles, abstracts, and full texts, yielding eight studies, from which 22 patients were included. No studies included a control. All studies were of lower quality and had at least moderate risk of bias. The initial botulinum toxin A injection dose ranged from 10-75 U. Time from surgical treatment to injection ranged from 1 month to 3 years. Seven studies, containing 17 patients, reported individual patient outcomes. Clinical improvement was reported in 16 patients lasting between 1-30 months post injection. Eight of 8 (100%) patients receiving at least 40 U botulinum toxin A had symptom improvement. Ten of 22 (45.5%) patients received a second botulinum toxin A injection due to return of pain at a mean of 3.8 months after the first injection. Seven of 22 (38.1%) patients had complete symptom resolution at a mean of 12.1 months. There were no reported injection complications, including: facial paralysis, infection, injection site reaction, and allergic reaction. Discussion: There are no controlled studies comparing intra-parotid botulinum toxin A to observation for FBS. However, botulinum toxin A appears to be a potentially safe, effective treatment.

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.

The Nasoseptal Flap for Reconstruction of Lateral Oropharyngectomy Defects: A Clinical Series.

OBJECTIVES/HYPOTHESIS: To study use of the nasoseptal flap (NSF) to reconstruct lateral transoral robotic surgery (TORS) oropharyngectomy defects. STUDY DESIGN: Retrospective case series. METHODS: A clinical series of six patients undergoing NSF reconstruction of lateral TORS oropharyngectomy defects was retrospectively studied. All patients underwent TORS for the treatment of intermediate-risk human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma of the lateral pharyngeal wall between January and June 2017. All patients underwent NSF reconstruction of lateral TORS defects with retrospective analysis of outcomes and complications. RESULTS: Six patients underwent NSF reconstruction of lateral TORS defects. Operative times decreased from 180 minutes to 90 minutes over the study period. There were two cases of partial flap dehiscence and partial necrosis. There were no major donor site complications. All patients had temporary nasal obstruction and crusting. Two experienced temporary aural fullness. In all patients, the lateral wall was mucosalized in 1-3 weeks. Cephalometric analysis of preoperative imaging revealed that patients with high-arched palates (>3 cm) and defect lengths that are longer than NSF flap lengths are poor candidates for this technique. CONCLUSIONS: This NSF is a vascularized, locoregional rotational flap that can reconstruct lateral TORS defects in salvages cases or those where the parapharyngeal carotid or mandibular bone are exposed. Postoperative morbidity is limited to temporary nasal dyspnea, aural fullness, and crusting. Preoperative imaging can determine which patient will have successful defect coverage. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:53-60, 2022.

Minimally invasive treatment of laryngoceles: a systematic review and pooled analysis.

Laryngoceles are best treated with surgery. The goal of this study is to compare patient outcomes and complications in patients undergoing removal of laryngoceles with either transoral endoscopic/microlaryngoscopic or robotic approaches. A systematic review of the published literature was conducted using Pubmed, Web of Science, and the Cochrane Clinical Trials databases. A pooled analysis of individual data was used to compare outcomes between robotic and endoscopic approaches. A total of 30 studies were included. Nine studies with 95 patients were included in the final analysis. Eighty-one (85.26%) were treated with microlaryngoscopic surgery and 14 (14.74%) were treated with robotic-assisted surgery. The rates of tracheostomy (RR = 1.44, 95% CI = 0.389-5.332), complications (RR = 0.329, 95% CI = 0.047-2.294) and recurrence (RR = 0.354, 95% CI = 0.021-5.897) were not statistically different between groups. Within the endoscopic subgroup, 66 laryngoceles (78.57%) were completely excised, while 18 (21.43%) laryngoceles were treated with marsupialization. Marsupialization was associated with an increased risk of recurrence (RR = 4.889, 95% CI = 1.202-19.891). In the robotic subgroup, there was an increased risk of nasogastric tube use (RR = 103.867, 95% CI = 6.379-1619.214) and a longer mean length of hospital stay (p = 0.0001). Transoral treatment of laryngoceles has complication and recurrence rates of 18.95% and 7.37%, respectively. Robotic approaches are associated with higher rates of NGT use and increased hospital stay, however much of this is due to one robotic surgeon's preference for routine NGT placement and higher rates of combined laryngocele removal via robotic approach. Complete excision of combined laryngoceles is possible with transoral approaches. Marsupialization, reported in traditional endoscopic approaches, is associated with a significantly higher rate of recurrence (22.22% vs. 4.76%).

Robotic transmaxillary approach to the lateral infratemporal fossa: A preclinical cadaveric study using a next-generation single-port robotic system.

Robotic transmaxillary skull base surgery has been described using multiport systems. This cadaveric study investigates the feasibility of transmaxillary skull base surgery using a next-generation robot. An extended Caldwell-Luc antrostomy, measuring 3.3 cm by 4.0 cm, was performed in 15 min using a Kerrison rongeur and the robotic endoscope. A single-port, robotic system (da Vinci Sp®, Intuitive Surgical, Inc, Sunnyvale, CA, USA) was then deployed throught the extended Caldwell-Luc approach and provided sufficient reach, visualization, and maneuverability to work within the pterygopalatine fossa (PPF) and the infratemporal fossa (ITF) using three surgical instruments. The ITF dissection was easiest with two instruments using the third instrument to retract the muscles of mastication. This study demonstrates the feasibility of single-port robotic transmaxillary approaches to the lateral ITF. Using a single-port robotic system, the operating surgeon can for the first time work in the PPF and ITF using two functional arms for tumor dissection and a third to retract.

Bleeding Complications After Transoral Robotic Surgery: A Meta-Analysis and Systematic Review.

OBJECTIVE: Postoperative hemorrhage is the most common complication of transoral robotic surgery (TORS), the severity of which can range from minor bleeding treated with observation to catastrophic hemorrhage leading to death. To date, little is known about the incidence, risk factors, and management of post-TORS hemorrhage. STUDY DESIGN: Systematic Review and Metanlysis. METHODS: A systematic review of the published literature using the Cochrane Handbook for Systematic Reviews of Interventions was performed and examined TORS, postoperative hemorrhage, and the use of prophylactic transcervical arterial ligation (TAL). RESULTS: A total of 13 articles were included in the analysis. To date, there have been 332 cases of hemorrhage following a total of 5748 TORS. The pooled median post-TORS hemorrhage rate was 6.47%. The overall incidence of minor and major hemorrhage was 5.29% and 2.90%. Patients with prior radiation (relative risk [RR] = 1.46, 95% confidence interval [CI] = 1.00-2.12), large tumors (RR = 2.11, 95% CI = 1.48-2.99), and those requiring perioperative coagulation (RR = 2.25, 95% CI = 1.54-3.28) had significantly higher relative risks of hemorrhage. There was no significant difference in the relative risk of overall hemorrhage with TAL. Looking at major hemorrhage, patients undergoing TAL had a large but insignificant relative risk reduction in post-TORS hemorrhage (RR = 0.40, 95% CI = 0.15-1.07). CONCLUSION: The incidence of post-TORS hemorrhage is low (5.78%), and for major hemorrhage requiring emergent embolization, TAL, or tracheotomy to control hemorrhage it is even lower (2.90%). Large tumors, perioperative anticoagulation, and prior radiation were associated with significantly increased risk of post-TORS hemorrhage. TAL does not reduce the overall incidence of post-TORS hemorrhage but may lead to fewer severe hemorrhages. LEVEL OF EVIDENCE: III Laryngoscope, 131:95-105, 2021.

Robotic-assisted transmaxillary approach for removal of juvenile nasopharyngeal angiofibroma of the pterygopalatine and infratemporal fossa.

Endoscopic transmaxillary approaches to remove juvenile nasopharyngeal angiofibromas (JNAs) have been described previously and are used for tumors that extend laterally in the pterygopalatine fossa (PPF) and infratemporal fossa (ITF). There is no previous description of robotic-assisted JNA removal in the literature. The video will demonstrate the success of this technique. Robotic transmaxillary approaches to the lateral PPF and ITF are easily achieved through an extended Caldwell-Luc antrostomy. Total operative time was 519 minutes. Total robotic operative time was 283 minutes. The endoscopic approach provided no assistance in tumor dissection or removal. Robotic-assisted transmaxillary JNA removal allows the operating surgeon to control the endoscope and to operate free of collisions from the robotic console while having an active assistant surgeon at the patient bedside. A video demonstrating the technique is found on Head & Neck's web site.

Reconstruction of TORS oropharyngectomy defects with the nasoseptal flap via transpalatal tunnel.

The nasoseptal flap (NSF) has been described as reconstructive option for soft palate defects following transoral robotic surgery (TORS). As described, this technique is does not provide adequate coverage of the lateral oropharyngeal wall, parapharyngeal space, exposed vessels, or exposed mandibular bone. The NSF for TORS reconstruction has been limited to soft palate reconstruction, given the limitations on length when passed via the nasopharynx. In this article, we describe (1) a novel technique for TORS reconstruction using direct transposition of the ipsilateral NSF into the oropharynx via a transpalatal tunnel at the hard-soft palate junction, and (2) its use in select patients.

The endoscopic endonasal approach for sinonasal and nasopharyngeal adenoid cystic carcinoma.

OBJECTIVE: To determine factors affecting outcomes for patients with sinonasal and nasopharyngeal adenoid cystic carcinoma (SNACC) treated using the endoscopic endonasal approach (EEA) with preservation of key structures followed by adjuvant radiotherapy (RT). METHOD: Retrospective case series of 30 patients treated at the University of Pittsburgh between 2000 and 2014. Hospital records were reviewed for clinical and pathologic data. Outcome measures included overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) rates. RESULTS: The majority of patients had T4a and T4b disease (23.3%, and 63.3%). Microscopically positive margins were present in 21 patients (63.6%). Positive margins were present in nine patients (30.0%). The mean and median follow-up were 3.97 and 3.29 years. Five-year OS, DFS, LRFS, and DMFS were 62.66%, 58.45%, 87.54%, and 65.26%. High-/intermediate-grade tumors had worse DFS (P = .023), and LRFS (P = .026) (HR = 4.837, 95% CI, 1.181-19.812). No factors were associated with significantly worse DMFS. No patient suffered CSF leak, optic nerve, or internal carotid injury. The mean and median length of hospital stay was 4.1 days and 2.0 days (range: 0-32 days). CONCLUSION: Organ-preserving EEA with adjuvant RT for low-grade SNACC offers 5-year survival similar to that reported by other studies, which include radical, open skull base surgery. Patients with high-grade disease do poorly and may benefit from novel treatment strategies. For low-grade disease, organ-preserving EEA with RT may be the best option, offering a balance of survival, quality of life, and decreased morbidity for patients with this difficult-to-cure disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1414-1421, 2020.

Injury of the Carotid Artery during Endoscopic Endonasal Surgery: Surveys of Skull Base Surgeons.

Objectives This study aimed to review endoscopic skull base surgeon experience with internal carotid artery (ICA) injuries during endoscopic endonasal surgery (EES) to provide an estimate of the incidence of ICA injury, the associated factors and identify the best training modalities for the management of this complication. Design Anonymous electronic survey of past participants at a well-established endoscopic skull base surgery course and a global online community of skull base surgeons. Main Outcome Measures Relative incidence of ICA injuries during EES, associated anatomic and intraoperative factors, and surgeon experience. Results At least 20% of surgeons in each surveyed population experienced a carotid artery injury. Reported carotid artery injuries were most common during tumor exposure and removal (48%). The parasellar carotid artery was the most commonly injured segment (39%). Carotid artery injuries were more common in high-volume surgeons, but only statistically significant in one of the two populations. Attendance at a skull base course or courses did not change the incidence of carotid artery injury in either surveyed population. In both surveys, respondents preferred live surgeries or active (not computer simulated) training models. Conclusions ICA injury is underreported and most common when manipulating the parasellar carotid artery for exposure and tumor dissection. Given the high morbidity and mortality associated with these injuries, vascular injury management should be prioritized and taught in a graduated approach by modern endoscopic skull base courses.

Current Role of Surgery in the Management of Oropharyngeal Cancer.

The 1990s saw an increased use of chemoradiotherapy protocols, commonly referred to as organ-sparing therapy, for the treatment of oropharyngeal cancer after the Groupe d'Oncologie Radiothérapie Tête et Cou trial. Since that time, human papillomavirus-associated oropharyngeal squamous cell carcinoma has been identified as a unique disease, with improved survival regardless of treatment modality. The improved outcomes of this population has led to re-evaluation of treatment paradigms in the past decade, with a desire to spare young, human papillomavirus-positive patients the treatment-related toxicities of chemoradiotherapy and to use new minimally invasive surgical techniques to improve outcomes. Numerous retrospective and prospective studies have investigated the role of surgery in treatment of oropharyngeal carcinoma and have demonstrated equivalent oncologic outcomes and improved functional outcomes compared with chemoradiotherapy protocols. Ongoing and future clinical trials may help delineate the role of surgery in the future.

The effects of dexamethasone and acyclovir on a cell culture model of delayed facial palsy.

HYPOTHESIS: Pretreatment with antiherpetic medications and steroids decreases likelihood of development of delayed facial paralysis (DFP) after otologic surgery. BACKGROUND: Heat-induced reactivation of herpes simplex virus type 1 (HSV1) in geniculate ganglion neurons (GGNs) is thought to cause of DFP after otologic surgery. Antiherpetic medications and dexamethasone are used to treat DFP. Pretreatment with these medications has been proposed to prevent development of DFP. METHODS: Rat GGN cultures were latently infected with HSV1 expressing a lytic protein-GFP chimera. Cultures were divided into pretreatment groups receiving acyclovir (ACV), acyclovir-plus-dexamethasone (ACV + DEX), dexamethasone alone (DEX), or untreated media (control). After pretreatment, all cultures were heated 43°C for 2 hours. Cultures were monitored daily for reactivation with fluorescent microscopy. Viral titers were determined from culture media. RESULTS: Heating cultures to 43°C for 2 hours leads to HSV1 reactivation and production of infectious virus particles (59 ± 6.8%); heating cultures to 41°C showed a more variable frequency of reactivation (60 ± 40%), compared with baseline rates of 14.4 ± 5%. Cultures pretreated with ACV showed lower reactivation rates (ACV = 3.7%, ACV + DEX = 1.04%) compared with 44% for DEX alone. Viral titers were lowest for cultures treated with ACV or ACV + DEX. CONCLUSION: GGN cultures harboring latent HSV1 infection reactivate when exposed to increased temperatures that can occur during otologic surgery. Pretreatment with ACV before heat provides prophylaxis against heat-induced HSV reactivation, whereas DEX alone is associated with higher viral reactivation rates. This study provides evidence supporting the use of prophylactic antivirals for otologic surgeries associated with high rates of DFP.