Long-Term Follow-Up of Post Radiation Complete Sinus Opacification in Sinonasal Cancer Patients.

OBJECTIVE: Treatment of sinonasal malignancies most often requires primary or postoperative radiation treatment. Post radiation sinonasal morbidity has been previously described; however, none addressed post-radiation sinus obstruction. Our objective was to investigate the long-term outcomes of post radiation complete isolated sinus opacification (CISO). METHODS: A retrospective analysis of sinonasal cancer patients treated with radiation therapy during the years 2002 to 2022. Clinical, imaging and treatment data were collected from patients' medical records. Only patients with at least 12 months of follow-up and available imaging for review were included. RESULTS: Out of 109 patients, 37 patients were identified to meet the inclusion criteria. Mean follow-up was 58 months. 35% of patients were diagnosed with persistent post radiation CISO with a mean onset of 4 months. All these patients remained asymptomatic, and their imaging remained stable during follow-up with none developing an expanding mucocele. Ethmoid sinus tumor involvement was found to be more prevalent in the CISO group (62% vs. 25%, p-value = 0.048) as well as chemotherapy/immunotherapy (54% vs. 38%, p-value = 0.046). Multivariant analysis revealed that ethmoid sinus involvement (OR = 9.516, p-value = 0.047) and adjuvant therapy, either chemotherapy/immunotherapy (OR = 10.75, p-value = 0.036) were found to be a predictive factor for complete opacification. CONCLUSION: Our study revealed that a substantial number of post-radiation patients develop a stable and persistent CISO, often in the frontal and sphenoid sinuses. These patients remained asymptomatic, and none required surgical intervention during nearly 5 years of follow-up. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Extended cervical approach for retrosternal multinodular goiter.

Objective: Partial or total sternotomy is required for 10% of retrosternal goiter. This study reviewed our experience with an extended cervicotomic approach as an alternative surgical solution for retrosternal goiter. Methods: A retrospective study was performed on patients who underwent partial or total thyroidectomy for retrosternal goiter between 2014 and 2019 at a tertiary medical centre. Data on clinical, radiologic, and pathologic factors were analysed. Peri- and postoperative outcomes were compared between extended and standard cervical approaches to predict the need for an extended cervical approach. Results: The cohort included 265 patients, of whom 245 (92.4%) were treated by standard thyroidectomy. In 17 (6.4%), the standard approach proved insufficient, and the horizontal incision was extended to a T-shape to improve access. The remaining 3 patients required a sternotomy. Use of the extended cervical approach was significantly associated with clinical features such as male gender, diabetes, high body mass index and postoperative hypocalcaemia. Conclusions: The extended cervicotomic approach is an alternative surgical solution for retrosternal goiter, with no increased risk of significant post-operative complications.

Management of first branchial anomalies in children: 20 years of experience.

PURPOSE: Branchial cleft anomalies (BCAs) are common pediatric head and neck lesions; however, only 1-4% involve the first branchial cleft. The rare occurrence of first BCAs, their presentation at a young age, and the possible facial nerve involvement make diagnosis and treatment challenging. METHODS: A retrospective chart review was conducted for children diagnosed with their first BCA between 2000 and 2020. Data on demographics, presenting symptoms, physical findings, imaging features, previous surgery, and treatment outcomes were collected and analyzed. RESULTS: The cohort included 17 patients with a median age of 5 years at presentation. Seven (41%) had undergone previous surgical intervention before definitive surgery. Eight were classified as Work Type II anomalies, and nine as Work Type I. Sixteen patients (94%) underwent definitive surgical excision at a median age of 6.9. A parotid approach was used in 10 (62%), with dissection of the mass from the facial nerve, and a retro-auricular or end-aural approach was used in 6 (38%). Complete excision was achieved in 14/16 patients (88%). Three patients had transient facial nerve paresis postoperatively. Recurrence was noted in 3/16 patients (18%). Enhancement in imaging was positively correlated with post-operative complications (R = 0.463, P = 0.018). CONCLUSIONS: First, BCA poses a diagnostic and surgical challenge; thus, definitive surgical treatment is often delayed. The surgical approach should be tailored to the type of anomaly (Work type I or II) and possible facial nerve involvement. Risk factors for post-operative complications are a history of recurrent infections and previous surgical interventions. The presence of contrast enhancement in preoperative imaging should alert surgeons to perioperative challenges and the risk of post-operative complications.

Novel prognostic factors for successful treatment of pediatric chronic rhinosinusitis using the sinus and nasal quality of life survey (SN-5H).

INTRODUCTION: Chronic rhinosinusitis (CRS) is strongly associated with significant impairment of quality of life (QoL) in children. The SN-5 questionnaire is an important assessment tool for pediatric CRS. This study aimed to evaluate potential prognostic factors for treatment of pediatric CRS within the Hebrew version of the SN-5 questionnaire. METHODS: A prospective study in pediatric otolaryngology unit. Patients were treated either surgically or pharmacologically. Following informed consent, parents of pediatric CRS patients completed the translated and validated Hebrew version (SN-5H) prior to treatment and after three months. We analyzed the results of both treatment arms according to success (achieving minimal clinically important difference; MCID). RESULTS: 102 children aged 5-12 years and their caregivers participated (74 CRS patients and 28 controls without CRS). SN-5H items scores were significantly higher in CRS patients compared to controls (p < 0.001). Baseline activity scores were higher, while baseline emotional scores were lower in MCID( +) CRS patients, compared to MCID(-) CRS patients (p < 0.05). High emotional stress and low activity scores at baseline were associated with poorer odds to achieve MCID. CONCLUSIONS: The SN-5H questionnaire is invaluable tool for assessing pediatric CRS patients. Psychosocial aspects of CRS significantly affect QoL and should be addressed in the office pre-treatment. The SN-5H can aid in highlighting patients in need for further reassurance and psychosocial support to manage expectations, and to improve QoL.

Effect of Opioid Receptor Activation and Blockage on the Progression and Response to Treatment of Head and Neck Squamous Cell Carcinoma.

Recent studies suggest that opioids have a role in the progression of HNSCC mediated by mu opioid receptors (MOR), however, the effects of their activation or blockage remains unclear. Expression of MOR-1 was explored in seven HNSCC cell lines using Western blotting (WB). XTT cell proliferation and cell migration assays were performed on four selected cell lines (Cal-33, FaDu, HSC-2, and HSC-3), treated with opiate receptor agonist (morphine), antagonist (naloxone), alone and combined with cisplatin. All four selected cell lines display an increased cell proliferation and upregulation of MOR-1 when exposed to morphine. Furthermore, morphine promotes cell migration, while naloxone inhibits it. The effects on cell signaling pathways were analyzed using WB, demonstrating morphine activation of AKT and S6, key proteins in the PI3K/AKT/mTOR axis. A significant synergistic cytotoxic effect between cisplatin and naloxone in all cell lines is observed. In vivo studies of nude mice harboring HSC3 tumor treated with naloxone demonstrate a decrease in tumor volume. The synergistic cytotoxic effect between cisplatin and naloxone is observed in the in vivo studies as well. Our findings suggest that opioids may increase HNSCC cell proliferation via the activation of the PI3K/Akt/mTOR signaling pathway. Moreover, MOR blockage may chemo-sensitize HNSCC to cisplatin.

Implementation of a Novel Protocol for Preventing Venous Thromboembolism in Otolaryngology Patients.

OBJECTIVE: Venous thromboembolism (VTE) is a preventable cause of postoperative morbidity and mortality. The Caprini risk assessment model (CRAM) is a validated tool for estimating the risk for postoperative VTE. Previous studies demonstrated a low risk of VTE among otorhinolaryngology-head and neck surgery (ORL-HNS). Hence, our objective was to modify the CRAM-based protocol to be applicable for otolaryngology patients and assess protocol efficacy and safety. STUDY DESIGN: Observational pilot study conducted on ORL-HNS patients undergoing surgery. SETTING: University-affiliated tertiary care center. METHODS: We constructed a modified protocol based on the CRAM and previous reports in the ORL-HNS literature using a reduced postoperative anticoagulation regimen. Primary end point was symptomatic VTE up to 3 months after surgery. Main secondary outcome was postoperative bleeding. RESULTS: A total of 508 patients were enrolled. Of them, 48% underwent head and neck surgery, 18% direct laryngoscopy and transoral robotic surgery, 15% endoscopic sinus surgery, and 11% otology surgery. Adherence to the protocol was 79%. Mean follow-up time was 115 days (range, 30-448 days). Only 1 patient developed deep vein thrombosis, and none developed pulmonary embolism. Two patients had major bleeding not related to the use of anticoagulation. CONCLUSIONS: Our novel CRAM-based protocol appears to be efficacious and safe for VTE prevention in otolaryngology. A larger-scale study is required to validate these findings. LEVEL OF EVIDENCE: Level 2b.

Safety of Endoscopic Sinus Surgery in the Elderly-Are Octogenarian Patients at a Higher Risk?

BACKGROUND: Surgeons are often faced with concerns regarding the risks versus benefits of endoscopic sinus surgery (ESS) in elderly patients. OBJECTIVE: To analyze the risk for complications of ESS in the elderly (age ≥70 years) compared to younger patients, with emphasis on octogenarians. METHODS: Retrospective review of medical charts of adult patients who underwent ESS at a tertiary referral center during the years 2014 to 2018. RESULTS: We compared 128 elderly patients with 276 matched younger patients. In the elderly group mean age was 76 years (range, 70-91 years ). Thirty-one elderly patients were 80 years or older. Surgical complications in the elderly patients were 3.9%. Minor complications were 2.3% and major complications were 1.7%. The surgical complications rate was similar in the younger group (8%, P value: .127). Medical complications were observed in 2.3% comparing to 0.7% in younger patients. Interestingly, age, revision surgery, extent and duration of surgery, and modality of anesthesia were not identified as risk factors. Only ischemic heart disease (IHD) was identified as a risk factor for complications in a multivariate analysis in elderly patients. Comparison of elderly patients younger than 80 years with octogenarians revealed no difference in complication rate between these groups. CONCLUSIONS: Overall, ESS was found to be a safe procedure in elderly patients compared to younger patients. Octogenarian patients should not be denied upfront surgery. IHD is a risk factor for complications in elderly patients.

The Impact of Traditional Anticoagulants, Novel Anticoagulants, and Antiplatelets on Epistaxis.

OBJECTIVE/HYPOTHESIS: Anticoagulant and antiplatelet medications (ACAP) are known to be associated with an increased risk for epistaxis. There are conflicting results regarding the impact of Novel Oral Anticoagulants (NOAC) on epistaxis and its severity. STUDY DESIGN: Retrospective chart review of patients who were admitted to the ED in our tertiary level hospital with a diagnosis of epistaxis during the years 2012 to 2018. METHODS: Retrospective analysis of patients presenting to tertiary level emergency otolaryngological care during the years 2012 to 2018. The impact of various ACAP medications on epistaxis severity, hospital admission, and recurrence was analyzed. RESULTS: A total of 470 patients were identified. Two hundred and twenty-nine patients (49%), were not on any anticoagulant/antiplatelet (ACAP) medications (controls) and 241 patients (51%) were taking at least one ACAP medication (ACAP group). Patients in the ACAP group were at a higher risk for severe epistaxis (OR = 1.8, P < .05) and were more likely to be hospitalized (OR = 2.17, P < .05). Surprisingly, the risk for recurrence was similar in the ACAP and control groups (15%, P > .05). Compared to controls, Warfarin and Enoxaparin increased the overall risk for severe epistaxis (OR = 4.4, P < .05) and for hospital admission (OR = 2.1, P < .05). Specifically, an increased risk for posterior tamponade (OR = 19, P < .001), significant blood loss (OR = 4.4, P = .032), and blood transfusion (OR = 4.7, P = .007) were identified as well. Interestingly, NOACs were not associated with increased risk for severe epistaxis, hospital admission, tamponade, and significant blood loss or blood transfusion compared to controls. CONCLUSIONS: Compared to older generation anticoagulants and antiplatelet medications, NOACs demonstrated an improved safety profile, in terms of epistaxis severity, need for hospital admission and outcomes. These results may suggest a more conservative approach and less hospitalization when treating epistaxis in patients receiving NOACs. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1946-1951, 2021.

CDK 4/6 Inhibition Overcomes Acquired and Inherent Resistance to PI3Kα Inhibition in Pre-Clinical Models of Head and Neck Squamous Cell Carcinoma.

Activating alterations in PIK3CA, the gene coding for the catalytic subunit of phosphoinositide-3-kinase (PI3K), are prevalent in head and neck squamous cell carcinoma (HNSCC) and thought to be one of the main drivers of these tumors. However, early clinical trials on PI3K inhibitors (PI3Ki) have been disappointing due to the limited durability of the activity of these drugs. To investigate the resistance mechanisms to PI3Ki and attempt to overcome them, we conducted a molecular-based study using both HNSCC cell lines and patient-derived xenografts (PDXs). We sought to simulate and dissect the molecular pathways that come into play in PIK3CA-altered HNSCC treated with isoform-specific PI3Ki (BYL719, GDC0032). In vitro assays of cell viability and protein expression indicate that activation of the mTOR and cyclin D1 pathways is associated with resistance to PI3Ki. Specifically, in BYL719-resistant cells, BYL719 treatment did not induce pS6 and pRB inhibition as detected in BYL719-sensitive cells. By combining PI3Ki with either mammalian target of rapamycin complex 1 (mTORC1) or cyclin D1 kinase (CDK) 4/6 specific inhibitors (RAD001 and abemaciclib, respectively), we were able to overcome the acquired resistance. Furthermore, we found that PI3Ki and CDK 4/6 inhibitors have a synergistic anti-tumor effect when combined in human papillomavirus (HPV)-negative/PIK3CA-WT tumors. These findings provide a rationale for combining PI3Ki and CDK 4/6 inhibitors to enhance anti-tumor efficacy in HNSCC patients.

Clinical and imaging evaluation of Congenital Midnasal Stenosis.

OBJECTIVES: To illustrate the clinical and radiological presentation of a rare etiology of nasal obstruction in neonates, midnasal stenosis (MNS), including a comparison of nasal dimensions with those of normal infants. METHODS: We retrospectively reviewed medical charts and computerized tomography (CT) imaging of neonates with nasal obstruction diagnosed as stenosis in the midnasal area in a tertiary pediatric medical center. MNS was defined clinically by inability to visualize the middle turbinate with an endoscope despite the absence of stenosis of the anterior aperture or any gross septal deviation. CT measurements of the midnasal width were taken by an experienced neuroradiologist. We compared widths between the bony inferior turbinate to the bony septum in the narrowest area of symptomatic patients, to widths in a control group of asymptomatic children. RESULTS: Nine neonates from birth to three months old presenting with nasal obstruction, severe stertor, and blocked nasal passage at the midnasal level in endoscopic examination, were diagnosed with MNS. 6/9 had CT scans. Four had isolated unilateral stenosis, two unilateral MNS and contralateral choanal atresia, and three bilateral MNS. All patients were managed conservatively, initially with nasal saline irrigation and local steroids and topical antibiotics; Median time to resolution of symptoms was 14 days. When comparing the dimensions at the midnasal narrowest area of the stenotic group with a control group of 139 healthy children, the median bony width was 1.7 mm vs. 3.2 mm, respectively (p < 0.00001). Average dimensions according to age groups until the age of 12 months are given. CONCLUSION: In neonates with nasal obstruction, when choanal atresia and pyriform aperture stenosis are excluded, stenosis of the midnasal area should be considered. Most of these neonates can be managed conservatively. LEVEL OF EVIDENCE: 4.

Prognostic factors for survival and nonfunctional larynx in patients with squamous cell carcinoma of the larynx.

OBJECTIVES/HYPOTHESIS: Prognostic variables upon presentation can assist in recommending the optimal treatment for patients and may help in management of patient's expectations and side effects. Our objective was to evaluate prognostic factors for survival and nonfunctional larynx in patients with laryngeal squamous cell carcinoma (SCC). STUDY DESIGN: Retrospective chart review. METHODS: All patients diagnosed as having laryngeal SCC from January 2007 through December 2016 in a tertiary, university-affiliated medical center were reviewed. Main outcomes were survival and nonfunctional larynx rate. RESULTS: Two hundred sixty-five patients were identified; the male:female ratio was 4.5:1. Mean age at diagnosis was 64 ± 11.8 years. Overall and disease-free survival were 7.9 and 6.7 years, respectively. A univariate analysis found that older age significantly affected survival. Alcohol abuse, diabetes mellitus, and advanced disease stage at presentation were also found to decrease survival but were not significant. A multivariate Cox regression found age, alcohol abuse, and advanced disease stage to significantly affect and lower survival (P < .05). Of the entire cohort 19% were defined as having a nonfunctional larynx (e.g., tracheostomy or feeding-tube dependent). A backward logistic regression found that male sex and advanced disease stage increased the risk, and anterior commissure involvement was found to lower the probability of nonfunctional larynx (P < .01). CONCLUSIONS: Older age, history of alcohol use, and advanced disease stage at presentation negatively affect survival in larynx cancer patients. Male gender and advanced disease stage increased the risk, and anterior commissure involvement was found to lower the risk for tracheostomy or feeding-tube dependency. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1202-1205, 2020.

Surgical intervention for acute mastoiditis: 10 years experience in a tertiary children hospital.

PURPOSE: To evaluate the clinical course of children with acute mastoiditis (AM) who required surgical intervention. MATERIAL AND METHODS: Clinical and biochemical characteristics at the moment of hospital admission were reviewed for patients who required surgery for AM. Children who were successfully managed conservatively during the last 3 years of study were chosen as a comparison group. RESULTS: During 2008-2017, 570 children were admitted with AM: 82(14%) underwent cortical mastoidectomy, including 31(38%) with decompression of epidural space and sigmoid sinus. The comparison group consisted of 167 children with AM who did not require surgery. The surgical group had a higher rate of acute otitis media before admission. At the time of hospital admission, the surgical group had a higher rate of prolonged fever, otorrhea, and sub-periosteal abscess. Their average temperature, WBC, neutrophil count, and CRP were significantly higher (39.2 vs. 37.9°. C, 20 K vs. 16.5 K, 67 vs. 55.8 percent, 17 vs. 8.8, respectively, p = 0.0001). Fusobacterium necrophorum was the most common pathogen in the surgical group (50%), and group A streptococcus in the comparison group (22%). Sub-periosteal abscess, sinus venous thrombosis, and epidural involvement were diagnosed in 95, 35, and 38 percent of patients, respectively. Average length of IV antibiotic treatment was 20 days in operated children, compared to 5.6 days in the comparison group (p = 0.0001). Since 2013, a significantly higher percentage of children were diagnosed with Fusobacterium mastoiditis (p = 0.0001) who required surgery (p = 0.008). CONCLUSION: In children with AM presenting with, high fever, leukocytosis, elevated CRP, and sub-periosteal abscess, early CT and surgical intervention were frequently required. The increase in Fusobacterium infection might be an explanation for the increase in complicated AM requiring surgery.