Managing Mandibular Osteoradionecrosis.

OBJECTIVE: Mandibular osteoradionecrosis (MORN) is a morbid complication of head and neck radiation therapy. Recent advances in surgical and medical therapies underscore the need for a shift in traditional treatment paradigms and a disease grading system that can guide appropriate management. DATA SOURCES: Pubmed/MEDLINE. REVIEW METHODS: We conducted a detailed review of publications related to MORN, specifically focusing on its staging and management techniques. Articles meeting inclusion criteria were synthesized into a final narrative review. CONCLUSION: There has been a paradigm shift away from hyperbaric oxygen therapy in the management of MORN. Growing evidence for the efficacy of pentoxifylline and tocopherol in early-stage disease and novel surgical techniques to manage moderate and late-stage disease warrant an updated staging stratification which is proposed. IMPLICATIONS FOR PRACTICE: This review summarizes the clinical efficacy of established and novel therapeutic modalities currently available in treating MORN, emphasizing the significant advances achieved over the last decade. It introduces a contemporary staging and treatment algorithm which incorporates traditional, evidence-supported surgical and medical management with effective early intervention strategies.

Analysis of antibiotic resistant infections associated with hirudotherapy.

OBJECTIVE: Given rising concern regarding antibiotic resistance, our objective was to evaluate antibiotic-resistant infections following leech therapy and to characterize the use of prophylactic antibiotics. METHODS: All reports of adverse events involving hirudotherapy (product code "NRN") were retrieved from the U.S. Food and Drug Administration MAUDE database between 2012 and 2021. Antibiotic resistance was defined by bacterial culture or infection after antibiotic administration. RESULTS: Nineteen cases of antibiotic resistance involving hirudotherapy were identified. Only three cases of antibiotic resistance were discovered on routine testing and the remaining 16 cases were associated with patient injury. Positive blood cultures or fever were present in 26.3 % (n = 5) of cases. Cultures of the infection grew Aeromonas hydrophilia (n = 13; 68.4 %), Vibrio vulnificus (n = 3; 15.8 %), Pseudomonas aeruginosa (n = 2; 10.5 %), and Proteus vulgaris (n = 1; 5.3 %). There were nine (47.4 %) multi-drug resistant infections. Infection was most commonly resistant to fluoroquinolones (n = 9; 47.4 %), trimethoprim-sulfamethoxazole (n = 9; 47.4 %) and ertapenem (n = 4; 21.1 %). CONCLUSION: Antibiotic-resistant infections involving hirudotherapy are frequently resistant to multiple drugs, including fluoroquinolones and trimethoprim-sulfamethoxazole. Resistance to ertapenem, a drug of last resort, was also documented. The findings presented in this study support growing literature that the trend in multi-drug resistance is more severe than previously reported.

Preoperative Hypoalbuminemia Predicts 30-day Complications in Head and Neck Microvascular Surgery.

INTRODUCTION: Hypoalbuminemia, a marker for poor nutritional status, has been associated with postoperative complications, including head and neck cancer surgery. This study investigates the impact of hypoalbuminemia on head and neck microvascular free tissue transfer reconstruction. METHODS: This retrospective cohort study queried the 2005-2021 American College of Surgeons National Surgical Quality Improvement Program databases. Reconstructive cases performed by otolaryngologists (CPT: 15756, 15757, 15758, 15842, 20955, 20956, 20957, 20962, 20969, 20970, 20972, 20973, 43116, 43496, 49006, and 49906) with available preoperative albumin, BMI, and age were included. Hypoalbuminemia was defined as a preoperative albumin <3.5 g/dL. Univariate and multivariable logistic regression were performed. RESULTS: A total of 3,886 cases met the inclusion criteria, of which 835 (21.5%) had hypoalbuminemia. The hypoalbuminemia cohort was older, had lower BMI, had higher ASA classification, and had worse functional health status. Adjusted multivariable logistic regression showed that hypoalbuminemia was associated with unplanned return to the operating room within 30 days (OR: 1.36, p < 0.01), unplanned reoperation (OR: 1.36, p < 0.01), any complication (OR: 1.77, p < 0.01), surgical complications (OR: 1.94, p < 0.01), and medical complications (OR: 1.34, p = 0.01). Hypoalbuminemia was correlated with a longer hospital stay, superficial surgical site infection, wound dehiscence, transfusion, deep vein thrombosis, and acute renal failure. CONCLUSION: Hypoalbuminemia is a risk factor for postoperative complications after microvascular free tissue transfer for head and neck reconstruction. This study suggests that preoperative optimization of hypoalbuminemia may be beneficial for these patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Positive Trends in Racial Disparities for Head and Neck Microvascular Reconstructive Surgery.

OBJECTIVE: To evaluate national trends in racial disparities for patients undergoing head and neck reconstructive surgery. METHODS: Retrospective analysis using the 2008 to 2021 American College of Surgeons National Surgical Quality Improvement Program database. Patients receiving microvascular free tissue transfer were eligible for inclusion. Pediatric patients and those treated by non-otolaryngologists were excluded. Outcomes were analyzed with univariate and multivariable models. RESULTS: A total of 5831 head and neck free flap cases were analyzed, 4869 (83.5%) were White, 560 (9.6%) were Black or African American, and 402 (6.9%) were Asian, Native American, or other groups (ANAOG). The proportion of Black or African American patients and ANAOG patients undergoing free tissue transfer increased significantly over the time period (p = 0.047 and p = 0.010, respectively). However, there was a downtrend that started around 2017. In a multivariable model, Black or African American race was not associated with readmission (OR = 0.99 [95% CI 0.74, 1.31], p > 0.05), returning to the operating room (OR = 1.20 [95% CI 0.96, 1.49], p > 0.05), or any post-operative complication (OR = 0.83 [95% CI 0.68, 1.01], p > 0.05). There were also no significant associations found in the ANAOG population on multivariate analysis (p > 0.05 for all). CONCLUSION: The percentage of free tissue transfer performed in patients from minority backgrounds with head and neck cancer has been increasing in the United States. Outcomes after head and neck microvascular reconstruction are similar when stratified by race. However, racial disparities remain and further work is necessary to reduce these disparities. LEVEL OF EVIDENCE: Level IV Laryngoscope, 2024.

Patterns of failure after salvage head and neck surgery.

BACKGROUND: Advancements in immunotherapy for recurrent head and neck cancer have necessitated a better understanding of salvage surgical outcomes. This study aimed to determine patterns of failure following salvage head and neck surgery. METHODS: A retrospective cohort study was conducted of 280 patients who underwent salvage surgery for recurrent mucosal squamous cell carcinoma from 1997 to 2018. Cumulative incidence was calculated using the nonparametric Aalen-Johansen estimator. Time to recurrence (TTR) and overall survival (OS) were estimated using the Kaplan-Meier method and multivariable Cox proportional hazard models were used to evaluate associated factors. RESULTS: The 2 and 5-year cumulative incidence rates of second recurrence were 48.3 % (95 % CI 42.4-54.3) and 54.9 % (95 % CI 48.9-60.8), respectively. At 5 years, second locoregional recurrence was twice as common as distant recurrence (41.5 % [95 % CI 35.6-47.4] vs. 21.7 % [95 % CI 16.8-26.6]). The median TTR was 21.1 months (95 % CI 4.4-34.8), which varied by site (38.2 larynx/hypopharynx, 13.9 oral cavity, 8.3 sinonasal, and 7.8 oropharynx, P=.0001). The median OS was 32.1 months (95 % CI 24.1-47.6) and was worse for patients who were Black (hazard ratio [HR] 2.15, 95 % CI 1.19-3.9), current smokers (HR 2.73, 95 % CI 1.53-4.88), former smokers (HR 2.00, 95 % CI 1.19-3.35), ≥ 60 years of age (HR 1.41, 95 % CI 1.01-1.97), or received multimodal primary therapy (HR 1.98, 95 % CI 1.26-3.13). CONCLUSION: Rates of recurrence and mortality after salvage surgery were poor but worse for patients who were Black, older, smoked, had initial multimodal therapy, or had sinonasal or oropharyngeal cancers.

Primary fit tracheoesophageal puncture in primary versus salvage laryngectomy: Short-term and long-term complications and functional outcomes.

BACKGROUND: Primary fit tracheoesophageal puncture (TEP) is widely preferred for individuals who have not undergone prior radiation. However, there is no consensus on the relative utility of primary-fit TEP in the setting of salvage laryngectomy. METHODS: A retrospective, single-center review was conducted of individuals undergoing laryngectomy with primary fit TEP between 2012 and 2018. Multivariable analysis was conducted to compare short-term and long-term complications, as well as speech and swallowing outcomes, of those who underwent primary versus salvage laryngectomy. RESULTS: In this study, 134 patients underwent total laryngectomy with primary fit TEP. Aside from a higher rate of peristomal dehiscence (13.1% vs. 1.4%) found in the salvage group, there was no difference in incidence of all other complications, including pharyngocutaneous fistula formation. The groups had comparable speech and swallow outcomes. CONCLUSION: Primary fit TEP is a safe and effective surgical choice for individuals undergoing salvage laryngectomy who desire a voice prosthesis.

Adverse events associated with anastomotic coupling devices in microvascular reconstruction.

OBJECTIVE: In light of the recent US Food and Drug Administration (FDA) Class 2 safety recall notice for anastomotic coupling devices, it is important to understand related adverse events. The aim of this study was to characterize adverse events in anastomotic coupling devices for microvascular reconstruction. METHODS: A retrospective cross-sectional analysis using the 2011 to 2021 US FDA Manufacturer and User Facility Device Experience (MAUDE) database. All reports of adverse events involving anastomotic coupling devices were retrieved from the MAUDE database. Descriptive statistics were used to analyze categorized events. RESULTS: There were a total of 293 documented adverse events related to anastomotic coupling devices. These adverse events resulted in 91 (31.1 %) patient injuries and 239 (81.6 %) device malfunctions. The most frequent patient problems were thrombosis/hematoma (n = 38; 41.8 %), unspecified injury (n = 31; 34.1 %), and failure to anastomose (n = 13; 14.3 %). Free flap necrosis was reported in 42 % of thrombosis/hematoma cases (n = 16). The most common malfunctions were devices operating differently than expected (n = 74; 31.0 %), connection problems (n = 41; 17.2 %), and twisted/bent material (n = 19; 7.9 %). There was no significant trend in the number of adverse events over the study period (p > 0.05). CONCLUSIONS: Adverse events from anastomotic coupling devices represent an important and modifiable factor in free tissue failure. Adverse events are predominately related to devices operating differently than expected and may result in vascular compromise of the free flap. Reconstructive surgeons should be cognizant of defective anastomotic coupling devices and be prepared to utilize traditional hand-sewn anastomosis.

Occult Nodal Metastases in Individuals with Clinically Node-Negative Salivary Gland Malignancies.

OBJECTIVES: Salivary gland malignancies comprise a heterogeneous group of pathologies, for which treatment of the clinically negative neck may vary depending on numerous factors. Herein we present data on occult nodal metastases (ONM) as well as survival and recurrence from a large series of cN0 salivary gland malignancies. METHODS: Retrospective chart review was conducted on 532 patients, with 389 patients with major salivary gland cancers and 143 patients with minor salivary gland cancers. Demographic and treatment data were included and rates of ONM, overall survival, local recurrence, regional recurrence, and distant recurrence were analyzed. RESULTS: We found that the overall rate of ONM for parotid was 27% (63/235), for submandibular/sublingual was 35% (18/52), and for minor was 15% (4/26). Analysis of ONM rate at each nodal level was also performed, finding higher rates of level IV and V ONM than prior studies. Submandibular/sublingual and minor salivary gland malignancies showed a predominance of ONMs at levels I-III. Our survival and recurrence rates were similar to those found in previous studies. CONCLUSION: Our data also demonstrate a predominance of ONM in levels I-III for submandibular/sublingual and minor salivary gland cancers, suggesting elective dissection in these levels. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1705-1715, 2024.

Margin Assessment Methods in Oral Cavity Squamous Cell Carcinoma and Recurrence: Tumor Bed vs Resection Specimen Sampling.

Importance: Positive margins and margin clearance are risk factors for recurrence in oral cavity squamous cell carcinoma (OCSCC), and these features are used to guide decisions regarding adjuvant radiation treatment. However, the prognostic value of intraoperative tumor bed vs resection specimen sampling is not well defined. Objective: To determine the prognostic implications of intraoperative margin assessment methods (tumor bed vs resection specimen sampling) with recurrence among patients who undergo surgical resection for OCSCC. Design, Setting, and Participants: This was a retrospective study of patients who had undergone surgical resection of OCSCC between January 1, 2000, and December 31, 2021, at a tertiary-level academic institution. Patients were grouped by margin assessment method (tumor bed [defect] or resection specimen sampling). Of 223 patients with OCSCC, 109 patients had localized tumors (pT1-T2, cN0), 154 had advanced tumors, and 40 were included in both cohorts. Disease recurrence after surgery was estimated by the cumulative incidence method and compared between cohorts using hazard ratios (HRs). Data analyses were performed from January 5, 2023, to April 30, 2023. Main Outcome and Measures: Recurrence-free survival (RFS). Results: The study population comprised 223 patients (mean [SD] age, 62.7 [12.0] years; 88 (39.5%) female and 200 [90.0%] White individuals) of whom 158 (70.9%) had defect-driven and 65 (29.1%) had specimen-driven margin sampling. Among the 109 patients with localized cancer, intraoperative positive margins were found in 5 of 67 (7.5%) vs 8 of 42 (19.0%) for defect- vs specimen-driven sampling, respectively. Final positive margins were 3.0% for defect- (2 of 67) and 2.4% for specimen-driven (1 of 42) margin assessment. Among the 154 patients with advanced cancer, intraoperative positive margins were found in 29 of 114 (25.4%) vs 13 of 40 (32.5%) for defect- and specimen-driven margins, respectively. Final positive margins were higher in the defect-driven group (9 of 114 [7.9%] vs 1 of 40 [2.5%]). When stratified by margin assessment method, the 3-year rates of local recurrence (9.7% vs 5.1%; HR, 1.37; 95% CI, 0.51-3.66), regional recurrence (11.0% vs 10.4%; HR, 0.85; 95% CI, 0.37-1.94), and distant recurrence (6.4% vs 5.0%; HR, 1.10; 95% CI, 0.36-3.35) were not different for defect- vs specimen-driven sampling cohorts, respectively. The 3-year rate of any recurrence was 18.9% in the defect- and 15.2% in the specimen-driven cohort (HR, 0.93; 95% CI, 0.48-1.81). There were no differences in cumulative incidence of disease recurrence when comparing defect- vs specimen-driven cases. Conclusions and Relevance: The findings of this retrospective cohort study indicate that margin assessment methods using either defect- or specimen-driven sampling did not demonstrate a clear association with the risk of recurrence after OCSCC resection. Specimen-driven sampling may be associated with reduced surgical margin positivity rates, which often necessitate concurrent chemotherapy with adjuvant radiation therapy.

Survival Outcomes of Advanced Thyroid Cancer Enriched in Brain Metastases Following Treatment With Small Molecule Inhibitors.

OBJECTIVE: Small molecule inhibitors (SMIs) are targeted therapies increasingly used in advanced thyroid carcinomas. This study aimed to evaluate the survival outcomes of thyroid cancer on SMI treatment, including in patients with brain metastases. METHODS: This retrospective study included patients with thyroid carcinomas who received at least one SMI between 2008 and 2022 at a tertiary level, academic institution. SMI included lenvatinib, sorafenib, dabrafenib-trametinib, selpercatinib, and cabozantinib. Patients were grouped by the presence of brain metastasis. Kaplan-Meier and log-rank tests modeled the overall survival (OS), defined from detection of first metastasis. RESULTS: In total, 116 patients (49.1% female, median age 61.1 years [IQR, 51.1-71.0]) were included. Thyroid cancer subtypes were: 57 (49.6%) papillary, 23 (19.8%) anaplastic, 23 (19.8%) medullary, and 13 (11.2%) follicular. There were 18 (15.5%) patients with brain metastases, and 98 (84.5%) with visceral metastases. Age, sex, thyroid subtype, SMI, and time to recurrence were not different between cohorts. OS was shorter in the brain metastasis cohort (31.7 vs 42.2 months, P =.44) and was not different after excluding anaplastic thyroid cancer (29.1 vs 62.3 months, P =.21). In the case of papillary thyroid cancer, patients with brain metastases trended toward worse OS (22.0 vs 59.9 months, P =.13). Nonanaplastic histology, total thyroidectomy (OR, 40.0; P <.001), number of unique therapies (OR, 10.9; P =.047), and mutation-directed therapy (OR, 24.7; P =.003) were associated with improved OS. CONCLUSION: This single-institutional analysis reports survival outcomes of 116 patients with advanced thyroid cancer on targeted therapies, including 18 patients with brain metastases. Mutation-directed therapy for BRAFV600E mutations, RET mutations, RET fusions, and NTRK fusions had superior survival.