Maackia amurensis seed lectin (MASL) and soluble human podoplanin (shPDPN) sequence analysis and effects on human oral squamous cell carcinoma (OSCC) cell migration and viability.

Maackia amurensis lectins serve as research and botanical agents that bind to sialic residues on proteins. For example, M. amurensis seed lectin (MASL) targets the sialic acid modified podoplanin (PDPN) receptor to suppress arthritic chondrocyte inflammation, and inhibit tumor cell growth and motility. However, M. amurensis lectin nomenclature and composition are not clearly defined. Here, we sought to definitively characterize MASL and its effects on tumor cell behavior. We utilized SDS-PAGE and LC-MS/MS to find that M. amurensis lectins can be divided into two groups. MASL is a member of one group which is composed of subunits that form dimers, evidently mediated by a cysteine residue in the carboxy region of the protein. In contrast to MASL, members of the other group do not dimerize under nonreducing conditions. These data also indicate that MASL is composed of 4 isoforms with an identical amino acid sequence, but unique glycosylation sites. We also produced a novel recombinant soluble human PDPN receptor (shPDPN) with 17 threonine residues glycosylated with sialic acid moieties with potential to act as a ligand trap that inhibits OSCC cell growth and motility. In addition, we report here that MASL targets PDPN with very strong binding kinetics in the nanomolar range. Moreover, we confirm that MASL can inhibit the growth and motility of human oral squamous cell carcinoma (OSCC) cells that express the PDPN receptor. Taken together, these data characterize M. amurensis lectins into two major groups based on their intrinsic properties, clarify the composition of MASL and its subunit isoform sequence and glycosylation sites, define sialic acid modifications on the PDPN receptor and its ability to act as a ligand trap, quantitate MASL binding to PDPN with KD in the nanomolar range, and verify the ability of MASL to serve as a potential anticancer agent.

Tuberculosis of the middle ear: A systematic review.

OBJECTIVE: Tuberculous otitis media (TOM) is a rare extrapulmonary manifestation of tuberculosis (TB) and remains challenging to diagnose due to non-specific symptoms. This systematic review identifies clinical characteristics, diagnostic evaluation, and outcomes in cases of TOM. METHODS: A comprehensive literature search utilizing the PubMed, CINAHL, Scopus, and Cochrane Library databases was conducted for relevant articles published between 2000 and 2021. Cases involving adult patients with TOM were included. Non-English studies, animal studies, and reviews were excluded. RESULTS: 41 case reports and 7 case series were included, comprising data from 67 patients. The mean age was 40 years (range, 19-87 years) and the majority were female (n = 46, 68.7 %). The mean symptom duration was 12.8 months (range, 0.25-120 months). Common symptoms included otorrhea (n = 60, 89.6 %), HL (n = 58, 86.6 %), otalgia (n = 19, 28.4 %), and FP (n = 18, 26.9 %). Otoscopy revealed tympanic membrane (TM) perforation in 45 patients (67.2 %). Most patients were diagnosed with tissue biopsy (n = 53, 79.1 %). Surgical interventions were performed in 48 patients (71.6 %) and 63 patients (94.0 %) were prescribed anti-TB chemotherapy. Long-term sequelae (e.g., HL, FP, and TM perforation) were noted in 39 patients (58.2 %) at a mean follow-up of 18.8 months (range, 1-120 months). CONCLUSION: TOM should be included in the differential diagnosis of chronic suppurative otitis media. Histopathological examination is a reliable diagnostic method. Early detection and management are recommended for optimizing outcomes. LEVEL OF EVIDENCE: 3b.

The Affordable Care Act: Implications for underserved populations with head & neck cancer.

PURPOSE: This study was done to determine the direct impact implementation of the Affordable Care Act (ACA) on patients with Head and Neck Cancer (HNCA) in states that chose to expand Medicaid compared to in states that did not, as well as assess whether this impact varied among different demographic groups. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for cases of HNCA diagnosed from 2011 to 2014. Rates of uninsured status were compared before and after Medicaid expansion and contrasted between states that did and did not expand coverage, stratified by patient and tumor characteristics, and assessed via multivariate regression. RESULTS: Overall rates of uninsured status (UR) were decreased by 63.08% in states that expanded coverage (ES) but only by 2.6% in states that did not (NS). In NS, there was an increase in proportion of black patients who were uninsured over the study period (13.7%, p = 0.077) whereas in ES, this proportion decreased by 73.3%. When stratified by primary site, patients with laryngeal cancer had the highest UR with an increase by 16.7% in NS and a decrease by 70.5% in ES. Multivariate analysis yielded predictors of uninsured status including residence in a NS, Hispanic ethnicity, and black race. CONCLUSIONS: Implementation of the ACA resulted in expanded insurance coverage for patients diagnosed with HNCA concentrated mainly in states that expanded Medicaid coverage and for patients derived from vulnerable populations, including black and Hispanic patients. In states that did not expand Medicaid, vulnerable populations were disproportionately affected.

Outcomes in microvascular head and neck reconstruction in the setting of restricted residency hours.

BACKGROUND: Resident duty hour restrictions can limit the frequency of resident flap checks at smaller institutions with "home" call. Institutions are compensating with adjuvant nursing flap checks as well as incorporating technology; however, this management remains controversial. METHODS: A prospective cohort of 122 free flaps for reconstruction of the head and neck by a single surgeon. Demographic information, operative details, postoperative care, and flap outcomes were recorded. RESULTS: Over 42 months, 122 free flaps were performed on 115 patients. The overall flap success rate was 96%. The flap success rate at 72 h was 98% and 96% at the time of discharge with reexploration rates of 11.6%. The intraoperative and postoperative salvage rates were 71% and 64.3% respectively. CONCLUSION: Limited resident flap checks combined hourly nurse flap checks and an implantable Doppler is an effective monitoring protocol for academic programs in the setting of residency duty hour restrictions.

Impact of diabetes on free flap surgery of the head and neck: A NSQIP analysis.

OBJECTIVE: Diabetes is associated with microvascular pathology and may predispose patients undergoing microvascular surgery to complications. This study assesses diabetes as a risk factor for complications following free flap surgery of the head and neck. PATIENTS AND METHODS: In this retrospective cohort study, data on free flap surgeries of the head and neck between 2005 and 2014 was collected from the National Surgical Quality Improvement Program (NSQIP) database. A propensity-matching algorithm (PSM) was used to equilibrate distribution of numerous covariates between the diabetic and nondiabetic cohorts. A sub-analysis was performed to examine the impact of insulin-dependency. RESULTS: The initial dataset contained 2187 free flaps of the head and neck. After implementing PSM, a new population was created containing 506 total cases with 253 DM patients. The majority of cases were male and white. The matched cohort did not contain any demographics or comorbidities associated with DM. Complications significantly elevated in the DM group were severe bleeding (P = .046), postoperative ventilation greater than 48 hours (P < .001), and pneumonia (P < .048). In patients with insulin-dependent diabetes, reintubation (P = .005), cardiac arrest (P = .010), severe bleeding (P = .006), overall surgical complications (P = .015), and overall complications (P = .005) were significantly increased. CONCLUSION: This study examines the impact of diabetes on postoperative complications following free flap reconstruction of the head and neck. Propensity score matching was utilized. Analysis of the PSM cohort suggests that diabetic patients have elevated rates of postoperative pulmonary complications. Additionally, patients with insulin-dependent diabetes have significantly elevated rates of medical and surgical complications.

The effect of training level on complications after free flap surgery of the head and neck.

OBJECTIVES: Analyze postoperative complications after free flap surgery based on PGY training level. METHODS: Data on free flap surgeries of the head and neck performed from 2005 to 2013 was collected from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. Cases identifying the status of resident participation in the surgery and the PGY level were included. RESULTS: There were 582 cases with primary surgeon data available. 63 cases were performed with a junior resident, 211 were performed with the assistance of a senior resident, 279 cases were performed with a fellow, and 29 cases were performed by an attending alone without resident involvement. The overall complication rate was 55.2%. There was no statistically significant difference in the rate of complications between groups (47.6%, 59.7%, 53.0%, 58.6%, p=0.277). After controlling for all confounding variables using multivariate analysis there was no significant difference in morbidity, mortality, readmissions, and reoperation amongst the groups. Furthermore, when comparing resident versus fellow involvement using multivariate analysis there were no significant differences in morbidity (OR=0.768[0.522-1.129]), mortality (OR=1.489[0.341-6.499]), readmissions (OR=1.018[0.458-2.262]), and reoperation (OR=0.863[0.446-1.670]). CONCLUSION: Resident and fellow participation in microvascular reconstructive cases does not appear to increase 30-day rates of medical, surgical, or overall complications.

Inpatient Complications After Transsphenoidal Surgery in Cushing's Versus Non-Cushing's Disease Patients.

OBJECTIVE: Transsphenoidal surgery (TSS) harbors a potential for hypopituitarism, cerebrospinal fluid (CSF) leaks, and other complications. We utilized the Nationwide Inpatient Sample Database (NIS) to compare inpatient complication rates between Cushing's disease (CD) and non-Cushing's disease (NCD) patients undergoing TSS. METHODS: Inpatient hospitalization data for 960 CD and 12 110 NCD patients who underwent TSS between 2002 and 2010 were accessed. Demographic information, outcomes, and complication rates were evaluated. RESULTS: Patients with CD had a female predilection (81.7%) and were younger (40.5 ± 14.4 years) than NCD patients (47.8% female; 52.1 ± 16.3 years) (P < .001). Length of stay and total charges did not differ between groups. Patients with CD had significantly greater postoperative diabetes insipidus rates (14.0% vs 9.6%, P < .001) and urinary/renal complications (1.7% vs 0.9%, P = .027). After adjusting for possible confounders, the relationship between urinary/renal complications and CD status strengthened. There was no difference in rates of CSF leak and iatrogenic pituitary disorders overall. CONCLUSION: No differences were noted in the rate of early CSF leaks between postoperative TSS CD and NCD patients. Postoperative diabetes insipidus did not significantly differ between groups after adjusting for confounders. Only odds of urinary/renal complications in CD patients was significant after adjustment.

Population-based trends in outcomes in adenoid cystic carcinoma of the oral cavity.

PURPOSE: Adenoid cystic carcinoma (ACC) is a rare malignant epithelial neoplasm of secretory glands of the upper aerodigestive tract. It accounts for 3-5% of head and neck malignancies and most commonly arises from the minor salivary glands of the oral cavity. The clinical behavior of ACC from specific anatomic subsites, including the oral cavity, is not well described in the literature. We aim to elucidate patient demographics, clinicopathologic features, incidence, and survival trends for oral cavity ACC (OCACC). METHODS: Retrospective population-based analysis of OCACC in the SEER database between 1973 and 2012. RESULTS: 1066 OCACC patients were identified, of which 57.7% were female (P<0.0001). Incidence was 0.049 per 100,000. Whites were most commonly affected (81.1%). The hard palate was the most commonly involved subsite (44.1%). Nodal involvement was seen in 8.4% of cases and distant metastasis was present in 6.2% of cases at the time of presentation. Disease-specific survival (DSS) rates at 1, 5, 10, 15, and 20years were 97.4%, 83.9%, 69.9%, 57.6%, and 46.2%, respectively. Females had a higher 5-year DSS (87.8%) than males (78.4%, P=0.0004). Cases treated with surgery had a favorable prognosis regardless of whether they received radiotherapy (P<0.0001). Nodal involvement reduced 5-year DSS by 51.6% (P<0.0001), while distant metastasis reduced 5-year DSS by 46.4% (P<0.0001). CONCLUSIONS: OCACC is a rare malignancy with females and whites being more commonly affected. At presentation, regional and distant metastases are uncommon. Poor prognostic indicators include male gender, nonsurgical therapy, nodal involvement, and distant metastasis.

Readability Assessment of Internet-Based Patient Education Materials Related to Parathyroid Surgery.

OBJECTIVES: Patient education is critical in obtaining informed consent and reducing preoperative anxiety. Written patient education material (PEM) can supplement verbal communication to improve understanding and satisfaction. Published guidelines recommend that health information be presented at or below a sixth-grade reading level to facilitate comprehension. We investigate the grade level of online PEMs regarding parathyroid surgery. METHODS: A popular internet search engine was used to identify PEM discussing parathyroid surgery. Four formulas were used to calculate readability scores: Flesch Reading Ease (FRE), Flesch-Kincaid Grade Level (FKGL), Gunning Frequency of Gobbledygook (GFOG), and Simple Measure of Gobbledygook (SMOG). RESULTS: Thirty web-based articles discussing parathyroid surgery were identified. The average FRE score was 42.8 (±1 standard deviation [SD] 16.3; 95% confidence interval [CI], 36.6-48.8; range, 6.1-71.3). The average FKGL score was 11.7 (±1 SD 3.3; 95% CI, 10.5-12.9; range, 6.1-19.0). The SMOG scores averaged 14.2 (±1 SD 2.6; 95% CI, 13.2-15.2; range, 10.7-21.9), and the GFOG scores averaged 15.0 (±1 SD 3.5; 95% CI, 13.7-16.3; range, 10.6-24.8). CONCLUSION: Online PEM on parathyroid surgery is written above the recommended sixth-grade reading level. Improving readability of PEM may promote better health education and compliance.

Academic Benchmarks for Otolaryngology Leaders.

OBJECTIVE: This study aimed to characterize current benchmarks for academic otolaryngologists serving in positions of leadership and identify factors potentially associated with promotion to these positions. METHODS: Information regarding chairs (or division chiefs), vice chairs, and residency program directors was obtained from faculty listings and organized by degree(s) obtained, academic rank, fellowship training status, sex, and experience. Research productivity was characterized by (a) successful procurement of active grants from the National Institutes of Health and prior grants from the American Academy of Otolaryngology-Head and Neck Surgery Foundation Centralized Otolaryngology Research Efforts program and (b) scholarly impact, as measured by the h-index. RESULTS: Chairs had the greatest amount of experience (32.4 years) and were the least likely to have multiple degrees, with 75.8% having an MD degree only. Program directors were the most likely to be fellowship trained (84.8%). Women represented 16% of program directors, 3% of chairs, and no vice chairs. Chairs had the highest scholarly impact (as measured by the h-index) and the greatest external grant funding. CONCLUSION: This analysis characterizes the current picture of leadership in academic otolaryngology. Chairs, when compared to their vice chair and program director counterparts, had more experience and greater research impact. Women were poorly represented among all academic leadership positions.

A case-control analysis of survival outcomes in sinonasal carcinosarcoma.

PURPOSE: Carcinosarcoma is a rare malignant tumor of mixed epithelial and mesenchymal origin. In the head and neck, carcinosarcoma most commonly affects the salivary glands. Primary sinonasal carcinosarcoma (SN-CS) is exceedingly rare. METHODS: We performed a retrospective analysis of 15 cases of SN-CS obtained from the Surveillance, Epidemiology and End Results (SEER) database from 1973 to 2010. Case-matched cohorts of non-sinonasal carcinosarcoma (NS-CS), salivary gland carcinosarcoma (SG-CS) and carcinosarcoma at all other head and neck sites (NonSNSG-CS) were used for comparison. RESULTS: Women made up 60.0% of the SN-CS cohort and whites 73.3%. Tumors originated in the nasal cavity in 46.7% of cases, and from the maxillary sinus in 33.3%. In 66.7% of cases, tumors were poorly differentiated (histologic grades III and IV). Surgery with radiotherapy was the primary treatment modality in 46.7% of cases. Five-year disease-specific survival (DSS) was 48.5% for SN-CS compared to 65.5% for the case-matched SG-CS cohort (p = 0.2950), whereas it was 76.9% for the case-matched NonSNSG-CS cohort (p =0.0406). CONCLUSION: SN-CS is a rare tumor. Here we present the largest known cohort of SN-CS and report on its demographic, clinicopathologic and survival features. Our results suggest that patients with SN-CS have DSS comparable to the case-matched cohort of SG-CS patients. However, SN-CS patients have significantly poor survival outcomes compared to the case-matched cohort of NonSNSG-CS patients.

Angiosarcoma arising from the frontal sinus.

Primary sinonasal angiosarcomas are very rare tumors. They typically occur in the nasal cavity of middle-aged patients. They are classically highly aggressive. Primary treatment is surgical excision when feasible. We describe a unique case of angiosarcoma in a young woman arising from the frontal sinus with distant metastasis. This case represents the first report of angiosarcoma arising from the frontal sinus in the English literature. The traditional treatment options for the advanced nature of her disease and overall poor prognosis are discussed. We further review the literature and discuss alternative treatments options. Newer chemotherapeutic regiments on the horizon show promise in helping to control this disease.

Diffuse large B-cell lymphoma of the sinonasal tract: analysis of survival in 852 cases.

PURPOSE: Diffuse large B-cell lymphomas (DLBCLs) are rare tumors of the head and neck that often have non-specific presentations and significant morbidity and mortality. In this analysis we use a large cohort to compare the demographic and disease-specific parameters affecting survival and incidence of DLBCLs. METHODS: The United States National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry was utilized to extract data regarding sinonasal diffuse large B-cell lymphoma between 1973 and 2009. A total of 852 cases of sinonasal DLBCLs were found. Presenting symptoms, demographics, disease specific survival, relative survival and survival by treatment modality were described for this rare tumor. RESULTS: Overall disease specific survival (DSS) at 1-year was 84.7% and at 5 years was 68.0%. DSS was significantly lower for those not treated with radiation therapy, with 1- and 5-year survival rates of 77.3% and 62.5%, versus those treated with radiation therapy, with 1- and 5-year rates of 89.2% and 71.5% (p<0.05). Prognosis was significantly better for patients treated with radiation therapy (HR 0.6, p<0.05) while it was poorer for patients with involvement of multiple sinuses (HR 1.5, 1.8, p<0.05). CONCLUSIONS: DLBCLs of the sinonasal tract are rare tumors of the head and neck. Survival is significantly improved for those treated with radiation therapy while the involvement of multiple sinuses is a negative prognostic indicator.

Squamous cell carcinoma of the parotid gland: a population-based analysis of 2545 cases.

PURPOSE: Squamous cell carcinoma (SCC) of the parotid gland is an uncommon tumor, which generally affects older patients. In this study, we explore various aspects of this entity using a national population-based database. METHODS: The Surveillance, Epidemiology, and End Results (SEER) registry was used to extract data on frequency, incidence, and disease-specific survival (DSS) from 1973 to 2009. Variables analyzed included age, gender, race, histologic grade, stage and treatment. Cox proportional hazards analysis was conducted. RESULTS: A total of 2545 cases were identified. Parotid SCC was most common in males (79.8%), whites (92.9%), and patients aged ≥75 years (51.4%). Incidence increased slightly over the past three decades (annual percent change 1.90%, p<0.05). Overall 5-year DSS was 54.4%. Statistically significant poor prognostic factors included black race, age ≥75 years, tumor T3 or greater, and higher clinical stage at diagnosis. Elective neck dissection (END) in patients staged N0 was associated with higher DSS (78.3% versus 51.1%, p<0.0001). The omission of END was associated with a three-fold greater hazard of death (hazard ratio 3.19, 95% confidence interval 1.53-7.26, p=0.0016), regardless of whether or not radiotherapy was given. CONCLUSION: Parotid SCC is uncommon, and data on treatment decisions are limited. Our study profiles the demographic, clinicopathologic, incidence, and survival features of this entity. Perhaps most notably, our results support the practice of END of the N0 neck.

Meningitis and legal liability: an otolaryngology perspective.

PURPOSE: Meningitis is a potential complication in otolaryngologic procedures and conditions. Severe sequelae make understanding factors involved in relevant malpractice litigation critical. We analyze pertinent litigation for awards, outcomes, patient demographic factors, and other alleged causes of malpractice. METHODS: Pertinent jury verdict and settlement reports were examined using the Westlaw legal database (Thomson Reuters, New York, NY). RESULTS: Twenty-three cases (60.5%) involved non-iatrogenic injuries, including inadequate treatment or failure to diagnose sinusitis or otitis media, while 15 (39.5%) involved iatrogenic cases, mostly rhinologic procedures. 36.8% of cases were resolved for the defendant, 28.9% with juries awarding damages, and 34.2% with settlements. Although not statistically significant, mean damages awarded were higher than settlements ($2.1 vs. 1.5M, p=0.056), and cases involving pediatric patients were more likely to be resolved with payment than those with adult litigants (80.0% vs. 52.2%, p=0.08 respectively). Other frequent alleged factors included permanent deficits (63.2%), requiring additional surgery (41.1%), death (34.2%), cognitive deficits (21.2%), deafness (15.8%), and inadequate informed consent (33.0% of iatrogenic cases). CONCLUSIONS: Practitioners facing litigation related to meningitis may wish to consider these findings, notably for cases involving death or permanent functional deficits, as cases with out of court settlements tended to be resolved with lower payments. Cases involving misdiagnosis may be more likely to be resolved with payment compared with iatrogenic cases. By understanding the issues detailed in this analysis and including them in the informed consent process for patients undergoing rhinologic and otologic procedures, otolaryngologists may potentially improve patient safety and decrease liability.

Adverse jaw outcomes from immune checkpoint inhibitors for head and neck cancer? Case reports.

Radiation treatment plays a mainstream role in the management of head and neck squamous cell carcinomas (HNSCCs). Adverse effects from radiation therapy include osteoradionecrosis of the jaw, and rarely, pathologic fracture. Immune checkpoint inhibitors (ICI) such as pembrolizumab are of growing relevance to the management of metastatic and recurrent HNSCCs. Adverse impacts on bone secondary to medications such as pembrolizumab and nivolumab have been sporadically documented in the literature. The objective of this manuscript is to raise awareness of possible increase in risk for adverse jaw outcomes in patients with HNSCCs exposed to both radiation treatment to the jaws and ICI therapy. This manuscript documents adverse jaw outcomes including osteonecrosis and pathologic fracture of the mandible in two patients receiving pembrolizumab for management of HNSCC who had received prior radiation treatment. A potential link between immunotherapy and adverse jaw outcomes is consistent with the growing understanding of osteoimmunology, investigating the closely interrelated processes in bone remodeling and immune system function, in health and disease. It is important to ascertain if pembrolizumab poses an incremental risk for such outcomes, beyond the risk from prior radiation, for patients managed with radiation treatment and ICI therapy for HNSCC. The general dental practitioner may encounter such patients either in the context of facilitating dental clearance prior to initiation of chemotherapy, or rarely, with poorly explained jaw symptoms and must be alert to the possibility of occurrence of such adverse jaw events to facilitate timely diagnosis and optimal patient management.

Otolaryngologic Side Effects After COVID-19 Vaccination.

OBJECTIVES: With widespread vaccination against COVID-19, concerns regarding side effects have been raised. We aim to assess the frequency of otolaryngologic adverse events (AEs) following COVID-19 vaccination as compared with other vaccines in a national database. STUDY DESIGN: Retrospective analysis of national registry. METHODS: The Food and Drug Administration's Vaccine Adverse Event Reporting System (VAERS) database was queried from December 2020 to May 2021 for all COVID-19 vaccination AEs. Complaints were categorized as otolaryngologic and sub stratified into different anatomic components. Reporting odds ratios (ROR) and proportional reporting ratios (PRR) were determined for AEs of clinical significance. RESULTS: The total number of AEs reported from vaccination with the Moderna, Pfizer-BioNTech, and Janssen vaccines equaled 1,280,950. Of these, 62,660 (4.9%) were otolaryngologic in nature, with 32.6% associated with the oropharynx/larynx, 18.3% with the nasal cavity/sinuses, 17.1% with the ears/vestibular system, 10.0% with the oral cavity, and 21.9% miscellaneous. Signal ratios reached significance levels for dysgeusia (n = 2124, PRR: 17.33, ROR: 16.36), ageusia (n = 1376, PRR: 2.81, ROR: 2.81), anosmia (n = 983, PRR: 4.01, ROR: 4.01), rhinorrhea (n = 2203, PRR: 2.99, ROR: 3.00), throat tightness (n = 3666, PRR: 4.99, ROR: 5.00), throat irritation (n = 3313, PRR: 4.51, ROR: 4.52), dysphagia (n = 2538, PRR: 2.07, ROR: 2.07), tinnitus (n = 4377, PRR: 3.97, ROR: 3.98), and vertigo (n = 2887, PRR: 3.93, ROR: 3.93). Signal ratios were not significant for facial paralysis, Bell's palsy, anaphylaxis, sinusitis, hearing disability, and ear pain. CONCLUSIONS: Although several otolaryngologic symptoms were reported, few were found to be clinically significant. Of note, facial paralysis, Bell's palsy, and anaphylaxis did not meet signal thresholds to be determined significant. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1163-1168, 2024.

Adverse jaw outcomes from immune checkpoint inhibitors for head-and-neck cancer? Case reports.

Radiation treatment plays a mainstream role in the management of head and neck cancers (HNSCC). Adverse effects from radiation therapy include osteoradionecrosis of the jaw, and rarely, pathological fracture. Immune checkpoint inhibitors (ICI) such as pembrolizumab are of growing relevance to the management of metastatic and recurrent HNSCC. Adverse impact on bone secondary to medications such as pembrolizumab and nivolumab have been sporadically documented in the literature. The objective of this manuscript is to raise awareness of possible increase in risk for adverse jaw outcomes in patients with HNSCC exposed to both radiation treatment to the jaws and ICI therapy. This manuscript documents adverse jaw outcomes including osteonecrosis and pathological fracture of the mandible in two patients receiving pembrolizumab for management of HNSCC and had received prior radiation treatment. A potential link between immunotherapy and adverse jaw outcomes is consistent with our growing understanding of osteoimmunology, investigating the closely interrelated processes in bone remodeling and immune system function, in health and disease. It is important to ascertain if pembrolizumab poses an incremental risk for such outcomes, beyond the risk from prior radiation, for patients managed with radiation treatment and ICI therapy for HNSCC. The general dentist may encounter such patients either in the context of facilitating dental clearance prior to initiation of chemotherapy, or rarely, with poorly explained jaw symptoms and must be alert to the possibility of occurrence of such adverse jaw events to facilitate timely diagnosis and optimal patient management.

Facility Volume and Changing Facilities for Postoperative Radiotherapy in Salivary Gland Cancer.

OBJECTIVES: Changing location of postoperative radiotherapy (PORT) after treatment at a high-volume facility (HVF) is associated with worse survival in various head and neck cancers. Our study investigates this relationship in salivary gland cancer (SGC). METHODS: The 2004-2016 National Cancer Database was queried for all cases of adult SGC treated with surgery and PORT with or without adjuvant chemotherapy. Patients with multiple cancer diagnoses, metastatic disease, or unknown PORT facility were excluded. Reporting facilities with >95th percentile annual case volume were classified as HVFs, the remainder were classified low-volume facilities (LVFs). RESULTS: A total of 7885 patients met inclusion criteria, of which 418 (5.3%) were treated at an HVF. Patients treated at an HVF had higher rates clinical nodal positivity (18.2% vs. 14.0%, p < 0.001) and clinical T3/T4 (27.3% vs. 20.7%, p = 0.001) disease. Patients at HVFs changed facility for PORT at lower rates (18.9% vs. 24.5%, p = 0.009). Patients treated at an HVF had higher 5-year overall survival (5-OS) than those treated at an LVF (79.0% vs. 72.0%, p = 0.042). Patients treated at an HVF that changed PORT facility had worse 5-OS (60.8% vs. 83.2%, p < 0.001). Radiation facility change was an independent predictor of worse survival in patients treated at an HVF (HR: 8.99 [3.15-25.67], p < 0.001) but not for patients treated at a LVF (HR: 1.11 [0.98-1.25], p = 0.109). CONCLUSIONS: Patients treated at an HVF changing facility for PORT for SGC experience worse survival. Our data suggest patients treated surgically at an HVF should be counseled to continue their PORT at the same institution. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Use of AlloDerm in primary reconstruction after resection of squamous cell carcinoma of the lip and oral commissure.

AlloDerm (LifeCell Corporation, Branchburg NJ) is an acellular dermal homograft processed from human cadaveric skin. AlloDerm has been used successfully for soft tissue reconstruction due to its lack of immunogenicity and minimal absorption. In the lip, it has been utilized for aesthetic lip augmentation and as an injectable filler. Description of its usage as an implant in primary lip reconstruction after tumor resection is limited. We describe the case of a 52 year old male with a squamous cell carcinoma of the oral commissure and lower lip. After resection, the defect was reconstructed using implanted AlloDerm for bulk, a buccal mucosal advancement flap, and a cheek rhomboid flap. Lip mobility and oral competence were normal 3 months postoperatively. The reconstruction achieved adequate augmentation without significant resorption. AlloDerm should be considered in primary lip reconstruction after cancer resection.