Cost-Effectiveness of [99mTc]Tilmanocept Relative to [99mTc]Sulfur Colloid for Sentinel Lymph Node Biopsy in Early Stage Oral Cavity Cancer.

BACKGROUND: Several studies have demonstrated varying rates of efficacy, reliability, and sensitivity of sentinel lymph node biopsy (SLNB) in identifying occult nodal disease for early stage oral cavity squamous cell carcinoma (OCSCC) depending on the radionuclide agent utilized. No head-to-head comparison of cost or clinical outcomes of SLNB when utilizing [99mTc]tilmanocept versus [99mTc]sulfur colloid has been performed. The goal of this study was to develop a decision model to compare the cost-effectiveness of [99mTc]tilmanocept versus [99mTc]sulfur colloid in early stage OCSCC. PATIENTS AND METHODS: A decision model of disease and treatment as a function of SLNB was created. Patients with a negative SLNB entered a Markov model of the natural history of OCSCC parameterized with published data to simulate five states of health and iterated over a 30-year time horizon. Treatment costs and quality-adjusted life-years (QALYs) for each health state were included. The incremental cost-effectiveness ratio (ICER) was then estimated using $100,000 per additional QALY as the threshold for determining cost-effectiveness. RESULTS: The base case cost-effectiveness analysis suggested [99mTc]tilmanocept was more effective than [99mTc]sulfur colloid by 0.12 QALYs (7.06 versus 6.94 QALYs). [99mTc]Tilmanocept was more costly, with a lifetime cost of $84,961 in comparison with $84,264 for sulfur colloid, however, the overall base case ICER was $5859 per additional QALY, well under the threshold for cost-effectiveness. Multiple one-way sensitivity analyses were performed, and demonstrated the model was robust to alternative parameter values. CONCLUSION: Our analysis showed that while [99mTc]tilmanocept is more costly upfront, these costs are worth the additional QALYs gained by the use of [99mTc]tilmanocept.

Effectiveness of smoking cessation interventions among persons with cancer: A systematic review.

OBJECTIVES: Continued smoking after cancer diagnosis is associated with worse outcomes, however, many persons diagnosed with cancer who smoke are unable to quit successfully. Effective interventions are needed to promote quitting in this population. The purpose of this systematic review is to understand the most effective interventions for smoking cessation among persons with cancer and to identify gaps in knowledge and methodology to suggest directions for future research. METHODS: Three electronic databases (The Cochrane Central Register of Controlled trials, MEDLINE, and EMBASE) were searched for studies of smoking cessation interventions among persons with cancer, published up to 1 July 2021. Title and abstract screening, full-text review, and data extraction was completed by two independent reviewers, via Covalence software, with any discordance resolved by a third reviewer. A quality assessment was completed using the Cochrane Risk of Bias Tool Version 2. RESULTS: Thirty-six articles were included in the review, including 17 randomized-controlled trials (RCTs) and 19 non-RCT studies. Of the 36 studies, 28 (77.8%) utilized an intervention that included both counseling and medication, with 24 (85.7%) providing medication to participants at no cost. Abstinence rates in the RCT intervention groups (n = 17) ranged from 5.2% to 75%, while the non-RCTs found abstinence rates ranging from 15% to 46%. Overall, studies met a mean of 2.28 out of seven quality items, ranging from 0 to 6. CONCLUSIONS: Our study highlights the importance of utilizing intensive combined behavioral and pharmacological interventions for persons with cancer. While combined therapy interventions seem to be the most effective, more research is needed, as current studies have several quality issues, including the lack of biochemical verification for abstinence.

Otolaryngology in the face of A pandemic.

Although infrequent, pandemics are serious public health concerns with unpredictable courses. The COVID-19 pandemic began over 2 years ago and is far from over. This pandemic has spread rapidly throughout the world and led to several million deaths, making it commonly compared to the deadly Spanish influenza pandemic. Policy and safety measures are constantly being adapted to reduce transmission rates. The pandemic places stress on all healthcare workers, but especially otolaryngology providers due to their direct contact with airway connected cavities. This puts them at high risk for infection and has impacted inpatient and outpatient otolaryngology care, as well as education, research, and mental health.

Educating School Nurses about Human Papillomavirus (HPV) Associated Cancers and the Importance of HPV Vaccination.

PURPOSE: To assess and improve school nurse knowledge of HPV-associated cancers. DESIGN: An experimental quality improvement study. METHODS: At a continuing education regional conference, an interactive HPV education session was provided. Pre- and post-education surveys were completed by attendees. FINDINGS: After the educational intervention, 89.9% of nurses indicated a change in knowledge and 83.2% indicated a planned change in practice. CONCLUSIONS: An education intervention aimed at school nurses can be impactful in broadening the understanding of HPV oncogenesis. CLINICAL EVIDENCE: Educational interventions can be a strategy to increase school nurse knowledge and subsequently patient knowledge about HPV associated cancers.

Characterizing Tobacco Usage in Otolaryngology Patients to Target Smoking Cessation Efforts.

Objective: Smoking cessation is critical in reducing incidence of head and neck cancers (HNC) and improving postoperative outcomes. Accurate documentation of tobacco usage is necessary to understand prevalence in patients to target smoking cessation. This study aims to characterize tobacco usage documentation, including electronic nicotine delivery systems (ENDS) use, among otolaryngology patients. Study Design: Retrospective chart review. Setting: Penn State Health Milton S. Hershey Medical Center (PSHMC). Methods: A retrospective chart review was conducted on adult otolaryngology patients seen from January 1, 2020 - December 31, 2020. Patient demographics, details of alcohol and tobacco usage, including type of tobacco, and subspecialty seen were collected. Associations were evaluated using chi-square tests and a multivariable logistic regression model. Results: Patients (n = 2137) were an average of 58.4 years old ±18.0, 59.3% female, and 78.0% white. Of participants with documented tobacco history (n = 944), 56.7% were never users, 28.9% were former users, and 14.4% were current users. Among current users (n = 308), 86.4% used cigarettes, and 5.2% used ENDS. The remainder used chew (4.9%) and cigars (3.25%). Odds of tobacco use were 1.5x greater for males (95% CI 1.19-2.00), 1.6x greater for unmarried patients (95% CI 1.24-2.09), 2.1x greater for those with no insurance vs government (95% CI 1.43-3.18), and 2.4x greater for those diagnosed with HNC (95% CI 1.64-3.49). Conclusion: Most patients report cigarette smoking when asked about tobacco use. Taking into consideration the rise of ENDS use, our sample showed ENDS use that was higher than the national average. There is significant opportunity for improved history taking, especially within general and head and neck oncology subspecialties for more comprehensive treatment.

Postoperative Urinary Complications in Head and Neck Free Flap Reconstructive Surgery.

OBJECTIVE: The purpose of this study is to evaluate the postoperative urinary complications and the optimal timing of foley catheter removal in patients who underwent free flap reconstructive surgery for head and neck pathology. METHODS: A retrospective case-control study of head and neck patients who underwent free flap reconstructive surgery at a single institution between January 2009 and December 2021 was conducted. Patient risk factors for postoperative urinary retention (POUR) were analyzed. Fisher Exact and Wilcoxon Rank Sum tests were used to evaluate rates of foley replacement, straight catheterization, and catheter-associated urinary tract infection (CAUTI) and associated risk factors. RESULTS: Two hundred and eleven patients were included in this study. Older age, lower BMI, lower intraoperative fluid volumes, and need for straight catheterization were statistically significant for POUR requiring foley replacement. Shorter total (P = .04) and postoperative (P = .01) foley duration showed statistical significance for POUR requiring straight catheterization. About 60% of patients who had straight catheterization required a foley replacement (P < .001). Only one patient (0.5%) developed a urinary tract infection (UTI). CONCLUSION: Foley catheter duration impacts the risk of POUR requiring straight catheterization and subsequently, foley replacement. Optimal timing for foley catheter removal in the postoperative period remains to be elucidated. Removal of catheters between 21 and 48 hours after surgery may decrease the risk of POUR without increasing the rate of CAUTI in patients with head and neck pathology undergoing free flap reconstructive surgery.

Elucidating survival and functional outcomes in patients with primary head and neck malignancies treated in academic versus community settings.

BACKGROUND: Differences in treatment outcomes between community or academic centers are incompletely understood. METHODS: Retrospective review of head and neck cancer patients between 2010 and 2020 in a rural health region. Kaplan-Meier curves and log-rank tests were used to evaluate survival outcomes, along with bivariate and multivariable Cox proportional hazards models. Linear regression was used for functional outcomes of tracheotomy and gastrostomy tube dependence. RESULTS: Two hundred and forty-eight patients treated at an academic center were compared with 94 patients treated in community centers. In multivariable analysis, the risk of death (HR = 0.60, p = 0.019), and risk of recurrence were lower (HR = 0.29, p < 0.001) for patients treated in academic centers. Patients treated in community centers had longer gastrostomy tube dependence (p = 0.002). CONCLUSION: Our findings suggest that treatment at an academic center was associated with a lower risk of recurrence and shorter gastrostomy tube dependence compared to treatment in the community.

American Head and Neck Society position statement on the use of PD-1 inhibitors for treatment of advanced cutaneous squamous cell carcinoma.

BACKGROUND: A position statement put forth by the American Head and Neck Society (AHNS) was constructed to provide evidence-based treatment recommendations for PD-1 inhibitor use in advanced cutaneous squamous cell carcinoma (cSCC). Secondarily, we sought to identify knowledge gaps warranting further investigation. METHODS: A literature search utilizing key terms: cutaneous squamous cell carcinoma, cutaneous cancer, checkpoint inhibitors, systemic therapy, Program Cell Death, PD-1 (PubMed, Cochrane, and Google Scholar) was carried out to generate evidence-based statements. The statements were distributed among the AHNS membership. Delphi methodology was applied to identify statements achieving 70% or greater consensus among the leadership team. RESULTS: Twenty-six position statements achieved consensus. Knowledge gaps for future research included: impact of immunosuppression on cSCC staging and associated treatment; role of PD-1 inhibitors in immunosuppressed patients. CONCLUSION: This comprehensive position statement put forth by the AHNS represents majority consensus by practicing head and neck surgeons throughout the country.

"How did you feel?": increasing child sexual abuse witnesses' production of evaluative information.

In child sexual abuse cases, the victim's testimony is essential, because the victim and the perpetrator tend to be the only eyewitnesses to the crime. A potentially important component of an abuse report is the child's subjective reactions to the abuse. Attorneys may ask suggestive questions or avoid questioning children about their reactions, assuming that children, given their immaturity and reluctance, are incapable of articulation. We hypothesized that How questions referencing reactions to abuse (e.g., "how did you feel") would increase the productivity of children's descriptions of abuse reactions. Two studies compared the extent to which children provided evaluative content, defined as descriptions of emotional, cognitive, and physical reactions, in response to different question-types, including How questions, Wh- questions, Option-posing questions (yes-no or forced-choice), and Suggestive questions. The first study examined children's testimony (ages 5-18) in 80 felony child sexual abuse cases. How questions were more productive yet the least prevalent, and Option-posing and Suggestive questions were less productive but the most common. The second study examined interview transcripts of 61 children (ages 6-12) suspected of being abused, in which children were systematically asked How questions regarding their reactions to abuse, thus controlling for the possibility that in the first study, attorneys selectively asked How questions of more articulate children. Again, How questions were most productive in eliciting evaluative content. The results suggest that interviewers and attorneys interested in eliciting evaluative reactions should ask children "how did you feel?" rather than more direct or suggestive questions.

Phrenic nerve schwannoma presenting as an asymptomatic neck mass.

Phrenic nerve schwannomas of the head and neck are exceedingly rare pathologies that can present as an asymptomatic neck mass. Surgery is the definitive treatment, and a conservative surgical approach is preferred if a benign pathology is suspected.

A Systematic Review of Oral Nutritional Supplement and Wound Healing.

OBJECTIVE: To explore the current literature for effects of oral nutritional supplement on wound healing rates in humans. METHODS: A systematic review of the literature was performed using the Medline and PubMed database following PRISMA guidelines. The PubMed database was searched using terms relating to oral nutritional supplement and wound healing from 1837 to March 2020. Study inclusion criteria were: (i) design: randomized controlled trials, clinical studies, observational studies, clinical trials; (ii) population: adults; and (iii) intervention: oral nutritional supplement. RESULTS: The search yielded 2433 studies, 313 of which were clinical trials or clinical studies. After abstract review, 28 studies qualified to be included in the review evaluating the following supplementation categories on wound healing: protein and amino acids (10), mineral, vitamin and antioxidants (9), probiotics (1), and mixed nutrients (8). Arginine and omega-3 supplement were shown to improve wound healing in head and neck cancer patients with surgical wounds by decreasing incidence of postoperative complications and reducing length of hospital stay. Mineral, vitamins, and antioxidants enriched supplements were more beneficial in increasing wound healing than non-enriched protein supplement for diabetic foot and pressure ulcers. CONCLUSIONS: Supplementation of a variety of nutrients had variable effects on improving wound healing in different types of wounds. However, further research on the impact of nutritional supplements on surgical wound healing is necessary. The impact of multiple nutrient formulations may also need to be further evaluated for efficacy.

Myelin repair is accelerated by inactivating CXCR2 on nonhematopoietic cells.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS and remyelination in MS ultimately fails. Although strategies to promote myelin repair are eagerly sought, mechanisms underlying remyelination in vivo have been elusive. CXCR2 is expressed on neutrophils and oligodendrocyte lineage cells in the CNS. CXCR2-positive neutrophils facilitate inflammatory demyelination in demyelination models such as experimental autoimmune encephalomyelitis (EAE) and cuprizone intoxication. Systemic injection of a small molecule CXCR2 antagonist at the onset of EAE decreased demyelinated lesions. These results left the cellular target of the CXCR2 antagonist uncertain and did not clarify whether CXCR2 blockade prevented demyelination or promoted remyelination. Here, we show that the actions of CXCR2 on nonhematopoietic cells unexpectedly delay myelin repair. Bone marrow chimeric mice (Cxcr2(+/-)-->Cxcr2(-/-) and Cxcr2(+/-)-->Cxcr2(+/+)) were subjected to two distinct models of myelin injury. In all cases, myelin repair was more efficient in Cxcr2(+/-)-->Cxcr2(-/-) animals. Oligodendrocyte progenitor cells (OPCs) in demyelinated lesions of Cxcr2(+/-)-->Cxcr2(-/-) mice proliferated earlier and more vigorously than in tissues from Cxcr2(+/-)--> Cxcr2(+/+) animals. In vitro demyelinated CNS slice cultures also showed better myelin repair when CXCR2 was blocked with neutralizing antibodies or was genetically deleted. Our results suggest that CXCR2 inactivation permits optimal spatiotemporal positioning of OPCs in demyelinating lesions to receive local proliferative and differentiating signals. Given that CXCR2 exerts dual functions that promote demyelination and decrease remyelination by actions toward hematopoietic cells and nonhematopoietic cells, respectively, our findings identify CXCR2 as a promising drug target for clinical demyelinating disorders.

Targeted injury of type II alveolar epithelial cells induces pulmonary fibrosis.

RATIONALE: Ineffective repair of a damaged alveolar epithelium has been postulated to cause pulmonary fibrosis. In support of this theory, epithelial cell abnormalities, including hyperplasia, apoptosis, and persistent denudation of the alveolar basement membrane, are found in the lungs of humans with idiopathic pulmonary fibrosis and in animal models of fibrotic lung disease. Furthermore, mutations in genes that affect regenerative capacity or that cause injury/apoptosis of type II alveolar epithelial cells have been identified in familial forms of pulmonary fibrosis. Although these findings are compelling, there are no studies that demonstrate a direct role for the alveolar epithelium or, more specifically, type II cells in the scarring process. OBJECTIVES: To determine if a targeted injury to type II cells would result in pulmonary fibrosis. METHODS: A transgenic mouse was generated to express the human diphtheria toxin receptor on type II alveolar epithelial cells. Diphtheria toxin was administered to these animals to specifically target the type II epithelium for injury. Lung fibrosis was assessed by histology and hydroxyproline measurement. MEASUREMENTS AND MAIN RESULTS: Transgenic mice treated with diphtheria toxin developed an approximately twofold increase in their lung hydroxyproline content on Days 21 and 28 after diphtheria toxin treatment. The fibrosis developed in conjunction with type II cell injury. Histological evaluation revealed diffuse collagen deposition with patchy areas of more confluent scarring and associated alveolar contraction. CONCLUSIONS: The development of lung fibrosis in the setting of type II cell injury in our model provides evidence for a causal link between the epithelial defects seen in idiopathic pulmonary fibrosis and the corresponding areas of scarring.

Cutaneous Head and Neck Cancers in the High-Risk Immunosuppressed Population.

The immunosuppressed (IS) population encompasses a diverse cohort of patients to include iatrogenically immunocompromised organ transplant recipients as well as patients with chronic lymphoid malignancies, human immunodeficiency virus/acquired immunodeficiency syndrome, and autoimmune disorders. Cutaneous cancers in this high-risk patient group are clinically distinct from the general immunocompetent population, showing aggressive behavior with associated poor outcomes. This article reviews the pathogenesis, epidemiology, incidence, prognosis, and special considerations required in managing cutaneous cancers in the IS patient population.

HPV-positive oral papillomas in an adolescent-A diagnostic dilemma.

Human papillomavirus oral papilloma is often sexually transmitted, but non-sexual modes of transmission should be considered, including autoinoculation from skin lesions. A patient-centered multimodality approach should be utilized in the pediatric population.

Gastrointestinal Pathology in Samples From Coronavirus Disease 2019 (COVID-19)-Positive Patients.

CONTEXT.­: Although primarily considered a respiratory illness, coronavirus disease 2019 (COVID-19) can cause gastrointestinal manifestations. OBJECTIVE.­: To evaluate histopathology and in situ hybridization for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in gastrointestinal samples from patients with recent and remote COVID-19. DESIGN.­: Patients with positive SARS-CoV-2 nasopharyngeal tests and a gastrointestinal tissue specimen were included. SARS-CoV-2 in situ hybridization (ISH) was performed on each sample. A subset had SARS-CoV-2 next-generation sequencing (NGS) performed. RESULTS.­: Twenty-five patients met inclusion criteria. Five had positive SARS-CoV-2 nasopharyngeal tests within 7 days of their gastrointestinal procedure. Two were ulcerative colitis patients on steroid therapy who lacked typical COVID-19 symptoms. Their colectomies showed severe ulcerative colitis; one demonstrated SARS-CoV-2 by NGS but a negative ISH. Another had an ischemic colon resected as a complication of the COVID-19 course; however, both ISH and NGS were negative. A fourth had a normal-appearing terminal ileum but positive ISH and NGS. The fifth patient had ileal ulcers with SARS-CoV-2 negativity by both modalities. The remaining 20 patients had positive nasopharyngeal tests an average of 53 days prior to procedure. None of their samples demonstrated SARS-CoV-2 ISH positivity, but one was positive on NGS despite a negative nasopharyngeal test. CONCLUSIONS.­: Gastrointestinal findings from SARS-CoV-2-infected patients ranged from normal with virus detected by ISH and NGS to bowel ischemia secondary to systemic viral effects without evidence of virus in the tissue. No distinct histologic finding was identified in those with gastrointestinal tissue specimens demonstrating SARS-CoV-2 positivity in this cohort.

Clinical Implication of Diagnostic and Histopathologic Discrepancies in Sinonasal Malignancies.

OBJECTIVES: To evaluate the incidence of histopathologic diagnostic discrepancy for patients referred to our institution, identify pathologies susceptible to diagnostic error, and assess the impact on survival of histopathologic diagnostic discrepancies. METHODS: Three hundred ninety-seven patients with sinonasal cancers were identified, and discordance between the outside pathologic report and MD Anderson Cancer Center pathologic report was assessed. Overall survival and disease-specific survival were analyzed using Kaplan-Meier and log rank methods. RESULTS: Discordance of major histopathologic diagnoses was present in 24% (97 of 397) of reports, with sinonasal undifferentiated carcinoma, sarcoma, neuroendocrine carcinoma, and poorly differentiated carcinoma pathologies having the highest change in diagnosis (P < .01). A further 61% (244 of 397) had minor changes such as histologic grade, subtype, or stage, with sarcoma and neuroendocrine carcinoma pathologies being most susceptible to change (P < .02). Overall, the 5-year overall survival (OS) and disease-specific survival (DSS) was reduced in patients with a major change in histopathologic diagnosis (59.2% vs. 70.2% (P = .02) and 72.9% vs. 81.2% (P = .02), respectively). Furthermore, patients with a major change in diagnosis and prior treatment experienced a significant reduction in 5-year OS (61.9% vs. 70.4%, P = .03 < .01) and DSS (72.4% vs. 81.5%, P = .04). CONCLUSION: Histopathological diagnosis of sinonasal tumors is complex and challenging given the rarity of the disease. Obtaining the correct diagnosis is important for treatment selection and survival. In histologies prone to misdiagnoses, obtaining a second opinion from experienced head and neck pathologists at a high-volume institution may potentially lead to a change in treatment recommendations that could result in improved survival in patients with sinonasal malignancies. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1468-E1475, 2021.

Commentary on the management of total laryngectomy patients during the COVID-19 pandemic.

The coronavirus disease-2019 (COVID-19) pandemic has rapidly spread across the world, placing unprecedented strain on the health care system. Health care resources including hospital beds, ICUs, as well as personal protective equipment are becoming increasingly rationed and scare commodities. In this environment, the laryngectomee (patient having previously undergone a total laryngectomy) continues to represent a unique patient with unique needs. Given their surgically altered airway, they pose a challenge to manage for the otolaryngologist within the current COVID-19 pandemic. In this brief report, we present special considerations and best practice recommendations in the management of total laryngectomy patients. We also discuss recommendations for laryngectomy patients and minimizing community exposures.

Prognostic performance of the American Joint Committee on Cancer 8th edition of the TNM staging system in patients with early oral tongue cancer.

BACKGROUND: The 8th edition of the American Joint Committee on Cancer's (AJCC) staging system for oral cavity cancer incorporates pathological features. We aimed to assess whether these changes results in better risk stratification of patients with early oral tongue squamous cell carcinoma (OTSCC). METHODS: Overall survival (OS) and disease-specific survival (DSS) of 244 patients were calculated using the Kaplan-Meier method. Multivariate analysis with stepwise selection was performed using Cox proportional hazards regression. RESULTS: Sixty-two patients (25%) were upstaged using the 8th edition. Multivariate analysis revealed that overall stage using the 8th edition of the AJCC staging system but not using the 7th edition was a significant predictor for both OS and DSS. The 8th edition had lower Akaike information criterion and improved concordance index values compared with the 7th edition. CONCLUSION: The 8th edition of AJCC allows better risk stratification and more precise counseling of patients with OTSCC who were previously considered at low risk.