Pembrolizumab-associated chronic rhinosinusitis: A new endotype and management considerations.

KEY POINTS: Patients treated with pembrolizumab experience an increase in paranasal sinus inflammation Use of topical triamcinolone in carboxymethylcellulose is a treatment option for such patients.

Layperson Perception of Symptoms Caused by the Sinuses.

OBJECTIVE: To assess the perceived symptoms caused by the sinuses as defined by otolaryngology patients and clinicians. STUDY DESIGN: Multi-institutional cross-sectional study. SETTING: Six academic outpatient otolaryngology practices. METHODS: We performed a multi-institutional, cross-sectional study using a semantics-based questionnaire. Consecutive patients were enrolled at 6 academic otolaryngology centers from June 2020 to May 2021. The primary outcome examined patient and provider definitions for the symptoms caused by the sinuses from a list of 28 proposed terms covering 6 general categories. These data were also collected from otolaryngology faculty at the same institutions. RESULTS: Responses were obtained from 451 patients (54% female, mean age 48.3 years) and 29 otolaryngologists (38% female, mean age 37.4 years). Patients selected a median of 12 terms, compared to 8.5 for otolaryngologists. Among patients, the most frequently selected symptom domains were mucus (419, 92.9%), airflow (412, 91.4%), and pain (389, 86.3%). Compared to clinicians, patients more frequently selected symptoms related to the ear (difference, 48.3%; 95% confidence interval [CI], 34.8%-59.3%), throat (difference, 35.7%, 95% CI, 22.0%-47.5%), systemic (difference, 34.4%, 95% CI, 21.2%-46.0%), mucus (difference, 20.5%, 95% CI, 10.2%-30.6%), and airflow domains (difference, 19.0%, 95% CI, 8.4%-29.3%). Multiple domains were selected by 98% of patients and 79% of providers. CONCLUSION: Semantic differences exist between patients and clinicians regarding the symptoms caused by the sinus with patients having a broader range of perceived symptoms. These differences may provide clues to improve communication between otolaryngologists and their patients.

Management paradigms for chronic rhinosinusitis in individuals with asthma: An evidence-based review with recommendations.

BACKGROUND: Despite the significant morbidity associated with chronic rhinosinusitis (CRS) in individuals with asthma (CRSwA), there is a paucity of codified, evidence-based management strategies for CRS in this population. METHODS: Using PubMed, Embase, and Cochrane Review Databases, a systematic review was performed covering management strategies for CRSwA. A total of 5903 articles were screened, and 70 were included for full-text analysis. After application of exclusion criteria, 53 articles comprised the qualitative synthesis. The level of evidence was graded and benefit-harm assessments, as well as value judgment and recommendations, were provided RESULTS: Strong evidence confirms the benefit of oral and topical medications on sinonasal-specific outcomes in individuals with CRSwA; there is low-grade evidence demonstrating that these agents improve lung function and/or asthma control. Moderate to strong evidence suggests that endoscopic sinus surgery (ESS) improves both sinonasal- and asthma-specific quality of life. Although there is insufficient to low evidence to indicate that ESS improves pulmonary function in this population, data indicate a positive impact of this intervention on asthma control. Biologic medications strongly improve both subjective and objective sinonasal- and asthma-specific outcomes. CONCLUSION: Evidence supports managing CRS in individuals with CRSwA in a stepwise fashion, starting with traditional nonbiologic oral and topical medication, and escalating to second-line treatments, such as ESS and biologics. Optimal treatment of individuals who have CRSwA often requires concurrent, directed management of asthma, as not all CRS interventions impact asthma status.

Postoperative Gabapentin's Effect on Opioid Consumption and Pain Control Following Sinonasal Surgery.

OBJECTIVE: This study investigates the impact of postoperative gabapentin on opioid consumption and pain control following endoscopic sinus surgery (ESS) and/or septoplasty. METHODS: Patients who underwent ESS and/or septoplasty at a single institution from 2021 to 2022 were enrolled. All patients received postoperative hydrocodone-acetaminophen for pain control. Half of the patients were also prescribed gabapentin for the first postoperative day in addition to hydrocodone-acetaminophen. Subjects completed the Revised American Pain Society Patient Outcome Questionnaire 24 h and 7 days after surgery. We conducted a multivariable regression analysis to assess opioid consumption and improvement in pain scores in the first week between gabapentin and non-gabapentin groups. RESULTS: A total of 102 subjects, 51 in each arm, were enrolled. The mean age was 52 years and 53% of participants were female. Controlling for important baseline demographic, clinical, and surgically related variables, the addition of postoperative gabapentin was associated with a 44% (9.5 mg from 21.6 mg) reduction in opioids consumed in the first postoperative week (B = -9.54, 95% C.I. = [-17.84, -1.24], p = 0.025). In addition, patients in both arms exhibited similar improvement in pain severity and sleep interference in the first 7 days (B = -1.59, 95% C.I. = [-5.03, 1.84], p = 0.36). CONCLUSION: To the best of our knowledge, this is the first study to investigate the impact of postoperative gabapentin on opioid consumption and pain control following ESS and/or septoplasty. Our analysis demonstrated that postoperative gabapentin effectively reduced opioid use during the first postoperative week without compromising pain control. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1065-1072, 2023.

What do we mean when we have a "sinus infection?"

INTRODUCTION: Sinus infections are a common reason patients seek medical care. However, the intended meaning of the term sinus infection among patients and otolaryngologists is incompletely understood. METHODS: In this multi-institutional cross-sectional study, a semantics-based questionnaire was provided to consecutive patients presenting to otolaryngology clinics at six academic centers from June 2020 until May 2021. The primary outcome was respondent definitions for sinus infection from a list of 28 proposed terms covering six general categories. Secondary outcome measures included differences between geographic regions. RESULTS: Responses were obtained from 560 patients (54% female, mean age 48.9 years) and 29 otolaryngologists (42% female, mean age 37.4 years). Patients and otolaryngologists selected a median of 10 and 11 terms, respectively, to define a sinus infection. Among patients the most frequently selected symptom categories were mucus (500, 89.3%), pressure/pain (480, 85.7%), and airflow (468, 83.6%). Compared to patients, clinicians selected with greater frequency the symptom categories of pressure/pain (14.3% difference; 95% CI, 7.6% to 22.5%), mucus (10.7% difference; 95% CI, 4.7% to 18.3%) and airflow (13.0% difference; 95% CI, 4.8% to 21.7%). Multiple categories were selected by 96% of patients and 100% of providers. CONCLUSION: The definition of sinus infection appears variable for both patients and otolaryngologists, though patients appear to apply a broader range of symptoms to the term sinus infection. There were no pronounced geographic differences in the description of a sinus infection in this US sample population. Patients commonly described sinus infection in the context of pain-related symptoms. Appreciation of these semantic differences may enable more effective patient-clinician communication.

Predictors of Death, Survival, Need for Intubation, and Need for Oxygen Support Among Admitted COVID-19 Patients of the Veterans Affairs Greater Los Angeles Healthcare System.

INTRODUCTION: While risk factors for severe COVID-19 infections have been well explored among the public, population-specific studies for the U.S. Veteran community are limited in the literature. By performing a comprehensive analysis of the demographics, comorbidities, and symptomatology of a population of COVID-19 positive Veterans Affairs (VA) patients, we aim to uncover predictors of death, survival, need for intubation, and need for nasal cannula oxygen support among this understudied community. MATERIALS AND METHODS: A retrospective review was conducted of 124 COVID-19 Veteran patients who were admitted from March to October 2020 to the VA Greater Los Angeles Healthcare System (IRB#2020-000272). Chi-square and Fisher's exact tests were employed to assess differences in baseline demographic and clinical variables between Veterans who survived COVID-19 versus those who succumbed to COVID-19 illness. Multivariate logistic regression and Cox regression analyses were employed to assess predictors of outcome variables, including death, survival, need for intubation, and need for oxygen support (via nasal cannula). Covariates included a wide range of demographic, comorbidity-related, symptom-related, and summary index variables. RESULTS: Our study population consisted of primarily senior (average age was 73) Caucasian and African American (52.5% and 40.7%, respectively) Veterans. Bivariate analyses indicated that need for intubation was significantly associated with mortality (P = 0.002). Multivariate analyses revealed that age (P < 0.001, adjusted odds ratio (OR) = 1.16), dyspnea (P = 0.015, OR = 7.73), anorexia (P = 0.022, OR = 16.55), initial disease severity as classified by WHO (P = 0.031, OR = 4.55), and having more than one of the three most common comorbidities (hypertension, diabetes, and cardiac disease) and symptoms (cough, fever, and dyspnea) among our sample (P = 0.009; OR = 19.07) were independent predictors of death. Furthermore, age (P < 0.001, hazard ratio (HR) = 1.14), cerebrovascular disease (P = 0.022, HR = 3.76), dyspnea (P < 0.001, HR = 7.71), anorexia (P < 0.001, HR = 16.75), and initial disease severity as classified by WHO (P = 0.025, HR = 3.30) were independent predictors of poor survival. Finally, dyspnea reliably predicted need for intubation (P = 0.019; OR = 29.65). CONCLUSIONS: Several independent predictors of death, survival, and need for intubation were identified. These risk factors may provide guidelines for risk-stratifying Veterans upon admission to VA hospitals. Additional investigations of COVID-19 prognosis should be conducted on the larger U.S. Veteran population to confirm our findings and add to the current body of literature.

Perioperative Antibiotic Use in Endoscopic Endonasal Skull Base Surgery.

Introduction Improved evidence-based guidelines on the optimal type and duration of antibiotics for patients undergoing endoscopic endonasal transsphenoidal surgery (EETS) are needed. We analyze the infectious complications among a large cohort of EETS patients undergoing a standardized regimen of cefazolin for 24 hours, followed by cephalexin for 7 days after surgery (clindamycin if penicillin/cephalosporin allergic). Methods A retrospective review of 132 EETS patients from 2018 to 2020 was conducted. Patient, tumor, and surgical characteristics were collected, along with infection rates. Multivariate logistic regression determined the variable(s) independently associated with infectious outcomes. Results Nearly all patients (99%) received postoperative antibiotics with 78% receiving cefazolin, 17% receiving cephalexin, 3% receiving clindamycin, and 2% receiving other antibiotics. Fifty-three patients (40%) had an intraoperative cerebrospinal fluid (CSF) leak, and three patients (2%) developed a postoperative CSF leak requiring surgical repair. Within 30 days, no patients developed meningitis. Five patients (4%) developed sinusitis, two patients (3%) developed pneumonia, and one patient (1%) developed cellulitis at a peripheral intravenous line. Two patients (2%) developed an allergy to cephalexin, requiring conservative management. After adjustment for comorbidities and operative factors, presence of postoperative infectious complications was independently associated with increased LOS ( ß = 3.7 days; p = 0.001). Conclusion Compared with reported findings in the literature, we report low rates of infectious complications and antibiotic intolerance, despite presence of a heavy burden of comorbidities and high intraoperative CSF leak rates among our cohort. These findings support our standardized 7-day perioperative antibiotic regimen.

Management of post-COVID-19 olfactory dysfunction.

Purpose of Review: Olfactory dysfunction is a frequent complication of SARS-CoV-2 infection. This review presents the current literature regarding the management of post-COVID-19 olfactory dysfunction (PCOD). Recent Findings: A systematic review of the literature using the PubMed/MEDLINE, EMBASE, and Cochrane databases for the following keywords, "Covid-19," "SARS-CoV-2," "anosmia," "olfactory," "treatment," and "management" was performed. While most cases of post-COVID-19 olfactory dysfunction resolve spontaneously within 2 weeks of symptom onset, patients with symptoms that persist past 2 weeks require medical management. The intervention with the greatest degree of supporting evidence is olfactory training, wherein patients are repeatedly exposed to potent olfactory stimuli. To date, no large-scale randomized clinical trials exist that examine the efficacy of pharmacologic therapies for PCOD. Limited clinical trials and prospective controlled trials suggest intranasal corticosteroids and oral corticosteroids may alleviate symptoms. Summary: Olfactory training should be initiated as soon as possible for patients with PCOD. Patients may benefit from a limited intranasal or oral corticosteroid course. Further research on effective pharmacologic therapies for PCOD is required to manage the growing number of patients with this condition.

Radial Forearm Free Flap Reconstruction of Glossectomy Defects Without Tracheostomy.

OBJECTIVES: To assess the feasibility of radial forearm free flap (RFFF) reconstruction of glossectomy defects without tracheostomy tube (TT). METHODS: Retrospective review of patients with at least oral tongue defects who underwent RFFF reconstruction. Pre- and intra-operative factors were documented. Post-operative respiratory complications included inability to extubate, pneumonia, or need for re-intubation or TT within 30 days. RESULTS: Twenty-one patients underwent RFFF reconstruction without TT, and 36 patients with TT. The average hospital length of stay was 1.5 days shorter in those without TT (P < .01). Two patients who underwent TT placement experienced a respiratory complication (P = .27). There were no respiratory complications among those without TT. After multivariate analyses, large tongue base defect (>25% resection, P < .001) and bilateral neck dissection (P < .001) were independently associated with TT placement. CONCLUSIONS: In our experience, RFFF reconstruction of glossectomy defects is feasible without TT among selected patients with small tongue base defects (≤25% resection) and unilateral neck dissection.

Assessment of Biomarker Heterogeneity in Sinus Versus Inferior Turbinate Tissue in Patients Without Chronic Rhinosinusitis.

BACKGROUND: Currently, no consensus exists on the appropriate control specimen site to utilize in studies evaluating for biomarkers in chronic rhinosinusitis (CRS). Studies thus far have utilized tissue from various anatomic sites despite regional heterogeneity. OBJECTIVE: We set out to quantify the differences in biomarker levels present in inferior turbinate versus sphenoid sinus mucosa in paired healthy control patients. We hypothesize that statistically significant differences in cytokine/chemokine expression exist between these two distinct sites. METHODS: A 38-plex commercially available cytokine/chemokine Luminex Assay was performed on 54 specimens encompassing paired inferior turbinate and sphenoid sinus mucosa samples from 27 patients undergoing endoscopic anterior skull base surgery. Patients with a history of CRS were excluded. Paired sample t-tests and Fisher's exact tests were performed. RESULTS: Twenty-seven patients were included in the study, including 10 male and 17 female patients with an average age of 48 years. The following 8 biomarkers had statistically significant concentration differences between inferior turbinate mucosa and sphenoid mucosa sites: Flt-3L, Fractalkine, IL-12p40, IL-1Ra, IP-10, MCP-1, MIP-1ß, and VEGF, with all P-values <0.01. CONCLUSION: No consensus exists regarding the optimal choice of control specimen for CRS research. We present statistically significant quantitative differences in biomarker levels between paired inferior turbinate and sphenoid mucosa samples. This confirms the presence of heterogeneity between different subsites of sinonasal mucosa and highlights the need for standardization in future CRS research.

Opiate Use After Endoscopic Endonasal Transsphenoidal Surgery.

BACKGROUND: The literature on opiate use after endoscopic endonasal transsphenoidal surgery (EETS) is limited. OBJECTIVE: To determine the risk factors for higher opiate use following EETS and the quantity of opiates used after discharge. METHODS: A retrospective review of 144 patients undergoing EETS from July 2018 to July 2020 was conducted. Patient, tumor, and surgical factors were documented. Pain scores and medications used on postoperative days (POD) 0 and 1, and discharge prescriptions, were recorded. Opiate use was quantified using morphine milligram equivalents (MME) dose. Multiple linear regression determined risk factors independently associated with POD0 to 1 opiate use. RESULTS: On POD 0 to 1, mean pain score was 4.9/10 (standard deviation [SD] ± 2.0). Mean acetaminophen use was 3.4 tablets (SD ± 1.6; 650 mg per tablet). Mean opiate use was 35.6 MME (SD ± 36.3), equivalent to 4.7 tablets (SD ± 4.8) of oxycodone 5 mg. Multiple linear regression showed that current smokers required an additional 37.1 MME (P = .011), and patients with grade 3 intraoperative cerebrospinal fluid leaks required an additional 36.7 MME (P = .046) on POD0 to 1. On discharge, mean opiate prescription was 117.7 MME (SD ± 102.1), equivalent to 15.7 tablets (SD ± 13.6) of oxycodone 5 mg. Thirty-nine patients (27.1%) did not require prescriptions. Only 10 patients (6.9%) required opiate refill(s) within 30 days after surgery. CONCLUSION: Patients undergoing EETS have higher opiate needs compared to those undergoing endoscopic sinus surgery, although the overall requirements are still considered low. Independent risk factors associated with higher opiate use in the immediate postoperative period included current smokers and grade 3 intraoperative cerebrospinal fluid leaks.

Sinonasal Quality of Life Outcomes after Endoscopic Endonasal Transsphenoidal Surgery with Posterior Septum Free Mucosal Graft Reconstruction.

Objective Quality of life (QoL) outcomes following endoscopic endonasal transphenoidal surgery (EETS) across a variety of reconstructive methods improve by 2 to 6 months. An option for sellar reconstruction, in the absence of a significant intraoperative cerebrospinal fluid (CSF) leak, is a free mucosal graft (FMG) from the posterior septum. We analyze sinonasal QoL outcomes in patients undergoing EETS with FMG reconstruction. Study Design This study was a retrospective review. Setting This study was conducted at tertiary care academic center. Participants This study group consisted of patients undergoing EETS for pituitary adenomas from 2013 to 2018. Main Outcome Measures Tumor and surgical factors were included, along with postoperative complications. Patients completed Sinonasal Outcome Test-22 (SNOT-22) questionnaires. Pre- and postoperative scores were compared among the entire cohort using linear multilevel regression. A subcohort analysis was performed among patients who completed questionnaires during the preoperative visit and two postoperative visits (within 1 month and between 2 and 3 months, respectively); pre- and postoperative total and individual domain SNOT-22 scores were compared using paired t -tests. Results A total of 243 patients underwent EETS with FMG reconstruction. Four patients (1.6%) developed a postoperative CSF leak requiring reoperation. Among the entire cohort, SNOT-22 scores increased at the first postoperative visit ( p < 0.01) but returned to baseline by the second, third, and fourth postoperative visits ( p = 0.27, p = 0.18, and p = 0.21). Among 48 patients who completed both preoperative and two postoperative questionnaires, scores increased within the first month ( p < 0.01) but returned to baseline at 2 to 3 months ( p = 0.67). Conclusion Posterior septum FMG reconstruction of sellar defects is an effective option, demonstrating early recovery of baseline sinonasal QoL by 2 to 3 months.

Role of Biologics in Chronic Rhinosinusitis With Nasal Polyposis: State of the Art Review.

OBJECTIVE: To review the current literature regarding the role of biologics in the treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP). DATA SOURCES: PubMed/MEDLINE, EMBASE, Cochrane Review, ClinicalTrials.gov. REVIEW METHODS: We conducted a comprehensive review of the literature on clinical studies investigating the efficacy of emerging biologics in CRSwNP, with a focus on randomized controlled trials. CONCLUSIONS: There appears to be promising evidence to support the safety and efficacy of biologics in CRSwNP with and without asthma for select patients. However, additional large-scale randomized studies with longer follow-up are necessary to determine which patients would benefit the most from these novel systemic treatments. IMPLICATIONS FOR PRACTICE: Chronic rhinosinusitis with nasal polyposis refractory to medical and surgical therapy remains a challenging clinical problem for otolaryngologists. However, emerging biologic therapies may offer a new therapeutic option for such patients with recalcitrant disease.

Expression of Iron-Regulatory Hormone Hepcidin and Iron Transporters Ferroportin and ZIP8 in Patients With and Without Chronic Rhinosinusitis.

Airway epithelia express intrinsic antimicrobial and nutrient-sequestering factors, which contribute to the host defense of the respiratory tract. Hepcidin is an endogenous peptide hormone that serves as a key regulator of iron metabolism, and ferroportin and ZIP8 are iron transporters. All exhibit innate antimicrobial activity. The purpose of this pilot study is to determine if molecules involved in iron regulation are expressed within sinus epithelia and to compare levels of expression between patients with and without chronic rhinosinusitis (CRS). Sinus mucosa was obtained from patients with (n = 19) and without (n = 14) CRS. Real-time polymerase chain reaction following RNA extraction was used to quantify expression of hepcidin, ferroportin, and ZIP8 mRNA. Hepcidin, ferroportin, and ZIP8 were all detected in the sinus epithelia of patients with and without CRS. However, only ZIP8 was significantly changed in CRS, with a 2.5-fold mean increase in mRNA expression relative to controls (P = .005). These findings suggest that ZIP8 may play a role in the innate epithelial defense of the paranasal sinuses.

Neurosarcoidosis Presenting Initially as Idiopathic Vocal Cord Paralysis.

INTRODUCTION:: The presentation, course, and management of a rare laryngeal manifestation of neurosarcoidosis due to central nervous system (as opposed to peripheral nervous system) injury are described. METHODS:: The authors present 3 cases of vocal cord paralysis as the initial symptom of isolated neurosarcoidosis at a tertiary care laryngology clinic. RESULTS:: Laryngoscopy diagnosed unilateral vocal cord paralysis. Laryngeal electromyography revealed high vagal injury, prompting workup on brain magnetic resonance imaging. On magnetic resonance imaging, 2 cases showed basilar leptomeningeal inflammation and 1 case showed a brainstem mass. Patients were found at follow-up to have severe, progressive vagal injury, with patients developing severe quality of life impairments and medical complications. CONCLUSIONS:: Neurosarcoidosis is not usually considered in the differential diagnosis of vocal cord paralysis. At initial presentation, all patients lacked other cranial neuropathies and systemic sarcoidosis manifestations, making diagnosis difficult. Otolaryngologists should be aware of this rare presentation, as prompt diagnosis by brain magnetic resonance imaging with or without central nervous system biopsy, as opposed to traditional chest radiography or computed tomography for the workup of peripheral nerve injury, is necessary. Serial laryngeal examinations are recommended for close monitoring of progressive disease and recommending treatment. Injection or medialization laryngoplasty can provide improvements in voicing but not swallow.

Socioeconomic disparities in a population of patients undergoing total thyroidectomy for benign disease.

BACKGROUND: This study examines the effect of insurance status (as a measure of socioeconomic status) on patient with benign thyroid disease. METHODS: A retrospective review was performed among 60 patients undergoing total thyroidectomy for benign thyroid disease. Univariate and multivariable analyses examined the relationship between insurance status and thyroid volume (sum of the left and right lobe volumes). RESULTS: Twenty-eight (47%) patients were considered of underinsured/uninsured status, and 32 (53%) patients were considered of private/government/military insurance status. Median pathologic whole thyroid volume was 66 mL (range, 2-855). After multivariable linear regression, underinsured/uninsured status was the only significant predictor of larger volume (correlation coefficient [r] = 118; 95% CI, 42 to 194; P = .003), after adjusting for age, sex, body mass index, and presence of concomitant thyroid disease and compressive symptoms. CONCLUSION: Patients of underinsured/uninsured status suffered more severe disease presentations at time of thyroidectomy, as measured by larger thyroid volumes.

Diagnostic Pathway of Oral Cavity Cancer in an Integrated Health Care System.

CONTEXT: Survival for patients with oral cavity squamous cell carcinoma (OCSCC) has remained relatively stagnant despite advances in treatment. Few studies have examined why advanced-stage disease is diagnosed in 40% of patients with OCSCC nationally. OBJECTIVE: To characterize the diagnostic pathway of OCSCC in an integrated health care system. DESIGN: Retrospective study of patients with OCSCC (2007-2010). MAIN OUTCOME MEASURES: Referral patterns and demographic, clinical, and tumor characteristics associated with time to diagnosis (diagnostic interval). RESULTS: Of 247 patients, 167 (68%) had early-stage (I/II) disease, 86 (35%) were referred by dentists, and 70 (28%) had a history of premalignancy. The median time (interquartile range) from symptom onset to care sought from a primary care physician (patient interval), from primary care physician to otolaryngologist, and from otolaryngologist to diagnosis was 8.6 (4.0-25.8), 1.0 (0.6-3.1), 0.0 (0.0-3.0) weeks, respectively. These intervals did not differ by demographic characteristics, clinical factors, or tumor stage. Prolonged diagnostic intervals were observed among patients with premalignant lesions. CONCLUSION: The patient interval was the largest component of the total diagnostic interval. The subsequent professional workup proceeded relatively efficiently. Prolonged diagnostic interval in patients with premalignant lesions may reflect the natural history of malignant transformation rather than a delay in diagnosis. However, nearly one-fourth of these cases were diagnosed at an advanced stage; closer surveillance may represent an opportunity for diagnosis at an earlier stage. Surveillance for premalignant lesions and facilitating referrals from dentists may expedite the diagnosis and treatment of OCSCC. Further investigation is warranted.

Mortality risk after clinical management of recurrent and metastatic adenoid cystic carcinoma.

BACKGROUND: Management of locoregional recurrence (LRR) and distant metastasis (DM) in adenoid cystic carcinoma (ACC) is guided by limited data. We investigated mortality risks in patients diagnosed and treated for recurrent ACC. METHODS: A retrospective review of ACC patients treated from 1989 to 2016 identified 36 patients with LRR or DM. High-risk disease was defined as skull base involvement (for LRR) or International Registry of Lung Metastases Group III/IV or extrapulmonary site of metastasis (for DM). Kaplan-Meier method, log-rank tests, and Cox proportional hazards were used for time-to-event analysis. RESULTS: Among 20 LRR and 16 DM patients, the median times to recurrence were 51 and 50 months, respectively. The median follow-up post-recurrence was 37.5 months (interquartile range (IQR)16.5-56.5). Post-recurrence 3-year overall survival (OS) was 78.5%, 73.3% for LRR and 85.1% for DM (p = 0.62). High-risk recurrences were associated with worse 3-year OS (68.8% for high-risk and 92.3% for low-risk, χ2 = 10.4, p = 0.001). Among LRR patients, 90% had surgery as part of their treatment. Multimodality therapy, age, and histopathologic features (size, margins, solid histology, lymphovascular or perineural invasion) were not associated with PFS or OS. High-risk LRR was the only variable associated with OS (χ2 = 5.9, p = 0.01). Among DM patients, six were initially managed with observation and ten received surgery, RT, or systemic therapy. Upfront therapy was not associated with improved PFS or OS. High-risk DM was the only variable associated with OS (χ2 = 4.7, p = 0.03). CONCLUSIONS: High-risk LRR and DM were associated with decreased 3-year OS. More effective therapies are needed for high-risk ACC recurrences.

Performance of p16INK4a ELISA as a primary cervical cancer screening test among a large cohort of HIV-infected women in western Kenya: a 2-year cross-sectional study.

OBJECTIVE: A biomarker with increased specificity for cervical dysplasia compared with human papillomavirus (HPV) testing would be an attractive option for cervical cancer screening among HIV-infected women in resource-limited settings. p16(INK4a) has been explored as a biomarker for screening in general populations. DESIGN: A 2-year cross-sectional study. SETTING: 2 large HIV primary care clinics in western Kenya. PARTICIPANTS: 1054 HIV-infected women in western Kenya undergoing cervical cancer screening as part of routine HIV care from October 2010 to November 2012. INTERVENTIONS: Participants underwent p16(INK4a) specimen collection and colposcopy. Lesions with unsatisfactory colposcopy or suspicious for cervical intraepithelial neoplasia 2+ (CIN2+; including CIN2/3 or invasive cervical cancer) were biopsied. Following biopsy, disease status was determined by histopathological diagnosis. PRIMARY AND SECONDARY OUTCOME MEASURES: We measured the sensitivity, specificity and predictive values of p16(INK4a) ELISA for CIN2+ detection among HIV-infected women and compared them to the test characteristics of current screening methods used in general as well as HIV-infected populations. RESULTS: Average p16(INK4a) concentration in cervical samples was 37.4 U/mL. After colposcopically directed biopsy, 127 (12%) women were determined to have CIN2+. Receiver operating characteristic analysis showed an area under the curve of 0.664 for p16(INK4a) to detect biopsy-proven CIN2+. At a p16(INK4a) cut-off level of 9 U/mL, sensitivity, specificity, positive and negative predictive values were 89.0%, 22.9%, 13.6% and 93.8%, respectively. The overall p16(INK4a) positivity at a cut-off level of 9 U/mL was 828 (78.6%) women. There were 325 (30.8%) cases of correct p16(INK4a) prediction to detect or rule out CIN2+, and 729 (69.2%) cases of incorrect p16(INK4a) prediction. CONCLUSIONS: p16(INK4a) ELISA did not perform well as a screening test for CIN2+ detection among HIV-infected women due to low specificity. Our study contributes to the ongoing search for a more specific alternative to HPV testing for CIN2+ detection.