Plerixafor for the Treatment of WHIM Syndrome.

WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis), a primary immunodeficiency disorder involving panleukopenia, is caused by autosomal dominant gain-of-function mutations in CXC chemokine receptor 4 (CXCR4). Myelokathexis is neutropenia caused by neutrophil retention in bone marrow. Patients with WHIM syndrome are often treated with granulocyte colony-stimulating factor (G-CSF), which can increase neutrophil counts but does not affect cytopenias other than neutropenia. In this investigator-initiated, open-label study, three severely affected patients with WHIM syndrome who could not receive G-CSF were treated with low-dose plerixafor, a CXCR4 antagonist, for 19 to 52 months. Myelofibrosis, panleukopenia, anemia, and thrombocytopenia were ameliorated, the wart burden and frequency of infection declined, human papillomavirus-associated oropharyngeal squamous-cell carcinoma stabilized, and quality of life improved markedly. Adverse events were mainly infections attributable to the underlying immunodeficiency. One patient died from complications of elective reconstructive surgery. (Funded by the National Institutes of Health.).

Laryngeal and pharyngeal actinomycosis: a systematic review and report of 3 cases.

INTRODUCTION: Actinomycosis is a granulomatous infection that rarely involves the larynx or pharynx. Three cases of actinomycosis of the larynx or pharynx from our institution were reviewed and a systematic literature review was performed to better define surgical management, antibiotic therapy, risk factors, and incidence of recurrence or complications. MATERIALS AND METHODS: PubMed/Medline, Cochrane, Embase, and Google Scholar were searched on November 30, 2021 using the terms "laryngeal actinomycosis", "pharyngeal actinomycosis", "actinomycosis AND larynx", and "actinomycosis AND pharynx." Articles which did not describe appropriate sites or were non-English were excluded. Results were collected for demographic information, site(s) of infection, comorbidities, lesion characteristics and treatments. RESULTS: Along with three cases reported from our institution, 40 unique cases were reviewed from 37 studies for a total of 43 patients (Table 1). 34 (81.0 %) of the patients were male with the highest incidence of infection in the seventh decade (54.8 %). The most common site for the infection was the larynx (69.0 %) followed by the pharynx (16.7 %). Risk factors included a history of radiation therapy, immunosuppression, inhalational irritant, and diabetes (Table 3). The duration of antibiotic therapy varied greatly, from one month to one year and total follow up ranged from 1 month to 2.5 years (Table 1). CONCLUSIONS: A comprehensive review of the literature on pharyngolaryngeal actinomycosis shows that this infection has increased prevalence within the head and neck cancer patient population. Similar to cervicofacial actinomycosis, these atypical sites have shown favorable responses to extended antibiotic therapy and generally do not require aggressive surgical management.

Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies.

BACKGROUND: Lifelong HIV antiretroviral therapy (ART) has prompted an interest in two-drug regimens to minimise cumulative drug exposure and toxicities. The safety, tolerability, and efficacy of dolutegravir and rilpivirine suggest potential compatibility and effectiveness as a two-drug regimen. We aimed to investigate this two-drug regimen in a phase 3 study. METHODS: We identically designed SWORD-1 and SWORD-2, which were open-label, parallel-group, multicentre, phase 3, randomised, non-inferiority studies in 12 countries evaluating efficacy and safety of once-daily dolutegravir 50 mg plus rilpivirine 25 mg versus current ART regimen (CAR). We included participants aged 18 years or older who were on first or second ART with stable plasma HIV-1 RNA (viral load <50 copies per mL) for 6 months or longer at screening. We randomly assigned participants (1:1) with stratification by third-agent class, age, and planned participation in a bone mineral density substudy. The primary endpoint was proportion of participants with viral load lower than 50 copies per mL at week 48 among those individuals who received one or more doses of study medication. Investigators monitored adverse events to assess safety. These trials are registered with ClinicalTrials.gov, numbers NCT02429791 (SWORD-1) and NCT02422797 (SWORD-2). FINDINGS: We screened for participants from April 14, 2015, to Oct 15, 2015, for SWORD-1 and from April 21, 2015, to Sept 25, 2015, for SWORD-2. We randomly assigned 516 participants to dolutegravir-rilpivirine and 512 to continue with CAR. At week 48 (last patient visit was Nov 22, 2016), in the pooled analysis of the intention-to-treat population, 95% of participants had viral loads lower than 50 copies per mL in each group (486 of 513 in the dolutegravir-rilpivirine group vs 485 of 511 in the CAR group), with an adjusted treatment difference of -0·2% (95% CI -3·0 to 2·5) and showed non-inferiority with a predefined margin of -8%. 395 (77%) of 513 participants in the dolutegravir-rilpivirine group and 364 (71%) of 511 participants in the CAR group reported adverse events. The most common adverse events were nasopharyngitis (49 [10%] for dolutegravir-rilpivirine vs 50 [10%] for CAR) and headache (41 [8%] vs 23 [5%]). More participants taking dolutegravir-rilpivirine (17 [3%]) reported adverse events leading to withdrawal than did participants taking CAR (three [<1%]). INTERPRETATION: Dolutegravir-rilpivirine was non-inferior to CAR over 48 weeks in participants with HIV suppression and showed a safety profile consistent with its components. Results support the use of this two-drug regimen to maintain HIV suppression. FUNDING: ViiV Healthcare and Janssen Pharmaceutica NV.

Impact of video technology on efficiency of pharmacist-provided anticoagulation counseling and patient comprehension.

BACKGROUND: Discharge anticoagulation counseling is important for ensuring patient comprehension and optimizing clinical outcomes. As pharmacy resources become increasingly limited, the impact of informational videos on the counseling process becomes more relevant. OBJECTIVE: To evaluate differences in pharmacist time spent counseling and patient comprehension (measured by the Oral Anticoagulation Knowledge [OAK] test) between informational videos and traditional face-to-face (oral) counseling. METHODS: This prospective, open, parallel-group study at an academic medical center randomized 40 individuals-17 warfarin-naïve ("New Start") and 23 with prior warfarin use ("Restart")-to receive warfarin discharge education by video or face-to-face counseling. "Teach-back" questions were used in both groups. RESULTS: Although overall pharmacist time was reduced in the video counseling group (P < 0.001), an interaction between prior warfarin use and counseling method (P = 0.012) suggests the difference between counseling methods was smaller in New Start participants. Following adjustment, mean total time was reduced 8.71 (95% CI = 5.15-12.26) minutes (adjusted P < 0.001) in Restart participants and 2.31 (-2.19 to 6.81) minutes (adjusted P = 0.472) in New Start participants receiving video counseling. Postcounseling OAK test scores did not differ. Age, gender, socioeconomic status, and years of education were not predictive of total time or OAK test score. CONCLUSION: Use of informational videos coupled with teach-back questions significantly reduced pharmacist time spent on anticoagulation counseling without compromising short-term patient comprehension, primarily in patients with prior warfarin use. Study results demonstrate that video technology provides an efficient method of anticoagulation counseling while achieving similar comprehension.

Practice patterns for initial management of oral leukoplakia amongst otolaryngologists and oral and maxillofacial surgeons.

OBJECTIVE: Oral leukoplakia is encountered frequently by otolaryngologists and oral and maxillofacial surgeons (OMFS). There are no consensus practice management guidelines for oral leukoplakia, resulting in heterogeneity in practice patterns. Characterization of practice patterns of providers who treat oral leukoplakia will be valuable to establish standards of care and future practice guidelines. MATERIAL AND METHODS: A survey was designed by the American Head and Neck Society Cancer Prevention Service collecting demographic and practice management data for treating oral leukoplakia. The survey was approved and distributed to members of the American Academy of Otolaryngology-Head and Neck Surgery and American Association of Oral and Maxillofacial Surgeons. Data analysis was performed using chi square and t-test where appropriate. RESULTS: 396 responses were collected: 83 OMFS, 81 head and neck fellowship-trained providers, and 232 otolaryngologists (non-head and neck fellowship-trained). Providers saw a wide volume of oral leukoplakia (23.0% >30 cases/year, 35.1% 11-30 cases/year, 41.2% 10 or less cases/year), with OMFS seeing more cases of oral leukoplakia. Factors most associated with consideration of initial biopsy included physical exam findings (94.4%), erythroplakia (82.3%), and smoking status (81.6%). The majority of respondents saw patients in follow-up within 1 month (24.8%) or within 1-3 months (46.5%). CONCLUSION: This survey identifies a range of practice patterns in initial management of oral leukoplakia, including indications for biopsy, and time for follow-up. This data provide insight into practice patterns amongst different groups of providers and can potentially lead to consensus guidelines for initial management of oral leukoplakia.

Regional distribution in female representation in US otolaryngology faculty.

Objectives: To quantify the current proportion of women in otolaryngology at different levels of professorship and determine whether these proportions differ by US region. Methods: Academic rank and gender at all ACGME-accredited otolaryngology programs in the United States were determined from departmental websites, Doximity, and LinkedIn from November 2021 to March 2022. Individuals were then further organized using US Census Bureau-designated regions. Results: Among the 2682 faculty positions at 124 ACGME-accredited programs, women held 706 (26.3%) of these positions. Female representation was highest at the assistant professorship level, with women holding 286 (37.2%) positions out of a total 769. At the associate professorship level, women held 141 (27.6%) of the 511 total positions. The largest gender disparity is seen at the full professorship level; only 69 (13.6%) positions out of 508 were held by women. Out of every region and rank, only assistant professorship in the West had no significant difference in percentages of men and women (p = .710). Female representation of professors in the Northeast was significantly lower than that of our reference group (the South; ß = -10.9, p = .020). Conclusions: Otolaryngology has exhibited great progress in increasing female representation, with assistant professorship in the West reaching gender parity. However, the gender gap at other faculty levels still leaves much to be desired, particularly in senior ranks. The lack of otolaryngologists at senior ranks is detrimental to mentorship of junior faculty, residents, and medical students. Renewed efforts should be made to decrease the gender disparity in the South, Northeast, and particularly at the professorship level.

Advice and perspectives from navigating the couples match in otolaryngology: A qualitative pilot study.

Introduction: There is a lack of qualitative analysis of the personal experiences within Couples Matching. In this qualitative study, we aim to record personal attitudes, reflections, and advice on experiences with the Couples Match process. Methods: Our survey, consisting of two open-ended questions regarding the experience of Couples Matching, was distributed from January 2022 to March 2022 via email to 106 otolaryngology program directors across the nation. Survey responses were analyzed iteratively using the constructivist grounded theory to construct themes related to pre-match priorities, match-related stressors, and post-match satisfaction. Themes were developed inductively and refined iteratively as the dataset evolved. Results: 18 Couples Match residents responded. In response to the first question: "What was the most difficult part of the process for you and/or your partner?", we identified the following themes: cost and financial burden, increased stress on the relationship, sacrificing top choices, and finalizing the match list. In response to the second question: "Using your experience as a previous applicant, what advice would you give to another couple planning on couples matching?", we identified four common themes: compromise, advocacy, dynamic conversations, and applying broadly. Conclusion: We sought to understand the Couples Match process through the perspective of previous applicants. Analyzing the views and attitudes of Couples Match applicants, our study captures the most challenging aspects of the experience and highlights possible areas to improve advising for couples, including important factors to consider when applying, ranking, and interviewing.

Large tracheoesophageal granular cell tumor: An atypical case presentation, location, and management.

INTRODUCTION: Granular cell tumors (GCT) are rare tumors that most frequently present in the oral cavity. While some present within the gastrointestinal tract, a GCT near the trachea is an extremely rare occurence. PRESENTATION OF CASE: A 42-year-old man presented to the Emergency Department after a motor vehicle accident. A computerized tomography (CT) scan revealed an incidental soft tissue 3.2 × 5.5 cm mass anterior to the esophagus and posterior to the trachea with no adjacent lymphadenopathy. The patient denied dyspnea, voice changes, or dysphagia. Due to its size and location, the patient underwent a transcervical excision of the retrotracheal tumor. Tumor cells were positive for CD68, CD163, S100, and SOX10, confirming a GCT. CONCLUSION: This is a distinctive presentation of a large (5 cm) GCT in the plane between the trachea and esophagus. GCTs are not often on the differential diagnosis of masses that present in this region.

Characterizing Lymph Node Burden With Elective Unilateral Neck Irradiation in Human Papillomavirus-Positive Tonsil Squamous Cell Carcinoma: Defining the Upper Limits.

Objectives Elective unilateral neck irradiation in well-lateralized tonsil carcinoma for N2b disease is controversial. Metrics regarding nodal burden beyond the N-stage to define the upper limit of this de-escalation approach remain limited. We investigated the role of nodal number, level, and volume on outcomes in patients with well-lateralized tonsil carcinoma treated with this approach. Methods A total of 37 patients received radiotherapy (RT) with unilateral neck coverage for well-lateralized tonsil cancer. Of patients, 95% had p16+ disease, and 81% were staged with positron emission tomography/computed tomography. The majority of patients received definitive chemoradiation on prospective de-escalation trials. Ten patients had ipsilateral neck dissections and were treated adjuvantly. The median RT dose to the ipsilateral neck (generally II-IV) was 45 Gy. The effects of nodal number, max dimension, volume, and level on recurrence-free survival (RFS) and overall survival (OS) were to be analyzed via Cox proportional hazards (Cox-PH). Results After a median follow-up of 3.9 years, two-year RFS and two-year OS were 100% and 97%, respectively. Given the 0% contralateral recurrence rate, Cox-PH analysis was not performed. Of patients, 70% were American Joint Committee on Cancer (AJCC) 7th edition N2b, with a median number of nodes, number of nodal levels, max dimension, and volume of two, one, 3.4 cm, and 15.6 cc, respectively. There were several patients with low-lying nodes; aggregate nodal volume measured was up to 85.4 cc. Conclusion Unilateral neck irradiation in well-lateralized tonsil carcinoma resulted in no contralateral recurrence. Nodal volume, level, and number do not seem to have a significant impact on outcomes.

Prior chemoradiotherapy adversely impacts outcomes of recurrent and second primary head and neck cancer treated with concurrent chemotherapy and reirradiation.

BACKGROUND: It has been shown that concomitant chemotherapy (C) with reirradiation (ReRT) is feasible and effective for select patients with recurrent or second primary head and neck cancer (HNC). To examine potential prognostic factors associated with survival, the authors of this report retrospectively reviewed the outcomes of patients who received CReRT. METHODS: The study cohort comprised previously irradiated patients with nonmetastatic disease from 9 consecutive phase 1 and 2 protocols for poor-prognosis HNC. For all patients, reirradiation (ReRT) was delivered with concurrent chemotherapy. Chemotherapy generally was 5-fluorouracil, hydroxyurea, and a third agent. RESULTS: One hundred sixty-six patients were identified, including 81 patients who underwent surgical resection or debulking before enrollment. The median ReRT dose was 66 gray. After a median follow-up of 53 months among surviving patients, the median overall survival (OS) was 10.3 months. The 2-year rates for OS, disease-free survival, locoregional control, and freedom from distant metastasis were 24.8%, 19.9%, 50.7%, and 61.4%, respectively. Thirty-three patients (19.9%) died of treatment-related toxicity. In subgroup analysis, survival was significantly reduced in patients who received previous concurrent chemoradiotherapy (CRT) compared with patients who were naive to CRT (2-year OS rate, 10.8% vs 28.4%; P = .0043). In multivariable analysis, prior CRT was associated independently with OS along with surgery before protocol treatment, full-dose ReRT, and radiotherapy interval. CONCLUSIONS: CReRT achieved a long-term cure for a small group of patients with recurrent or second primary HNC. Previous treatment with CRT was among the important prognostic factors for survival. Because of the associated risk of severe toxicity, CReRT should be limited only to carefully selected patients.

Multi-disciplinary management of patients with benign airway strictures: A review.

Histologically benign airway strictures are frequently misdiagnosed as asthma or COPD and may present with severe symptoms including respiratory failure. A clear understanding of pathophysiology and existing classification systems is needed to determine the appropriate treatment options and predict clinical course. Clinically significant airway strictures can involve the upper and central airways extending from the subglottis to the lobar airways. Optimal evaluation includes a proper history and physical examination, neck and chest computed tomography, pulmonary function testing, endoscopy and serology. Available treatments include medical therapy, endoscopic procedures and open surgery which are based on the stricture's extent, location, etiology, morphology, severity of airway narrowing and patient's functional status. The acuity of the process, patient's co-morbidities and operability at the time of evaluation determine the need for open surgical or endoscopic interventions. The optimal management of patients with benign airway strictures requires the availability, expertise and collaboration of otolaryngologists, thoracic surgeons and interventional pulmonologists. Multidisciplinary airway teams can facilitate accurate diagnosis, guide management and avoid unnecessary procedures that could potentially worsen the extent of the disease or clinical course. Implementation of a complex airway program including multidisciplinary clinics and conferences ensures that such collaboration leads to timely, patient-centered and evidence-based interventions. In this article we outline algorithms of care and illustrate therapeutic techniques based on published evidence.

Dose and Volume De-Escalation for Human Papillomavirus-Positive Oropharyngeal Cancer is Associated with Favorable Posttreatment Functional Outcomes.

PURPOSE: To report functional outcomes for patients with human papillomavirus-positive oropharyngeal cancer treated on a phase 2 protocol of risk- and induction chemotherapy response-adapted dose and volume de-escalated radiation therapy (RT)/chemoradiation (CRT). METHODS AND MATERIALS: Patients were stratified as low risk (LR) or high risk (HR) according to T/N-stage and smoking history. Induction chemotherapy was followed by radiographic response assessment. LR patients with ≥50% response received 50 Gy RT (RT50), whereas LR patients with 30% to 50% response or HR patients with ≥50% response received 45 Gy CRT (CRT45). All other patients received 75 Gy CRT (CRT75) with RT limited to the first echelon of uninvolved nodes. Pre- and post-RT/CRT modified barium swallow studies were performed. Percutaneous endoscopic gastrostomy (PEG) tube placement, body mass index (BMI), and narcotic use were recorded. Statistical comparisons used linear or logistic regression, the Mann-Whitney U test, the χ2 test, or Fisher's exact test as appropriate. RESULTS: Twenty-eight LR and 34 HR patients were enrolled; 49 completed RT50/CRT45 and 11 completed CRT75. PEG-tube dependency at the end of RT/CRT and 3 months post-RT/CRT significantly differed according to risk and treatment groups (all P < .05). Treatment intensity was independently associated with 3-month PEG status while adjusting for risk group (P = .002). The CRT75 group had a median -8.42% change from baseline BMI at 1 year post-RT/CRT versus -2.54% for the RT50/CRT45 group (P = .01). At the end of RT/CRT, CRT75 patients were less likely to tolerate a normal diet, more likely to have swallowing performance status scale scores ≥4, more likely to have Rosenbek's penetration-aspiration scores ≥7, more likely to have developed trismus, and more likely to require narcotics >2 months (all P < .05). CONCLUSIONS: Induction chemotherapy followed by risk- and response-adapted dose and volume de-escalated RT/CRT is associated with clinically meaningful functional outcomes including (1) improved swallowing function, (2) higher BMI, and (3) shorter narcotic use for patients receiving de-escalation.

Aneurysmal Bone Cyst of the Maxillary Sinus with USP6 Rearrangement: Case Report of a Rare Entity and Review of the Literature.

Aneurysmal bone cysts (ABCs) are benign lesions which most frequently occur in the long bones of pediatric patients. Long thought to be reactive, recent molecular advances have demonstrated that the majority of primary ABCs harbor rearrangements of the USP6 gene, confirming their neoplastic nature. Secondary ABCs arising from other lesions do not demonstrate this recurrent genetic anomaly. ABCs rarely occur in the craniofacial bones, and sinonasal ABCs are exceedingly rare. We report a case of a primary ABC arising the maxillary sinus of a 14-year-old female, which was found to harbor USP6 rearrangement. We describe the clinical, radiologic, and pathologic features of this case, and review the current literature on craniofacial ABCs. Careful histologic evaluation and genetic studies are warranted in order to confirm the rare occurrence of a primary sinonasal ABC.

Mucoepidermoid Carcinoma: A Comparison of Histologic Grading Systems and Relationship to MAML2 Rearrangement and Prognosis.

Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy, but categorization is complicated by variability in grading systems and uncertain prognostic significance of MAML2 rearrangement. The aims of this study were to determine the prognostic significance of MEC grading systems and MAML2 rearrangement status. Fifty-three carcinomas originally diagnosed as MEC (45 primary; 8 recurrent) of major and minor salivary glands were graded according to modified Healey, Brandwein, AFIP, and Katabi systems. Fluorescence in situ hybridization for MAML2 rearrangement was performed. Clinical features and outcomes were recorded. Twenty-five (47%) carcinomas scored the same in all grading systems. The most common histologic feature leading to a diagnosis of intermediate grade was isolated solid growth. Brandwein assigned the highest percentage of high grade (29%) and AFIP the highest percentage of low grade (80%). MAML2 was rearranged in 37/46 (80%) cases. Forty-three (81%) were morphologically compatible with MEC, and these were more likely to be low-intermediate grade and MAML2-rearranged. Of primary carcinomas, 6 (13%) recurred. Statistically significant univariate risk factors for recurrence included non-MEC morphology, stage T4, and high Brandwein grade. Margin status, MAML2 rearrangement, and isolated solid growth were not predictive of recurrence. A binary grading system (Brandwein high vs. low-plus-intermediate) could be considered to better reflect biological behavior in MEC. Our study confirms that MAML2 wildtype tumors more likely represent high grade non-MECs, and prior studies demonstrating worse prognosis in MAML2-nonrearranged MECs may be diluted by high-grade non-MECs.

Efficacy and safety of dolutegravir-rilpivirine for maintenance of virological suppression in adults with HIV-1: 100-week data from the randomised, open-label, phase 3 SWORD-1 and SWORD-2 studies.

BACKGROUND: Primary analyses of the SWORD-1 and SWORD-2 trials at 48 weeks showed that switching to a two-drug regimen of dolutegravir plus rilpivirine was non-inferior to continuing a standard three-drug or four-drug antiretroviral regimen for maintenance of virological suppression in people with HIV-1. Here, we present efficacy and safety data from the 100-week analysis of the trials. METHODS: SWORD-1 and SWORD-2 are identically designed, randomised, open-label phase 3 studies at 65 centres in 13 countries and 60 centres in 11 countries, respectively. Adults aged 18 years or older who were on a standard three-drug or four-drug antiretroviral therapy (ART) and had had fewer than 50 HIV-1 RNA copies per mL of plasma for at least 6 months were randomly assigned (1:1) to 50 mg dolutegravir plus 25 mg rilpivirine orally once daily (early-switch group) or to continue their standard regimen for 52 weeks before switching to the dolutegravir plus rilpivirine combination (ie, the late-switch group). In this analysis of week 100 data, the efficacy endpoint of interest was the proportion of participants with fewer than 50 copies of HIV-1 RNA per mL of plasma (per the US Food and Drug Administration snapshot algorithm). This outcome was assessed in all randomly assigned participants who received at least one dose of the study drug. Data were analysed after the last participant completed week 100 (Sept 15, 2017) and verified through the data cutoff (Nov 21, 2017). SWORD-1 and SWORD-2 are registered with ClinicalTrials.gov, numbers NCT02429791 and NCT02422797, respectively. FINDINGS: 513 participants were randomly assigned to dolutegravir plus rilpivirine (ie, the early-switch group) and 511 to continue their standard ART regimen, 477 of whom then switched to dolutegravir plus rilpivirine at week 52 (ie, the late-switch group). At week 100, 456 (89% [95% CI 86-92]) of 513 participants in the early-switch group and 444 (93% [91-95]) of 477 in the late-switch group had fewer than 50 HIV-1 RNA copies per mL. Drug-related adverse events occurred in 103 (20%) participants in the early-switch group and 58 (12%) in the late-switch group. The most common drug-related adverse events were headache (11 participants in the early-switch group [2%] vs eight [2%] in the late-switch group) and nausea (eight [2%] vs five [1%]). INTERPRETATION: The combination of dolutegravir plus rilpivirine sustained virological suppression of HIV-1, was associated with a low frequency of virological failure, and had a favourable safety profile, which support its use as a nucleoside reverse transcriptase inhibitor-sparing and protease inhibitor-sparing alternative to three-drug regimens that reduces overall exposure to ART. FUNDING: ViiV Healthcare and Janssen Pharmaceutica.

Definitive chemoradiation for locally-advanced oral cavity cancer: A 20-year experience.

OBJECTIVES: Definitive chemoradiation (CRT) for oral cavity squamous cell carcinoma (OC-SCC) is often criticized for poor efficacy or toxicity. We describe a favorable 20-year experience of primary CRT for locally-advanced OC-SCC. MATERIALS AND METHODS: Patients with locally-advanced, stage III/IV OC-SCC receiving primary concomitant CRT on protocols from 1994 to 2014 were analyzed. Chemotherapy included fluorouracil and hydroxyurea with other third agents. Radiotherapy (RT) was delivered once or twice daily to a maximum dose of 70-75 Gy. Intensity-modulated RT (IMRT) was exclusively used after 2004. Progression-free survival (PFS), overall survival (OS), locoregional control (LRC), and distant control (DC) were calculated by the Kaplan-Meier method and compared across treatment decades using the log-rank test. Rates of osteoradionecrosis (ORN) requiring surgery were compared across treatment decades using the Chi-square test. RESULTS: 140 patients with locally-advanced OC-SCC were treated with definitive CRT. Of these, 75.7% had T3/T4 disease, 68.6% had ≥N2 nodal disease, and 91.4% had stage IV disease. Most common primary sites were oral tongue (47.9%) and floor of mouth (24.3%). Median follow-up was 5.7 years. Five-year OS, PFS, LRC, and DC were 63.2%, 58.7%, 78.6%, and 87.2%, respectively. Rates of ORN and long-term feeding tube dependence were 20.7% and 10.0%, respectively. Differences in LRC (P = 0.90), DC (P = 0.24), PFS (P = 0.38), OS (P = 0.10), or ORN (P = 0.38) were not significant across treatment decades. CONCLUSION: Definitive CRT is a viable and feasible strategy for organ preservation for patients with locally-advanced OC-SCC.

Utility of lip biopsy in the diagnosis and treatment of Sjogren's syndrome.

OBJECTIVE: Sjogren's syndrome (SS) is an autoimmune disease involving primarily the salivary and lacrimal glands ("sicca" symptoms) with extraglandular features including joint and nervous system involvement. In patients with a questionable diagnosis of SS but severe extraglandular symptoms, a lip biopsy is often performed to firmly establish the diagnosis of SS. This study was undertaken to identify areas of uncertainty regarding the accuracy of biopsy interpretation and the diagnostic benefits of the procedure. STUDY DESIGN: : Retrospective review of clinical and pathologic data. METHODS: Clinical data from 47 patients referred to the otolaryngology-head and neck surgery service for lip biopsy were reviewed. Archival pathologic specimens were scored using the currently accepted grading system. RESULTS: The grading system was incorrectly applied during initial interpretation of 45% (n = 21) of specimens. This resulted in five (10%) pathologic misdiagnoses and 16 (34%) nondiagnoses. On re-interpreting the specimens with consistent application of the grading system, 62% (n = 29) of the biopsies were definitely positive, and 36% (n = 17) were negative. Neither positive serology nor the presence of sicca symptoms predicted a positive biopsy (likelihood ratio = 0.95 and 0.96, respectively). Lip biopsy guided treatment in at least 65% (n = 31) of patients but was ignored in the presence of other clinical findings in 17% (n = 8) of patients. CONCLUSIONS: Consistent application of the grading system is essential in avoiding incorrect diagnosis and aiding clinical decisions. However, not all patients undergoing lip biopsy will derive diagnostic benefit from the procedure. In this series, clinical symptoms and serology did not predict positive lip biopsy.

Salivary Gland Secretory Carcinoma With High-Grade Transformation, CDKN2A/B Loss, Distant Metastasis, and Lack of Sustained Response to Crizotinib.

BACKGROUND: Salivary gland secretory carcinoma is usually a low-grade neoplasm. However, high-grade transformation can occur and has important implications for clinical outcome. METHODS: A patient presented with an enlarging buccal mass. Magnetic resonance imaging (MRI) showed a tumor with a biphasic appearance along the right parotid duct. Local excision and histopathologic examination confirmed the diagnosis of secretory carcinoma with high-grade transformation. ETV6-NTRK3 translocation and loss of CDKN2A/B were identified. RESULTS: The patient subsequently presented with cough and dyspnea and was found to have pleural metastases. Carboplatin and paclitaxel exacerbated the symptoms. Crizotinib resulted in initial symptomatic and radiographic improvement; however, the patient soon succumbed to progressive intrathoracic disease. CONCLUSIONS: High-grade salivary gland secretory carcinoma can have a biphasic appearance on MRI. Diagnosis is confirmed by the histologic appearance and associated ETV6-NTRK3 fusion. Additional molecular genetic events leading to transformation are unknown; however, loss of CDKN2A/B may have contributed. Treatment with multimodal chemotherapy was of limited benefit.

Teaching professionalism in graduate medical education: What is the role of simulation?

BACKGROUND: We systematically reviewed the literature concerning simulation-based teaching and assessment of the Accreditation Council for Graduate Medical Education professionalism competencies to elucidate best practices and facilitate further research. METHODS: A systematic review of English literature for "professionalism" and "simulation(s)" yielded 697 abstracts. Two independent raters chose abstracts that (1) focused on graduate medical education, (2) described the simulation method, and (3) used simulation to train or assess professionalism. Fifty abstracts met the criteria, and seven were excluded for lack of relevant information. The raters, 6 professionals with medical education, simulation, and clinical experience, discussed 5 of these articles as a group; they calibrated coding and applied further refinements, resulting in a final, iteratively developed evaluation form. The raters then divided into 2 teams to read and assess the remaining articles. Overall, 15 articles were eliminated, and 28 articles underwent final analysis. RESULTS: Papers addressed a heterogeneous range of professionalism content via multiple methods. Common specialties represented were surgery (46.4%), pediatrics (17.9%), and emergency medicine (14.3%). Sixteen articles (57%) referenced a professionalism framework; 14 (50%) incorporated an assessment tool; and 17 (60.7%) reported debriefing participants, though in limited detail. Twenty-three (82.1%) articles evaluated programs, mostly using subjective trainee reports. CONCLUSION: Despite early innovation, reporting of simulation-based professionalism training and assessment is nonstandardized in methods and terminology and lacks the details required for replication. We offer minimum standards for reporting of future professionalism-focused simulation training and assessment as well as a basic framework for better mapping proper simulation methods to the targeted domain of professionalism.

Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer.

PURPOSE: The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. METHODS AND MATERIALS: Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%. RESULTS: 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. CONCLUSIONS: The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further investigation of cetuximab may be warranted in the neoadjuvant setting and with non-platinum-based chemoradiation.