Rigid Esophagoscopy for Head and Neck Cancer Staging and the Incidence of Synchronous Esophageal Malignant Neoplasms.

IMPORTANCE: Rigid esophagoscopy (RE) was once an essential part of the evaluation of patients with head and neck squamous cell carcinoma (HNSCC) due to the high likelihood of identifying a synchronous malignant neoplasm in the esophagus. Given recent advances in imaging and endoscopic techniques and changes in the incidence of esophageal cancer, the current role for RE in HNSCC staging is unclear. OBJECTIVE: To analyze the current role of RE in evaluating patients with HNSCC, and to determine the incidence of synchronous esophageal malignant neoplasms in patients with HNSCC. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective study performed at an academic tertiary care center, 582 patients were studied who had undergone RE for HNSCC staging from July 1, 2004, through October 31, 2012. To assess the incidence of synchronous esophageal malignant neoplasms, a literature review was performed, and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) data set was queried. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the incidence of synchronous esophageal malignant neoplasms, as measured by retrospective review at our institution, SEER data set analysis, and literature review. Secondary outcome measures were RE complications and nonmalignant findings during RE. RESULTS: A total of 601 staging REs were performed in 582 patients. The mean age was 60.2 years and 454 (78.0%) were men. There were 9 complications (1.5%), including 1 esophageal perforation (0.2%). Rigid esophagoscopy was aborted in 50 cases. Of the 551 completed REs, no abnormal findings were noted in 523 patients (94.9%), and nonmalignant pathologic findings were identified in 28 patients (5.1%). No synchronous primary esophageal carcinomas were detected. The incidence of synchronous esophageal malignant neoplasms found on screening endoscopy based on literature review and on SEER data set analysis was very low and has decreased from 1980 to 2010 in North America. The incidence reported in South America and Asia was relatively high. CONCLUSIONS AND RELEVANCE: Rigid esophagoscopy is safe, but the utility is low for cancer staging and for detection of nonmalignant esophageal disease. Review of the literature and analysis of a large national cancer data set indicate that the incidence of synchronous esophageal malignant neoplasms in patients with HNSCC is low and has been decreasing during the past 3 decades. Thus, screening esophagoscopy should be limited to patients with HNSCC who are at high risk for synchronous esophageal malignant neoplasms.

Utility of abdominal imaging to assess for liver metastasis in patients with head and neck cancer and abnormal liver function tests.

PURPOSE: To determine the utility of abdominal imaging to further evaluate abnormal pre-operative liver function tests (LFTs) in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Records of patients evaluated by the head and neck surgery service from January 2004 through December 2009 were reviewed. For patients with abnormal alkaline phosphatase, alanine transaminase, or aspartate transaminase, subsequent abdominal imaging was assessed. RESULTS: Of the 862 patients with HNSCC who had documented LFTs, 109 (12.6%) had one or more abnormal values. In the same time period, LFTs were also obtained on 361 patients with benign head and neck tumors; of these, 40 (11.1%) had abnormalities. Of the 109 patients with HNSCC and abnormal LFTs, 78 (71.6%) underwent abdominal imaging (ultrasound, CT, MRI, or PET/CT). Overall, liver metastasis was demonstrated in only 1 of 109 patients with abnormal LFTs (0.92%) and in only 1 of 862 patients with HNSCC (0.12%). CONCLUSIONS: While HNSCC patients rarely present with liver metastasis, they often have abnormal LFTs. Although the presence of liver metastasis can dramatically change patient management, the yield of follow-up liver imaging for all patients with elevated LFTs is exceedingly low. Thus, the use of risk-stratified abdominal imaging may be prudent and cost effective in a select group of patients in whom distant metastasis is more likely. However, characteristics of this group are difficult to define given the rarity of liver metastasis in HNSCC.

p16, Cyclin D1, and HIF-1α Predict Outcomes of Patients with Oropharyngeal Squamous Cell Carcinoma Treated with Definitive Intensity-Modulated Radiation Therapy.

We evaluated a panel of 8 immunohistochemical biomarkers as predictors of clinical response to definitive intensity-modulated radiotherapy in patients with oropharyngeal squamous cell carcinoma (OPSCC). 106 patients with OPSCC were treated to a total dose of 66-70 Gy and retrospectively analyzed for locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). All tumors had p16 immunohistochemical staining, and 101 tumors also had epidermal growth factor receptor (EGFR) staining. 53% of the patients had sufficient archived pathologic specimens for incorporation into a tissue microarray for immunohistochemical analysis for cyclophilin B, cyclin D1, p21, hypoxia-inducible factor-1α (HIF-1α), carbonic anhydrase, and major vault protein. Median followup was 27.2 months. 66% of the tumors were p16 positive, and 34% were p16 negative. On univariate analysis, the following correlations were statistically significant: p16 positive staining with higher LRC (P = 0.005) and longer DFS (P < 0.001); cyclin D1 positive staining with lower LRC (P = 0.033) and shorter DFS (P = 0.002); HIF-1α positive staining with shorter DFS (P = 0.039). On multivariate analysis, p16 was the only significant independent predictor of DFS (P = 0.023). After immunohistochemical examination of a panel of 8 biomarkers, our study could only verify p16 as an independent prognostic factor in OPSCC.

p16 not a prognostic marker for hypopharyngeal squamous cell carcinoma.

OBJECTIVE: To investigate the prognostic significance of p16 in patients with hypopharyngeal squamous cell carcinoma (HPSCC) and to evaluate the relationship between p16 and human papillomavirus (HPV). Unlike in oropharyngeal SCC (OPSCC), the prognostic significance of p16 in HPSCC and its association with HPV is unclear. DESIGN: Retrospective medical chart review. SETTING: University tertiary referral center. PATIENTS: A total of 27 patients with HPSCC treated with definitive radiation therapy between 2002 and 2011 whose tissue was available for immunohistochemical analysis. INTERVENTIONS: Twenty-two patients were treated with chemoradiation, and 5 with radiation alone. All tumor biopsy specimens were analyzed for p16 and, when sufficient tissue was available, for HPV DNA. MAIN OUTCOME MEASURES: Overall survival (OS), locoregional control (LRC), disease-free survival (DFS), and laryngoesophageal dysfunction-free survival (LEDFS) were analyzed according to p16 status. RESULTS: Findings for p16 were positive in 9 tumors and negative in 18 tumors. Median follow-up was 29.3 months. There was no significant difference in OS, LRC, DFS, or LEDFS for patients with p16-positive vs p16-negative tumors. Only 1 of the 19 tumors tested for HPV was found to be HPV positive. When used as a test for HPV, p16 had a positive predictive value of 17%. CONCLUSIONS: In contrast to OPSCC, p16 expression in patients with HPSCC had a low positive predictive value for HPV and did not predict improved OS, LRC, DFS, or LEDFS. Thus, for HPSCC, p16 is not a prognostic biomarker. Caution must be taken when extrapolating the prognostic significance of p16 in patients with OPSCC to patients with head and neck SCC of other subsites.

Immediate postoperative extubation in patients undergoing free tissue transfer.

OBJECTIVES/HYPOTHESIS: Extubation (cessation of ventilatory support) is often delayed in free flap patients to protect the microvascular anastomosis, presumably by reducing emergence-related agitation. We sought to determine if immediate extubation in the operating room (OR) would improve the postoperative course compared to delayed extubation in the intensive care unit (ICU). STUDY DESIGN: Retrospective chart review. METHODS: Medical records of all patients undergoing free tissue transfer for head and neck reconstruction between January 2009 and July 2010 were reviewed (n = 52). Patients extubated immediately postoperatively in the OR (immediate group, n = 26) were compared to patients extubated in the ICU (delayed group, n = 26). RESULTS: Tobacco use, alcohol use, pulmonary history, case length, and free flap type were not significantly different between the two groups. Although the average ICU stay for the immediate group was significantly shorter than the delayed group (2.0 days vs. 3.4 days; P = .008), the reduction in overall hospital stay for the immediate group did not achieve statistical significance (8.2 days vs. 9.5 days; P = .21). Use of treatment for agitation (27% vs. 65%) and physical restraints (8% vs. 69%) were significantly lower in the immediate versus delayed group (P = .01 and P < .001, respectively). Although flap-related, surgical, and medical complication rates were not significantly different between the two groups, the delayed extubation group had a significantly higher incidence of pneumonia (15% vs. 0%; P = .05). CONCLUSIONS: Immediate postoperative extubation in the OR following head and neck microvascular free tissue transfer reduces ICU stay, anxiolytic use, restraint use, and incidence of pneumonia without an increase in flap- or wound-related complications.

Primary nasopharyngeal interdigitating dendritic cell tumor presentation and response to radiation therapy.

We report the case of a primary nasopharyngeal interdigitating dendritic cell tumor (IDDCT). A 25-year old male presented with bilateral decreased hearing, double vision, and ataxia. Flexible nasopharyngoscopy reviewed a large mass obstructing and filling the entire nasopharynx. MRI and PET-CT confirmed the presence of the primary tumor and demonstrated bilateral cervical lymphadenopathy. Biopsy of the nasopharynx revealed a hematolymphoid neoplasm with dendritic cell differentiation, most consistent with an IDDCT. The lesion was unresectable. The patient was treated with definitive radiotherapy to 66 Gy to the primary tumor and 50 Gy to the bilateral cervical lymphatics using an IMRT technique. A complete response was achieved and the patient remains disease free at the primary site 23 months after completion of radiotherapy.

Clinical nodal staging of T1-2 tonsillar squamous cell carcinoma stratified by p16 status and implications for ipsilateral neck irradiation.

BACKGROUND AND PURPOSE: Previous studies have reported <5% incidence of contralateral nodal metastasis in patients with T1-2 tonsillar squamous cell carcinoma. We analyzed the nodal staging of T1-2 tonsillar squamous cell carcinoma stratified for p16 status, a marker of human papillomavirus positivity. MATERIALS AND METHODS: Clinical and radiographic nodal staging and p16 status of 41 T1-2 tonsillar squamous cell carcinoma patients who were treated between January 2002 and June 2009 were retrospectively analyzed. Patients with a history of prior head and neck cancer, synchronous cancers, base of tongue or soft palate invasion, or distant metastases at diagnosis were excluded. RESULTS: Of the 41 patients, 28 (68.2%) had p16+ tumors and 13 (31.7%) had p16- tumors. Seven patients (17.0%) presented with contralateral cervical nodal disease, all of whom had p16+ tumors. Furthermore, 25.0% of patients with p16+ tumors presented with contralateral cervical nodal disease compared with 0% of patients with p16- tumors. CONCLUSIONS: Patients with p16+ T1-2 tonsillar squamous cell carcinoma present with a higher incidence of contralateral nodal spread than those patients with p16- disease. This may have clinical implications when determining which patients are good candidates for ipsilateral cervical nodal irradiation.

Intensity-modulated radiotherapy outcomes for oropharyngeal squamous cell carcinoma patients stratified by p16 status.

BACKGROUND: Patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with intensity-modulated radiotherapy (IMRT) were stratified by p16 status, neck dissection, and chemotherapy to correlate these factors with outcomes. METHODS: A total of 112 patients with OPSCC treated with IMRT from 2002 to 2008 were retrospectively analyzed. All patients received RT to 66-70 Gray. Forty-five of the tumors were p16 positive (p16+), 27 were p16 negative (p16-), and 41 had unknown p16 status. Sixty-two patients had postradiation neck dissections. Nine patients with p16- tumors and 28 patients with p16+ tumors received chemotherapy. The distribution of T, N, and stage grouping among the p16+ and p16- patients was not significantly different, and 87.5% patients had stage III/IV disease. RESULTS: The median follow-up was 26.3 months. For patients with p16+ tumors, p16- tumors, and the overall cohort, the actuarial 3-year locoregional progression-free survival rate was 97.8%,73.5%, and 90.5% respectively (P = .006) and the disease-free survival rate was 88.2%, 61.4%, and 81.7%, respectively (P = .004). Patients with p16+ tumors had an 89.5% and 87.5% pathologic complete response (CR) on neck dissection with and without chemotherapy, respectively. In contrast, patients with p16- tumors had a 66.7% and 25.0% pathologic CR on neck dissection with and without chemotherapy, respectively. CONCLUSIONS: In this series, p16 status was found to be a significant predictive biomarker and patients with p16+ tumors had much better outcomes than patients with p16- tumors. Further investigation is warranted to determine whether less intense therapy is appropriate for selected patients with p16+ OPSCC, whereas more aggressive strategies are needed to improve outcomes in patients with p16- disease.

Predicting residual neck disease in patients with oropharyngeal squamous cell carcinoma treated with radiation therapy: utility of p16 status.

OBJECTIVE: To identify factors that predict complete response of cervical nodal disease to radiation therapy (RT) in patients with oropharyngeal squamous cell carcinoma (OP-SCCA). DESIGN: Histologic analysis of prospectively collected specimens and retrospective medical chart review. SETTING: Tertiary referral center. SUBJECTS: Sixty-nine patients with OP-SCCA treated from January 1, 2002, through June 1, 2008. INTERVENTION: Definitive RT, with or without chemotherapy and with or without neck dissection (ND). MAIN OUTCOME MEASURE: Presence of a viable tumor in post-RT ND specimen. RESULTS: Tissue specimens from 69 patients with OP-SCCA treated primarily with RT, with or without chemotherapy, were evaluated. Of these, 47 (68.1%) were strongly and diffusely positive for p16 expression by immunohistochemical analysis, signifying human papillomavirus positivity. Patients with p16-positive and p16-negative tumors (hereinafter, p16+ and p16-, respectively) had similarly sized primary tumors on presentation, but p16+ primary tumors were associated with more advanced neck disease (nodal stages N2c-N3; 31.9% vs 4.5% for p16- tumors) and more contralateral nodes (27.7% vs 4.5% for p16- tumors). Forty-seven patients (59.0%) underwent planned posttreatment ND (a total of 55 NDs). The NDs performed for p16- tumors were significantly more likely to have viable tumor in the specimen (50.0% vs 18.0% for p16+ tumors; P = .02). In addition, p16+ necks with residual viable cancer were characterized by incomplete response on post-RT imaging, tobacco and alcohol use, and extracapsular spread on pretreatment imaging. CONCLUSIONS: In conjunction with other clinical parameters, p16 status can help predict the need for post-RT ND in patients with OP-SCCA. Although close observation may be warranted in selected patients with p16+ tumors, patients with p16- tumors are at much higher risk for residual neck disease, even when initial nodal disease is less advanced.

Esthesioneuroblastoma: continued follow-up of a single institution's experience.

OBJECTIVES: To analyze outcomes and to provide follow-up for our increasing patient cohort with esthesioneuroblastoma. DESIGN: Retrospective cohort analysis. SETTING: Patients were examined from September 1, 1976, to May 30, 2004, in a tertiary care academic hospital. PATIENTS: Fifty consecutive patients diagnosed as having esthesioneuroblastoma were treated with a standardized protocol during a 28-year period. Patients with tumors staged Kadish A or B received preoperative radiotherapy followed by craniofacial resection, while patients with Kadish stage C disease were treated with preoperative sequential chemotherapy and radiotherapy followed by a craniofacial resection. The mean follow-up is 93 months (range, 1-330 months). RESULTS: The disease-free survival was 86.5% and 82.6% at 5 and 15 years, respectively. There were 17 patients (34%) who developed recurrent disease, most of which was locoregional (12 patients [71%]). There was a long interval to relapse (mean, 6 years), with the longest time to regional recurrence being 10 years. Distant relapses occurred sooner, with poorer outcomes. Of these 17 patients, 7 (41%) underwent successful salvage surgery, while 3 remain alive with disease. CONCLUSIONS: Excellent outcomes for esthesioneuroblastoma are achievable. Long-term follow-up is necessary because of the extended interval for recurrent disease; unlike most sinonasal malignancies, surgical salvage is possible.

Correlation of pH probe-measured laryngopharyngeal reflux with symptoms and signs of reflux laryngitis.

OBJECTIVES/HYPOTHESIS: Laryngitis secondary to gastric acid reflux is a prevalent, yet incompletely understood, otolaryngological disorder. Further characterization of the relationship between symptoms and signs and reflux severity is needed. STUDY DESIGN: Prospective clinical trial. METHODS: Forty-two consecutive, nonsmoking patients with one or more reflux laryngitis symptoms were recruited to complete a symptom questionnaire, videostrobolaryngoscopy, and 24-hour, dual-sensor pH probe testing. Twenty-nine patients had more than four episodes of laryngopharyngeal reflux, and the remaining 13 served as control subjects. Symptom scores were produced by multiplying the severity by the frequency for the following: hoarseness, throat pain, "lump-in-throat" sensation, throat clearing, cough, excessive phlegm, dysphagia, odynophagia, and heartburn. Endoscopic laryngeal signs included erythema and edema of the vocal folds and arytenoids, and interarytenoid irregularity. RESULTS: Symptom scores varied significantly, with throat clearing being greater than the rest. None of the symptoms, except heartburn, correlated with reflux (laryngopharyngeal and esophageal) severity. Patients with worse laryngopharyngeal reflux were found to have worse esophageal reflux. Endoscopic laryngeal signs were rated as mild, on average, and did not correlate with laryngopharyngeal reflux severity. The number of laryngopharyngeal reflux episodes (per 24 h) ranged from 0 to 40 (mean number, 10.6 episodes). CONCLUSIONS: Throat clearing was the most intense symptom in the present group of patients with proven reflux laryngitis. Dual-sensor pH probe testing could not predict the severity of patient's reflux laryngitis symptoms or signs. Only the heartburn symptom correlated with laryngopharyngeal and esophageal reflux.

Sinonasal undifferentiated carcinoma: the search for a better outcome.

OBJECTIVE: To evaluate the clinical outcomes of a standardized treatment approach for sinonasal undifferentiated carcinoma (SNUC). STUDY DESIGN: Single-center, retrospective case series. METHODS: Fifteen patients with newly diagnosed SNUC were seen in the Department of Otolaryngology-Head and Neck Surgery at the University of Virginia from 1991 to 2000. Long-term follow-up on five additional patients diagnosed between 1986 and 1991 was also analyzed. RESULTS: Overall, 10 patients were treated with curative intent with neoadjuvant chemoradiotherapy followed by craniofacial resection (CFR). The majority of the remainder was treated with palliative radiotherapy or chemoradiotherapy alone. Four patients who underwent CFR are currently free of disease at 4, 36, 49, and 164 months postoperatively. The 2-year survival of all evaluable patients, regardless of treatment, was 47%. Two-year survival was 64% in the group treated by CFR and 25% in the group treated with chemo- and/or radiotherapy (P =.076). CONCLUSION: For patients with good performance status and limited intracranial or intraorbital disease, we continue to advocate initial chemoradiotherapy followed by craniofacial resection. Patients who are deemed inoperable as a result of advanced disease may nevertheless experience significant palliation with chemoradiotherapy only.

Pitfalls in the endoscopic drainage of subperiosteal orbital abscesses secondary to sinusitis.

OBJECTIVE: To review the safety and efficacy of endoscopic drainage of subperiosteal orbital abscesses (SPOAs) secondary to sinusitis and to evaluate risk factors that may be associated with failure. STUDY DESIGN: Retrospective chart review. METHODS: All patients admitted to the University of the Virginia Health System with a diagnosis of SPOA between 1992 and 1999 were reviewed. RESULTS: Seven of the 10 SPOAs identified, each located medially, resolved without complication after endoscopic drainage. The remaining three patients required a second drainage. One patient had an inferiorly located SPOA, which recurred laterally after endoscopic drainage. A second pediatric patient, who did not undergo a routine second-look procedure, developed middle turbinate lateralization and synechiae, which led to recurrent SPOAs. A third patient with a significant history of sinusitis was found to have an ethmoid sinus mucocele extending into the medial and posterior orbit. All patients eventually resolved their symptoms. CONCLUSIONS: Endoscopic drainage of medial SPOAs appears to be safe and effective. However, several risk factors must be recognized when present. Management of these risk factors is discussed.