James F. Reibel

Preliminary report: endoscopic versus external surgery in the management of inverting papilloma.

Since January 1977, twenty‐four patients with inverting papilloma of the nose and paranasal sinuses have been treated at the University of Virginia. Two patients had bilateral disease, for a total of 26 surgically treated sides. Patients were aged from 10 to 83 years, and 71% were male. Most tumors originated on the lateral nasal wall, with 62% involving the adjacent sinuses. Nineteen sides were treated by external approach and 7 were treated intranasally. There was a total of 5 recurrences in 4 patients and no associated squamous cell carcinomas. Seven patients were treated with endoscopic excision (4 primary tumors and 3 recurrences). There have been no recurrences since endoscopic treatment. These preliminary data give further evidence that endoscopic excision is a viable surgical option for many inverting papillomas.

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).

Conservative Surgical Treatment of Chondrosarcoma of the Larynx

Chondrosarcoma of the larynx is a rare malignant tumor sometimes encountered by otolaryngologists. Since they are usually of low grade malignancy, total laryngectomy is indicated only in cases of high grade malignancy or where total excision by conservative (partial) laryngectomy is not feasible. This paper reviews chondrosarcoma of the larynx, discusses a patient who developed this tumor, and describes a method of conservative surgical excision and laryngotracheal reconstruction when the tumor involves the cricoid, the most common site of occurrence in the larynx.

Schwannoma of the cervical sympathetic chain. The Virginia experience.

We present 4 cases of schwannomas arising from the cervical sympathetic chain. These lesions are uncommon and most often present as an asymptomatic solitary neck mass. Preoperative diagnosis can be difficult, even with the aid of computed tomography, magnetic resonance imaging, ultrasound, and angiography. While a paraganglioma can often be ruled out, exact determination of the nerve of origin is frequently elusive until the time of surgery. Operative excision remains the treatment of choice, often requiring sacrifice of a portion of the sympathetic chain. Postoperative Horners syndrome is common, but does not appear to have an adverse effect on the patient.

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

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.

Outcomes of Patients With Head-and-Neck Cancer of Unknown Primary Origin Treated With Intensity-Modulated Radiotherapy

PURPOSE To analyze survival, failure patterns, and toxicity in patients with head-and-neck carcinoma of unknown primary origin (HNCUP) treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS Records from 27 patients with HNCUP treated during the period 2002-2008 with IMRT were reviewed retrospectively. Nodal staging ranged from N1 to N3. The mean preoperative dose to gross or suspected disease, Waldeyers ring, and uninvolved bilateral cervical nodes was 59.4, 53.5, and 51.0 Gy, respectively. Sixteen patients underwent neck dissection after radiation and 4 patients before radiation. Eight patients with advanced nodal disease (N2b-c, N3) or extracapsular extension received chemotherapy. RESULTS With a median follow-up of 41.9 months (range, 25.3-93.9 months) for non deceased patients, the 5-year actuarial overall survival, disease-free survival, and nodal control rates were 70.9%, 85.2%, and 88.5%, respectively. Actuarial disease-free survival rates for N1, N2, and N3 disease were 100%, 94.1%, and 50.0%, respectively, at 5 years. When stratified by non advanced (N1, N2a nodal disease without extracapsular spread) vs. advanced nodal disease (N2b, N2c, N3), the 5-year actuarial disease-free survival rate for the non advanced nodal disease group was 100%, whereas for the advanced nodal disease group it was significantly lower at 66.7% (p = 0.017). Three nodal recurrences were observed: in 1 patient with bulky N2b disease and 2 in patients with N3 disease. No nodal failures occurred in patients with N1 or N2a disease who received only radiation and surgery. CONCLUSION Definitive IMRT to 50-56 Gy followed by neck dissection results in excellent nodal control and overall and disease-free survival, with acceptable toxicity for patients with T0N1 or non bulky T0N2a disease without extracapsular spread. Patients with extracapsular spread, advanced N2 disease, or N3 disease may benefit from concurrent chemotherapy, targeted therapeutic agents, or accelerated radiation regimens in addition to surgery.

Immediate postoperative extubation in patients undergoing free tissue transfer

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).

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.

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.

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.