Extraprimary Local Recurrence of Esthesioneuroblastoma: Case Series and Literature Review.

OBJECTIVES: Esthesioneuroblastoma (ENB) is a rare sinonasal malignancy arising from olfactory neuroepithelium. Recurrence typically occurs locoregionally at the primary site or in the form of cervical metastasis. Delayed local recurrence away from the initial primary site is exceedingly rare. METHODS: Retrospective review of 4 patients with histologically confirmed extraprimary local recurrence of ENB was performed with review of the literature. RESULTS: All cases initially presented with ENB isolated to the cribriform plate(s) treated with primary surgical resection and adjuvant radiotherapy. The first patient had ENB recurrence 8 years posttreatment involving the right orbit. She later developed metastases to the spine, neck, and mandible requiring composite resection and 4 courses of radiotherapy. The second patient had ENB recurrence of the dorsal septum 9 years posttreatment with cervical metastases requiring septectomy, bilateral neck dissection, and radiotherapy. The third patient had ENB recurrence 7 years posttreatment in the posterior nasopharynx requiring endonasal nasopharyngectomy. Finally, the fourth patient had ENB recurrence 12 years posttreatment in the sphenopalatine foramen, which was endoscopically resected. At the time of this review, all 4 patients were disease free at 32, 21, 4, and 24 months posttreatment follow-ups, respectively. CONCLUSIONS: This case series describes the rare phenomenon of delayed extraprimary local recurrence of histologically confirmed ENB. Treatment of extraprimary recurrences, analogous to other forms of ENB, should include primary surgical resection with adjuvant radiotherapy for generally favorable outcomes. Long-term close follow-up based on symptoms, endoscopy, and imaging is essential because of the risk of delayed recurrence.

Primary Surgery vs Chemoradiation Treatment of Advanced-Stage Hypopharyngeal Squamous Cell Carcinoma.

IMPORTANCE: There is no consensus whether primary surgery followed by either adjuvant radiotherapy (RT) or adjuvant chemoradiation (CRT) or definitive CRT should be the standard treatment approach to advanced-stage hypopharyngeal squamous cell carcinoma (HP SCC). OBJECTIVES: To determine survival outcomes for patients with advanced-stage HP SCC treated at a single institution with either primary surgery plus RT or CRT or definitive CRT. EVIDENCE AND DATA ACQUISITION: We conducted a retrospective analysis of prospectively collected medical records in an institutional database for patients with HP SCC newly diagnosed between January 1999 and April 2013. Overall survival (OS) and recurrence-free survival (RFS) were calculated and compared between treatment groups using the Kaplan-Meier method, with multivariate Cox regression analysis used to control for demographic and clinicopathologic features. RESULTS: We identified 166 consecutively treated patients, 90 of whom did not meet study criteria. Of the 76 included patients, 48 (63%) had undergone definitive CRT, and 28 (37%) had undergone primary surgery with adjuvant RT or CRT. The groups were well balanced by age, smoking history, and alcohol use. Five-year OS and RFS for patients treated surgically were 66.3% and 53.6%, respectively; for patients treated with definitive CRT, OS and RFS were 41.3% and 34.5%, respectively. Multivariate Cox regression analysis showed that surgical management was associated with clinically improved OS (hazard ratio [HR], 4.78; 95% CI, 0.91-25.03; P = .06) and RFS (HR, 2.97; 95% CI, 0.76-11.53; P = .12), although the difference was not statistically significant. CONCLUSIONS AND RELEVANCE: Patients with advanced-stage HP SCC treated surgically with adjuvant RT or CRT showed a trend toward clinically improved OS and RFS compared with patients treated with definitive CRT. However, the difference was not statistically significant, and further investigation with larger controlled trials using modern approaches should be undertaken to optimize the initial management of advanced-stage HP SCC.

Widefield optical imaging of changes in uptake of glucose and tissue extracellular pH in head and neck cancer.

The overall objective of this study was to develop an optical imaging approach to simultaneously measure altered cell metabolism and changes in tissue extracellular pH with the progression of cancer using clinically isolated biopsies. In this study, 19 pairs of clinically normal and abnormal biopsies were obtained from consenting patients with head and neck cancer at University of California, Davis Medical Center. Fluorescence intensity of tissue biopsies before and after topical delivery of 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose) and Alexa 647-pHLIP [pH (low) insertion peptide] was measured noninvasively by widefield imaging, and correlated with pathologic diagnosis. The results of widefield imaging of clinical biopsies demonstrated that 2-NBDG and pHLIP peptide can accurately distinguish the pathologically normal and abnormal biopsies. The results also demonstrated the potential of this approach to detect subepithelial lesions. Topical application of the contrast agents generated a significant increase in fluorescence contrast (3- to 4-fold) in the cancer biopsies as compared with the normal biopsies, irrespective of the patient and location of the biopsy within a head and neck cavity. This unpaired comparison across all the patients with cancer in this study highlights the specificity of the imaging approach. Furthermore, the results of this study indicated that changes in intracellular glucose metabolism and cancer acidosis are initiated in the early stages of cancer, and these changes are correlated with the progression of the disease. In conclusion, this novel optical molecular imaging approach to measure multiple biomarkers in cancer has a significant potential to be a useful tool for improving early detection and prognostic evaluation of oral neoplasia.

Laryngotracheal transplantation: technical modifications and functional outcomes.

OBJECTIVES/HYPOTHESIS: Laryngeal transplantation offers the potential for patients without a larynx to recover their voice, which is critical in our communication age. We report clinical and functional outcomes from a laryngotracheal transplant. Widespread adoption of this technique has been slowed due to the ethical concerns of life-long immunosuppression after a nonvital organ transplant. Our patient was already on immunosuppressive medication from prior kidney-pancreas transplantation, and therefore was not exposed to added long-term risk. We describe the unique technical advances, clinical course, and rehabilitation of this patient and the implications for future laryngeal transplantation. STUDY DESIGN: Case report. METHODS: A laryngotracheal transplantation was performed in a 51-year-old prior kidney-pancreas transplant recipient presenting with complete laryngotracheal stenosis. Surgical modifications were made in the previously described technique related to retrieval, vascular supply, and reinnervation. This resulted in a robustly vascularized organ with well-perfused long-segment tracheal transplant and early return of motor reinnervation. RESULTS: A multidisciplinary approach resulted in a successful transplant without evidence of rejection to date. Postoperatively, the patient continues to rely on a tracheotomy but has had the return of an oral and nasal airway, vocalization, smell, and taste, all experienced for the first time in 11 years. CONCLUSIONS: We have demonstrated that our methods may result in a successful laryngotracheal transplant. We describe the preparation, surgical technique, rehabilitation, and interventions employed in achieving optimal outcomes. This report contributes valuable information on this rarely performed composite transplant.

High-resolution optical molecular imaging of changes in choline metabolism in oral neoplasia.

This study was aimed at developing an optical molecular imaging approach to measure differences in uptake and intracellular retention of choline in clinically isolated tissue biopsies from head and neck cancer patients. An optically detectable analogue of choline (propargyl choline) was synthesized and evaluated in 2D and 3D models and clinically isolated paired biopsies (n = 22 biopsies). Fluorescence contrast between clinically abnormal and normal tissues based on uptake and intracellular retention of propargyl choline was measured and correlated with pathologic diagnosis. Results in 2D and 3D models demonstrated a rapid uptake of propargyl choline in cancer cells, uniform permeation in tissue models, and specific detection of intracellular entrapped propargyl choline using the click chemistry reaction with an azide-modified Alexa 488 dye. Fluorescence imaging measurements following topical delivery of propargyl choline in clinically isolated biopsies showed that the mean fluorescence intensity (MFI) of neoplastic tissues was four-fold to five-fold higher than the MFI of clinically and pathologically normal samples. This difference in fluorescence contrast was measured on the basis of comparison of paired biopsy sets isolated from individual patients as well as comparison of clinically abnormal and normal biopsies independent of anatomic locations in the head and neck cavity and across diverse patients. In conclusion, a novel imaging approach based on monoalkyne-modified choline was developed and validated using cell and tissue models. Results in clinically isolated tissue biopsies demonstrate a significant fluorescent contrast between neoplastic and normal tissues and illustrate high specificity of the optical imaging approach.

Optical molecular imaging detects changes in extracellular pH with the development of head and neck cancer.

Noninvasive localized measurement of extracellular pH in cancer tissues can have a significant impact on the management of cancer. Despite its significance, there are limited approaches for rapid and noninvasive measurement of local pH in a clinical environment. In this study, we demonstrate the potential of noninvasive topical delivery of Alexa-647 labeled pHLIP (pH responsive peptide conjugated with Alexa Fluor(®) 647) to image changes in extracellular pH associated with head and neck squamous cell carcinoma using widefield and high resolution imaging. We report a series of preclinical analyses to evaluate the optical contrast achieved after topical delivery of Alexa-647 labeled pHLIP in intact fresh human tissue specimens using widefield and high-resolution fluorescence imaging. Using topical delivery, Alexa-647 labeled pHLIP can be rapidly delivered throughout the epithelium of intact tissues with a depth exceeding 700 µm. Following labeling with Alexa-647 labeled pHLIP, the mean fluorescent contrast increased four to eight fold higher in clinically abnormal tissues as compared to paired clinically normal biopsies. Furthermore, the imaging approach showed significant differences in fluorescence contrast between the cancer and the normal biopsies across diverse patients and different anatomical sites (unpaired comparison). The fluorescence contrast differences between clinically abnormal and normal tissues were in agreement with the pathologic evaluation. Topical application of fluorescently labeled pHLIP can detect and differentiate normal from cancerous tissues using both widefield and high resolution imaging. This technology will provide an effective tool to assess tumor margins during surgery and improve detection and prognosis of head and neck cancer.

Treatment of embryonal rhabdomyosarcoma of the sinus and orbit with chemotherapy, radiation, and endoscopic surgery.

Parameningeal rhabdomyosarcoma in children has a lower survival than rhabdomyosarcoma at other more favorable sites. This report describes the case of a 14-year-old girl who was successfully treated with multimodal therapy including chemotherapy, radiation, and endoscopic surgery.