Endoplasmic Reticulum Stress Enhances Mitochondrial Metabolic Activity in Mammalian Adrenals and Gonads.

The acute response to stress consists of a series of physiological programs to promote survival by generating glucocorticoids and activating stress response genes that increase the synthesis of many chaperone proteins specific to individual organelles. In the endoplasmic reticulum (ER), short-term stress triggers activation of the unfolded protein response (UPR) module that either leads to neutralization of the initial stress or adaptation to it; chronic stress favors cell death. UPR induces expression of the transcription factor, C/EBP homology protein (CHOP), and its deletion protects against the lethal consequences of prolonged UPR. Here, we show that stress-induced CHOP expression coincides with increased metabolic activity. During stress, the ER and mitochondria come close to each other, resulting in the formation of a complex consisting of the mitochondrial translocase, translocase of outer mitochondrial membrane 22 (Tom22), steroidogenic acute regulatory protein (StAR), and 3ß-hydroxysteroid dehydrogenase type 2 (3ßHSD2) via its intermembrane space (IMS)-exposed charged unstructured loop region. Stress increased the circulation of phosphates, which elevated pregnenolone synthesis by 2-fold by increasing the stability of 3ßHSD2 and its association with the mitochondrion-associated ER membrane (MAM) and mitochondrial proteins. In summary, cytoplasmic CHOP plays a central role in coordinating the interaction of MAM proteins with the outer mitochondrial membrane translocase, Tom22, to activate metabolic activity in the IMS by enhanced phosphate circulation.

Ancillary studies in determining human papillomavirus status of squamous cell carcinoma of the oropharynx: a review.

Squamous cell carcinoma (SCC) of the oral cavity and pharynx represents the sixth most common form of malignancy worldwide. A significant proportion of these cases are related to human papillomavirus (HPV) infection. In general, HPV-associated SCC is more commonly nonkeratinizing and poorly differentiated, whereas non-HPV-associated SCC is typically keratinizing and moderately differentiated. Nevertheless, significant overlap in morphology is seen between these two forms of SCC. The purpose of this paper is to highlight the utility of ancillary studies in the establishment of HPV status of oropharyngeal SCC, including p16 immunohistochemistry, high-risk HPV in situ hybridization, polymerase chain reaction, and newer HPV detection modalities.

Frontal sinus schwannoma: case report and review of literature.

Although schwannomas are frequently found in the head and neck region, sinonasal tract involvement is extremely rare, especially those of the frontal sinus. We report a patient with an incidentally found right frontal sinus lesion. The patient underwent resection of the tumor via a right craniotomy. The histological diagnosis was consistent with a schwannoma. There has been no radiographic recurrence on 2-year follow-up.

Functional and oncologic results following transoral laser microsurgical excision of base of tongue carcinoma.

OBJECTIVE: The study objective was to determine survival and functional results in patients who underwent transoral laser excision of base of tongue squamous cell carcinoma. STUDY DESIGN: This was a case series with chart review. SUBJECTS AND METHODS: Patients with biopsy-proven base of tongue squamous cell carcinoma primarily treated with transoral laser excision and followed for at least 24 months were included. Disease-specific and overall survival data were determined. Quality-of-life data were obtained using the University of Washington Quality of Life instrument. RESULTS: Of the 71 patients treated, one (1.4%), nine (12.7%), seven (9.9%), and 54 (76.1%) were stage I, II, III, and IV, respectively, at diagnosis. At 24 months, overall survival was 90 percent; disease-specific survival was 94 percent. Locoregional recurrence occurred in 10 percent. Given the low number of deaths, no significance was detectable between survival and gender, overall stage, tumor size, nodal status, or adjuvant therapy. Quality-of-life data, obtained for 46 patients, revealed the majority of patients had mild or no pain, minimally impaired to normal swallowing, and normal speech. CONCLUSION: Transoral laser excision offers an acceptable treatment approach in terms of survival and quality of life for patients with base of tongue squamous cell carcinoma.

Phase I adjuvant radiation with docetaxel in high-risk head and neck cancer.

BACKGROUND: This phase I study was designed to determine the maximum tolerated dose (MTD) and preliminary efficacy of docetaxel with concurrent radiotherapy (RT), in high-risk squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Eligible patients had resected squamous cell carcinoma of the head and neck, histologically involved lymph nodes, and/or extranodal disease, and/or involved surgical margins and performance status 0 to 1. Treatment included weekly docetaxel with concurrent RT in a dose-finding study; a subsequent small cohort of patients was treated using the MTD of docetaxel. RESULTS: Twenty patients were enrolled. Planned accrual was 25, but the study was closed prematurely because of slow accrual. The MTD was 15 mg/m2. Dose-limiting toxicity was oral stomatitis. Therapy was well tolerated. Five patients experienced locoregional relapse at a median follow-up of 32 months. CONCLUSION: Docetaxel with concurrent RT has acceptable toxicity. This approach warrants further investigation in a phase II trial.

Glossopharyngeal schwannoma of the suprahyoid carotid space: case report and discussion of the relationship to the carotid artery.

BACKGROUND: The distinction between lesions of the deep parotid space and those of the carotid space has been greatly facilitated by cross-sectional imaging, particularly magnetic resonance imaging (MRI), due to 1) good assessment of parapharyngeal fat displacement, and 2) reliable and consistent identification of the carotid artery. While masticator space masses consistently displace the carotid artery posteriorly, it is generally assumed that carotid space masses, particularly schwannomas, displace the carotid artery anteriorly. We report on a patient with a rare glossopharyngeal schwannoma of the carotid space that caused posterior displacement of the carotid artery. METHODS: A 38-year-old female presented with headaches and a pharyngeal sensation of a foreign body without dysgeusia and dysphagia. Computed tomography (CT) and MRI showed a left carotid space mass, suggestive of a schwannoma, although the internal carotid artery was displaced posteriorly. The mass was hypovascular at angiography. The patient underwent surgical excision of her lesion via a left cervical-parotid approach. RESULTS: In our patient with a carotid space mass, all imaging features suggested a schwannoma, except for posterior displacement of the carotid artery. A glossopharyngeal nerve schwannoma was found at surgery. Schwannomas of the glossopharyngeal nerve are uncommon, and those originating from the extracranial course of the nerve are extremely rare. CONCLUSIONS: Schwannomas of the suprahyoid carotid space most commonly arise from the vagus nerve and have a typical pattern, which includes anterior displacement of the carotid artery. A rare exception to this has been reported in schwannomas of the sympathetic nerve, which may displace the carotid artery posteromedially. Our patient had a schwannoma of the extracranial glossopharyngeal nerve, which caused posterolateral carotid displacement.

Primary tumor thickness as a risk factor for contralateral cervical metastases in T1/T2 oral tongue squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: Contralateral cervical metastases represent an avoidable source of failure in squamous cell carcinoma (SCCa) of the oral tongue. We sought to identify risk factors for the development of contralateral cervical metastases in T1/T2 oral tongue SCCa. STUDY DESIGN: Retrospective review. METHODS: We reviewed the medical records of 50 sequential cases of Stage I/II SCCa of the oral tongue treated with surgery between 1983 and 2003 at Loyola University Medical Center and Hines VA Hospital. Clinical staging, primary tumor thickness, results of neck dissection, adjuvant treatment, site and date of recurrence, and final outcome were recorded. Follow-up ranged from 0.2 to 17 years, with a mean of 5 years. Data were analyzed using multivariate logistic, Cox regression analysis, and a classification and logistic regression tree analysis. RESULTS: The odds ratio for risk of developing contralateral neck metastasis was 5% for each 1 mm increase in tumor thickness (P = .68). The risk did not change when controlling for the presence of ipsilateral metastasis. There was a significant relationship between contralateral cervical metastases and the development of recurrent disease at any site (P = .005). Classification tree analysis determined the risk for contralateral metastases and was greatest for patients with tumors > 3.75 mm thick and < or = 9.5 mm thick. CONCLUSIONS: This report is the first to our knowledge that evaluates thickness as a risk factor for contralateral cervical metastasis in oral tongue SCCa. We recommend consideration be given to treating the contralateral neck in cases where the primary tumor is > 3.75 mm thick.

Oral cavity metastasis of renal cell carcinoma: a case report.

INTRODUCTION: Despite being reported rarely, renal cell carcinoma is the third most frequent neoplasm to metastasize to the head and neck region preceded only by breast and lung cancer. Little information exists regarding the presentation and work-up of metastatic renal cell carcinoma in the oral cavity. CASE PRESENTATION: We report the case of a 63-year-old Caucasian man presenting with an oral cavity lesion that was painful and that had grown substantially over several months. Biopsy resulted in persistent bleeding requiring cautery and manual pressure. Immunoperoxidase testing was necessary to make the diagnosis of metastatic renal cell carcinoma and rule out other clear cell carcinomas of salivary gland origin. CONCLUSION: Metastatic renal cell carcinoma is part of the differential diagnosis for patients presenting with a new head or neck lesion in the setting of a history of kidney cancer. The physician needs to be prepared for the increased risk of bleeding and understand the importance of immunohistochemical staining to differentiate between metastatic renal cell carcinoma and malignancies of salivary origin. Unfortunately, the prognosis is invariably poor in these patients.

Peripheral ameloblastoma of the maxilla: a case report and literature review.

Peripheral ameloblastoma is a rare, benign, extraosseous neoplasm of the odontogenic epithelium. We report a case of peripheral ameloblastoma, detail our surgical therapy and review important elements in the pathological diagnosis and treatment of this unusual neoplasm.

Intratemporal Grafting of the Facial Nerve following Lateral Skull Base Tumor Resection.

UNLABELLED: Intratemporal skull base tumors may invade the facial nerve in the horizontal (tympanic) or descending (vertical) segments, while parotid malignancies typically infiltrate the facial nerve at the stylomastoid foramen. This article will describe our results following intratemporal facial nerve grafting in 44 patients. METHODS: This was a retrospective analysis of 44 patients requiring intratemporal facial nerve repair following lateral skull base tumor resection at our tertiary care, academic medical center. RESULTS: Tumor histology included 17 parotid cancers, 13 temporal bone malignancies, 9 glomus tumors, 3 facial neuromas, and 2 endolymphatic sac tumors. The greater auricular nerve was used in 25 patients and the sural nerve was used in 19 cases. Forty patients were available for facial function assessment at 2 years. Using the House-Brackmann (H-B) recovery scale, the breakdown of patients by facial function was as follows: Grade I, 0 patients; Grade II, 4 patients; Grade III, 29 patients; Grade IV, 4 patients; Grade V, 3 patients; and Grade VI, 0 patients. CONCLUSIONS: Facial paralysis may occur from intrinsic or external lateral skull base invasion of the facial nerve. Intratemporal interposition grafting resulted in favorable facial function (H-B II or III) in 33 of the 40 (82.5%) patients at the 2-year assessment.

Impact of mandibular condyle preservation on patterns of failure in head and neck cancer.

OBJECTIVE: To determine the role of native condyle preservation in local recurrence after segmental mandibulectomy in patients with head and neck squamous cell carcinoma. METHODS: Retrospective chart review with main outcome measuring local control of cancer. RESULTS: Between 1994 and 2003, 72 patients (48 men, 24 women) with an average age of 73.5 years without previous treatment underwent segmental mandibulectomy. Fifty-four cases (n = 54) involved the mandible posterior to the mental foramen and are the subject of this review. In 36 patients, the condyle was preserved and mandibular continuity was restored. In 18 patients, condyle and ramus were resected without mandibular reconstruction. Reconstructive modalities included primary closure (3), split-thickness skin graft (3), pedicle flap (19), and free tissue reconstructions (29). Overall local-regional recurrence rate was 22 percent (12 of 54); no recurrences were identified in patients who underwent condylar resection. Recurrences were observed in patients with mandibular reconstruction by both plate and pedicle flap (5 of 9) or (osteo) myocutaneous free flap (7 of 27). CONCLUSION: Condylar preservation may predispose patients to local recurrence after segmental mandibulectomy. This does not translate into overall reduction in survival.

Lacrimal sac melanoma.

A 48-year-old woman presented with a 5-month history of unilateral epiphora and progressive growth of a left-sided medial canthus mass. CT revealed a nonenhancing soft tissue mass of the left lacrimal sac with widening and erosion of the nasolacrimal canal. The tumor was resected and pathologically confirmed to be malignant melanoma. Despite wide resection and adjuvant radiotherapy, the patient developed metastases to the chest wall. The patient currently is receiving combined immunotherapy and chemotherapy. The clinical course and treatment strategies are reviewed for this highly aggressive and rare neoplasm.

Life after total laryngectomy: a measure of long-term survival, function, and quality of life.

OBJECTIVES: To analyze postoperative clinical, functional, and quality-of-life (QOL) outcomes in patients after total laryngectomy (TL) and to determine the effect of preoperative variables (including age, sex, comorbidities, prior chemotherapy or radiation therapy, and tumor site and stage) on long-term survival and quality of life. DESIGN: We performed a retrospective cohort follow-up study of patients who underwent TL for cancer between July 28, 1994, and August 11, 2005. SETTING: University tertiary care facility. PATIENTS: One hundred forty-three patients who underwent TL were identified, and their hospital medical records were reviewed. Ninety-one patients (63.6%) underwent TL for primary carcinoma and 52 (36.4%) for recurrent cancer. At follow-up, 58 patients (40.6%) were alive. MAIN OUTCOME MEASURES: Baseline characteristics and preoperative clinical variables were collected. Follow-up data on function and QOL were collected from patients who were alive at the time of study via the Head and Neck Cancer Inventory, a previously validated questionnaire. Survival was estimated using the Kaplan-Meier method. Univariate and multivariate analysis was used to determine factors significant for survival. RESULTS: The overall median survival for the cohort was 23.0 months (mean +/- SD, 50 +/- 29 months). On univariate analysis, the following 5 factors were significant predictors of long-term survival: cancer site in the larynx, T3 stage, N0 to N1 stage, presence of no more than 2 comorbidities, and absence of cardiovascular comorbidities at the time of cancer diagnosis (P<.05). On multivariate analysis, only T stage maintained significance as a predictor of survival (P =.04), while cancer site was nonsignificant at P =.07. For patients alive at the time of study, functional and QOL outcomes for 5 domains (speech, eating, social disruption, aesthetics, and overall QOL) ranged from intermediate (score, 31-69) to high (score, 70-100) categories. Pretreatment patient-related factors that correlated with notably better functional and QOL outcomes in at least 1 domain were age older than 65 years at diagnosis, presence of no more than 2 comorbidities, no history of previous chemoradiation therapy, and primary tracheoesophageal puncture placement. CONCLUSIONS: Pretreatment clinical variables (including primary tumor site, tumor stage, regional metastases, and number and type of comorbidities) have an effect on long-term survival after TL. Despite common belief, many patients who have undergone TL maintain a good QOL overall. This study sheds light on which patient-related factors may affect health-related QOL outcomes after TL. These findings may be used to select patients who are good candidates for TL based on anticipated functional and QOL outcomes.

Contemporary management of tumors of the salivary glands.

Management of tumors of the salivary glands requires a detailed understanding of the anatomy and pathologic processes affecting these glands. Salivary glands give rise to benign and malignant neoplasms and are affected by a variety of systemic diseases. CT remains the most common primary imaging study; magnetic resonance imaging and ultrasound have also been explored. Fine-needle aspiration as part of the diagnostic evaluation remains controversial due to varying sensitivities and specificities. Surgical extirpation is the primary modality for management of tumors of the salivary glands. Parotid surgery carries a potentially high morbidity with possible unsightly scarring and facial nerve damage. Nontraditional surgical approaches and instrumentation, as well as facial nerve monitoring, can decrease the morbidity of a parotidectomy. In specific instances, malignant salivary gland tumors warrant cervical lymphadenectomy. Adjuvant therapy is primarily accomplished with radiation. Chemotherapy continues to play a palliative role in salivary gland malignancies; however, newer trials are investigating the therapeutic role of chemotherapy.

Combined anterior and anterolateral approaches to the cranial base: complication analysis, avoidance, and management.

OBJECTIVE: During the past decade, applications of anterior and anterolateral cranial approaches for both benign and malignant pathologies have expanded in frequency and application. Complications associated with these procedures impact significantly on patient outcome. The primary aim of this study is to detail the strategies for complication management and avoidance developed from experience with 120 patients who underwent anterior and anterolateral cranial base procedures during the past 14 years. METHODS: Between July 1990 and February 2004, 62 male and 58 female patients underwent 120 combined (neurological surgery and otolaryngology joint participation) anterior and anterolateral cranial base procedures. Fifty-four percent had malignant pathology, and 46% had benign pathology. The approaches taken were transfacial (10%), extended subfrontal (33%), lateral craniofacial (23%), and anterior craniofacial (35%). Thirty-day morbidity and mortality were analyzed. RESULTS: Twenty (17%) patients experienced at least one complication. Malignancy and reoperation, regardless of histology, appeared to affect the complication rate. A decline in complications occurred with experience, in part because of changes in management that reflected the complication experience (25% in Patients 0-31, 18% in Patients 32-70, 10% in Patients 71-120). Methodology is detailed for avoidance and management of retraction injury, infection, tension pneumocephalus, cerebrospinal fluid leak, pericranial flap failure, free flap sizing, dural banding, intracranial hypotension, and cerebrovascular events. Individual patient analysis, complications timing, and strategy for management are discussed. CONCLUSION: Improved patient outcomes for anterior and anterolateral cranial base surgery are, in part, directly related to the ability to avoid and manage associated complications. Experience, avoidance, and interdiction are key factors in complication management.

Recurrent pleomorphic adenoma of the parotid gland.

OBJECTIVES: To assess the long-term results in the management of 42 patients with recurrent pleomorphic adenoma of the parotid gland. STUDY DESIGN: A retrospective analysis of 42 patients who underwent parotidectomy for recurrent pleomorphic adenoma was performed to study presenting clinicoradiographic features, surgical technique, facial nerve management, and the long-term risk of recurrence. RESULTS: All 42 patients had multi-focal, nontender recurrent nodules following one to four prior surgical procedures and 6 patients underwent prior radiotherapy. Surgical procedures included subtotal parotidectomy in 12 patients, total parotidectomy in 18 patients, parotidectomy with facial nerve resection in 7 cases, and subtotal petrosectomy with facial nerve resection in 5 individuals. The 2 patients with malignant transformation died of disseminated lung and bone metastasis. Twenty-nine of the remaining 40 patients had no recurrent disease. Seven patients developed local parotid bed or cutaneous recurrent disease, 2 patients died of unrelated causes, and 2 patients were lost to follow-up. CONCLUSIONS: All 7 patients with recurrent disease underwent subtotal parotidectomy with "negative" surgical margins. Total parotidectomy or subtotal petrosectomy with facial nerve resection in selected cases may reduce the risk of multiple episodes of pleomorphic adenoma recurrence. Two of 42 patients were found to have carcinoma ex-pleomorphic adenoma, both of these patients underwent prior radiotherapy, and both died of metastatic disease.