Meredith August

Three-Dimensional Computed Tomographic Analysis of Airway Anatomy in Patients With Obstructive Sleep Apnea

PURPOSE To identify abnormalities in airway size and shape that correlate with the presence and severity of obstructive sleep apnea (OSA). MATERIALS AND METHODS This was a retrospective case series of patients undergoing treatment of OSA who had preoperative computed tomographic (CT) scans of the upper airway available. Patients who had undergone CT scanning for nonairway pathologic features during the same period served as the controls. Digital 3D-CT reconstructions were made and 12 parameters of airway size and 4 of shape were analyzed. The posterior airway space, middle airway space, and hyoid to mandibular plane distance were measured on the lateral cephalograms of the patients with OSA. Bivariate analysis was used to identify the factors associated with the presence and severity of OSA as measured by the respiratory disturbance index (RDI). Multiple regression analysis identified the factors that correlated with the RDI. RESULTS Of the 44 patients with OSA, 15 (10 men and 5 women) had pre- and postoperative CT scans available. In addition, 17 patients (11 men and 6 women) were used as controls. The airway length was significantly increased in the patients with OSA (P < .01). On bivariate analysis, the length, lateral/retroglossal anteroposterior dimension ratio and genial tubercle to hyoid bone distance were associated with the RDI (P < .03). On multiple regression analysis, length (P < .01) had a positive correlation and the lateral/retroglossal anteroposterior dimension ratio (P = .04) an inverse correlation with the RDI. CONCLUSIONS The results of this study indicate that the presence of OSA is associated with an increase in airway length. Airways that were more elliptical in shape and mediolaterally oriented (greater lateral/retroglossal anteroposterior dimension ratio) had a decreased tendency toward obstruction.

Quality of Life Implications of Bisphosphonate-Associated Osteonecrosis of the Jaw

PURPOSE Potentially debilitating, osteonecrosis of the jaw (ONJ) is an emerging complication of bisphosphonates. However, its effect on quality of life (QoL) is unknown. We determined the ONJ-related QoL decline in a cancer patient cohort. PATIENTS AND METHODS Thirty-four cancer patients with bisphosphonate-associated ONJ completed a telephone survey (October 2007 through May 2008). The Oral Health Impact Profile 14 (OHIP) retrospectively assessed participant oral health-related QoL before and after ONJ. Standardized ONJ descriptions were developed in a multidisciplinary, iterative process and were evaluated with three frequently used preference-based QoL measurement methods on a 0 (death) to 1 (perfect health) scale: Visual Analogue Scale (VAS), Time Trade-Off (TTO), and EQ-5D. RESULTS ONJ significantly (p < .001) increased OHIP scores (worse QoL) for additive (3.56-16.53) and weighted (7.0-17.5) methods. Seven individual OHIP items significantly increased (Bonferroni correction p < .0035): pain, eating discomfort, self-consciousness, unsatisfactory diet, interrupted meals, irritability, and decreased life satisfaction. Mean preference-based QoL values significantly decreased (p < .001) with worsening ONJ stage (VAS, TTO, and EQ-5D): no ONJ (0.76, 0.86, 0.82), ONJ stage 1 (0.69, 0.82, 0.78), ONJ stage 2 (0.51, 0.67, 0.55), and ONJ stage 3 (0.37, 0.61, 0.32). As ONJ worsened, EQ-5D domain scores significantly increased (p < .001). Pain/discomfort and anxiety/depression contributed most to declining QoL. CONCLUSIONS ONJ significantly affects QoL, a detriment that increases with worsening ONJ. QoL impairments for ONJ stages 2 and 3 are similar to other treatment side effects that influence decision-making. Bisphosphonate-associated ONJ QoL is an important consideration for patients, clinicians, and policy makers.

Complications associated with therapeutic neck radiation.

PURPOSE This retrospective study of patients who underwent neck radiation as part of their treatment for squamous cell carcinoma of the oral cavity sought to identify and quantify the morbidity associated with this treatment. PATIENTS AND METHODS Thirty-five patients who received neck radiation between 1985 and 1992 were randomly recalled for examination. All patients had been treated in a standardized fashion by the Department of Radiation Oncology. The long-term effects of neck radiation on skin changes, thyroid function, and neck range of motion, of atherosclerotic carotid artery disease, xerostomia, and glottic structures were measured. RESULTS Fifty-seven percent of patients demonstrated grade 1 skin changes. No severe changes were noted, and no development of secondary neoplasia was observed. There was no linear trend observed between radiation dose and skin changes. Hypothyroidism developed in 14.3% of patients within 3.5 years posttreatment. Logistic regression demonstrated a significant association between hypothyroidism and radiation dose. Limitation of neck mobility was the most significant complication with deficits demonstrated in all ranges of motion. Carotid bruits were documented in 14.3% of patients, with a significant association between the higher neck dosage in N+ cases. Xerostomia was found in 68% of patients. There was persistent glottic erythema in 11.4% of patients. CONCLUSIONS The results of this study indicate that there are persistent complications after neck radiation, which include limitation of neck movement, diminished thyroid function, accelerated carotid artery narrowing, and skin and salivary changes.

αEβ7 (CD103) Expression Identifies a Highly Active, Tonsil-Resident Effector-Memory CTL Population

The characterization of antiviral CTL responses has largely been limited to assessing Ag-specific immune responses in the peripheral blood. Consequently, there is an incomplete understanding of the cellular immune responses at mucosal sites where many viruses enter and initially replicate and how the Ag specificity and activation status of CTL derived from these mucosal sites may differ from that of blood-derived CTL. In this study, we show that EBV-specific CTL responses in the tonsils are of comparable specificity and breadth but of a significantly higher magnitude compared with responses in the peripheral blood. EBV-specific, tonsil-resident, but not PBMC-derived, T cells expressed the integrin/activation marker CD103 (αEβ7), consistent with the detection of its ligand, E-cadherin, on tonsillar squamous cells. These CD8-positive, CD103-positive, tonsil-derived CTL were largely CCR7- and CD45RA- negative effector-memory cells and responded to lower Ag concentrations in in vitro assays than their CD103-negative PBMC-derived counterparts. Thus, EBV-specific CTL in the tonsil, a crucial site for EBV entry and replication, are of greater magnitude and phenotypically distinct from CTL in the peripheral blood and may be important for effective control of this orally transmitted virus.

Fine-needle aspiration biopsy of intraosseous jaw lesions

PURPOSE This study assessed diagnostic accuracy, determined reasons for error, and evaluated modifications to improve the reliability of fine-needle aspiration biopsy (FNAB) of primary jaw lesions. PATIENTS AND METHODS This was a retrospective review of 32 FNABs of intraosseous jaw lesions performed at the Massachusetts General and Childrens Hospital between 1993 and 1998. A consistent, standardized technique was used, and each case was evaluated for 1) adequacy of cells to allow diagnosis, 2) presence of malignant cells, and 3) correlation between FNAB diagnosis and the final histopathology. RESULTS Material obtained by FNAB was adequate for evaluation in 30 of 32 cases. No complications were reported. Malignant cells were found in 5 of 30 cases. FNAB diagnosis was confirmed by histopathology in all 5 of these specimens (100% accuracy). The FNAB diagnosis of benign lesions was confirmed in 17 of 25 cases (68%). The most common benign lesions were odontogenic cysts, ameloblastomas, and fibro-osseous and giant cell lesions. Incorrect diagnosis was related to lack of architectural context of the FNAB material, sampling of a nonrepresentative part of a large lesion, and inadequate quantity or quality of the aspirate. CONCLUSIONS FNAB is a useful technique to distinguish between malignant and benign intraosseous jaw lesions. Its simplicity, suitability as an outpatient procedure, rapidity of interpretation, and minimal morbidity potentially make it the diagnostic tool of choice in the hospital setting.

Use of the fixed mandibular implant in oral cancer patients: A retrospective study

PURPOSE A retrospective review of the fixed mandibular implant (FMI) in oral cancer patients is presented. Success of the device and associated complications are discussed. PATIENTS AND METHODS Eighteen oral cancer patients with an FMI were identified. All were treated at a single institution. Information was obtained from medical records, radiographs, and recall examination. Demographic data, surgical history, prosthesis design, and functional data were analyzed. Results were statistically compared with outcome data for the FMI in noncancer controls. RESULTS The average patient age was 64 years. Seventeen of the 18 patients had squamous cell carcinoma, most being T3 or T4 lesions at diagnosis. Four of 18 patients received radiation therapy (XRT) followed by resection, 11 had resection followed by XRT, two had XRT alone, and one had surgery alone. The average XRT dose to the mandible was 65.4 Gy. Two of the patients received hyperbaric oxygen (HBO). Sixteen of the implants had been loaded and followed an average of 16.4 months. Early complications included soft tissue overgrowth around pins (4 of 18); tongue ulceration (2 of 18), and intraoral wound dehiscence (2 of 18). Late complications included fistula formation (3 of 18); submental erythema (2 of 18), and persistent tissue overgrowth around pins (1 of 19). No complications required removal of the implant. Only the rate of fistula formation was statistically greater than in controls (P = .005). Average time between FMI placement and prosthesis delivery was 3.6 months. Fourteen of the 16 patients with a prosthesis reported improved ability to eat solid foods and improved articulation. All 16 patients reported improved aesthetics and increased comfort in social settings. CONCLUSIONS The FMI is a valuable device for dental rehabilitation in oral cancer patients. Success was shown in radiated patients. The complication rate is acceptable, and stability was shown over the follow-up period. Rapid rehabilitation and functional and aesthetic improvements were also reported.

The role of panoramic radiography in determining an increased risk of cervical atheromas in patients treated with therapeutic irradiation

PURPOSE Therapeutic irradiation of the neck is a common component of treatment for those with carcinoma of the oral cavity, pharynx, and larynx. Such irradiation, however, has been implicated as the cause of accelerated atherosclerosis of the cervical carotid artery and subsequent stroke. Panoramic radiography, previously shown to be capable of identifying carotid artery atherosclerosis in non-irradiated individuals, was used to assess the carotid vasculature of patients who had been treated for cancer with therapeutic irradiation. METHODS The panoramic radiographs of 33 male subjects who had received therapeutic irradiation (> or = 50 Gy) to the neck 30 or more months previously were assessed for the presence of calcified carotid artery atherosclerotic lesions. Age-matched controls, similarly liable for oropharyngeal malignancy and atherosclerosis by virtue of their medical and habitual risk factors (hypertension, smoking, obesity) were assessed in a like manner. RESULTS The panoramic radiographs of the irradiation-treated subjects (age range, 32 to 84 years; mean age, 66.1 years) showed that 21% (7 of 33 subjects) had calcified atherosclerotic lesions. The mean age of these seven subjects was 64.6 years; four had unilateral lesions and three had bilateral lesions. The radiographs of the control subjects showed that 4.7% (5 of 107 subjects) had calcified atherosclerotic lesions. The mean age of these five subjects was 67; three had unilateral lesions and two had bilateral lesions. The lesions seen in the two populations had similar morphologic appearances. The discrete radiopaque calcifications were located within the soft tissues of the neck, approximately 2.5 cm inferior-posterior to the angle of the mandible. CONCLUSIONS Subjects who had received therapeutic irradiation of the neck had a statistically higher risk (p = 0.007, according to Fishers Exact Test) of the development of calcified carotid artery atherosclerotic lesions than age-matched, risk-matched, non-irradiated control subjects. These lesions can be detected on routine panoramic radiographs.

Osteosarcoma of the Jaws: Factors Influencing Prognosis

PURPOSE To evaluate patient, tumor, and treatment variables associated with survival in patients with jaw osteosarcoma (JOS) and to compare survival in patients treated before 1991 with those managed with more aggressive treatment protocols since 1992. PATIENTS AND METHODS This is a retrospective cohort study of patients with JOS treated at Massachusetts General Hospital from 1967 through 2007. Patients were divided by treatment date into Group 1, 1967 to 1991 (n = 30) and Group 2, 1992 to 2009 (n = 17). Medical records were reviewed to collect the following: demographic, radiographic, tumor-specific, treatment, and survival data. The 2 subgroups were statistically compared. RESULTS There were 47 patients (32 males, 15 females) with a mean age of 30.9 years (range 4 to 74). Mandibular location showed a trend toward improved survival (P = .06). Average tumor size was 4.38 cm (range 0.5 to 9.0 cm). Larger tumors were associated with decreased overall survival (P = .016). Higher grade tumors had decreased overall survival (P = .01). Clear surgical margins were obtained in 67% of patients. Clear surgical margins correlated with improved survival (P = .002). Maxillary JOS constituted 83% of those with positive margins. Overall, 5-year survival was 68%. Improved 5-year survival was noted in group 2 (77%) compared with group 1 (52%) [P = .0073]. Patients who developed secondary osteosarcomas (n = 10) had 4.5-fold increased risk of death (P = .01). Recurrence was associated with 7-fold increased risk of death (P = .0008). Thirteen patients died of JOS. CONCLUSIONS Improved survival was noted in treatment group 2. This group benefited from improved imaging, earlier diagnosis and more aggressive treatment that included improved surgical clearance. A clear survival advantage for neoadjuvant chemotherapy was not demonstrated.

Immunohistochemical Evaluation of Giant Cell Tumors of the Jaws Using CD34 Density Analysis

PURPOSE To compare CD34 expression in both aggressive and nonaggressive giant cell lesions of the jaws and identify any associations between tumor vascular density and biologic behavior. MATERIALS AND METHODS This was a retrospective study of subjects treated for giant cell lesions of the jaws at Massachusetts General Hospital from 1992 to 2006. The primary predictor variable was tumor classification (aggressive or nonaggressive); tumors were considered aggressive if they were greater than 5 cm in size, recurred after treatment, or exhibited 3 of the following: presence of root resorption, tooth displacement, or cortical bone thinning or perforation. Secondary predictor variables, recorded for each patient, were demographic, anatomic, and clinical measures. The outcome variable was the average CD34 staining density of histologic specimens quantified in 2 different areas. Descriptive and bivariate statistics were computed to identify predictors associated with vascular density. RESULTS The study sample was composed of 32 subjects with a mean age of 24.4 +/- 19.77 years (range: 2-83); 23 subjects (71.8%) were female. Of the tumors included, 11 (34.4%) were located in the maxilla, 21 (65.6%) in the mandible. Twenty-six tumors (81.2%) were classified as aggressive; the remainder (18.8%) were nonaggressive. There were no statistically significant differences between subjects with aggressive versus nonaggressive tumors with regard to age, gender, or location. Subjects with aggressive tumors had a significantly higher CD34 staining density (P = .02). None of the secondary predictors was associated with vascular density. CONCLUSION Vascular density of giant cell tumors of the jaws is significantly increased in aggressive tumors.

Preoperative Incisional and Intraoperative Frozen Section Biopsy Techniques Have Comparable Accuracy in the Diagnosis of Benign Intraosseous Jaw Pathology

PURPOSE To compare the accuracy of intraoperative frozen section (FS) and preoperative incisional biopsy (IB) techniques to diagnose benign intraosseous jaw lesions. MATERIALS AND METHODS This is a retrospective cohort study composed of subjects with benign intraosseous jaw lesions. The predictor variable was the technique for establishing a preliminary diagnosis of the lesion, preoperative IB or intraoperative FS. The outcome variable was the accuracy of the biopsy technique when compared with the final histologic diagnosis and was classified as concordant or discordant. The comparative diagnostic accuracy of the techniques was assessed with the χ(2) test. RESULTS A total of 71 subjects met inclusion criteria. The mean age was 39 years (range, 5 to 85 years), and 58% (41) were male patients. Of the subjects, 20 (28%) underwent IB. In 14 (70%) of these, the results of biopsy agreed with the final diagnosis. 51 (72%) underwent intraoperative FS and in 31 (62%) of these, the results of biopsy agreed with the final diagnosis. The difference in diagnostic accuracy between IB (70%) and FS (61%) was statistically insignificant (P = .48). Sources of biopsy error included sampling error (46%), insufficient epithelial tissue (15%), inflammation (15%), pathologists experience (8%), and artifact (4%). CONCLUSIONS Preoperative IB and intraoperative FS provide comparable accuracy of diagnosis in patients with benign intraosseous jaw pathology. Sampling error was the most common reason for discordant results.