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Objective: To determine demographics and cost for outpatients undergoing parathyroid surgery at hospitals belonging to the University Health System Consortium (UHC)., Study Design: UHC data were accessed in 2011 and reflected data collected from 2005 through 2010 (24 quarters). Searching strategy was based on diagnoses of parathyroid disease and patients undergoing parathyroidectomy across all UHC member facilities. Complications evaluated in this analysis included: hypocalcemia, hypoparathyroidism, aspiration pneumonia, hematoma, wound infection, stroke, myocardial infarction, deep venous thrombosis/pulmonary embolism (PE), and death., Setting: The University Health System Consortium, Oak Brook, Illinois, was formed in 1984 and consists of 112 academic medical centers and 250 of their affiliated hospitals. This represents 90% of the nonprofit academic medical centers in the United States (www.uhc.edu)., Subjects and Methods: Patients enrolled in the UHC database were studied retrospectively. Data were compiled from discharge summaries into a secure, interactive, Web-based database. The outpatient data collection set has been a recent addition to the originally established UHC inpatient discharge database., Results: There were 21,057 patients who had outpatient parathyroid surgery. The average age was 59.0 (0.8-96.2) yrs. Seventy-six percent of patients were female. Outpatient parathyroidectomy had lower charges than inpatient surgery ($12,738 and $14,657, respectively; P = 0.004, Wilcoxon signed-rank test). Complications were low but were likely underreported., Conclusion: Parathyroid surgery is increasingly being done in the outpatient setting in the United States. By virtue of omitting inpatient hospitalization, the outpatient approach becomes a more economical way to manage parathyroid disease. This is the largest known series reporting experience with outpatient parathyroid surgery.

Objectives: To determine if standardized uptake values (SUV) on positron emission tomography (PET) are predictive of thyroid pathology and the significance of serial SUV measurements of thyroid nodules over time., Study Design: Case series with chart review., Setting: Academic health center., Subjects: In total, 23,384 PET and PET/computed tomography (CT) scans were performed between December 2001 and April 2011., Methods: Patients with incidental thyroid uptake were identified. SUV(max), age, sex, size of thyroid lesion, indication for PET scan, and cytology/pathology were collected., Results: Incidental thyroid uptake was noted in 1309 PET scans (5.60%), focal uptake in 690 (2.95%), and diffuse uptake in 619 (2.65%). Complete data were available for 359 PET scans from 103 patients. Malignancy was identified in 28 patients (27%). Twenty-five of the 28 lesions (89%) were primary thyroid malignancies. A significant difference between malignant SUV(max) and benign SUV(max) was found (mean ± SD, 7.04 ± 7.88 for malignancies vs 3.85 ± 3.06 for benign tumors, P = .0292). Receiver operating characteristics curves were constructed on patients with PET data within 3 months of diagnosis and indicated that a SUV(max) of 4.2 differentiated maximally between benign and malignant lesions. Serial SUV uptake had no significant change over time., Conclusion: All thyroid nodules with focal uptake on (18)F-fluorodeoxyglucose-PET/CT should be considered at higher risk of malignancy than those discovered incidentally by other imaging modalities. Higher SUV(max) values are more indicative of malignant lesions. All lesions should be evaluated with ultrasonography ± fine-needle aspiration if no clinical contraindications exist. Size of the primary nodule does not influence SUV(max) uptake.

Background: Cervical lymph node metastases from differentiated thyroid cancer (DTC) are common. Thirty to eighty percent of patients with papillary thyroid cancer harbor lymph node metastases, with the central neck being the most common compartment involved. The goals of this study were to: (1) identify appropriate methods for determining metastatic DTC in the lateral neck and (2) address the extent of lymph node dissection for the lateral neck necessary to control nodal disease balanced against known risks of surgery., Methods: A literature review followed by formulation of a consensus statement was performed., Results: Four proposals regarding management of the lateral neck are made for consideration by organizations developing management guidelines for patients with thyroid nodules and DTC including the next iteration of management guidelines developed by the American Thyroid Association (ATA). Metastases to lateral neck nodes must be considered in the evaluation of the newly diagnosed thyroid cancer patient and for surveillance of the previously treated DTC patient., Conclusions: Lateral neck lymph nodes are a significant consideration in the surgical management of patients with DTC. When current guidelines formulated by the ATA and by other international medical societies are followed, initial evaluation of the DTC patient with ultrasound (or other modalities when indicated) will help to identify lateral neck lymph nodes of concern. These findings should be addressed using fine-needle aspiration biopsy. A comprehensive neck dissection of at least nodal levels IIa, III, IV, and Vb should be performed when indicated to optimize disease control.

Background: The role of prophylactic central lymph node dissection in papillary thyroid cancer (PTC) is controversial in patients who have no pre- or intraoperative evidence of nodal metastasis (clinically N0; cN0). The controversy relates to its unproven role in reducing recurrence rates while possibly increasing morbidity (permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury)., Methods and Results: We examined the design and feasibility of a multi-institutional prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC. Assuming a 7-year study with 4 years of enrollment, 5 years of average follow-up, a recurrence rate of 10% after 7 years, a 25% relative reduction in the rate of the primary endpoint (newly identified structural disease; i.e., persistent, recurrent, or distant metastatic disease) with central lymph node dissection and an annual dropout rate of 3%, a total of 5840 patients would have to be included in the study to achieve at least 80% statistical power. Similarly, given the low rates of morbidity, several thousands of patients would need to be included to identify a significant difference in rates of permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury., Conclusion: Given the low rates of both newly identified structural disease and morbidity after surgery for cN0 PTC, prohibitively large sample sizes would be required for sufficient statistical power to demonstrate significant differences in outcomes. Thus, a prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC is not readily feasible.

Objective: Describe data from patients undergoing thyroid surgeries for benign and malignant disease at US academic medical centers., Study Design: Retrospective, database search., Setting: The University Health System (UHC) Consortium (Oak Brook, Illinois) data compiled from discharge summaries., Subjects and Methods: Discharge data were collected from the first quarter of 2002 through the fourth quarter of 2009. Searching strategy was based on diagnosis of thyroid disease and patients undergoing thyroid surgery across all UHC facilities. Demographic information was collected as well as length of stay (LOS) and costs. Complications were evaluated in this analysis., Results: During the study period, 68,014 thyroidectomies were performed, with 27,200 for thyroid cancer. During the same period 6365 neck dissections were performed, with 1539 as stand-alone procedures. Total thyroidectomy was the procedure of choice for malignant disease. More total thyroidectomies and fewer hemithyroidectomies were being performed for benign thyroid disease in the inpatient setting. Almost all postoperative complications were more frequent after surgery for cancer except myocardial infarction and aspiration pneumonia. On average, LOS was longer for benign disease, but costs were higher for malignant disease., Conclusion: This is the largest series reporting inpatient LOS and mortality for thyroid surgery. The limitation of this study is that it reports patients whose stays were more than 23 hours, leaving out a significant number of thyroid surgeries that are performed as outpatients. Although the results contribute greatly to characterizing inpatient surgery, the results may not reflect current US trends for thyroid surgery.

Objective: To describe a technique that assists in the surgical management of recurrent local regional well-differentiated thyroid cancer (WDTC)., Study Design: Case series with chart review., Setting: Two academic health centers from 2001 to 2009., Subjects and Methods: Patients operated upon by the senior surgeon (BCS) for recurrent WDTC., Results: Thirteen patients with recurrent WDTC were operated upon with radioguided surgical (RGS) technique to indentify recurrence for excision. Eight patients had iodine avid disease and were candidates for RGS with (131)I. The remaining 5 patients had cancer with a proven loss of iodine avidity and were, therefore, operated upon with a fluorodeoxygluocose (FDG) RGS technique., Conclusion: RGS is a feasible approach to identify recurrent disease in an operated field and ensure its successful excision. Although focal disease may be identified with this technique, this is not a tool for limited excisions ("berry picking").

Objective: To determine the safety and efficacy of photodynamic therapy in the treatment of oral leukoplakia with 5-aminolevulinic acid and pulsed dye laser., Design: Nonrandomized, single-arm, single-site phase 1/2 pilot study., Setting: Academic referral center., Patients: A total of 23 patients, aged 37 to 79 years, having a confirmed diagnosis of leukoplakia with or without dysplasia measuring at least 10 mm in diameter., Interventions: Application of 5-aminolevulinic acid to lesions followed by activation with high-power 585-nm pulsed dye laser., Main Outcome Measures: Maximum tolerated dose of laser, postprocedure complications, objective response to treatment, and immunohistochemical changes in treated tissue., Results: No significant adverse events occurred; minor local adverse effects were observed during and following photodynamic therapy in the safety phase of the study. The maximum tolerated dose was 8 J/cm(2). Of 17 patients, 7 (41%) had more than 75% regression (significant response) and 9 (53%) had more than 25% regression (partial response), for an overall response rate of 94% at 90 days. This response rate was far higher than the null-hypothesis 20% rate (P < 10(-10)) and the alternative-hypothesis 50% rate (P = .0001) for which the study was powered. When compared with baseline levels immunohistochemically, p53 expression was increased in 8 of 11 available samples (73%) and Ki-67 expression was decreased in 7 of 12 available samples (58%)., Conclusions: Photodynamic therapy with 5-aminolevulinic acid and pulsed dye laser could be used to achieve regression of oral leukoplakia. The treatment is safe and well tolerated. An application time of 1.5 hours and laser radiant exposure of 8 J/cm(2) with 1.5-ms pulse time were found to be the optimal settings in this study. The high-power laser used in this study allows completion of laser therapy within 1 to 3 minutes. Further studies are necessary to determine the optimal laser radiant exposure and drug application to maximize the response rate.

Positron emission tomography (PET) positive lesions are common in the thyroid. The uptake can be focal or diffuse. Diffuse thyroid uptake is thought to be indicative of autoimmune thyroiditis and not for lesions of malignant potential. Hashimoto's thyroiditis as a cause for diffusely positive thyroid glands has been demonstrated. We determine the incidence of diffuse thyroid PET positivity in hypothyroid patients, presumed to have Hashimoto's thyroiditis. The study design was retrospective database and electronic medical record review. The study setting includes tertiary care and academic health sciences center. The subjects were patients at our medical center who underwent positron emission tomography. Hypothyroid patients were identified who had total body PET imaging performed for any reason. Patients were excluded if they were not taking levothyroxine, had a history of neck surgery, neck irradiation, Graves' disease, taking lithium, thalidomide, amiodarone or interleukin. Patients remaining after the application of these exclusion criteria were presumed to be hypothyroid from Hashimoto's thyroiditis. Only 9.5% of PET scans of hypothyroid patients display diffuse thyroid activity. Only a small minority of presumed Hashimoto's thyroiditis patients will display diffuse thyroid activity after PET imaging. The etiology of this effect is unknown. Diffuse thyroid activity rarely requires surgical intervention.

Intraoperative neuromonitoring during thyroidectomy has become a tool available to modern thyroid surgeons. There is ongoing debate as to its effectiveness in reducing intraoperative complications, particularly vocal cord paresis and paralysis. Proponents of its use believe it increases the safety of performing thyroidectomy by improving the ability to identify and preserve the recurrent and superior laryngeal nerves. Some surgeons use it in every case, some only in selected more complicated cases and some choose not to use it at all. There are many reasons why surgeons choose to use or not use this new technology. There are no current consensus guidelines for using intraoperative neuromonitoring and the technology continues to evolve. In this article, we will outline the current scientific literature surrounding the use of neuromonitoring in thyroid surgery and will attempt to give an unbiased current assessment of this technology that is available to actively practicing thyroid surgeons.

Objectives: To determine the prevalence of professional burnout among microvascular free-flap (MVFF) head and neck surgeons and to identify modifiable risk factors with the intent to reduce MVFF surgeon burnout., Design: A cross-sectional, observational study., Setting: A questionnaire mailed to MVFF surgeons in the United States., Participants: A total of 60 MVFF surgeons., Main Outcomes Measures: Professional burnout was quantified using the Maslach Burnout Inventory- Human Services Study questionnaire, which defines burnout as the triad of high emotional exhaustion (EE), high depersonalization (DP), and low personal accomplishment. Additional data included demographic information and subjective assessment of professional stressors, satisfaction, self-efficacy, and support systems using Likert score scales. Potential risk factors for burnout were determined via significant association (P < .05) by Fisher exact tests and analyses of variance., Results: Of the 141 mailed surveys, 72 were returned, for a response rate of 51%, and 60 of the respondents were practicing MVFF surgeons. Two percent of the responding MVFF surgeons experienced high burnout (n = 1); 73%, moderate burnout (n = 44); and 25%, low burnout (n = 15). Compared with other otolaryngology academic faculty and department chairs, MVFF surgeons had similar or lower levels of burnout. On average, MVFF surgeons had low to moderate EE and DP scores. High EE was associated with excess workload, inadequate administration time, work invading family life, inability to care for personal health, poor perception of control over professional life, and frequency of irritable behavior toward loved ones (P < .001). On average, MVFF surgeons experienced high personal accomplishment., Conclusions: Most MVFF surgeons experience moderate professional burnout secondary to moderate EE and DP. This may be a problem of proper balance between professional obligations and personal life goals. Most MVFF surgeons, nonetheless, experience a high level of personal accomplishment in their profession.

Metallopanstimulin-1 (MPS-1) is a multifunctional ribosomal protein RPS27 that contains a zinc finger domain of the C(4) type. MPS-1 has been found to be increased in the sera of a number of different cancers, including head and neck squamous cell carcinoma (HNSCC). However, little is known about the effect of a high-level MPS-1 in regulating cancer cell behavior. In this study, we overexpressed MPS-1 protein in the HNSCC cell line UMSCC-1. We found MPS-1 distributes not only in the cytosol, but also in the nuclei. In addition, MPS-1 is secreted into the culture medium. In vitro and in vivo experiments show that growth of UMSCC-1 cells transfected with MPS-1 is dramatically inhibited. Moreover, we also found that with overexpressing MPS-1, UMSCC-1 cells were arrested on G0/G1 phase, cell proliferation rate was reduced, and tumor angiogenesis was impaired. Further gene array analysis, immunohistochemistry staining and Western blotting reveal that MPS-1 reduces paxillin mRNA and protein levels in UMSCC-1 cells both in vitro and in vivo. Together, these data indicate that when MPS-1 is overexpressed, it has an extraribosomal function as a strong inhibitor of HNSCC tumor cell growth, which may be exerted by reduced paxillin gene expression.

Background: The primary goals of this interdisciplinary consensus statement are to review the relevant anatomy of the central neck compartment, to identify the nodal subgroups within the central compartment commonly involved in thyroid cancer, and to define a consistent terminology relevant to the central compartment neck dissection., Summary: The most commonly involved central lymph nodes in thyroid carcinoma are the prelaryngeal (Delphian), pretracheal, and the right and left paratracheal nodal basins. A central neck dissection includes comprehensive, compartment-oriented removal of the prelaryngeal and pretracheal nodes and at least one paratracheal lymph node basin. A designation should be made as to whether a unilateral or bilateral dissection is performed and on which side (left or right) in unilateral cases. Lymph node "plucking" or "berry picking" implies removal only of the clinically involved nodes rather than a complete nodal group within the compartment and is not recommended. A therapeutic central compartment neck dissection implies that nodal metastasis is apparent clinically (preoperatively or intraoperatively) or by imaging (clinically N1a). A prophylactic/elective central compartment dissection implies nodal metastasis is not detected clinically or by imaging (clinically N0)., Conclusion: Central neck dissection at a minimum should consist of removal of the prelaryngeal, pretracheal, and paratracheal lymph nodes. The description of a central neck dissection should include both the indication (therapeutic vs. prophylactic/elective) and the extent of the dissection (unilateral or bilateral).

Objective: To evaluate free tissue transfer (FTT) as a safe and effective reconstructive technique to treat arteriovenous malformations. Vascular lesions that present a significant clinical challenge to the head and neck reconstructive surgeon are often difficult to treat and can leave large, complex defects., Methods: Retrospective, single-institution case series., Results: We describe 8 patients treated for extensive lesions in various parts of the head and neck reconstructed with free flaps. These malformations have a tendency to recur, which was the case in 75% of our patients (6 of 8) during a mean follow-up period of 5 years. Revision procedures are expected at a mean rate of 6.75 per person in our series., Conclusions: Arteriovenous malformations are uncommon and challenging lesions. Use of FTT can ameliorate the large defects resulting from excision of these lesions.

Background: Technetium 99m sestamibi scans have become a principal means of localizing parathyroid adenomas. Its accuracy and reliability has allowed for the proliferation of minimal access parathyroidectomy. Localizing interpretation of these scans often drives referral of hyperparathyroid patients for surgery. Interpretation of these scans may differ between nuclear medicine physicians and surgeons., Methods: We reviewed patients (N = 65) with digital images from an academic medical center with the diagnosis of primary hyperparathyroidism. We assessed the willingness to define an adenoma's location, the interrater reliability, and the accuracy of technetium (Tc-99m) sestamibi read by a surgeon and a nuclear medicine physician., Results: There was poor correlation between both readers for assessment of quality of images (k = 0.54, 0.07) but very good correlation for adenoma location (k = 0.81)., Conclusion: Both readers had good accuracy in predicting the location of the parathyroid adenoma. The surgeon was more likely to call a scan positive.

Objectives: To reexamine the "Norman rule" (affected parathyroid gland would contain at least 20% radioactivity compared with background), report normative radiation data, offer alternative ratios, and explore the effect of lapsed time on minimally invasive parathyroidectomy (MIRP)., Design: Retrospective analysis., Setting: Tertiary care academic medical center., Patients: A total of 116 consecutive patients who had a diagnosis of primary hyperparathyroidism, positive findings on sestamibi scan, and complete study data from 2000 to 2005 at a single institution., Interventions: Minimally invasive radio-guided parathyroidectomy (MIRP) for primary hyperparathyroidism., Main Outcome Measures: Ten-second gamma radiation counts at key procedural steps. Various ratios of measured radioactivity counts were studied., Results: A total of 116 patients who underwent MIRP had complete data; 91 patients waited 4 or more hours until surgery (78%), with some waiting 8 or more hours. Every patient had a successful surgery and was observed for 1 year thereafter. The Norman ratio of radiation counts (ex vivo to background) was compared with other radiation ratios using Spearman correlation; the comparisons included skin to background (rho = 0.579), in vivo to background (rho = 0.770), basin to background (rho = 0.525), and in vivo-basin to background (rho = 0.788). Regression analysis indicated that the Norman ratio decreased over time at 11% per hour (P = .31)., Conclusions: Alternative ratios to the Norman ratio are reported. An ex vivo to background ratio greater than 20% as a rule of successful parathyroid adenoma excision was observed in all but 2 cases in our series.

Thyroid cancer incidence is increasing, and its diagnosis can be challenging. Fine needle biopsy, the principal clinical tool to make a tissue diagnosis, leads to inconclusive diagnoses in up to 30% of the cases, leading to surgery. Advances in proteomics are improving abilities to diagnose malignant conditions using small samples of tissue or body fluids. We hypothesized that analysis of serum growth factors would uncover diagnostically informative differences between benign and malignant thyroid conditions. Using xMAP profiling, we evaluated concentrations of 19 cytokines, chemokines, and growth factors. We used sera from 23 patients with cancer (Malignant group), 24 patients with benign nodular thyroid disease (Benign group), and 23 healthy subjects (Normal group). In univariate analysis, five factors (epithelial growth factor, hepatocyte growth factor, Interleukins-5 and -8, and regulated upon activation, normally T-expressed and presumably secreted (RANTES) distinguished subjects with thyroid disease from the Normal group. In multivariate analysis, the set {Interleukin-8, hepatocyte growth factor, monocyte-induced γ interferon, interleukin-12 p40} achieved noteworthy discrimination between Benign and Malignant groups (area under the receiver operating characteristics curve was 0.81 (95% confidence interval: 0.65-0.90)). Multiplex panels of serum biomarkers may be promising tools to diagnose cancer in patients presenting with evidence of nodular thyroid disease.

Background: Ultrasound-guided fine-needle aspiration biopsy (ultrasound-guided FNAB) is considered the diagnostic test of choice when a fine-needle aspiration biopsy (FNAB) returns an inconclusive diagnosis because of cytologic ambiguity or paucity of specimen., Methods: Cost-effectiveness analysis utilizing a decision tree was used to model the diagnostic strategies. The decision analysis model was parameterized using costs from a large, academic medical center and probabilities from existing literature. Outcomes included the incremental cost per additional case correctly diagnosed., Results: All data are reported as frontline ultrasound-guided FNAB strategy versus FNAB strategy-expected cost: $1329 versus $1312; expected number of cases correctly diagnosed (per 1000 biopsies): 980 versus 920; incremental cost per additional correctly diagnosed case: $289., Conclusion: The use of ultrasound-guided FNAB as the initial modality for tissue biopsy of a thyroid nodule is more effective than traditional FNAB at an additional cost of $289 per additional correct diagnosis.

Purpose of Review: In the last year, several groups have used various methods to calculate economic costs to patients with early- and late-stage head and neck cancer, cost comparisons of palliative treatments, patient time costs associated with cancer care, and the impact of new diagnostic technologies which need formal cost-effectiveness assessment to determine their value., Recent Findings: Late-stage oral and oropharyngeal cancer treatment is more expensive than early-stage. Photodynamic therapy is cost-effective for esophageal cancer. Head and neck cancer patients spend more time receiving care than control cancer. Multimodal therapy for oropharynx cancer has a higher inpatient utilization than a radio (chemo) approach. Positron emission tomography in combination with computed tomography has a high accuracy, positive predictive value, and ability to find unknown primaries. Soluble CD44 and methylation status are highly sensitive and specific for detecting head and neck cancer. The Washington University head and neck cancer comorbidity index was successful at predicting 5-year costs of head and neck cancer., Summary: Evidence-based studies to inform head and neck cancer care providers are limited. As this available literature proliferates, it should inform providers and policy makers about optimizing the quality and cost of healthcare expenses.

Chordomas are rare tumors of notochordal origin that arise along the vertebral axis. These slowly growing yet highly destructive tumors are associated with an alarming rate of recurrence, although surgical resection followed by proton, proton/photon, or conventional radiotherapy has been somewhat successful in terms of recurrence-free survival. Still, recurrent disease as a result of metastasis or surgical pathway seeding does occur. We retrospectively reviewed the case of a 64-year-old woman who presented with a left neck mass at level II. She had a history of recurrent chordomas involving the occipital portion of the clivus that had been treated with multiple resections and proton-beam irradiations over a period of several years. The new mass was found to have infiltrated the superior end of the sternocleidomastoid muscle. Neck dissection was performed. Pathology revealed no lymphoid tissue in the main specimen and no evidence of chordoma in any of the lymph nodes. We believe that this latest clival chordoma might have occurred as a result of surgical pathway seeding during a previous operation anterior to the sternocleidomastoid muscle, although metastasis cannot be ruled out. We also review the literature on clival and skull base chordomas as it relates to recurrence, metastasis, and seeding.

Objective: Sialolithiasis is a frequent condition seen and treated by otolaryngologists. Salivary stones typically affect the submandibular and parotid glands and can arise from electrolyte disturbances, stasis, or a chronic infectious origin. Primary hyperparathyroidism (pHPT) is associated with 'stone disease', but this has been universally considered to refer to kidney stones. Few case reports exist reporting the relationship between pHPT and sialolithiasis., Design: A retrospective patient series from a single surgical practice., Setting: A single-specialty referral clinic with a practice limited to parathyroid surgery., Main Outcome Measure(s): Descriptive data and statistics., Results: We report a series of 18 patients from among 3,000 consecutive patients treated from March 2003 to May 2007. We describe demographics and characteristics of sialolithiasis that occur in the context of underlying pHPT., Conclusion: The parathyroid surgeon should be aware of sialolithiasis as a potential comorbidity for pHPT and manage it appropriately. Conversely, practitioners encountering salivary gland stone disease should at least consider hyperparathyroidism as a possible etiology., (Copyright 2008 S. Karger AG, Basel.)

Background/aims: After nearly 100 years of inertia in the field of thyroid surgery, the last 5 years have seen substantial changes in how patients with thyroid disease are approached surgically. Much of this evolution has been technologically driven, particularly as a result of advances in high-resolution endoscopy and ultrasonic technology, intraoperative image guidance, and cranial nerve monitoring., Methods: State-of-the-art review., Results: Three emerging technologies that are gradually becoming embraced by thyroid surgeons are reviewed in detail., Conclusion: Modern endocrine-head and neck surgeons bear an obligation to cautiously consider value-adding technologies when a benefit to their patients is apparent., (Copyright 2008 S. Karger AG, Basel.)

Metalloproteins are a group of catalytic proteins, which play significant roles in cell cycle and death. Matrix metalloproteinases (MMPs) are a family of endopeptidases that are capable of digesting extracellular matrix components. They have been implicated in carcinogenesis and recent developments have been made to use MMPs clinically to predict outcomes. In the future, selective inhibition of these proteins and their regulatory pathways may prove useful in anticancer therapeutics. We present a review article on the clinical applications of metalloproteins in head and neck squamous cell carcinoma (HNSCC). Metalopanstimulin is highlighted as a putative metalloprotein of interest for those treating HNSCC. Expression of particular metalloproteins has correlation with lymph node metastasis, tumor invasiveness, and overall prognosis in HNSCC.

Objective: To use decision analysis to compare the costs associated with minimally invasive parathyroidectomy (MIP) and bilateral neck exploration (BNE) in patients with primary hyperparathyroidism with regard to treatment of incidental synchronous thyroid disease., Design: We developed a decision tree model to evaluate the cost of managing thyroid pathology in primary hyperparathyroidism with the following 3 approaches: MIP, MIP with preoperative ultrasonography, and routine BNE with intraoperative thyroid evaluation. We tested the robustness of the optimal decision with sensitivity analyses., Setting: A tertiary care academic medical center., Main Outcome Measure: Total costs from a provider perspective., Results: Minimally invasive parathyroidectomy without an active search for thyroid abnormalities was determined to have the lowest expected cost ($5275 per patient). Parathyroid surgery with routine preoperative thyroid ultrasonography and further thyroid treatment as indicated had an expected cost of $5910 per patient. Bilateral neck exploration with intraoperative thyroid evaluation and treatment of the thyroid gland had an expected cost of $5916 per patient. Sensitivity analyses confirmed the robustness of the results across a reasonable range of surgical and imaging costs., Conclusions: Minimally invasive parathyroidectomy is not contraindicated on the basis of cost by an inability to screen for synchronous thyroid disease. In addition, ultrasonographic screening of the thyroid glands of patients undergoing MIP is not cost prohibitive and, in fact, is less costly than BNE. Ultrasonography has the added advantage of confirming the location of the offending parathyroid.

Objective: To study the feasibility of using laryngeal mask anesthesia (LMA) with bronchoscopic evaluation of recurrent laryngeal nerve (RLN) integrity when stimulated., Design: Single-institution prospective case series., Setting: A single, mid-Atlantic region academic medical center., Patients: Twenty-seven adult volunteers., Interventions: Laryngeal mask anesthesia for thyroid surgery, monitored by flexible laryngoscopy and nerve integrity testing., Main Outcome Measures: Success rates for LMA use in thyroid surgery, bronchoscopic visualization of laryngeal glottis, and documentation of RLN integrity following surgery., Results: We report our experience on 27 consecutive cases in which LMA with RLN stimulation was used for thyroid surgery. Twenty-five of 27 patients underwent successful LMA and visual documentation of RLN integrity by bronchoscopic inspection of nerve stimulation., Conclusions: Direct visualization of vocal cords using a fiberoptic bronchoscope via an LMA provides a safe and feasible method of laryngeal assessment following thyroid dissection. Continuous real-time video monitoring may be the next step in development of this technique as a patient safety measure for thyroid and parathyroid surgery.

Objective: To determine whether the general Charlson Comorbidity Index (CCI) and the head and neck cancer-specific Washington University Head and Neck Cancer Comorbidity Index (WUHNCCI) were useful for predicting cost of treatment for elderly patients with head and neck cancer., Design: Retrospective, observational study., Patients: A total of 1780 Medicare patients with head and neck cancer, who were treated between 1984 and 1994, were analyzed using the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database., Main Outcome Measures: Total Medicare payments were accumulated for each patient up to 1 and 5 years. Linear regression was used to estimate the impact of the comorbidity indexes on costs, controlling for demographics, site, stage, and treatment modality., Results: Neither the WUHNCCI nor the CCI was significantly associated with 1-year costs. However, the effect of the WUHNCCI on 5-year costs was statistically significant (P<.001). A 1-point increase in the WUHNCCI from 4 to 5 was associated with an increase in 5-year costs of $2105. A 1-point increase in the WUHNCCI from 9 to 10 was associated with an increase in 5-year costs of $2837., Conclusion: These results suggest that comorbidity indexes for head and neck cancer may be useful for prognostication of patient outcomes and predicting costs.

Objective: To compare the cost-effectiveness of fine-needle aspiration biopsy, iodine 131 scintigraphy, and ultrasonography for the initial diagnostic workup of a solitary palpable thyroid nodule., Design: A deterministic cost-effectiveness analysis was conducted using a decision tree to model the diagnostic strategies., Setting: A single, mid-Atlantic academic medical center., Main Outcome Measures: Expected costs, expected number of cases correctly diagnosed, and incremental cost per additional case correctly diagnosed., Results: Relative to the routine use of fine-needle aspiration biopsy, the incremental cost per case correctly diagnosed is 24,554 dollars for the iodine 131 scintigraphy strategy and 1212 dollars for the ultrasound strategy., Conclusions: A diagnostic strategy using initial fine-needle aspiration biopsy for palpable thyroid nodules was found to be cost-effective compared with the other approaches as long as a payor's willingness to pay for an additional correct diagnosis is less than 1212 dollars. Prospective studies are needed to validate these finding in clinical practice.

Objective and Importance: Symptomatic complications related to screw migration and extrusion after anterior cervical disc fusion are uncommon., Clinical Presentation: We report a case of significant dysphagia owing to late screw migration., Intervention: An endoscopic transpharyngeal removal was performed without pharyngeal closure and with relief of symptoms., Conclusion: A transpharyngeal endoscopic approach to remove loose anterior cervical hardware is feasible and warrants further evaluation.

Objective: To determine whether the use of additional preoperative imaging was cost-effective compared with bilateral neck exploration (BNE) for the treatment of primary hyperparathyroidism in patients with negative findings on scans with technetium Tc 99m sestamibi., Design: We performed a cost-effectiveness analysis. The decision whether to proceed to BNE or obtain additional preoperative imaging using ultrasonography (US) or single-photon emission computed tomography with technetium Tc 99m sestamibi (SPECT) was modeled using decision analysis. We obtained probabilities of cure, detection of pathologic glands, and the correct side of the neck from recent literature., Main Outcome Measures: Expected cost, cure rate, and the incremental cost per cured case using the preoperative imaging strategies compared with BNE., Results: The US strategy dominated the SPECT and BNE strategies, with a lower expected cost (USD $6030 vs USD $7131 and $8384, respectively) and a greater expected cure rate (99.42% vs 99.26% and 97.69%, respectively). Threshold analysis suggests that the preoperative imaging strategies continued to dominate unless the cost of BNE was less than USD $5400 or the cost of unilateral neck exploration exceeded USD $6500. The US strategy dominated SPECT as a preoperative imaging strategy if the cost of SPECT exceeded $12 or the cost of a US test was less than $1300., Conclusions: For the treatment of primary hyerparathyroidism in the patient with negative findings on technetium Tc 99m sestamibi scans, a strategy that uses additional preoperative US imaging appears to be cost-effective compared with SPECT or BNE.

Objectives/hypothesis: The purpose of this study was to assess the relationship between perioperative changes in parathyroid hormone (PTH) level and the likelihood of postthyroidectomy hypocalcemia., Study Design: In a series of 78 patients undergoing total or completion thyroidectomy, PTH levels were measured before surgery and at 10 minutes after removal of the thyroid gland., Methods: A prospective, nonrandomized collection of serum from 78 consecutive total or completion thyroidectomy procedures performed by a single surgeon was carried out over 18 months. Analysis is made of PTH levels, serum calcium values, need for calcium supplementation, and symptoms of hypocalcemia., Results: Both a PTH change of 75% and an absolute postoperative PTH of 7 pg/mL are accurate standards for predicting symptomatic hypocalcemia after total or completion thyroid surgery., Conclusions: Perioperative PTH levels are a tool for the prediction of postoperative symptomatic hypocalcemia after thyroidectomy. A PTH level drawn 10 minutes after removal of the thyroid predicts the likelihood of postoperative hypocalcemia.

Paclitaxel is used as a single agent, and in combination with other drugs, as a standard of care in the treatment of squamous cell carcinoma of the head and neck (SCCHN). However, the use of paclitaxel for therapy of SCCHN may be accompanied by serious side effects. Paclitaxel is a known cytotoxic inhibitor of cell proliferation that acts by stabilizing microtubules and inducing apoptosis. Opioid growth factor (OGF), [Met(5)]-enkephalin, is an endogenous peptide that has tonically active inhibitory effects on the growth of SCCHN in vitro and in vivo. OGF action is rapid, reversible, mediated by the nuclear-associated OGF receptor (OGFr), and is not cytotoxic (nor apoptotic related). The present study was designed to examine whether a combination of chemotherapy with paclitaxel and biotherapy with OGF is more effective than either agent alone in inhibiting tumor growth. Moreover, focus was placed on whether there are changes in the side effects known to occur with paclitaxel alone, following this combined therapy. Human SCC-1 cells, derived from a well differentiated SCCHN, were transplanted into athymic mice. The mice were randomized to receive intraperitoneal (i.p.) injections of sterile saline (controls), OGF (10 mg/kg, daily), paclitaxel (8 mg/kg, every other day), or both paclitaxel (8 mg/kg, every other day) and OGF (10 mg/kg, daily) beginning on the day of tumor inoculation. OGF, but not paclitaxel, delayed measurable and visible tumor appearance of mice with SCCHN. Treatment with paclitaxel, but not with other agents, had a marked effect on the body weights. Survival only was reduced in the paclitaxel group, with an average life span of 34.3+/-3.1 days recorded, in comparison to the 50-day survival (date of termination) for all other groups. Beginning after week 4 of tumor inoculation and drug treatment, the tumor weight of the paclitaxel/OGF group was significantly reduced from the control, OGF, and paclitaxel-exposed mice. The OGFr number of the SCCHN tumors was 2.1-fold greater in the animals exposed to OGF or paclitaxel, and elevated 38% in the paclitaxel/OGF group; significant differences from the control group were found for the OGF and paclitaxel groups. These data suggest that combined chemotherapy (i.e., paclitaxel) and biotherapy (OGF) provides a valuable alternative to the standard of care for SCCHN patients.

Objective: To investigate the histopathological features of pathologic parathyroid specimens associated with negative preoperative technetium Tc 99m sestamibi scans., Design: Retrospective study., Setting: Tertiary care center., Patients: One hundred fourteen patients who underwent sestamibi scans before surgical exploration for primary hyperparathyroidism between 1996 and 2001., Interventions: Surgical exploration and removal of parathyroid adenomas., Main Outcome Measures: Histopathological characteristics associated with true-positive and false-negative sestamibi scans, including parathyroid specimen weight, size, relative oxyphil and chief cell content, parathyroid hormone staining patterns, cellular architecture, and various immunohistochemical staining patterns., Results: Twenty-three (24%) of 98 patients with parathyroid adenomas had negative sestamibi scan results. Among 20 age- and sex-matched patients with false-negative results vs 20 patients with true-positive results, tumor size (P = .04) and oxyphil cell content (P = .03) were found to be significantly different., Conclusion: Parathyroid gland size and oxyphil content are descriptive and predict differences between sestamibi properties of parathyroid adenomas but have no current therapeutic implications for parathyroid surgery.

Background: Metallopanstimulin (MPS-1) is a ribosomal protein that is found in elevated amounts in the sera of patients with head and neck squamous cell carcinoma (HNSCC). We used a test, denoted MPS-H, which detects MPS-1 and MPS-1-like proteins, to determine the relationship between MPS-H serum levels and clinical status of patients with, or at risk for, HNSCC., Patients and Methods: A total of 125 patients were prospectively enrolled from a university head and neck oncology clinic. Participants included only newly diagnosed HNSCC patients. Two control groups, including 25 non-smokers and 64 smokers, were studied for comparison. A total of 821 serum samples collected over a twenty-four month period were analyzed by the MPS-H radioimmunoassay., Results: HNSCC, non-smokers, and smokers had average MPS-H values of 41.5 ng/mL, 10.2 ng/mL, and 12.8 ng/mL, respectively (p = 0.0001)., Conclusion: We conclude that MPS-1 and MPS-1-like proteins are elevated in patients with HNSCC, and that MPS-H appears to be a promising marker of presence of disease and response to treatment in HNSCC patients.

Purpose: New and more consistent biomarkers of head and neck squamous cell carcinoma (HNSCC) are needed to improve early detection of disease and to monitor successful patient management. The purpose of this study was to determine whether a new proteomic technology could correctly identify protein expression profiles for cancer in patient serum samples., Experimental Design: Surface-enhanced laser desorption/ionization-time of flight-mass spectrometry ProteinChip system was used to screen for differentially expressed proteins in serum from 99 patients with HNSCC and 102 normal controls. Protein peak clustering and classification analyses of the surface-enhanced laser desorption/ionization spectral data were performed using the Biomarker Wizard and Biomarker Patterns software (version 3.0), respectively (Ciphergen Biosystems, Fremont, CA)., Results: Several proteins, with masses ranging from 2778 to 20800 Da, were differentially expressed between HNSCC and the healthy controls. The serum protein expression profiles were used to develop and train a classification and regression tree algorithm, which reliably achieved a sensitivity of 83.3% and a specificity of 100% in discriminating HNSCC from normal controls., Conclusions: We propose that this technique has potential for the development of a screening test for the detection of HNSCC.

Background: New and more consistent biomarkers of head and neck squamous cell carcinoma (HNSCC) are needed to improve early detection of disease and to monitor successful patient management., Objective: To determine if a new proteomic technology can correctly identify protein expression profiles for cancer in patient serum samples as well as detect the presence of a known tumor marker., Design: Direct proteomic analysis and comparison., Methods: The surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF) ProteinChip system was used to screen for differentially expressed proteins in serum samples from 99 patients with HNSCC, 25 "healthy" smokers, and 102 healthy (normal) controls. Protein peak clustering and classification analyses of the SELDI spectral data were performed., Results: Several proteins, with masses ranging from 2778 to 20,800 Da, were differentially expressed between patients with HNSCC and the normal controls. The serum protein expression profiles were used to develop a classification tree algorithm, which achieved a sensitivity of 83.3% and a specificity of 90% in discriminating HNSCC from normal and healthy smoker controls. The positive and negative predictive values were 80% and 92%, respectively. A peak with an average mass of 10,068 Da was detected in sera from HNSCC patients and identified as the known biomarker metallopanstimulin-1 (MPS-1), based on mass. Peak relative intensity of the 10,068-Da protein correlated consistently with MPS-1 levels detected by radioimmunoassay in serum samples of HNSCC patients and controls. The 10,068-Da peak was provisionally identified as MPS-1 by SELDI immunoassay., Conclusion: We propose that this technique may allow for the development of a reliable screening test for the early detection and diagnosis of HNSCC, as well as the potential identification of tumor biomarkers.

Opioid growth factor (OGF), [Met5]-enkephalin, interacts with the OGF receptor (OGFr) to inhibit the growth of human squamous cell carcinoma of the head and neck (SCCHN) in vitro. Administration of OGF by daily intraperitoneal injection (i.p.) to animals with xenografts of CAL-27, a poorly differentiated SCCHN, is known to repress tumorigenic events. In this study, the ubiquity of OGF action on SCCHN was investigated by examination of OGF activity on SCC-1 tumors; this human cell line is well-differentiated and highly invasive. Mice receiving daily i.p. injections (10 mg/kg) of OGF had more than a 3-day delay in tumor appearance, and decreases in tumor volume ranging from 51 to 64% in comparison to controls throughout the experimental period. Receptor binding analysis for OGFr showed that binding capacity (Bmax) was 2.2-fold greater than control values, but binding affinity (Kd) was comparable. Plasma OGF levels did not vary between OGF and control groups. Mice receiving OGF by continuous infusion using minipumps, or by daily intratumoral injection, had characteristics of tumorigenicity similar to their corresponding control animals, although the OGF levels in mice receiving the OGF by minipump were elevated 18-fold greater than the control group. These data indicate that: i) the inhibitory action of OGF may be ubiquitous for SCCHN, ii) OGF treatment alters the characteristics of the OGF receptor but not of plasma OGF levels, and iii) the magnitude of effects of OGF on SCCHN is dependent on the route of administration.

Improved microsurgical technique has resulted in a high percentage of successful free tissue transfers. When a tissue transfer fails in the head and neck, however, the results are orocutaneous fistulas, carotid artery exposure, and deformity that adds morbidity, expense, and may delay adjuvant therapy. Postoperative monitoring of tissue perfusion can detect early problems in free tissue transfer that may allow for early intervention and salvage. The authors have demonstrated that reflectance photoplethysmography can detect perfusion changes in free tissue transfer within 5 minutes of a pedicle "insult" intraoperatively. Normative data for viable flaps from various donor sites have been established. The authors now report their initial experience with a newly developed reflectance photoplethysmograph based on a hand-held computer for routine clinical use. Their results are compared with a conventional surveillance protocol that included observation, bleeding to pin prick, and bedside duplex scanning of the vascular pedicle. In a series of 30 free tissue transfers (29 patients), there was one ischemic event (skin paddle loss only), which was detected by the monitor. The monitor was able to predict correctly (one flap) survival of a free tissue transfer even when duplex ultrasonic data were indicative of an absence of perfusion. Personal digital assistant-based photoplethysmography appears to be a promising device for bedside diagnosis of free tissue transfer viability or ischemia.

Facial plastic surgeons often must make decisions with imperfect information. Statistical inference is fundamentally the practice of using data to draw conclusions about uncertain phenomena. It is important, therefore, that facial plastic surgeons engaged both in clinical practice and in research have an understanding of statistical concepts to conduct research with results that are meaningful, to assess the validity of published research, and to adopt the most effective techniques and treatments. The purpose of this article is to provide an overview of classical statistical methods that are encountered frequently in facial plastic surgery research, discuss issues of interpretation of results, and introduce an alternative paradigm for conducting statistical inference.

Objective: Studies of tumor angiogenesis in head and neck squamous cell carcinoma (HNSCC) in regard to correlation with prognostic significance have yielded inconclusive results. To determine whether the microvessel density (MVD) within the tumor of advanced (Stages III and IV) HNSCC has any impact on tumor response to 2-3 courses of paclitaxel (Taxol) and carboplatin, we prospectively studied pre-chemotherapy specimens from patients with previously untreated, advanced stage HNSCC. We also attempted to study residual tumors after chemotherapy to determine if the MVD within the tumor had changed., Study Design: The MVD within the tumor was obtained by immunohistochemical staining of the tumors with Q-Bend 10 (CD34). The "hot-spot" areas of each tumor (ie., areas with most intense blood neovascularization) were considered for evaluation. Results were expressed as the Average number of microvessels identified in 5-400x microscope fields (ie., the number of microvessels counted in 5-400x microscope fields divided by 5)., Setting: Tertiary University Medical Center., Intervention: Two to 3 courses of chemotherapy with paclitaxel and carboplatin., Main Outcome Measures: Progression-free and overall survival with 5 years follow-up,, Results: The tumoral MVD in 32 HNSCC specimens before chemotherapy ranged from 4.0-39.0 (mean, 14.8; median, 14.2). Eight out of 32 patients achieved pathologically complete remission; their tumoral MVD revealed a mean of 10.9. The 24 remaining patients had pathologically-confirmed residual tumor post-chemotherapy; their tumoral MVD revealed a mean of 16.5., Conclusion: Statistical analyses revealed no evidence of a relationship between remission and a MVD > or < 10 or > or < 16.5. There was no correlation of tumoral MVD with overall or progression-free survival. In 15 patients, tumoral MVD results were also available on the post-chemotherapy specimens. The greater the difference of the tumoral MVD between the pre- and post-chemotherapy specimens, the shorter the patients overall and progression-free survival (p = 0.042).