Introduction of the American Academy of Facial Plastic and Reconstructive Surgery FACE TO FACE Database.

The American Academy of Facial Plastic and Reconstructive Surgery FACE TO FACE database was created to gather and organize patient data primarily from international humanitarian surgical mission trips, as well as local humanitarian initiatives. Similar to cloud-based Electronic Medical Records, this web-based user-generated database allows for more accurate tracking of provider and patient information and outcomes, regardless of site, and is useful when coordinating follow-up care for patients. The database is particularly useful on international mission trips as there are often different surgeons who may provide care to patients on subsequent missions, and patients who may visit more than 1 mission site. Ultimately, by pooling data across multiples sites and over time, the database has the potential to be a useful resource for population-based studies and outcome data analysis. The objective of this paper is to delineate the process involved in creating the AAFPRS FACE TO FACE database, to assess its functional utility, to draw comparisons to electronic medical records systems that are now widely implemented, and to explain the specific benefits and disadvantages of the use of the database as it was implemented on recent international surgical mission trips.

Hyperactive ERK and persistent mTOR signaling characterize vemurafenib resistance in papillary thyroid cancer cells.

Clinical studies evaluating targeted BRAFV600E inhibitors in advanced thyroid cancer patients are currently underway. Vemurafenib (BRAFV600E inhibitor) monotherapy has shown promising results thus far, although development of resistance is a clinical challenge. The objective of this study was to characterize development of resistance to BRAFV600E inhibition and to identify targets for effective combination therapy. We created a line of BCPAP papillary thyroid cancer cells resistant to vemurafenib by treating with increasing concentrations of the drug. The resistant BCPAP line was characterized and compared to its sensitive counterpart with respect to signaling molecules thought to be directly related to resistance. Expression and phosphorylation of several critical proteins were analyzed by Western blotting and dimerization was evaluated by immunoprecipitation. Resistance to vemurafenib in BCPAP appeared to be mediated by constitutive overexpression of phospho-ERK and by resistance to inhibition of both phospho-mTOR and phospho-S6 ribosomal protein after vemurafenib treatment. Expression of potential alternative signaling molecule, CRAF, was not increased in the resistant line, although formation of CRAF dimers appeared increased. Expression of membrane receptors HER2 and HER3 was greatly amplified in the resistant cancer cells. Papillary thyroid cancer cells were capable of overcoming targeted BRAFV600E inhibition by rewiring of cell signal pathways in response to prolonged vemurafenib therapy. Our study suggests that in vitro culture of cancer cells may be useful in assessing molecular resistance pathways. Potential therapies in advanced thyroid cancer patients may combine vemurafenib with inhibitors of CRAF, HER2/HER3, ERK, and/or mTOR to delay or abort development of resistance.

mTOR inhibitors sensitize thyroid cancer cells to cytotoxic effect of vemurafenib.

Treatment options for advanced metastatic thyroid cancer patients are limited. Vemurafenib, a BRAFV600E inhibitor, has shown promise in clinical trials although cellular resistance occurs. Combination therapy that includes BRAFV600E inhibition and avoids resistance is a clinical need. We used an in vitro model to examine combination treatment with vemurafenib and mammalian target of rapamycin (mTOR) inhibitors, metformin and rapamycin. Cellular viability and apoptosis were analyzed in thyroid cell lines by trypan blue exclusion and TUNEL assays. Combination of vemurafenib and metformin decreased cell viability and increased apoptosis in both BCPAP papillary thyroid cancer cells and 8505c anaplastic thyroid cancer cells. This combination was also found to be active in vemurafenib-resistant BCPAP cells. Changes in expression of signaling molecules such as decreased mTOR expression in BCPAP and enhanced inhibition of phospho-MAPK in resistant BCPAP and 8505c were observed. The second combination of vemurafenib and rapamycin amplified cell death in BCPAP cells. We conclude that combination of BRAFV600E and mTOR inhibition forms the basis of a treatment regimen that should be further investigated in in vivo model systems. Metformin or rapamycin adjuvant treatment may provide clinical benefits with minimal side effects to BRAFV600E-positive advanced thyroid cancer patients treated with vemurafenib.

MRI findings of causalgia of the lower extremity following transsphenoidal resection of pituitary tumor.

Background. Causalgia is continuing pain, allodynia, or hyperalgesia after nerve injury with edema, changes in skin blood flow, or abnormal sudomotor activity. Here we report a case of lower extremity causalgia following elective transsphenoidal resection of a pituitary tumor in a young man. Clinical Presentation. A 33-year-old man with acromegaly underwent elective sublabial transsphenoidal resection of his pituitary tumor. During the three-hour surgery, the lower limbs were kept in a supine, neutral position with a pillow under the knees. The right thigh was slightly internally rotated with a tape to expose fascia lata, which was harvested to repair the sella. Postoperatively, he developed causalgia in a distal sciatic and common peroneal nerve distribution. Pain was refractory to several interventions. Finally, phenoxybenzamine improved his pain significantly. Conclusions. Malpositioning in the operating room resulted in causalgia in this young man. Phenoxybenzamine improved, and ultimately resolved, his symptoms. Improvement in his pain symptoms correlated with resolution of imaging changes in the distal sciatic and peroneal nerves on the side of injury.

Estrogen activity as a preventive and therapeutic target in thyroid cancer.

Thyroid cancer is the most common endocrine-related cancer with increasing incidences during the last five years. Interestingly, according to the American Thyroid Association, the incidences of thyroid proliferative diseases occur four to five times more in women than in men with the risk of developing thyroid disorders being one in every eight females. Several epidemiological studies have suggested a possible correlation between incidences of thyroid malignancies and hormones but the precise contribution of estrogen in thyroid proliferative disease initiation, and progression is not well understood. This review is an attempt to define the phenotypic and genotypic modulatory effects of estrogen on thyroid proliferative diseases. The significance and relevance of expression of estrogen receptors, α and ß, in normal and malignant thyroid tissues and their effects on different molecular pathways involved in growth and function of the thyroid gland are discussed. These novel findings open up areas of developing alternative therapeutic treatments and preventive approaches which employ the use of antiestrogen to treat thyroid malignancies.

Inhibition of uPAR and uPA reduces invasion in papillary thyroid carcinoma cells.

OBJECTIVES/HYPOTHESIS: We analyzed the expression of urokinase plasminogen activator (uPA) and its receptor (uPAR) in papillary thyroid carcinoma (PTC) and normal thyroid tissue and examined in vitro how uPA and uPAR contribute to an invasive/metastatic phenotype, and the functional consequences of inhibiting this system. STUDY DESIGN: Retrospective chart review of PTC patients, followed by prospective study using previously obtained patient tissue and PTC cellular models. METHODS: uPA and uPAR RNA and protein levels were analyzed in PTC patient tissue samples, PTC and normal thyroid tissue culture cells, and conditioned media (CM) using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and/or Western blotting. The plasminogen-activating ability of CM was examined using dark-quenched casein fluorimetry and casein-plasminogen gel zymography. The invasive potentials of the PTC and normal thyroid epithelial cell lines were assessed using an in vitro cellular invasion/migration system. RESULTS: uPA and uPAR RNA and protein levels were increased in PTC patient samples and PTC cells relative to controls. uPA and uPAR RNA were also significantly higher in patients with metastatic disease. Casein-plasminogen zymography and Western blotting demonstrated increased active uPA secreted by PTC cells compared with normal thyroid cells. Fluorimetric assays revealed that the PTC cells' CM was able to activate plasminogen, resulting in measurable casein hydrolysis. This casein hydrolysis was prevented by the addition of several specific uPA inhibitors. Finally, the in vitro invasion phenotypes of PTC cells were augmented by the addition of plasminogen, and this augmentation was reversed by inhibitory anti-uPA and anti-uPAR antibodies. CONCLUSIONS: These data provide new functional evidence of the uPA/uPAR system's role in PTC invasion/metastasis and demonstrate the attractiveness of uPA and uPAR as molecular biomarkers and therapeutic targets.

Comparison of three common tonsillectomy techniques: a prospective randomized, double-blinded clinical study.

OBJECTIVE: To evaluate three current tonsillectomy techniques--intracapsular microdebridement, intracapsular coblation, and traditional extracapsular electrocautery dissection--comparing surgical parameters, efficacy, and morbidity in the treatment for obstructive sleep disordered breathing in children. STUDY DESIGN: Prospective, double-blinded study with follow-up by telephone interview. METHOD: From February 2004 to July 2006, a total of 156 patients between the ages of 6 months and 22 years scheduled for adenotonsillectomy were randomly assigned to electrocautery, coblator, and microdebrider groups. OUTCOME MEASURES: 1) Patient demographics; 2) Intraoperative time; 3) Surgeon's perception of difficulty; 4) Indicators of postoperative morbidity: pain, use of pain medication, return to diet, and activity level; 5) Complications; 6) Cost. RESULTS: Microdebrider technique produced the shortest total surgical time, averaging 16 minutes. Use of coblation resulted in 2 less days of pain medication compared to electrocautery. Patients in the coblator and microdebrider groups returned to a normal diet 1.51 days and 1.77 days earlier, respectively, than in the electrocautery group. They also returned to preoperative activity levels 1.85 days and 2.06 days earlier than in the electrocautery group. Of all three methods, the microdebrider was the most cost effective. The coblator and microdebrider did not differ significantly from each other in all other parameters. The three techniques showed no statistically significant difference in assessment of difficulty, average pain scores, or postoperative complications. CONCLUSIONS: Postoperative recovery following intracapsular adenotonsillectomy in children with obstructive sleep apnea is significantly earlier with use of either the coblator or microdebrider versus traditional extracapsular tonsillectomy with electrocautery. Microdebrider and coblator were comparable in all other areas except for shorter operative time and less cost for the microdebrider.

Neurosurgical implications of allergic fungal sinusitis.

OBJECT: Allergic fungal sinusitis (AFS) is a form of paranasal mycosis that often involves bone destruction and extension into the orbit and anterior skull base. Treatment consists of surgical extirpation and a course of corticosteroids. Despite frequent intracranial involvement, AFS is rarely reported in the neurosurgical literature. METHODS: The records of 21 patients with the histological diagnosis of AFS were reviewed. The histological diagnosis was based on findings of branching septated fungi interspersed with eosinophilic mucin and Charcot-Leyden crystals without fungal invasion of soft tissue. The average age of the 21 patients in this study was 25 years (range 9-46) and the male/female ratio was 3.75:1. All patients were immunocompetent. All had a history of chronic sinusitis and imaging findings of expansile disease involving multiple sinuses. Fifteen patients had nasal polyposis, eight had erosion of bone, which was observed on computerized tomography (CT) scans, eight had disease extending intracranially, and six had disease that involved the lamina papyracea. All patients underwent transnasal and/or transmaxillary endoscopic approaches for debridement and irrigation, six underwent orbital decompression, and three underwent a bifrontal craniotomy for removal of intracranial extradural disease. No patient had a cerebrospinal fluid leak. Postoperatively, one patient was treated with amphotericin B and the other 20 were treated with a short course of corticosteroids. The follow-up period ranged from 2 to 19 years. CONCLUSIONS: Allergic fungal sinusitis is a unique form of fungal disease that may mimic anterior skull base and paranasal sinus tumors. A cranial base team approach of neurosurgeons and otolaryngologists is recommended. Most cases can be successfully managed with transnasal and/or transmaxillary endoscopic techniques. A craniotomy is rarely indicated unless there is the suspicion of dural invasion or extensive intracranial and/or intraorbital involvement that is inaccessible from below.

Zones of approach for craniofacial resection: minimizing facial incisions for resection of anterior cranial base and paranasal sinus tumors.

OBJECTIVE: Anterior cranial base tumors are surgically resected with combined craniofacial approaches that frequently involve disfiguring facial incisions and facial osteotomies. The authors outline three operative zones of the anterior cranial base and paranasal sinuses in which tumors can be resected with three standard surgical approaches that minimize transfacial incisions and extensive facial osteotomies. METHODS: The zones were defined by performing dissections on 10 cadaveric heads and by evaluating radiographic images of patients with anterior cranial base tumors. The three approaches performed on each cadaver were transbasal, transmaxillary, and extended transsphenoidal. RESULTS: Three zones of approach were defined for accessing tumors of the anterior cranial base, nasal cavity, and paranasal sinuses. Zone 1 is exposed by the transbasal approach, which is limited anteriorly by the supraorbital rim, posteriorly by the optic chiasm and clivus, inferiorly by the palate, and laterally by the medial orbital walls. This approach allows access to the entire anterior cranial base, nasal cavity, and the majority of maxillary sinuses. The limitation imposed by the orbits results in a blind spot in the superolateral extent of the maxillary sinus. Zone 2 is exposed by a sublabial maxillotomy approach and accesses the entire maxillary sinus, including the superolateral blind spot and the ipsilateral anterior cavernous sinus. However, access to the anterior cranial base is limited. Zone 3 is exposed by the transsphenoidal approach. This approach accesses the midline structures but is limited by the lateral nasal walls and intracavernous carotid arteries. An extended transsphenoidal approach allows further exposure to the anterior cranial base, clivus, or cavernous sinuses. The use of the endoscope facilitates tumor resection in the nasal cavity and paranasal sinuses. CONCLUSION: The operative zones outlined offer minimally invasive craniofacial approaches to accessing lesions of the anterior cranial base and paranasal sinuses, obviating facial incisions and facial osteotomies. Case illustrations demonstrating the approach selection paradigm are presented.