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

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

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

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

The FACE TO FACE international humanitarian missions program was created by the nonprofit Education and Research Foundation for the American Academy of Facial Plastic and Reconstructive Surgery (AAFPRS) in 1992. To date, it is estimated that AAFPRS volunteer surgeons have operated on thousands of patients worldwide, and educational activities have helped countless other patients. However, there has been no standard, easily accessible system in place to track these data. Effective documentation and retrieval of patient data and outcomes for surgeries performed abroad are critical to the long-term success of humanitarian mission sites.1-4 To address these challenges, the web-based FACE TO FACE database was developed to promote more efficient storage and retrieval of patient data. This database is unique in that it is available to any AAFPRS surgeon on a FACE TO FACE–sanctioned mission trip and thus allows for longitudinal tracking of patient care