Person:

Talbot, Simon

Objective: Upper extremity (UE) transplantation is the most commonly performed composite tissue allotransplantation worldwide. However, there is a lack of imaging standards for pre- and posttransplant evaluation. This study highlights the protocols and findings of UE allotransplantation toward standardization and implementation for clinical trials. Methods: Multimodality imaging protocols for a unilateral hand transplant candidate and a bilateral mid-forearm level UE transplant recipient include radiography, computed tomography (CT), magnetic resonance (MR) imaging, catheter angiography, and vascular ultrasonography. Pre- and posttransplant findings, including dynamic CT and MR performed for assessment of motor activity of transplanted hands, are assessed, and image quality of vessels and bones on CT and MR evaluated. Results: Preoperative imaging demonstrates extensive skeletal deformity and variation in vascular anatomy and vessel patency. Posttransplant images confirm bony union in anatomical alignment and patency of vascular anastomoses. Mild differences in rate of vascular enhancement and extent of vascular networks are noted between the 2 transplanted limbs. Dynamic CT and MR demonstrate a 15° to 30° range of motion at metacarpophalangeal joints and 90° to 110° at proximal interphalangeal joints of both transplanted hands at 8 months posttransplant. Image quality was slightly better for CT than for MR in the first subject, while MR was slightly better in the second subject. Conclusion: Advanced vascular and musculoskeletal imaging play an important role in surgical planning and can provide novel posttransplantation data to monitor the success of the procedure. Implementation of more standardized protocols should enable a more comprehensive assessment to evaluate the efficacy in clinical trials.

Purpose To identify genes related to angiogenesis/metastasis that predict locoregional failure in patients with laryngopharyngeal cancer (LPC) undergoing chemoradiotherapy (CRT) treatment. Methods Tumor tissue was collected and snap-frozen from 35 sequential patients with histologically confirmed LPC being treated with CRT. Gene expression analysis was performed using a novel cDNA array consisting of 277 genes functionally associated with angiogenesis (n 152) and/or metastasis (n 125). Locoregional response was correlated to the gene expression profiles to identify genes associated with outcome. These genes were internally validated by real-time reverse transcriptase polymerase chain reaction (RT-PCR) and validated externally by immunohis- tochemistry analysis on an independent set of patients. Results Locoregional failure occurred in nine of 35 patients. Seventeen genes from the cDNA microarray correlated with locoregional failure (two-sample t test, P .05). Seven genes were chosen for additional analysis based on the availability of antibodies for immunohistochemistry. Of these seven genes, real-time RT-PCR validated four genes: MDM2, VCAM-1, erbB2, and H-ras (Wilcoxon rank sum test, P .008, .02, .04, and .04, respectively). External validation by immunohistochem- istry confirmed MDM2 and erbB2 as being predictive of locoregional response. Controlling for stage of disease, positivity for MDM2 or erbB2 was an independent negative predictor of locoregional disease-free survival. Conclusion Genomic screening by cDNA microarray and validation internally by real-time RT-PCR and externally by immunohistochemistry have identified two genes (MDM2 and erbB2) as predictors of locoregional failure in LPC patients treated with CRT. The role of these genes in treatment selection and the functional basis for their activity in CRT response merit additional consideration.

Summary: Liquid silicone is inexpensive, minimally antigenic, and likely noncarcinogenic. Its simplicity of use has made it popular as a soft-tissue filler in some parts of the world for patients seeking rapid soft-tissue augmentation of the face, breast, and buttocks. However, multiple reports describe the complications of silicone injections such as cellulitis, abscess, ulceration, and foreign body migration. We present an unusual complication of granulomatous reaction secondary to silicone injection for buttock augmentation, with a literature review of this entity and treatment options. Our patient was a 54-year-old woman who underwent bilateral buttock augmentation in the Dominican Republic using percutaneous injection of liquid silicone. She presented to our facility 1 year after this procedure with pain and inflammation of both buttocks. She was diagnosed with multiple silicone granulomas. Her symptoms completely resolved with a 3-week course of minocycline. Granulomatous reactions to silicone may occur months to years after the silicone injection. The incidence of such complications may be increased when nonmedical-grade silicone is used, and hence, when these procedures are performed in developing countries. Tetracycline antibiotics, especially minocycline, may be used to achieve sustained remission.

Background: The present study is aimed at identifying potential candidate genes as prognostic markers in human oral tongue squamous cell carcinoma (SCC) by large scale gene expression profiling. Methods: The gene expression profile of patients (n=37) with oral tongue SCC were analyzed using Affymetrix HG_U95Av2 high-density oligonucleotide arrays. Patients (n=20) from which there were available tumor and matched normal mucosa were grouped into stage (early vs. late) and nodal disease (node positive vs. node negative) subgroups and genes differentially expressed in tumor vs. normal and between the subgroups were identified. Three genes, GLUT3, HSAL2, and PACE4, were selected for their potential biological significance in a larger cohort of 49 patients via quantitative real-time RT-PCR. Results: Hierarchical clustering analyses failed to show significant segregation of patients. In patients (n=20) with available tumor and matched normal mucosa, 77 genes were found to be differentially expressed (P< 0.05) in the tongue tumor samples compared to their matched normal controls. Among the 45 over-expressed genes, MMP-1 encoding interstitial collagenase showed the highest level of increase (average: 34.18 folds). Using the criterion of two-fold or greater as overexpression, 30.6%, 24.5% and 26.5% of patients showed high levels of GLUT3, HSAL2 and PACE4, respectively. Univariate analyses demonstrated that GLUT3 over-expression correlated with depth of invasion (P<0.0001), tumor size (P=0.024), pathological stage (P=0.009) and recurrence (P=0.038). HSAL2 was positively associated with depth of invasion (P=0.015) and advanced T stage (P=0.047). In survival studies, only GLUT3 showed a prognostic value with disease-free (P=0.049), relapse-free (P=0.002) and overall survival (P=0.003). PACE4 mRNA expression failed to show correlation with any of the relevant parameters. Conclusion: The characterization of genes identified to be significant predictors of prognosis by oligonucleotide microarray and further validation by real-time RT-PCR offers a powerful strategy for identification of novel targets for prognostication and treatment of oral tongue carcinoma.