Current trends in surgical society membership: What does the future hold?

BACKGROUND: Motivations for joining and maintaining surgical society memberships include networking, educational, and social opportunities. We hypothesized surgeons have membership lapses despite these benefits. We aimed to assess society members motivations for joining, satisfaction with membership, any lapses and if so, reasons for these lapses. METHODS: A survey was sent via email to members of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), American Society for Metabolic and Bariatric Surgery (ASMBS), and the Society for Surgery of the Alimentary Tract (SSAT), using society directories. RESULTS: The majority (60%) of respondents felt satisfied with membership. However, 68% reported a lapse in membership. The most common reason for lapse was cost, followed closely by time constraints. CONCLUSION: Despite a high rate of member satisfaction, a majority of respondents had allowed a membership to lapse, with cost and time constraints being the most common reasons. Surgical societies should take these trends into account as they expand and recruit new membership.

Phase 2 Study of Pomalidomide (CC-4047) Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors.

INTRODUCTION: Treatment of recurrent primary pediatric brain tumors remains a major challenge, with most children succumbing to their disease. We conducted a prospective phase 2 study investigating the safety and efficacy of pomalidomide (POM) in children and young adults with recurrent and progressive primary brain tumors. METHODS: Patients with recurrent and progressive high-grade glioma (HGG), diffuse intrinsic pontine glioma (DIPG), ependymoma, or medulloblastoma received POM 2.6 mg/m2/day (the recommended phase 2 dose [RP2D]) on days 1-21 of a 28-day cycle. A Simon's Optimal 2-stage design was used to determine efficacy. Primary endpoints included objective response (OR) and long-term stable disease (LTSD) rates. Secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: 46 patients were evaluable for response (HGG, n = 19; DIPG, ependymoma, and medulloblastoma, n = 9 each). Two patients with HGG achieved OR or LTSD (10.5% [95% CI, 1.3%-33.1%]; 1 partial response and 1 LTSD) and 1 patient with ependymoma had LTSD (11.1% [95% CI, 0.3%-48.2%]). There were no ORs or LTSD in the DIPG or medulloblastoma cohorts. The median PFS for patients with HGG, DIPG, ependymoma, and medulloblastoma was 7.86, 11.29, 8.43, and 8.43 weeks, respectively. Median OS was 5.06, 3.78, 12.02, and 11.60 months, respectively. Neutropenia was the most common grade 3/4 adverse event. CONCLUSIONS: Treatment with POM monotherapy did not meet the primary measure of success in any cohort. Future studies are needed to evaluate if POM would show efficacy in tumors with specific molecular signatures or in combination with other anticancer agents. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03257631; EudraCT, identifier 2016-002903-25.

RKIP Inhibits Local Breast Cancer Invasion by Antagonizing the Transcriptional Activation of MMP13.

Raf Kinase Inhibitory Protein or RKIP was initially identified as a Raf-1 binding protein using the yeast 2-hybrid screen. RKIP inhibits the activation phosphorylation of MEK by Raf-1 by competitively inhibiting the binding of MEK to Raf-1 and thus exerting an inhibitory effect on the Raf-MEK-Erk pathway. RKIP has been identified as a metastasis suppressor gene. Expression of RKIP is low in cancer metastases. Although primary tumor growth remains unaffected, re- expression of RKIP inhibits cancer metastasis. Mechanistically, RKIP constrains metastasis by inhibiting angiogenesis, local invasion, intravasation, and colonization. The molecular mechanism of how RKIP inhibits these individual steps remains undefined. In our present study, using an unbiased PCR based screening and by analyzing DNA microarray expression datasets we observe that the expression of multiple metalloproteases (MMPs) including MMP1, MMP3, MMP10 and MMP13 are negatively correlated with RKIP expression in breast cancer cell lines and clinical samples. Since expression of MMPs by cancer cells is important for cancer metastasis, we hypothesize that RKIP may mediate suppression of breast cancer metastasis by inhibiting multiple MMPs. We show that the expression signature of RKIP and MMPs is better at predicting high metastatic risk than the individual gene. Using a combination of loss- and gain-of-function approaches, we find that MMP13 is the cause of RKIP-mediated inhibition of local cancer invasion. Interestingly expression of MMP13 alone is not sufficient to reverse the inhibition of breast cancer cell metastasis to the lung due to the expression of RKIP. We find that RKIP negatively regulates MMP13 through the Erk2 signaling pathway and the repression of MMP13 by RKIP is transcription factor AP-1 independent. Together, our findings indicate that RKIP inhibits cancer cell invasion, in part, via MMP13 inhibition. These data also implicate RKIP in the regulation of MMP transcription, suggesting a potential mechanism by which RKIP inhibits tumor progression and metastasis.

Nano-sized ultrasound contrast agent: salting-out method.

Tumor imaging by ultrasound is greatly enhanced by the use of ultrasound contrast agents (UCAs), stabilized, gas-filled bodies. They are generally less than 7 microm to pass freely through the capillary bed. Development of a nano-sized agent would enable them to extravasate through the leaky pores of angiogenic vessels. We describe the development of an echogenic, nano-sized polylactic acid UCA by adaptation of a salting-out method. The viscosity of the initial colloidal suspension (concentration and molecular weight of protective colloid [polyvinyl alcohol (PVA)] and concentration of polymer) was key in determining particle size and polydispersity (increasing viscosity increased both). Addition of the porogens ammonium carbonate and camphor, required to produce hollow echogenic capsules, also increased the size (eg, 5 wt% PVA, mean solid nanocapsule size 386 +/- 25 nm, polydispersity index 0.367 +/- 0.14, and mean UCA size 640 +/- 18 nm, polydispersity index 0.308 +/- 0.027). Viscosity had the opposite effect on echogenicity of the resultant nano-UCA, which ranged from 21.69 +/- 0.78 dB for 2% PVA to 12.1 +/- 0.8 dB for 10% PVA. The UCA prepared with 10% PVA, however, had a longer half-life in the ultrasound beam (t(1/2) > 15 minutes vs t(1/2) < 10 minutes), suggesting a thicker shell. Optimization will require compromise among size, echogenicity, and stability.