Ranking NIH Funding of Surgical Departments Based Upon a Modified Index.

BACKGROUND: The Blue Ridge Institute for Medical Research (BRIMR) reports a ranking of surgical department NIH funding each fiscal year based on more than 41,000 individual investigators. This report is used to measure the research productivity of the faculty or department. However, this method includes institutional grants awarded to Cancer Centers or Centers for Research, which do not reflect individual or departmental research. To measure the research productivity of a surgical department more directly, we created a modified BRIMR index excluding grants to cancer or research centers. We evaluated how our modified index of surgical departments compared to the rankings by BRIMR. METHODS: Publicly available BRIMR data was filtered for all grants awarded to principal investigators in a surgical department within a medical school. All funding for Cancer Centers or Centers for Research was excluded. The remaining grants were totaled, producing a new ranking of surgical departments. RESULTS: After excluding $42,761,752 in grants to Cancer Centers and Centers for Research, there was individual movement of 33 surgical departments on the ranking list. However, only four departments moved either up or down one quartile. No surgical department moved 2 or more quartiles. CONCLUSIONS: NIH funding for Cancer Centers and Centers for Research comprised 10% of all NIH funding for medical school-associated surgical departments. Exclusion of this funding resulted in no significant change within surgical department quartile rankings. This suggests the BRIMR measure of research productivity does not need modification.

Cdk5 drives formation of heterogeneous pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous population of neoplasms that arise from hormone-secreting islet cells of the pancreas and have increased markedly in incidence over the past four decades. Non-functional PanNETs, which occur more frequently than hormone-secreting tumors, are often not diagnosed until later stages of tumor development and have poorer prognoses. Development of successful therapeutics for PanNETs has been slow, partially due to a lack of diverse animal models for pre-clinical testing. Here, we report development of an inducible, conditional mouse model of PanNETs by using a bi-transgenic system for regulated expression of the aberrant activator of Cdk5, p25, specifically in ß-islet cells. This model produces a heterogeneous population of PanNETs that includes a subgroup of well-differentiated, non-functional tumors. Production of these tumors demonstrates the causative potential of aberrantly active Cdk5 for generation of PanNETs. Further, we show that human PanNETs express Cdk5 pathway components, are dependent on Cdk5 for growth, and share genetic and transcriptional overlap with the INS-p25OE model. The utility of this model is enhanced by the ability to form tumor-derived allografts. This new model of PanNETs will facilitate molecular delineation of Cdk5-dependent PanNETs and the development of new targeted therapeutics.

Accurate Therapeutic Response Assessment of Pancreatic Ductal Adenocarcinoma Using Quantitative Dynamic Contrast-Enhanced Magnetic Resonance Imaging With a Point-of-Care Perfusion Phantom: A Pilot Study.

OBJECTIVES: The aim of this study was to test the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with concurrent perfusion phantom for monitoring therapeutic response in patients with pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: A prospective pilot study was conducted with 8 patients (7 men and 1 woman) aged 46 to 78 years (mean age, 66 years). Participants had either locally advanced (n = 7) or metastatic (n = 1) PDAC, and had 2 DCE-MRI examinations: one before and one 8 ± 1 weeks after starting first-line chemotherapy. A small triplicate perfusion phantom was imaged with each patient, serving as an internal reference for accurate quantitative image analysis. Tumor perfusion was measured with K using extended Tofts model before and after phantom-based data correction. Results are presented as mean ± SD and 95% confidence intervals (CIs). Statistical difference was evaluated with 1-way analysis of variance. RESULTS: Tumor-size change of responding group (n = 4) was -12% ± 4% at 8 weeks of therapy, while that of nonresponding group (n = 4) was 18% ± 15% (P = 0.0100). Before phantom-based data correction, the K change of responding tumors was 69% ± 23% (95% CI, 32% to 106%) at 8 weeks, whereas that of nonresponding tumors was -1% ± 41% (95% CI, -65% to 64%) (P = 0.0247). After correction, the data variation in each group was significantly reduced; the K change of responding tumors was 73% ± 6% (95% CI, 64% to 82%) compared with nonresponding tumors of -0% ± 5% (95% CI, -7% to 8%) (P < 0.0001). CONCLUSIONS: Quantitative DCE-MRI measured the significant perfusion increase of PDAC tumors responding favorably to chemotherapy, with decreased variability after correction using a perfusion phantom.