Popliteal Artery Entrapment Syndrome.

Popliteal artery entrapment syndrome (PAES) may be implicated as a cause of lower leg pain in active individuals. Though a relatively rare syndrome, it is likely underdiagnosed. History often includes exertional lower leg pain, cramping, and/or paresthesias rather quickly relieved by rest, though examination may be benign. When suspected, imaging is recommended to assess anatomic variations versus functional entrapment of the artery in the calf. Because there are a number of diagnostic modalities available, it seems prudent to begin with noninvasive testing, such as ultrasound with Doppler and provocative maneuvers. Thereafter, advanced imaging (magnetic resonance imaging/magnetic resonance angiography) or arteriography may help identify a specific anatomic obstruction. Once confirmed, surgical exploration has historically been the treatment of choice, though less invasive interventions have been proposed. Though most patients reportedly return to high-level training, decision-making remains highly individualized. Further study of younger, active individuals with PAES will help to further define these criteria.

Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling.

Kinase inhibitors constitute an important new class of cancer drugs, whose selective efficacy is largely determined by underlying tumor cell genetics. We established a high-throughput platform to profile 500 cell lines derived from diverse epithelial cancers for sensitivity to 14 kinase inhibitors. Most inhibitors were ineffective against unselected cell lines but exhibited dramatic cell killing of small nonoverlapping subsets. Cells with exquisite sensitivity to EGFR, HER2, MET, or BRAF kinase inhibitors were marked by activating mutations or amplification of the drug target. Although most cell lines recapitulated known tumor-associated genotypes, the screen revealed low-frequency drug-sensitizing genotypes in tumor types not previously associated with drug susceptibility. Furthermore, comparing drugs thought to target the same kinase revealed striking differences, predictive of clinical efficacy. Genetically defined cancer subsets, irrespective of tissue type, predict response to kinase inhibitors, and provide an important preclinical model to guide early clinical applications of novel targeted inhibitors.