Beyond task time: automated measurement augments fundamentals of laparoscopic skills methodology.

BACKGROUND: Laparoscopic psychomotor skills are challenging to learn and objectively evaluate. The Fundamentals of Laparoscopic Skills (FLS) program provides a popular, inexpensive, widely-studied, and reported method for evaluating basic laparoscopic skills. With an emphasis on training safety before efficiency, we present data that explore the metrics in the FLS curriculum. MATERIALS AND METHODS: A multi-institutional (n = 3) cross-sectional study enrolled subjects (n = 98) of all laparoscopic skill levels to perform FLS tasks in an instrumented box trainer. Recorded task videos were postevaluated by faculty reviewers (n = 2) blinded to subject identity using a modified Objective Structured Assessment of Technical Skills (OSATS) protocol. FLS scores were computed for each completed task and compared with demographically established skill levels (training level and number of procedures), video review scoring, and objective performance metrics including path length, economy of motion, and peak grasping force. RESULTS: Three criteria used to determine expert skill, training and experience level, blinded review of performance by faculty via OSATS, and FLS scores, disagree in establishing concurrent validity for determining "true experts" in FLS tasks. FLS-scoring exhibited near-perfect correlation with task time for all three tasks (Pearson r = 0.99, 1.00, 1.00 with P <0.00000001). FLS error penalties had negligible effect on FLS scores. Peak grasping force did not correlate with task time or FLS scores. CONCLUSIONS: FLS technical skills scores presented negligible benefit beyond the measurement of task time. FLS scoring is weighted more toward speed than precision and may not significantly address poor tissue handling skills, especially regarding excessive grasping force. Categories of experience or training level may not form a suitable basis for establishing proficiency thresholds or for construct validity studies for technical skills.

mir-17-92, a cluster of miRNAs in the midst of the cancer network.

MicroRNAs (miRNAs) are an abundant class of small non-coding RNAs (ncRNAs) that function to regulate gene expression at the post-transcriptional level. Although their functions were originally described during normal development, miRNAs have emerged as integral components of the oncogenic and tumor suppressor network, regulating nearly all cellular processes altered during tumor formation. In particular, mir-17-92, a miRNA polycistron also known as oncomir-1, is among the most potent oncogenic miRNAs. Genomic amplification and elevated expression of mir-17-92 were both found in several human B-cell lymphomas, and its enforced expression exhibits strong tumorigenic activity in multiple mouse tumor models. mir-17-92 carries out pleiotropic functions during both normal development and malignant transformation, as it acts to promote proliferation, inhibit differentiation, increase angiogenesis, and sustain cell survival. Unlike most protein coding genes, mir-17-92 is a polycistronic miRNA cluster that contains multiple miRNA components, each of which has a potential to regulate hundreds of target mRNAs. This unique gene structure of mir-17-92 may underlie the molecular basis for its pleiotropic functions in a cell type- and context-dependent manner. Here we review the recent literature on the functional studies of mir-17-92 and highlight its potential impacts on the oncogene network. These findings on mir-17-92 indicate that miRNAs are integrated components of the molecular pathways that regulate tumor development and tumor maintenance.

miR-19 is a key oncogenic component of mir-17-92.

Recent studies have revealed the importance of multiple microRNAs (miRNAs) in promoting tumorigenesis, among which mir-17-92/Oncomir-1 exhibits potent oncogenic activity. Genomic amplification and elevated expression of mir-17-92 occur in several human B-cell lymphomas, and enforced mir-17-92 expression in mice cooperates with c-myc to promote the formation of B-cell lymphomas. Unlike classic protein-coding oncogenes, mir-17-92 has an unconventional gene structure, where one primary transcript yields six individual miRNAs. Here, we functionally dissected the individual components of mir-17-92 by assaying their tumorigenic potential in vivo. Using the Emu-myc model of mouse B-cell lymphoma, we identified miR-19 as the key oncogenic component of mir-17-92, both necessary and sufficient for promoting c-myc-induced lymphomagenesis by repressing apoptosis. The oncogenic activity of miR-19 is at least in part due to its repression of the tumor suppressor Pten. Consistently, miR-19 activates the Akt-mTOR (mammalian target of rapamycin) pathway, thereby functionally antagonizing Pten to promote cell survival. Our findings reveal the essential role of miR-19 in mediating the oncogenic activity of mir-17-92, and implicate the functional diversity of mir-17-92 components as the molecular basis for its pleiotropic effects during tumorigenesis.