Validated specialty-specific models for multi-disciplinary microsurgery training laboratories: a systematic review.

BACKGROUND: Laboratory simulation is increasingly important for teaching microsurgical skills. Training microsurgeons of different specialties within the same simulation laboratory increases efficiency of resource use. For maximal benefit, simulations should be available for trainees to practice specialty-specific, higher-order skills. Selection of appropriate simulations requires knowledge of the efficacy and validity of the numerous described laboratory models. Here we present a systematic review of validated training models that may serve as useful adjuncts to achieving competency in specialty elements of microsurgery, and appraise the evidence behind them. METHODS: In setting up a multi-disciplinary microsurgery training course, we performed a systematic review according to preferred reporting items for systematic reviews and meta-analyses guidelines. EMBASE, MEDLINE, Cochrane and PubMed databases were searched for studies describing validated, microscope-based, specialty-specific simulations, and awarded a level of evidence and level of recommendation based on a modified Oxford Centre for Evidence-Based Medicine classification. RESULTS: A total of 141 papers describing specialty-specific microsimulation models were identified, 49 of which included evidence of validation. Eleven were in the field of neurosurgery, 21 in otolaryngology/head and neck surgery, two in urology/gynaecology and 15 plastic and reconstructive surgery. These papers described synthetic models in 19 cases, cadaveric animals in 10 cases, live animals in 12 cases and human cadaveric material in 10 cases. CONCLUSION: Numerous specialty-specific models for use in the microscope laboratory are available, but the quality of evidence for them is poor. Provision of models that span numerous specialties may encourage use of a microscope lab whilst still enabling more specific skills training over a 'one-size-fits-all' approach.

Australian general practitioners' attitudes and knowledge of sentinel lymph node biopsy in melanoma management.

BACKGROUND AND OBJECTIVES: In Australia, the uptake of the sentinel lymph node biopsy (SLNB) appears low despite clinical practice guideline recommendations. The aim of this study was to describe the knowledge and attitudes of general practitioners (GPs) to SLNB. METHOD: GPs were recruited at an annual conference and a skin cancer skills workshop, and using GP professional communications. A mixed methods approach comprised a cross-sectional questionnaire and, for a subset of participants, semi-structured interviews. RESULTS: Overall, 231 GPs completed the questionnaire, of whom 23 were interviewed. One-third (32%) described themselves as quite or very familiar with the guidelines, and two-thirds (68%) thought that SLNB had an important role in the management of patients with melanoma. Of GPs who would discuss SLNB with eligible patients, <40% correctly identified that SLNB is recommended for patients with an invasive melanoma >1 mm thick. DISCUSSION: GPs were generally supportive of SLNB. Familiarity with the guidelines was low, particularly regarding which patients should be considered for SLNB.

Quantification of Head Shape and Cranioplasty Outcomes: Six-compartment Volume Method Applied to Sagittal Synostosis.

BACKGROUND: Premature fusion of the sagittal (midline) suture between 2 parietal bones is the most common form of craniosynostosis. Surgical correction is mandated to improve head shape and to decrease the risk of raised intracranial pressure. This study evaluated the utility of 3-dimensional (3D) imaging to quantify the volumetric changes of surgical correction. Currently there is no standardized method used to quantify the outcomes of surgery for craniosynostosis, with the cranial index (width: length ratio) being commonly used. METHODS: A method for quantification of head shape using 3D imaging is described in which the cranium is divided up into 6 compartments and the volumes of 6 compartments are quantified and analyzed. The method is size invariant, meaning that it can be used to assess the long-term postoperative outcomes of patients through growth. The method is applied to a cohort of sagittal synostosis patients and a normal cohort, and is used to follow up a smaller group of synostotic patients 1, 2, and 3 years postoperatively. RESULTS: Statistical analysis of the results shows that the 6-compartment volume quantification method is more accurate in separating normal from synostotic patient head shapes than the cranial index. CONCLUSIONS: Spring-mediated cranioplasty does not return head shape back to normal, but results in significant improvements in the first year following surgery compared with the preoperative sagittal synostosis head shape. 3D imaging can be a valuable tool in assessing the volumetric changes due to surgery and growth in craniosynstosis patients.

Association between VEGF splice isoforms and progression-free survival in metastatic colorectal cancer patients treated with bevacizumab.

PURPOSE: Bevacizumab improves survival for patients with metastatic colorectal cancer with chemotherapy, but no proven predictive markers exist. The VEGF-A splice form, VEGF(165)b, anti-angiogenic in animal models, binds bevacizumab. We tested the hypothesis that prolonged progression-free survival (PFS) would occur only in patients with low relative VEGF(165)b levels treated with bevacizumab. EXPERIMENTAL DESIGN: Blinded tumor samples from the phase III trial of FOLFOX4 ± bevacizumab were assessed for VEGF(165)b and VEGF(total) by immunohistochemistry and scored relative to normal tissue. A predictive index (PI) was derived from the ratio of VEGF(165)b:VEGF(total) for 44 samples from patients treated with FOLFOX + bevacizumab (arm A) and 53 samples from patients treated with FOLFOX4 (arm B), and PFS, and overall survival (OS) analyzed on the basis of PI relative to median ratio. RESULTS: Unadjusted analysis of PFS showed significantly better outcome for individuals with VEGF(165)b:VEGF(total) ratio scores below median treated with FOLFOX4 + bevacizumab compared with FOLFOX4 alone (median, 8.0 vs. 5.2 months; P < 0.02), but no effect of bevacizumab on PFS in patients with VEGF(165)b:VEGF(total) ratio >median (5.9 vs. 6.3 months). These findings held after adjustment for other clinical and demographic features. OS was increased in arm A (median, 13.6 months) compared with arm B (10.6 months) in the low VEGF(165)b group, but this did not reach statistical significance. There was no difference in the high VEGF(165)b:VEGF(total) group between FOLFOX + bevacizumab (10.8 months) and FOLFOX alone (11.3 months). CONCLUSION: Low VEGF(165)b:VEGF(total) ratio may be a predictive marker for bevacizumab in metastatic colorectal cancer, and individuals with high relative levels may not benefit.

Recombinant human VEGF165b inhibits experimental choroidal neovascularization.

PURPOSE: Vascular endothelial growth factor (VEGF-A) is the principal stimulator of angiogenesis in wet age-related macular degeneration (AMD). However, VEGF-A is generated by alternate splicing into two families, the proangiogenic VEGF-A(xxx) family and the antiangiogenic VEGF-A(xxx)b family. It is the proangiogenic family that is responsible for the blood vessel growth seen in AMD. METHODS: To determine the role of antiangiogenic isoforms of VEGF-A as inhibitors of choroidal neovascularization, the authors used a model of laser-induced choroidal neovascularization in the mouse eye and investigated VEGF-A(165)b effects on endothelial cells and VEGFRs in vitro. RESULTS: VEGF-A(165)b inhibited VEGF-A(165)-mediated endothelial cell migration with a dose effect similar to that of ranibizumab and bevacizumab and 200-fold more potent than that of pegaptanib. VEGF-A(165)b bound both VEGFR1 and VEGFR2 with affinity similar to that of VEGF-A(165). After laser injury, mice were injected either intraocularly or subcutaneously with recombinant human VEGF-A(165)b. Intraocular injection of rhVEGF-A(165)b gave a pronounced dose-dependent inhibition of fluorescein leakage, with an IC(50) of 16 pg/eye, neovascularization (IC(50), 0.8 pg/eye), and lesion as assessed by histologic staining (IC(50), 8 pg/eye). Subcutaneous administration of 100 microg twice a week also inhibited fluorescein leakage and neovascularization and reduced lesion size. CONCLUSIONS: These results show that VEGF-A(165)b is a potent antiangiogenic agent in a mouse model of age-related macular degeneration and suggest that increasing the ratio of antiangiogenic-to-proangiogenic isoforms may be therapeutically effective in this condition.