Electronic learning can facilitate student performance in undergraduate surgical education: a prospective observational study

BACKGROUND: Our institution recently introduced a novel internet accessible computer aided learning (iCAL) programme to complement existing surgical undergraduate teaching methods. On graduation of the first full cycle of undergraduate students to whom this resource was available we assessed the utility of this new teaching facility. METHOD: The computer programme prospectively records usage of the system on an individual user basis. We evaluated the utilisation of the web-based programme and its impact on class ranking changes from an entry-test evaluation to an exit examination in surgery. RESULTS: 74.4% of students were able to access iCAL from off-campus internet access. The majority of iCAL usage (64.6%) took place during working hours (08:00–18:00) with little usage on the weekend (21.1%). Working hours usage was positively associated with improvement in class rank (P = 0.025, n = 148) but out-of hours usage was not (P = 0.306). Usage during weekdays was associated with improved rank (P = 0.04), whereas weekend usage was not (P = 0.504). There were no significant differences in usage between genders (P = 0.3). Usage of the iCAL system was positively correlated with improvement in class rank from the entry to the exit examination (P = 0.046). Students with lower ranks on entry examination, were found to use the computer system more frequently (P = 0.01). CONCLUSION: Electronic learning complements traditional teaching methods in undergraduate surgical teaching. Its is more frequently used by students achieving lower class ranking with traditional teaching methods, and this usage is associated with improvements in class ranking

CA 15-3 is predictive of response and disease recurrence following treatment in locally advanced breast cancer

BACKGROUND: Primary chemotherapy (PC) is used for down-staging locally advanced breast cancer (LABC). CA 15-3 measures the protein product of the MUC1 gene and is the most widely used serum marker in breast cancer. METHODS: We retrospectively investigated the role of CA 15-3 in conjunction with other clinico-pathological variables as a predictor of response and time to disease recurrence following treatment in LABC. Pre and post primary chemotherapy serum concentrations of CA 15-3 together with other variables were reviewed and related to four outcomes following primary chemotherapy (clinical response, pathological response, time to recurrence and time to progression). Persistently elevated CA 15-3 after PC was considered as consecutively high levels above the cut off point during and after PC. RESULTS: 73 patients were included in this study. Patients received PC (AC or AC-T regimen) for locally advanced breast cancer. 54 patients underwent surgery. The median follow up was 790 days. Patients with high concentrations of CA 15-3 before PC treatment had a poor clinical (p = 0.013) and pathological (p = 0.044) response. Together with Her-2/neu expression (p = 0.009) and tumour lympho-vascular space invasion (LVI) (p = 0.001), a persistently elevated CA 15-3 post PC (p = 0.007) was an independent predictive factor of recurrence following treatment in LABC. CONCLUSION: Elevated CA 15-3 level is predictive of a poor response to chemotherapy. In addition, persistently elevated CA 15-3 levels post chemotherapy in conjunction with lympho-vascular invasion and HER2 status predict a reduced disease free survival following treatment in locally advanced breast cancer

ADAM8 expression in invasive breast cancer promotes tumor dissemination and metastasis

International audienceThe transmembrane metalloprotease-disintegrin ADAM8 mediates cell adhesion and shedding of ligands, receptors and extracellular matrix components. Here, we report that ADAM8 is abundantly expressed in breast tumors and derived metastases compared to normal tissue, especially in triple-negative breast cancers (TNBCs). Furthermore, high ADAM8 levels predicted poor patient outcome. Consistently, ADAM8 promoted an aggressive phenotype of TNBC cells in culture. In a mouse orthotopic model, tumors derived from TNBC cells with ADAM8 knockdown failed to grow beyond a palpable size and displayed poor vascularization. Circulating tumor cells and brain metastases were also significantly reduced. Mechanisti-cally, ADAM8 stimulated both angiogenesis through release of VEGF-A and transendothelial cell migration via β1-integrin activation. In vivo, treatment with an anti-ADAM8 antibody from the time of cell inoculation reduced primary tumor burden and metastases. Furthermore, antibody treatment of established tumors profoundly decreased metastases in a resection model. As a non-essential protein under physiological conditions, ADAM8 represents a promising novel target for treatment of TNBCs, which currently lack targeted therapies and frequently progress with fatal dissemination

Sentinel lymph node biopsy in elderly irish patients with malignant melanoma.

In patients with malignant melanoma, Breslow depth increases with age. However, studies suggest that the frequency of sentinel lymph node metastases in malignant melanoma decreases with age. We investigated whether this applied to the cohort of patients undergoing sentinel lymph node biopsy (SLNB) in our institution. In a prospectively accrued database we identified 149 patients undergoing SLNB from 1997 to 2005. Tumour thickness as measured by Breslow depth was assessed in stratified age groups. We assessed the relationship between SLNB positivity and age using the Chi-square for trend. We directly examined the relationship between SLNB positivity in patients aged less than 65 and aged 65 years of age and over. Disease-free and overall survival in patients aged less than 65 and aged 65 years of age and over were also assessed. Comparing the age groups, there was no significant difference identified in Breslow depth (years, median Breslow > or = 1.2 mm (range 0.2-9.7); > or =65 years, median Breslow > or = 1.4 mm (range 0.12-8.5); p > or = 0.06, Mann-Whitney U). Chi-square for trend identified no significant relationship between SLNB positivity and age. We found n=120 patientsSLNB, of which 26 (21.7%) were positive. In patients =65, n=29 had SLNB of which 3 (10.3%) were positive. These differences were not statistically significant (Fisher's exact test, p > or = 0.2). There was no difference in disease-free or overall survival between patients agedor =65 who had SLNB (median follow-up 37.5 months (range 5-70); disease-free survival, p > 0.08; overall survival, p > or = 0.3, Logrank test). We did not find that elderly patients with malignant melanoma had a demonstrable difference in tumour thickness when compared to younger patients. In those patients who underwent SLNB there was no significant difference in node positivity between the age groups. Disease-free and overall survival were not significantly different between the age groups. Further study and longer follow-up will help establish the relationship between age and SLNB positivity.</p

High-throughput oncogene mutation profiling shows demographic differences in BRAF mutation rates among melanoma patients

Because of advances in targeted therapies, the clinical evaluation of cutaneous melanoma is increasingly based on a combination of traditional histopathology and molecular pathology. Therefore, it is necessary to expand our knowledge of the molecular events that accompany the development and progression of melanoma to optimize clinical management. The central objective of this study was to increase our knowledge of the mutational events that complement melanoma progression. High-throughput genotyping was adapted to query 159 known single nucleotide mutations in 33 cancer-related genes across two melanoma cohorts from Ireland (n = 94) and Belgium (n = 60). Results were correlated with various clinicopathological characteristics. A total of 23 mutations in 12 genes were identified, that is - BRAF, NRAS, MET, PHLPP2, PIK3R1, IDH1, KIT, STK11, CTNNB1, JAK2, ALK, and GNAS. Unexpectedly, we discovered significant differences in BRAF, MET, and PIK3R1 mutations between the cohorts. That is, cases from Ireland showed significantly lower (P &lt;0.001) BRAF(V600E) mutation rates (19%) compared with the mutation frequency observed in Belgian patients (43%). Moreover, MET mutations were detected in 12% of Irish cases, whereas none of the Belgian patients harbored these mutations, and Irish patients significantly more often (P = 0.027) had PIK3R1-mutant (33%) melanoma versus 17% of Belgian cases. The low incidence of BRAF(V600E)-mutant melanoma among Irish patients was confirmed in five independent Irish cohorts, and in total, only 165 of 689 (24%) Irish cases carried mutant BRAF(V600E). Together, our data show that melanoma-driving mutations vary by demographic area, which has important implications for the clinical management of this disease