The impact of virtual reality simulation training on operative performance in laparoscopic cholecystectomy: meta-analysis of randomized clinical trials

BACKGROUND: Simulation training can improve the learning curve of surgical trainees. This research aimed to systematically review randomized clinical trials (RCT) evaluating the performance of junior surgical trainees following virtual reality training (VRT) and other training methods in laparoscopic cholecystectomy. METHODS: MEDLINE (PubMed), Embase (Ovid SP), Web of Science, Scopus and LILACS were searched for trials randomizing participants to VRT or no additional training (NAT) or simulation training (ST). Outcomes of interest were the reported performance using global rating scores (GRS), the Objective Structured Assessment of Technical Skill (OSATS) and Global Operative Assessment of Laparoscopic Skills (GOALS), error counts and time to completion of task during laparoscopic cholecystectomy on either porcine models or humans. Study quality was assessed using the Cochrane Risk of Bias Tool. PROSPERO ID: CRD42020208499. RESULTS: A total of 351 titles/abstracts were screened and 96 full texts were reviewed. Eighteen RCT were included and 15 manuscripts had data available for meta-analysis. Thirteen studies compared VRT and NAT, and 4 studies compared VRT and ST. One study compared VRT with NAT and ST and reported GRS only. Meta-analysis showed OSATS score (mean difference (MD) 6.22, 95%CI 3.81 to 8.36, P < 0.001) and time to completion of task (MD -8.35 min, 95%CI 13.10 to 3.60, P = <0.001) significantly improved after VRT compared with NAT. No significant difference was found in GOALS score. No significant differences were found between VRT and ST groups. Intraoperative errors were reported as reduced in VRT groups compared with NAT but were not suitable for meta-analysis. CONCLUSION: Meta-analysis suggests that performance measured by OSATS and time to completion of task is improved with VRT compared with NAT for junior trainee in laparoscopic cholecystectomy. However, conclusions are limited by methodological heterogeneity and more research is needed to quantify the potential benefit to surgical training

Adjuvant bevacizumab in patients with melanoma at high risk of recurrence (AVAST-M): preplanned interim results from a multicentre, open-label, randomised controlled phase 3 study

Background Bevacizumab, a monoclonal antibody that targets VEGF, has shown restricted activity in patients with advanced melanoma. We aimed to assess the role of bevacizumab as adjuvant treatment for patients with resected melanoma at high risk of recurrence. We report results from the preplanned interim analysis. Methods We did a multicentre, open-label, randomised controlled phase 3 trial at 48 centres in the UK between July 18, 2007, and March 29, 2012. Patients aged 16 years or older with American Joint Committee on Cancer stage (AJCC) stage IIB, IIC, and III cutaneous melanoma were randomly allocated (1:1), via a central, computer-based minimisation procedure, to receive intravenous bevacizumab 7·5 mg/kg, every 3 weeks for 1 year, or to observation. Randomisation was stratifi ed by Breslow thickness of the primary tumour, N stage according to AJCC staging criteria, ulceration of the primary tumour, and patient sex. The primary endpoint was overall survival; secondary endpoints included disease-free interval, distant-metastases interval and quality of life. Analysis was by intention-to-treat. This trial is registered as an International Standardised Randomised Controlled Trial, number ISRCTN81261306. Findings 1343 patients were randomised to either the bevacizumab group (n=671) or the observation group (n=672). Median follow-up was 25 months (IQR 16ñ37) in the bevacizumab group and 25 months (17ñ37) in the observation group. At the time of interim analysis, 286 (21%) of 1343 enrolled patients had died: 140 (21%) of 671 patients in the bevacizumab group, and 146 (22%) of 672 patients in the observation group. 134 (96%) of patients in the bevacizumab group died because of melanoma versus 139 (95%) in the observation group. We noted no signifi cant di┎ erence in overall survival between treatment groups (hazard ratio [HR] 0·97, 95% CI 0·78ñ1·22; p=0·76); this fi nding persisted after adjustment for stratifi cation variables (HR 1·03; 95% CI 0·81ñ1·29; p=0·83). Median duration of treatment with bevacizumab was 51 weeks (IQR 21ñ52) and dose intensity was 86% (41ñ96), showing good tolerability. 180 grade 3 or 4 adverse events were recorded in 101 (15%) of 671 patients in the bevacizumab group, and 36 (5%) of 672 patients in the observation group. Bevacizumab resulted in a higher incidence of grade 3 hypertension than did observation (41 [6%] vs one [<1%]). There was an improvement in disease-free interval for patients in the bevacizumab group compared with those in the observation group (HR 0·83, 95% CI 0·70ñ0·98, p=0·03), but no signifi cant di┎ erence between groups for distant-metastasis-free interval (HR 0·88, 95% CI 0·73ñ1·06, p=0·18). No signifi cant di┎ erences were noted between treatment groups in the standardised area under the curve for any of the quality-of-life scales over 36 months. Three adverse drug reactions were regarded as both serious and unexpected: one patient had optic neuritis after the fi rst bevacizumab infusion, a second patient had persistent erectile dysfunction, and a third patient died of a haemopericardium after receiving two bevacizumab infusions and was later identifi ed to have had signifi cant predisposing cardiovascular risk factors. Interpretation Bevacizumab has promising tolerability. Longer follow-up is needed to identify an e┎ect on the primary endpoint of overall survival at 5 years. Funding Cancer Research U

Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth.

Prostate cancer is the most common cancer in men and it is estimated that over 350,000 men worldwide die of prostate cancer every year. There remains an unmet clinical need to improve how clinically significant prostate cancer is diagnosed and develop new treatments for advanced disease. Aberrant glycosylation is a hallmark of cancer implicated in tumour growth, metastasis, and immune evasion. One of the key drivers of aberrant glycosylation is the dysregulated expression of glycosylation enzymes within the cancer cell. Here, we demonstrate using multiple independent clinical cohorts that the glycosyltransferase enzyme GALNT7 is upregulated in prostate cancer tissue. We show GALNT7 can identify men with prostate cancer, using urine and blood samples, with improved diagnostic accuracy than serum PSA alone. We also show that GALNT7 levels remain high in progression to castrate-resistant disease, and using in vitro and in vivo models, reveal that GALNT7 promotes prostate tumour growth. Mechanistically, GALNT7 can modify O-glycosylation in prostate cancer cells and correlates with cell cycle and immune signalling pathways. Our study provides a new biomarker to aid the diagnosis of clinically significant disease and cements GALNT7-mediated O-glycosylation as an important driver of prostate cancer progression

Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth

Prostate cancer is the most common cancer in men and it is estimated that over 350,000 men worldwide die of prostate cancer every year. There remains an unmet clinical need to improve how clinically significant prostate cancer is diagnosed and develop new treatments for advanced disease. Aberrant glycosylation is a hallmark of cancer implicated in tumour growth, metastasis, and immune evasion. One of the key drivers of aberrant glycosylation is the dysregulated expression of glycosylation enzymes within the cancer cell. Here, we demonstrate using multiple independent clinical cohorts that the glycosyltransferase enzyme GALNT7 is upregulated in prostate cancer tissue. We show GALNT7 can identify men with prostate cancer, using urine and blood samples, with improved diagnostic accuracy than serum PSA alone. We also show that GALNT7 levels remain high in progression to castrate-resistant disease, and using in vitro and in vivo models, reveal that GALNT7 promotes prostate tumour growth. Mechanistically, GALNT7 can modify O-glycosylation in prostate cancer cells and correlates with cell cycle and immune signalling pathways. Our study provides a new biomarker to aid the diagnosis of clinically significant disease and cements GALNT7-mediated O-glycosylation as an important driver of prostate cancer progression