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44 result(s) for "Mason, Sam E"
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Next-generation robotics in gastrointestinal surgery
The global numbers of robotic gastrointestinal surgeries are increasing. However, the evidence base for robotic gastrointestinal surgery does not yet support its widespread adoption or justify its cost. The reasons for its continued popularity are complex, but a notable driver is the push for innovation — robotic surgery is seen as a compelling solution for delivering on the promise of minimally invasive precision surgery — and a changing commercial landscape delivers the promise of increased affordability. Novel systems will leverage the robot as a data-driven platform, integrating advances in imaging, artificial intelligence and machine learning for decision support. However, if this vision is to be realized, lessons must be heeded from current clinical trials and translational strategies, which have failed to demonstrate patient benefit. In this Perspective, we critically appraise current research to define the principles on which the next generation of gastrointestinal robotics trials should be based. We also discuss the emerging commercial landscape and define existing and new technologies.The evidence base for robotic gastrointestinal surgery does not yet support its widespread adoption. Here, Kinross et al. discuss this evidence base and the principles on which future gastrointestinal surgical trials should be based, as well as emerging technologies.
Insights from a global snapshot of the change in elective colorectal practice due to the COVID-19 pandemic
There is a need to understand the impact of COVID-19 on colorectal cancer care globally and determine drivers of variation. To evaluate COVID-19 impact on colorectal cancer services globally and identify predictors for behaviour change. An online survey of colorectal cancer service change globally in May and June 2020. Attending or consultant surgeons involved in the care of patients with colorectal cancer. Changes in the delivery of diagnostics (diagnostic endoscopy), imaging for staging, therapeutics and surgical technique in the management of colorectal cancer. Predictors of change included increased hospital bed stress, critical care bed stress, mortality and world region. 191 responses were included from surgeons in 159 centers across 46 countries, demonstrating widespread service reduction with global variation. Diagnostic endoscopy was reduced in 93% of responses, even with low hospital stress and mortality; whilst rising critical care bed stress triggered complete cessation (p = 0.02). Availability of CT and MRI fell by 40-41%, with MRI significantly reduced with high hospital stress. Neoadjuvant therapy use in rectal cancer changed in 48% of responses, where centers which had ceased surgery increased its use (62 vs 30%, p = 0.04) as did those with extended delays to surgery (p<0.001). High hospital and critical care bed stresses were associated with surgeons forming more stomas (p<0.04), using more experienced operators (p<0.003) and decreased laparoscopy use (critical care bed stress only, p<0.001). Patients were also more actively prioritized for resection, with increased importance of co-morbidities and ICU need. The COVID-19 pandemic was associated with severe restrictions in the availability of colorectal cancer services on a global scale, with significant variation in behaviours which cannot be fully accounted for by hospital burden or mortality.
Enhanced triacylglycerol catabolism by carboxylesterase 1 promotes aggressive colorectal carcinoma
The ability to adapt to low-nutrient microenvironments is essential for tumor cell survival and progression in solid cancers, such as colorectal carcinoma (CRC). Signaling by the NF-κB transcription factor pathway associates with advanced disease stages and shorter survival in patients with CRC. NF-κB has been shown to drive tumor-promoting inflammation, cancer cell survival, and intestinal epithelial cell (IEC) dedifferentiation in mouse models of CRC. However, whether NF-κB affects the metabolic adaptations that fuel aggressive disease in patients with CRC is unknown. Here, we identified carboxylesterase 1 (CES1) as an essential NF-κB-regulated lipase linking obesity-associated inflammation with fat metabolism and adaptation to energy stress in aggressive CRC. CES1 promoted CRC cell survival via cell-autonomous mechanisms that fuel fatty acid oxidation (FAO) and prevent the toxic build-up of triacylglycerols. We found that elevated CES1 expression correlated with worse outcomes in overweight patients with CRC. Accordingly, NF-κB drove CES1 expression in CRC consensus molecular subtype 4 (CMS4), which is associated with obesity, stemness, and inflammation. CES1 was also upregulated by gene amplifications of its transcriptional regulator HNF4A in CMS2 tumors, reinforcing its clinical relevance as a driver of CRC. This subtype-based distribution and unfavorable prognostic correlation distinguished CES1 from other intracellular triacylglycerol lipases and suggest CES1 could provide a route to treat aggressive CRC.
Patient-related risk factors for urinary retention following ambulatory general surgery: a systematic review and meta-analysis
Postoperative urinary retention (POUR) is a source of avoidable patient harm. The aim of this review is to identify and quantify the role of patient-related risk factors in the development of POUR following ambulatory general surgery. Studies published until December 2014 were identified by searching MEDLINE, EMBASE, and PsycINFO databases. Risk factors assessed in 3 or more studies were meta-analyzed. Twenty-one studies were suitable for inclusion consisting of 7,802 patients. The incidence of POUR was 14%. Increased age and the presence of lower urinary tract symptoms significantly increased risk with odds ratios [ORs] of 2.11 (95% confidence interval [CI] 1.15 to 3.86) and 2.83 (1.57 to 5.08), respectively. Male sex was not associated with developing POUR (OR .96, 95% CI .62 to 1.50). Preoperative α-blocker use significantly decreased the incidence of POUR with an OR of .37 (95% CI .15 to .91). Increased age and the presence of lower urinary tract symptoms increase the risk of POUR, while α-blocker use confers protection. Male sex was not associated with POUR. These findings assist in preoperative identification of patients at high risk of POUR. •POUR is an avoidable source of patient harm.•This review identifies patient-related risk factors in ambulatory general surgery.•Increased age and lower urinary tract symptoms increase the risk of POUR.•Male sex does not increase the risk of POUR.•Preoperative α-blocker use is protective in the development of POUR.
Pathobionts in the tumour microbiota predict survival following resection for colorectal cancer
Background and aims The gut microbiota is implicated in the pathogenesis of colorectal cancer (CRC). We aimed to map the CRC mucosal microbiota and metabolome and define the influence of the tumoral microbiota on oncological outcomes. Methods A multicentre, prospective observational study was conducted of CRC patients undergoing primary surgical resection in the UK ( n  = 74) and Czech Republic ( n  = 61). Analysis was performed using metataxonomics, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS), targeted bacterial qPCR and tumour exome sequencing. Hierarchical clustering accounting for clinical and oncological covariates was performed to identify clusters of bacteria and metabolites linked to CRC. Cox proportional hazards regression was used to ascertain clusters associated with disease-free survival over median follow-up of 50 months. Results Thirteen mucosal microbiota clusters were identified, of which five were significantly different between tumour and paired normal mucosa. Cluster 7, containing the pathobionts Fusobacterium nucleatum and Granulicatella adiacens , was strongly associated with CRC ( P FDR  = 0.0002). Additionally, tumoral dominance of cluster 7 independently predicted favourable disease-free survival (adjusted p  = 0.031). Cluster 1, containing Faecalibacterium prausnitzii and Ruminococcus gnavus , was negatively associated with cancer ( P FDR  = 0.0009), and abundance was independently predictive of worse disease-free survival (adjusted p  = 0.0009). UPLC-MS analysis revealed two major metabolic (Met) clusters. Met 1, composed of medium chain (MCFA), long-chain (LCFA) and very long-chain (VLCFA) fatty acid species, ceramides and lysophospholipids, was negatively associated with CRC ( P FDR  = 2.61 × 10 −11 ); Met 2, composed of phosphatidylcholine species, nucleosides and amino acids, was strongly associated with CRC ( P FDR  = 1.30 × 10 −12 ), but metabolite clusters were not associated with disease-free survival ( p  = 0.358). An association was identified between Met 1 and DNA mismatch-repair deficiency ( p  = 0.005). FBXW7 mutations were only found in cancers predominant in microbiota cluster 7. Conclusions Networks of pathobionts in the tumour mucosal niche are associated with tumour mutation and metabolic subtypes and predict favourable outcome following CRC resection. E9vQ1bxk-JdT4E6GMYGhRX Video Abstract
Robotic surgery: disruptive innovation or unfulfilled promise? A systematic review and meta-analysis of the first 30 years
Background Robotic surgery has been in existence for 30 years. This study aimed to evaluate the overall perioperative outcomes of robotic surgery compared with open surgery (OS) and conventional minimally invasive surgery (MIS) across various surgical procedures. Methods MEDLINE, EMBASE, PsycINFO, and ClinicalTrials.gov were searched from 1990 up to October 2013 with no language restriction. Relevant review articles were hand-searched for remaining studies. Randomised controlled trials (RCTs) and prospective comparative studies (PROs) on perioperative outcomes, regardless of patient age and sex, were included. Primary outcomes were blood loss, blood transfusion rate, operative time, length of hospital stay, and 30-day overall complication rate. Results We identified 99 relevant articles (108 studies, 14,448 patients). For robotic versus OS, 50 studies (11 RCTs, 39 PROs) demonstrated reduction in blood loss [ratio of means (RoM) 0.505, 95 % confidence interval (CI) 0.408–0.602], transfusion rate [risk ratio (RR) 0.272, 95 % CI 0.165–0.449], length of hospital stay (RoM 0.695, 0.615–0.774), and 30-day overall complication rate (RR 0.637, 0.483–0.838) in favour of robotic surgery. For robotic versus MIS, 58 studies (21 RCTs, 37 PROs) demonstrated reduced blood loss (RoM 0.853, 0.736–0.969) and transfusion rate (RR 0.621, 0.390–0.988) in favour of robotic surgery but similar length of hospital stay (RoM 0.982, 0.936–1.027) and 30-day overall complication rate (RR 0.988, 0.822–1.188). In both comparisons, robotic surgery prolonged operative time (OS: RoM 1.073, 1.022–1.124; MIS: RoM 1.135, 1.096–1.173). The benefits of robotic surgery lacked robustness on RCT-sensitivity analyses. However, many studies, including the relatively few available RCTs, suffered from high risk of bias and inadequate statistical power. Conclusions Our results showed that robotic surgery contributed positively to some perioperative outcomes but longer operative times remained a shortcoming. Better quality evidence is needed to guide surgical decision making regarding the precise clinical targets of this innovation in the next generation of its use.
Postoperative hypothermia and surgical site infection following peritoneal insufflation with warm, humidified carbon dioxide during laparoscopic colorectal surgery: a cohort study with cost-effectiveness analysis
Background Surgical Site Infection (SSI) occurs in 9 % of laparoscopic colorectal surgery. Warming and humidifying carbon dioxide (CO 2 ) used for peritoneal insufflation may protect against SSI by avoiding postoperative hypothermia (itself a risk factor for SSI). This study aimed to assess the impact of CO 2 conditioning on postoperative hypothermia and SSI and to perform a cost-effectiveness analysis. Methods A retrospective cohort study of patients undergoing elective laparoscopic colorectal resection was performed at a single UK specialist centre. The control group ( n  = 123) received peritoneal insufflation with room temperature, dry CO 2 , whereas the intervention group ( n  = 123) received warm, humidified CO 2 (using HumiGard™, Fisher & Paykel Healthcare). The outcomes were postoperative hypothermia, SSI and costs. Multivariate analysis was performed. Results A total of 246 patients were included in the study. The mean age was 68 (20–87) and mean BMI 28 (15–51). The primary diagnosis was cancer ( n  = 173), and there were no baseline differences between the groups. CO 2 conditioning significantly decreased the incidence of postoperative hypothermia (odds ratio 0.10, 95 % CI 0.04–0.23), with hypothermic patients found to be at increased risk of SSI (odds ratio 4.0, 95 % CI 1.25–12.9). Use of conditioned CO 2 significantly decreased the incidence of SSI by 66 % ( p  = 0.04). The intervention group incurred costs of £155 less per patient. The incremental cost-effectiveness ratio was negative. Conclusion CO 2 conditioning during laparoscopic colorectal surgery is a safe, feasible and a cost-effective intervention. It improves the quality of surgical care relating to SSI and postoperative hypothermia.
Optical Technologies for Endoscopic Real-Time Histologic Assessment of Colorectal Polyps: A Meta-Analysis
Accurate, real-time, endoscopic risk stratification of colorectal polyps would improve decision-making and optimize clinical efficiency. Technologies to manipulate endoscopic optical outputs can be used to predict polyp histology in vivo; however, it remains unclear how accuracy has progressed and whether it is sufficient for routine clinical implementation. A meta-analysis was conducted by searching MEDLINE, Embase, and the Cochrane Library. Studies were included if they prospectively deployed an endoscopic optical technology for real-time in vivo prediction of adenomatous colorectal polyps. Polyposis and inflammatory bowel diseases were excluded. Bayesian bivariate meta-analysis was performed, presenting 95% confidence intervals (CI). One hundred two studies using optical technologies on 33,123 colorectal polyps were included. Digital chromoendoscopy differentiated neoplasia (adenoma and adenocarcinoma) from benign polyps with sensitivity of 92.2% (90.6%-93.9% CI) and specificity of 84.0% (81.5%-86.3% CI), with no difference between constituent technologies (narrow-band imaging, Fuji intelligent Chromo Endoscopy, iSCAN) or with only diminutive polyps. Dye chromoendoscopy had sensitivity of 92.7% (90.1%-94.9% CI) and specificity of 86.6% (82.9%-89.9% CI), similarly unchanged for diminutive polyps. Spectral analysis of autofluorescence had sensitivity of 94.4% (84.0%-99.1% CI) and specificity of 50.9% (13.2%-88.8% CI). Endomicroscopy had sensitivity of 93.6% (85.3%-98.3% CI) and specificity of 92.5% (81.8%-98.1% CI). Computer-aided diagnosis had sensitivity of 88.9% (74.2%-96.7% CI) and specificity of 80.4% (52.6%-95.7% CI). Prediction confidence and endoscopist experience alone did not significantly improve any technology. The only subgroup to demonstrate a negative predictive value for adenoma above 90% was digital chromoendoscopy, making high confidence predictions of diminutive recto-sigmoid polyps. Chronologic meta-analyses show a falling negative predictive value over time. A significant publication bias exists. This novel approach to meta-analysis demonstrates that existing optical technologies are increasingly unlikely to allow safe \"resect and discard\" strategies and that step-change innovation may be required. A \"diagnose and leave\" strategy may be supported for diminutive recto-sigmoid polyps diagnosed with high confidence; however, limitations exist in the evidence base for this cohort.
New horizons for targeted treatment of neuroendocrine tumors
Neuroendocrine tumors (NETs) are rare and heterogeneous tumors and there is a paucity of randomized clinical trials evaluating the different therapeutic strategies. Over recent years, some important molecular aspects have been investigated and multiple targeted therapies are currently available. One of the most promising targets for the therapy of NETs are the mTOR and angiogenic growth factor receptors. The advent of the inhibitors of the mTOR pathway, tyrosine kinase inhibitors and of somatostatin analogs have shown their efficacy in randomized clinical trials in terms of implementing clinical hormone-induced syndromes and progression-free survival of advanced NETs. This article summarizes the standard therapies and new perspectives in NET's treatment, which remains still very heterogeneous and little known entity.