Evidence is growing that the gut microbiota modulates the host response to chemotherapeutic drugs, with three main clinical outcomes: facilitation of drug efficacy; abrogation and compromise of ...anticancer effects; and mediation of toxicity. The implication is that gut microbiota are critical to the development of personalized cancer treatment strategies and, therefore, a greater insight into prokaryotic co-metabolism of chemotherapeutic drugs is now required. This thinking is based on evidence from human, animal and in vitro studies that gut bacteria are intimately linked to the pharmacological effects of chemotherapies (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and novel targeted immunotherapies such as anti-PD-L1 and anti-CLTA-4 therapies. The gut microbiota modulate these agents through key mechanisms, structured as the 'TIMER' mechanistic framework: Translocation, Immunomodulation, Metabolism, Enzymatic degradation, and Reduced diversity and ecological variation. The gut microbiota can now, therefore, be targeted to improve efficacy and reduce the toxicity of current chemotherapy agents. In this Review, we outline the implications of pharmacomicrobiomics in cancer therapeutics and define how the microbiota might be modified in clinical practice to improve efficacy and reduce the toxic burden of these compounds.
Colonoscopy reduces the incidence of colorectal cancer (CRC) by allowing detection and resection of neoplastic polyps. Evidence shows that many small polyps are missed on a single colonoscopy. There ...has been a successful adoption of artificial intelligence (AI) technologies to tackle the issues around missed polyps and as tools to increase the adenoma detection rate (ADR).
The aim of this review was to examine the diagnostic accuracy of AI-based technologies in assessing colorectal polyps.
A comprehensive literature search was undertaken using the databases of Embase, MEDLINE, and the Cochrane Library. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. Studies reporting the use of computer-aided diagnosis for polyp detection or characterization during colonoscopy were included. Independent proportions and their differences were calculated and pooled through DerSimonian and Laird random-effects modeling.
A total of 48 studies were included. The meta-analysis showed a significant increase in pooled polyp detection rate in patients with the use of AI for polyp detection during colonoscopy compared with patients who had standard colonoscopy (odds ratio OR 1.75, 95% CI 1.56-1.96; P<.001). When comparing patients undergoing colonoscopy with the use of AI to those without, there was also a significant increase in ADR (OR 1.53, 95% CI 1.32-1.77; P<.001).
With the aid of machine learning, there is potential to improve ADR and, consequently, reduce the incidence of CRC. The current generation of AI-based systems demonstrate impressive accuracy for the detection and characterization of colorectal polyps. However, this is an evolving field and before its adoption into a clinical setting, AI systems must prove worthy to patients and clinicians.
PROSPERO International Prospective Register of Systematic Reviews CRD42020169786; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020169786.
The rapid rise of obesity and type 2 diabetes poses a global threat to healthcare and is a major cause of mortality and morbidity. Bariatric surgery has revolutionised the treatment of both these ...conditions but is invasive and associated with an increased risk of complications. The EndoBarrier is a device placed endoscopically in the duodenum, which is designed to mimic the effects of gastric bypass surgery with the aim of inducing weight loss and improving glycaemic control. This review outlines the current clinical evidence of the device, its efficacy, potential mechanisms of action, and utility in clinical practice.
Fecal calprotectin (FC) is a relatively new marker of intraluminal intestinal inflammation. Using meta-analytical techniques, the study aimed to evaluate the diagnostic precision of FC for ...inflammatory bowel disease (IBD) and colorectal cancer (CRC) in adults and children.
Quantitative meta-analysis was performed on prospective studies, comparing FC levels against the histological diagnosis. Sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated for each study. Summary receiver-operating characteristic (sROC) curves and subgroup analysis were undertaken. Study quality and heterogeneity were evaluated.
Thirty studies of 5,983 patients were included. FC levels in patients with IBD were higher by 219.2 micrograms per gram (microg/g) compared with normal patients (P < 0.001). sROC curve analysis showed a sensitivity of 0.95 (95% CI 0.93-0.97), specificity of 0.91 (95% CI 0.86-0.91), and an area under the curve (AUC) of 0.95 for the diagnosis of IBD. Patients with colorectal neoplasia had nonsignificantly higher FC levels by 132.2 microg/g compared with noncancer controls (P= 0.18). Sensitivity and specificity of FC for the diagnosis of CRC were 0.36 and 0.71, respectively, with an AUC of 0.66. The diagnostic precision of FC for IBD was higher in children than adults with better accuracy at a cutoff level of 100 microg/g versus 50 microg/g. Sensitivity analysis and metaregression analysis did not significantly alter the results.
FC cannot be recommended as a screening test for CRC in the general population. FC appeared to offer a good diagnostic precision in distinguishing IBD from non-IBD diagnoses, with higher precision at a cutoff of 100 microg/g.
Background
This pilot study assessed the diagnostic accuracy of rapid evaporative ionization mass spectrometry (REIMS) in colorectal cancer (CRC) and colonic adenomas.
Methods
Patients undergoing ...elective surgical resection for CRC were recruited at St. Mary’s Hospital London and The Royal Marsden Hospital, UK. Ex vivo analysis was performed using a standard electrosurgery handpiece with aspiration of the electrosurgical aerosol to a Xevo G2-S iKnife QTof mass spectrometer (Waters Corporation). Histological examination was performed for validation purposes. Multivariate analysis was performed using principal component analysis and linear discriminant analysis in Matlab 2015a (Mathworks, Natick, MA). A modified REIMS endoscopic snare was developed (Medwork) and used prospectively in five patients to assess its feasibility during hot snare polypectomy.
Results
Twenty-eight patients were recruited (12 males, median age 71, range 35–89). REIMS was able to reliably distinguish between cancer and normal adjacent mucosa (NAM) (AUC 0.96) and between NAM and adenoma (AUC 0.99). It had an overall accuracy of 94.4 % for the detection of cancer versus adenoma and an adenoma sensitivity of 78.6 % and specificity of 97.3 % (AUC 0.99) versus cancer. Long-chain phosphatidylserines (e.g., PS 22:0) and bacterial phosphatidylglycerols were over-expressed on cancer samples, while NAM was defined by raised plasmalogens and triacylglycerols expression and adenomas demonstrated an over-expression of ceramides. REIMS was able to classify samples according to tumor differentiation, tumor budding, lymphovascular invasion, extramural vascular invasion and lymph node micrometastases (AUC’s 0.88, 0.87, 0.83, 0.81 and 0.81, respectively). During endoscopic deployment, colonoscopic REIMS was able to detect target lipid species such as ceramides during hot snare polypectomy.
Conclusion
REIMS demonstrates high diagnostic accuracy for tumor type and for established histological features of poor prognostic outcome in CRC based on a multivariate analysis of the mucosal lipidome. REIMS could augment endoscopic and imaging technologies for precision phenotyping of colorectal cancer.
Medical Devices in Obesity Treatment Ruban, Aruchuna; Doshi, Akash; Lam, Erika ...
Current diabetes reports,
10/2019, Letnik:
19, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Purpose of Review
Obesity is increasing at an alarming rate and now poses a global threat to humankind. In recent years, we have seen the emergence of medical devices to combat the obesity epidemic. ...These therapeutic strategies are discussed in this review dividing them into gastric and duodenal therapies.
Recent Findings
Traditionally, medical devices for obesity such as the intragastric balloon have focused on reducing gastric size, but more recently there has been a shift towards developing devices that modulate neural and hormonal responses to induce early satiety thus reducing oral intake.
Summary
Medical devices for obesity treatment may have a role in those patients who are struggling to control their weight despite significant lifestyle modifications such as diet and exercise and who decline or are unfit for bariatric surgery. For the wider adoption and integration of these devices in the obesity treatment paradigm, more long-term efficacy and safety data from randomised controlled trials are required.
Summary Background Colonoscopy is the gold-standard test for investigation of symptoms suggestive of colorectal cancer; computed tomographic colonography (CTC) is an alternative, less invasive test. ...However, additional investigation after CTC is needed to confirm suspected colonic lesions, and this is an important factor in establishing the feasibility of CTC as an alternative to colonoscopy. We aimed to compare rates of additional colonic investigation after CTC or colonoscopy for detection of colorectal cancer or large (≥10 mm) polyps in symptomatic patients in clinical practice. Methods This pragmatic multicentre randomised trial recruited patients with symptoms suggestive of colorectal cancer from 21 UK hospitals. Eligible patients were aged 55 years or older and regarded by their referring clinician as suitable for colonoscopy. Patients were randomly assigned (2:1) to colonoscopy or CTC by computer-generated random numbers, in blocks of six, stratified by trial centre and sex. We analysed the primary outcome—the rate of additional colonic investigation—by intention to treat. The trial is an International Standard Randomised Controlled Trial, number 95152621. Findings 1610 patients were randomly assigned to receive either colonoscopy (n=1072) or CTC (n=538). 30 patients withdrew consent, leaving for analysis 1047 assigned to colonoscopy and 533 assigned to CTC. 160 (30·0%) patients in the CTC group had additional colonic investigation compared with 86 (8·2%) in the colonoscopy group (relative risk 3·65, 95% CI 2·87–4·65; p<0·0001). Almost half the referrals after CTC were for small (<10 mm) polyps or clinical uncertainty, with low predictive value for large polyps or cancer. Detection rates of colorectal cancer or large polyps in the trial cohort were 11% for both procedures. CTC missed 1 of 29 colorectal cancers and colonoscopy missed none (of 55). Serious adverse events were rare. Interpretation Guidelines are needed to reduce the referral rate after CTC. For most patients, however, CTC provides a similarly sensitive, less invasive alternative to colonoscopy. Funding NIHR Health Technology Assessment Programme, NIHR Biomedical Research Centres funding scheme, Cancer Research UK, EPSRC Multidisciplinary Assessment of Technology Centre for Healthcare, and NIHR Collaborations for Leadership in Applied Health Research and Care.
Mass spectrometry is a powerful tool in the investigation of the human fecal metabolome. However, current approaches require time-consuming sample preparation, chromatographic separations, and ...consequently long analytical run times. Rapid evaporative ionization mass spectrometry (REIMS) is a method of ambient ionization mass spectrometry and has been utilized in the metabolic profiling of a diverse range of biological materials, including human tissue, cell culture lines, and microorganisms. Here, we describe the use of an automated, high-throughput REIMS robotic platform for direct analysis of human feces. Through the analysis of fecal samples from five healthy male participants, REIMS analytical parameters were optimized and used to assess the chemical information obtainable using REIMS. Within the fecal samples analyzed, bile acids, including primary, secondary, and conjugate species, were identified, and phospholipids of possible bacterial origin were detected. In addition, the effect of storage conditions and consecutive freeze/thaw cycles was determined. Within the REIMS mass spectra, the lower molecular weight metabolites, such as fatty acids, were shown to be significantly affected by storage conditions for prolonged periods at temperatures above −80 °C and consecutive freeze/thaw cycles. However, the complex lipid region was shown to be unaffected by these conditions. A further cohort of 50 fecal samples, collected from patients undergoing bariatric surgery, were analyzed using the optimized REIMS parameters and the complex lipid region mass spectra used for multivariate modeling. This analysis showed a predicted separation between pre- and post-surgery specimens, suggesting that REIMS analysis can detect biological differences, such as microbiome-level differences, which have traditionally been reliant upon methods utilizing extensive sample preparations and chromatographic separations and/or DNA sequencing.
The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12 months and for 12 months after explantation.
This is the largest ...randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery.
In this multicenter open-label RCT, 170 adults with inadequately controlled T2DM and obesity were randomized to intensive medical care with or without the DJBL. Primary outcome was the percentage of participants achieving a glycated hemoglobin reduction of ≥20% at 12 months. Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24 months.
There were no significant differences in the percentage of patients achieving the primary outcome between both groups at 12 months DJBL 54.6% (n = 30) vs control 55.2% (n = 32); odds ratio (OR) 0.93, 95% confidence interval (CI): 0.44-2.0; P = 0.85. Twenty-four percent (n = 16) patients achieved ≥15% weight loss in the DJBL group compared to 4% (n = 2) in the controls at 12 months (OR 8.3, 95% CI: 1.8-39; P = .007). The DJBL group experienced superior reductions in systolic blood pressure, serum cholesterol, and alanine transaminase at 12 months. There were more adverse events in the DJBL group.
The addition of the DJBL to intensive medical care was associated with superior weight loss, improvements in cardiometabolic risk factors, and fatty liver disease markers, but not glycemia, only while the device was in situ. The benefits of the devices need to be balanced against the higher rate of adverse events when making clinical decisions.
ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership reference 12/10/04.
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