Duodenal-Jejunal Bypass Liner for the management of Type 2 Diabetes Mellitus and Obesity: A Multicenter Randomized Controlled Trial.

OBJECTIVE: 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. SUMMARY BACKGROUND DATA: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership reference 12/10/04.

A case for improved assessment of gut permeability: a meta-analysis quantifying the lactulose:mannitol ratio in coeliac and Crohn's disease.

BACKGROUND: A widely used method in assessing small bowel permeability is the lactulose:mannitol test, where the lactulose:mannitol ratio (LMR) is measured. However, there is discrepancy in how the test is conducted and in the values of LMR obtained across studies. This meta-analysis aims to determine LMR in healthy subjects, coeliac and Crohn's disease. METHODS: A literature search was performed using PRISMA guidance to identify studies assessing LMR in coeliac or Crohn's disease. 19 studies included in the meta-analysis measured gut permeability in coeliac disease, 17 studies in Crohn's disease. Outcomes of interest were LMR values and comparisons of standard mean difference (SMD) and weighted mean difference (WMD) in healthy controls, inactive Crohn's, active Crohn's, treated coeliac and untreated coeliac. Pooled estimates of differences in LMR were calculated using the random effects model. RESULTS: Pooled LMR in healthy controls was 0.014 (95% CI: 0.006-0.022) while pooled LMRs in untreated and treated coeliac were 0.133 (95% CI: 0.089-0.178) and 0.037 (95% CI: 0.019-0.055). In active and inactive Crohn's disease, pooled LMRs were 0.093 (95% CI: 0.031-0.156) and 0.028 (95% CI: 0.015-0.041). Significant differences were observed in LMR between: (1) healthy controls and treated coeliacs (SMD = 0.409 95% CI 0.034 to 0.783, p = 0.032), (2) healthy controls and untreated coeliacs (SMD = 1.362 95% CI: 0.740 to 1.984, p < 0.001), (3) treated coeliacs and untreated coeliacs (SMD = 0.722 95% CI: 0.286 to 1.157, p = 0.001), (4) healthy controls and inactive Crohn's (SMD = 1.265 95% CI: 0.845 to 1.686, p < 0.001), (5) healthy controls and active Crohn's (SMD = 2.868 95% CI: 2.112 to 3.623, p < 0.001), and (6) active Crohn's and inactive Crohn's (SMD = 1.429 (95% CI: 0.580 to 2.278, p = 0.001). High heterogeneity was observed, which was attributed to variability in protocols used across different studies. CONCLUSION: The use of gut permeability measurements in screening and monitoring of coeliac and Crohn's disease is promising. LMR is useful in performing this function with significant limitations. More robust alternative tests with higher degrees of clinical evidence are needed if measurements of gut permeability are to find widespread clinical use.

Diagnostic Accuracy of Artificial Intelligence and Computer-Aided Diagnosis for the Detection and Characterization of Colorectal Polyps: Systematic Review and Meta-analysis.

BACKGROUND: 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). OBJECTIVE: The aim of this review was to examine the diagnostic accuracy of AI-based technologies in assessing colorectal polyps. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020169786; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020169786.

International Cancer Microbiome Consortium consensus statement on the role of the human microbiome in carcinogenesis.

OBJECTIVE: In this consensus statement, an international panel of experts deliver their opinions on key questions regarding the contribution of the human microbiome to carcinogenesis. DESIGN: International experts in oncology and/or microbiome research were approached by personal communication to form a panel. A structured, iterative, methodology based around a 1-day roundtable discussion was employed to derive expert consensus on key questions in microbiome-oncology research. RESULTS: Some 18 experts convened for the roundtable discussion and five key questions were identified regarding: (1) the relevance of dysbiosis/an altered gut microbiome to carcinogenesis; (2) potential mechanisms of microbiota-induced carcinogenesis; (3) conceptual frameworks describing how the human microbiome may drive carcinogenesis; (4) causation versus association; and (5) future directions for research in the field.The panel considered that, despite mechanistic and supporting evidence from animal and human studies, there is currently no direct evidence that the human commensal microbiome is a key determinant in the aetiopathogenesis of cancer. The panel cited the lack of large longitudinal, cohort studies as a principal deciding factor and agreed that this should be a future research priority. However, while acknowledging gaps in the evidence, expert opinion was that the microbiome, alongside environmental factors and an epigenetically/genetically vulnerable host, represents one apex of a tripartite, multidirectional interactome that drives carcinogenesis. CONCLUSION: Data from longitudinal cohort studies are needed to confirm the role of the human microbiome as a key driver in the aetiopathogenesis of cancer.

Evaluation of Direct from Sample Metabolomics of Human Feces Using Rapid Evaporative Ionization Mass Spectrometry.

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.

Medical Devices in Obesity Treatment.

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. 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.

A Review of New and Emerging Techniques For Optical Diagnosis of Colonic Polyps.

BACKGROUND AND AIMS: Endoscopic imaging is a rapidly progressing field and benefits from miniaturization of advanced imaging technologies, which may allow accurate real-time characterization of lesions. The concept of the "optical biopsy" to predict polyp histology has gained prominence in recent years and may become clinically applicable with the advent of new imaging technology. This review aims to discuss current evidence and examine the emerging technologies as applied to the optical diagnosis of colorectal polyps. METHODS: A structured literature search and review has been carried out of the evidence for diagnostic accuracy of image-enhanced endoscopy and emerging endoscopic imaging technologies. The image-enhanced endoscopy techniques are reviewed, including their basic scientific principles and current evidence for effectiveness. These include the established image-enhancement technologies such as narrow-band imaging, i-scan, and Fuji intelligent chromoendoscopy. More recent technologies including optical enhancement, blue laser imaging, and linked color imaging are discussed. Adjunctive imaging techniques in current clinical use are discussed, such as autofluorescence imaging and endocytoscopy. The emerging advanced imaging techniques are reviewed, including confocal laser endomicroscopy, optical coherence tomography, and Raman spectroscopy. CONCLUSIONS: Large studies of the established image-enhancement techniques show some role for the optical diagnosis of polyp histology, although results have been mixed, and at present only the technique of narrow-band imaging is appropriate for the diagnosis of low-risk polyps when used by an expert operator. Other image-enhancement techniques will require further study to validate their accuracy but show potential to support the use of a "resect-and-discard" approach to low-risk polyps. New technologies show exciting potential for real-time diagnosis, but further clinical studies in humans have yet to be performed.

Haemolytic uraemic syndrome - a rare case report of bloody diarrhoea in adults.

BACKGROUND: Haemolytic uraemic syndrome is a rarely seen in adults often leading to critical illness. This case highlights how difficult it can be to establish a diagnosis and treat when a patient presents with bloody diarrhoea. CASE PRESENTATION: A 17-year-old Iraqi man presented to the emergency department with abdominal pain and bloody diarrhoea. He was initially treated as acute appendicitis, undergoing an appendectomy but following a recurrence in his symptoms a colonoscopy was performed. A diagnosis of shiga toxin-producing Escherichia coli leading to HUS was suspected following histology obtained at colonoscopy and this was confirmed on antibody testing. Despite intravenous fluids and supportive therapy the patient's symptoms and condition deteriorated. He developed seizures and acute renal failure requiring intubation and plasma exchange in the intensive care setting. He eventually required treatment with ecluzimab therapy; a monoclonal antibody and subsequently made a full recovery. CONCLUSIONS: Haemolytic uraemic syndrome is a triad of progressive renal failure, thrombocytopenia and haemolytic anaemia which is a condition rarely seen in adults. It is usually associated with an E. coli infection and supportive therapy remains the mainstay of treatment.

A novel methodology for in vivo endoscopic phenotyping of colorectal cancer based on real-time analysis of the mucosal lipidome: a prospective observational study of the iKnife.

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.

Identification of Extracolonic Pathologies by Computed Tomographic Colonography in Colorectal Cancer Symptomatic Patients.

BACKGROUND & AIMS: Symptoms suggestive of colorectal cancer may originate outside the colorectum. Computed tomographic colonography (CTC) is used to examine the colorectum and abdominopelvic organs simultaneously. We performed a prospective randomized controlled trial to quantify the frequency, nature, and consequences of extracolonic findings. METHODS: We studied 5384 patients from 21 UK National Health Service hospitals referred by their family doctor for the investigation of colorectal cancer symptoms from March 2004 through December 2007. The patients were assigned randomly to groups that received the requested test (barium enema or colonoscopy, n = 3574) or CTC (n = 1810). We determined the frequency and nature of extracolonic findings, subsequent investigations, ultimate diagnosis, and extracolonic cancer diagnoses 1 and 3 years after testing patients without colorectal cancer. RESULTS: Extracolonic pathologies were detected in 959 patients by CTC (58.7%), in 42 patients by barium enema analysis (1.9%), and in no patients by colonoscopy. Extracolonic findings were investigated in 142 patients (14.2%) and a diagnosis was made for 126 patients (88.1%). Symptoms were explained by extracolonic findings in 4 patients analyzed by barium enema (0.2%) and in 33 patients analyzed by CTC (2.8%). CTC identified 72 extracolonic neoplasms, however, barium enema analysis found only 3 (colonoscopy found none). Overall, CTC diagnosed extracolonic neoplasms in 72 of 1634 patients (4.4%); 26 of these were malignant (1.6%). There were significantly more extracolonic malignancies detected than expected 1 year after examination, but these did not differ between patients evaluated by CTC (22.2/1000 person-years), barium enema (26.5/1000 person-years; P = .43), or colonoscopy (32.0/1000 person-years; P = .88). CONCLUSIONS: More than half of the patients with symptoms of colorectal cancer are found to have extracolonic pathologies by CTC analysis. However, the proportion of patients found to have extracolonic malignancies after 1 year of CTC examination is not significantly greater than after barium enema or colonoscopy examinations. International Standard Randomised Controlled Trials no: 95152621.isrctn.com.

Looking towards objective quality evaluation in colonoscopy: Analysis of visual gaze patterns.

BACKGROUND AND AIM: There are currently limited training and assessment tools available to novice endoscopists. A potential tool for the objective assessment of endoscopist visual search strategy is eye-tracking technology. The aim of this study is to assess whether eye-tracking technology can be used to differentiate the visual gaze patterns (VGP) of experienced and novice endoscopists, and to characterize any differences arising between the two groups. METHOD: With the use of portable eye-tracking glasses, VGP of novice (n = 20) and experienced (n = 14) endoscopists were compared while viewing a colonoscopy withdrawal through the hepatic flexure. Analysis was performed by comparing the central versus peripheral distribution and the horizontal distribution of novice and experienced endoscopist fixations, along with comparison of basic eye-tracking metrics. RESULTS: This study found that experienced endoscopists had a significantly higher percentage of fixations within the periphery of the screen (13.4% vs 23.0%, P = 0.013). Experienced endoscopists also had a significantly greater percentage of fixations on the left side of the screen (18.6% vs 33.5%, P = 0.005) that displayed the poorly visualized "inside bend" of the hepatic flexure. CONCLUSION: This study has detailed specific VGP acquired through expertise, which can potentially explain why adenomas are regularly missed at the hepatic flexure during colonoscopy. These may be useful for the training of novice colonoscopists, and further validation may utilize VGP in the development of an objective proficiency based curriculum to improve the detection of pathology and overall quality in endoscopy.

Colorectal endoscopic submucosal dissection: Systematic review of mid-term clinical outcomes.

With a drive towards minimally invasive surgery, endoscopic submucosal dissection (ESD) is now gaining popularity. In a number of East Asian countries, ESD is now the treatment of choice for early non-metastatic gastric cancer, but the outcomes of ESD for colorectal lesions are unclear. The present review summarizes the mid-term outcomes of colorectal ESD including complication and recurrence rates. A systematic literature search was done in May 2014, identifying 20 publications reporting the outcomes of colorectal ESD which were included in this review. En-bloc resection rates, complete (R0) resection rates, endoscopic clearance rates, complication and recurrences rates were analyzed. Statistical pooling was done to calculate weighted means using random effects modeling. Twenty studies reporting the outcomes of 3060 colorectal ESD procedures were reported. Overall weighted en-bloc resection rate was 89% (95% CI: 83-94%), R0 resection rate 76% (95% CI: 69-83%), endoscopic clearance rate 94% (95% CI: 90-97%) and recurrence rate 1% (95% CI: 0.5-2%). Studies that followed up patients for over 1 year were found to have an en-bloc resection rate of 91% (95% CI: 86-96%), R0 resection rate of 81% (95% CI: 75-88%), endoscopic clearance rate 93% (95% CI: 90-97%) and recurrence rate of 0.8% (95% CI: 0.4-1%). Colorectal ESD can be carried out effectively and safely with a 1% recurrence rate. Further studies with longer follow-up periods are required to determine whether colorectal ESD is a viable alternative to conventional surgical therapy.

Consumer demand for surgical innovation: a systematic review of public perception of NOTES.

BACKGROUND: The full scope of benefits offered by NOTES over traditional laparoscopy, if any, is not yet fully clear. Perceived patient demand for truly "scarless surgery" is often referenced one of the driving factors in the continued development of this relatively new technique. The true scale of patient preference and demand for NOTES as a surgical technique is unknown. This review aims to summarise currently available literature on the topic of patient perceptions of NOTES to guide future development of the technique. METHODS: A comprehensive search of PubMed and Web of Science electronic databases was performed on 1st Jan 2014. To be considered for inclusion, articles were required to assess and report the perception of NOTES in a sample of laypersons (patients or general public). The primary endpoint assessed was acceptance or preference rates expressed by patients for NOTES procedures. Reasons given for preference or rejection of NOTES were recorded, as well as preferred access routes and any predicting factors of NOTES acceptance. RESULTS: Initial search returned 1,334 results, resulting in 15 articles included in final data synthesis. These polled a total of 4,420 subjects. Acceptance of NOTES ranged between 41 and 84 %. Compared to a laparoscopic approach, preference rates for NOTES ranged from 0 to 78 %. Reasons for preferring NOTES were largely centred on potentially reduced recovery time, complications (particularly with reference to hernias) and postoperative pain. Improved cosmesis also played a role, but was secondary to the above issues. Overall, study quality was poor. CONCLUSIONS: This review suggests significant public interest in NOTES and scarless surgery in general. Further research and consideration of differences in public perceptions across regions, countries and cultures are required.

Evaluation of a novel flexible snake robot for endoluminal surgery.

BACKGROUND: Endoluminal therapeutic procedures such as endoscopic submucosal dissection are increasingly attractive given the shift in surgical paradigm towards minimally invasive surgery. This novel three-channel articulated robot was developed to overcome the limitations of the flexible endoscope which poses a number of challenges to endoluminal surgery. The device enables enhanced movement in a restricted workspace, with improved range of motion and with the accuracy required for endoluminal surgery. OBJECTIVE: To evaluate a novel flexible robot for therapeutic endoluminal surgery. DESIGN: Bench-top studies. SETTING: Research laboratory. INTERVENTION: Targeting and navigation tasks of the robot were performed to explore the range of motion and retroflexion capabilities. Complex endoluminal tasks such as endoscopic mucosal resection were also simulated. MAIN OUTCOME MEASUREMENTS: Successful completion, accuracy and time to perform the bench-top tasks were the main outcome measures. RESULTS: The robot ranges of movement, retroflexion and navigation capabilities were demonstrated. The device showed significantly greater accuracy of targeting in a retroflexed position compared to a conventional endoscope. LIMITATIONS: Bench-top study and small study sample. CONCLUSIONS: We were able to demonstrate a number of simulated endoscopy tasks such as navigation, targeting, snaring and retroflexion. The improved accuracy of targeting whilst in a difficult configuration is extremely promising and may facilitate endoluminal surgery which has been notoriously challenging with a conventional endoscope.

Computed tomographic colonography versus barium enema for diagnosis of colorectal cancer or large polyps in symptomatic patients (SIGGAR): a multicentre randomised trial.

BACKGROUND: Barium enema (BE) is widely available for diagnosis of colorectal cancer despite concerns about its accuracy and acceptability. Computed tomographic colonography (CTC) might be a more sensitive and acceptable alternative. We aimed to compare CTC and BE for diagnosis of colorectal cancer or large 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 radiological investigation of the colon. Patients were randomly assigned (2:1) to BE or CTC by computer-generated random numbers, in blocks of six, stratified by trial centre and sex. We analysed the primary outcome-diagnosis of colorectal cancer or large (≥10 mm) polyps-by intention to treat. The trial is an International Standard Randomised Controlled Trial, number 95152621. FINDINGS: 3838 patients were randomly assigned to receive either BE (n=2553) or CTC (n=1285). 34 patients withdrew consent, leaving for analysis 2527 assigned to BE and 1277 assigned to CTC. The detection rate of colorectal cancer or large polyps was significantly higher in patients assigned to CTC than in those assigned to BE (93 [7.3%] of 1277 vs 141 [5.6%] of 2527, relative risk 1.31, 95% CI 1.01-1.68; p=0.0390). CTC missed three of 45 colorectal cancers and BE missed 12 of 85. The rate of additional colonic investigation was higher after CTC than after BE (283 [23.5%] of 1206 CTC patients had additional investigation vs 422 [18.3%] of 2300 BE patients; p=0.0003), due mainly to a higher polyp detection rate. Serious adverse events were rare. INTERPRETATION: CTC is a more sensitive test than BE. Our results suggest that CTC should be the preferred radiological test for patients with symptoms suggestive of colorectal cancer. 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.

Computed tomographic colonography versus colonoscopy for investigation of patients with symptoms suggestive of colorectal cancer (SIGGAR): a multicentre randomised trial.

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.

Endoscopic horizon stabilization in natural orifice translumenal endoscopic surgery: a randomized controlled trial.

BACKGROUND: Spatial orientation in natural orifice translumenal endoscopic surgery (NOTES) has been identified as a potential barrier to clinical application. We aim to evaluate a triaxial inertial sensor and software that automatically corrects any movements on the roll axis of the flexible endoscope, allowing for stabilization of the image horizon during NOTES operations in a randomized controlled trial. METHODS: A total of 18 participants (11 surgeons/7 gastroenterologists) performed a transgastric task in the ELITE simulator, which included navigation to the appendix and gallbladder, diathermy of the appendix base and gallbladder fossa, and clipping of the cystic duct using a single-channel gastroscope. Each participant performed the task twice with randomization to horizon stabilization occurring at the second attempt. The primary end point was change in overall performance (time taken and errors made) between the first and second attempt, and secondary end points were absolute performances in the second attempt and subjective evaluation. RESULTS: Without horizon stabilization, there was a median improvement of 42.4% in time taken and 38% in number of errors made from the first to the second attempt; however, with the software turned on, there was a statistically significant deterioration of 4.9% (P = .038) in time taken and an increase in errors made of 183% (P = ns). CONCLUSIONS: Although the software corrects the view to that preferred during surgery, the endoscopic control mechanism as well as the exit point of the instrument are altered in this process, leading to a deterioration of overall performance. Potential solutions include deploying intermittent horizon stabilization or using a robotic interface to achieve fully aligned perceptual-motor control.

Education and training in NOTES: a systematic review.

INTRODUCTION: Since the first published work on natural orifice translumenal endoscopic surgery (NOTES) a decade ago, progress has been made in the domain of education and training, although questions posed by the original White Paper remain. This article aims to review the current status of education and training in NOTES. METHODS: A review of the literature was conducted to evaluate the following: (1) What are the current training methods/modalities used for NOTES; what is the level of evidence to support their use? (2) How has NOTES clinical training been quantified; what is the evidence relating to performance of different NOTES operators? (3) What clinical NOTES training programs have been established and what are the wider training needs? RESULTS: A total of 25 studies were included: 11 nonanimal studies, 8 animal studies, and 6 descriptions of education programs. Several animal and simulator models demonstrated construct validity, but no study showed human predictive validity. Logarithmic learning curves in animal models demonstrate 10 to 15 cases achieving a proficiency level. Current trends are that gastroenterologists prefer it for diagnostic and basic procedures, whereas surgeons prefer it for complex therapeutic cases. CONCLUSION: The development of a new specialty is intriguing but currently unviable. Training programs have been initiated, but information is limited; the common theme is surgeons receiving endoscopic training. Despite the research done, our knowledge of training and educating in NOTES procedures is limited, preventing a meta-analysis or formal review from being performed. Further research is needed to integrate NOTES into routine clinical procedure.

The effects of natural orifice translumenal endoscopic surgery (NOTES) on cardiorespiratory physiology: a systematic review.

INTRODUCTION: Despite the increasing awareness of natural orifice translumenal endoscopic surgery (NOTES), there remain obstacles to its wider implementation. We aim to examine the current evidence for the effects of variable uncontrolled insufflation pressures using either air or carbon dioxide in NOTES, as well the effects of NOTES procedures themselves, on physiological parameters. METHOD: We undertook a systematic review of all publications relating to the effects of NOTES on physiology, in particular compared with laparoscopy. RESULTS: Eleven reports were identified comprising comparative trials involving a total of 237 pigs. With one exception, no difference was found between the effect of NOTES and laparoscopic surgery on cardiopulmonary parameters. No difference was found also for the effect on inflammatory mediators such as interleukin-6. Two studies also assessed the effects choice of insufflation gas, with no change in inflammatory markers. Two further studies assessing the effects of variable pneumoperitoneal pressures found negative cardiorespiratory effects with higher pressures. DISCUSSION: Existing evidence is limited to small-sample animal trials but appears to show noninferiority for NOTES compared with laparoscopy. The development of a pressure regulation device for NOTES must be considered.

A quantitative scale to define endoscopic torque control during natural orifice surgery.

INTRODUCTION: The drive to perform procedures with the least impact on the patient has meant that interest in natural orifice translumenal endoscopic surgery (NOTES) continues to proliferate. However, endoscope control within the extralumenal environment remains a significant challenge. This study aims to define a method to quantitatively assess endoscopic torque control as an indication of performance. MATERIAL AND METHODS: Fourteen endoscopists performed a ten-target navigational task within a simulated NOTES environment whilst wrist movements were tracked with an optical motion tracker. Patterns of wrist movements were translated to a binary form enabling differentiation of the specified movement from no movement. Three patterns were discernable suggesting the discrimination of purposeful over random manipulations. Three independent assessors scored 140 patterns on a scale of 1 to 3 determined by which pattern was the most appropriate fit. RESULTS: Mean score for novices was 16 (± 3) and for clinicians 22 (± 7). Inter-rater reliability (kappa statistic function) between the assessors ranged from 0.637 to 0.751 p < 0.001 referred to as a substantial assessment tool. The internal consistency between all variables using Chronbach's alpha function was 0.948 (p < 0.001). CONCLUSIONS: Pattern of movements extrapolated from the wrist can be used as a method of measuring endoscope torque control during a translumenal navigation task.