G-EYE colonoscopy is superior to standard colonoscopy for increasing adenoma detection rate: an international randomized controlled trial (with videos).

BACKGROUND AND AIMS: Colorectal cancer (CRC) is largely preventable with routine screening and surveillance colonoscopy; however, interval cancers arising from precancerous lesions missed by standard colonoscopy still occur. An increased adenoma detection rate (ADR) has been found to be inversely associated with interval cancers. The G-EYE device includes a reusable balloon integrated at the distal tip of a standard colonoscope, which flattens haustral folds, centralizes the colonoscope's optics, and reduces bowel slippage. The insufflated balloon also aims to enhance visualization of the colon during withdrawal, thereby increasing the ADR. METHODS: In this randomized, controlled, international, multicenter study (11 centers), patients (aged ≥50 years) referred to colonoscopy for screening, surveillance, or changes in bowel habits were randomized to undergo either balloon-assisted colonoscopy by using an insufflated balloon during withdrawal or standard high-definition colonoscopy. The primary endpoint was the ADR. RESULTS: One thousand patients were enrolled between May 2014 and September 2016 to undergo colonoscopy by experienced endoscopists; 803 were finally analyzed (standard colonoscopy n = 396; balloon-assisted colonoscopy n = 407). Baseline parameters were similar in both groups. Balloon-assisted colonoscopy provided a 48.0% ADR compared with 37.5% in the standard colonoscopy group (28% increase; P = .0027). Additionally, balloon-assisted colonoscopy provided for a significant increase in detection of advanced (P = .0033) flat adenomas (P < .0001) and sessile serrated adenomas/polyps (P = .0026). CONCLUSION: Balloon-assisted colonoscopy yielded a higher ADR and increased the detection of advanced, flat, and sessile serrated adenomas/polyps when compared with standard colonoscopy. Improved detection by the G-EYE device could impact the quality of CRC screening by reducing miss rates and consequently reducing interval cancer incidence. (Clinical trial registration number: NCT01917513.).

Development and validation of the SIMPLE endoscopic classification of diminutive and small colorectal polyps.

BACKGROUND: Prediction of histology of small polyps facilitates colonoscopic treatment. The aims of this study were: 1) to develop a simplified polyp classification, 2) to evaluate its performance in predicting polyp histology, and 3) to evaluate the reproducibility of the classification by trainees using multiplatform endoscopic systems. METHODS: In phase 1, a new simplified endoscopic classification for polyps - Simplified Identification Method for Polyp Labeling during Endoscopy (SIMPLE) - was created, using the new I-SCAN OE system (Pentax, Tokyo, Japan), by eight international experts. In phase 2, the accuracy, level of confidence, and interobserver agreement to predict polyp histology before and after training, and univariable/multivariable analysis of the endoscopic features, were performed. In phase 3, the reproducibility of SIMPLE by trainees using different endoscopy platforms was evaluated. RESULTS: Using the SIMPLE classification, the accuracy of experts in predicting polyps was 83 % (95 % confidence interval [CI] 77 % - 88 %) before and 94 % (95 %CI 89 % - 97 %) after training (P â€Š= 0.002). The sensitivity, specificity, positive predictive value, and negative predictive value after training were 97 %, 88 %, 95 %, and 91 %. The interobserver agreement of polyp diagnosis improved from 0.46 (95 %CI 0.30 - 0.64) before to 0.66 (95 %CI 0.48 - 0.82) after training. The trainees demonstrated that the SIMPLE classification is applicable across endoscopy platforms, with similar post-training accuracies for narrow-band imaging NBI classification (0.69; 95 %CI 0.64 - 0.73) and SIMPLE (0.71; 95 %CI 0.67 - 0.75). CONCLUSIONS: Using the I-SCAN OE system, the new SIMPLE classification demonstrated a high degree of accuracy for adenoma diagnosis, meeting the ASGE PIVI recommendations. We demonstrated that SIMPLE may be used with either I-SCAN OE or NBI.

G-EYE advanced colonoscopy for improved polyp detection rates - a randomized tandem pilot study with different endoscopists.

BACKGROUND AND AIMS: The most commonly missed polyps in colonoscopy are those located behind haustral folds. The G-EYE system is a standard colonoscope consisting of re-processable balloon at its distal tip. The G-EYE balloon improves the detection of polyps by straightening the haustral folds. In our back-to-back tandem study, we aimed to determine whether and to what extent the G-EYE system could reduce adenoma miss rates in screening colonoscopy. METHODS: Patients referred to colonoscopy were randomized into 2 groups. Group A underwent a standard colonoscopy (SC) followed by balloon colonoscopy (BC), and Group B underwent BC followed by SC. In this randomized tandem study, the investigator's level of training and the endoscopists themselves were changed after each withdrawal. Each endoscopist was blinded to the results of the first withdrawal. RESULTS: Fifty-eight patients were enrolled and randomized into 2 groups with similar baseline characteristics. Nine patients were excluded from the study. Twenty-five patients underwent SC followed by BC while 24 underwent BC followed by SC. The adenoma miss rate for SC was 41 %, with an additional detection rate of 69 % for BC (ratio 1.69). The overall miss rate for polyps was 60 % for SC, with an additional detection rate of 150 % for BC (ratio 2.5). Experienced investigators who used BC were able to identify an additional 7 polyps while inexperienced investigators. CONCLUSIONS: Although our results could not clearly confirm that BC improves adenoma detection, the investigator's experience appears to be a major determinant of the adenoma detection rate.

The Manchester Triage System (MTS): a score for emergency management of patients with acute gastrointestinal bleeding.

BACKGROUND: Suspected gastrointestinal (GI) bleeding is a common initial diagnosis in emergency departments. Despite existing endoscopic scores to estimate the risk of GI bleeding, the primary clinical assessment of urgency can remain challenging. The 5-step Manchester Triage System (MTS) is a validated score that is often applied for the initial assessment of patients presenting in emergency departments. METHODS: All computer-based records of patients who were admitted between January 2014 and December 2014 to our emergency department in a tertiary referral hospital were analyzed retrospectively. The aim of our retrospective analysis was to determine if patient triage using the MTS is associated with rates of endoscopy and with presence of active GI bleeding. RESULTS: In summary, 5689 patients with a GI condition were treated at our emergency department. Two hundred eighty-four patients (4.9 %) presented with suspected GI bleeding, and 165 patients (58 %) received endoscopic diagnostic. Endoscopic intervention for hemostasis was needed in 34 patients (21 %). In patients who underwent emergency endoscopy, triage into MTS categories with higher urgency was associated with higher rates of endoscopic confirmation of suspected GI bleeding (79 % of patients with MTS priority levels 1 or 2, 53 % in level 3 patients, and 40 % in levels 4 or 5 patients; p = 0.024). CONCLUSIONS: The MTS is an established tool for triage in emergency departments and could have a potential to guide early clinical decision-making with regards to urgency of endoscopic evaluation in patients with suspected GI bleeding.

A multicenter experience of through-the-scope balloon-assisted enteroscopy in surgically altered gastrointestinal anatomy.

BACKGROUND: Surgically altered gastrointestinal anatomy poses challenges for deep enteroscopy. Current overtube-assisted methods have long procedure times and utilize endoscopes with smaller working channels that preclude use of standard accessories. A through-the-scope balloon-assisted enteroscopy (TTS-BAE) device uses standard endoscopes with a large working channel to allow metallic and plastic stent insertion. We aim to determine the efficacy and safety of TTS-BAE in patients with altered surgical anatomy. METHODS: A retrospective, multicenter study of TTS-BAE in altered anatomy patients at two USA and one German institution was performed between January 2013 and December 2014. Type of anatomy, procedure indication and duration, adverse events, and target, technical, and clinical success were recorded. RESULTS: A total of 32 patients (mean age 54 years, Caucasian 81.6%, female 42.1%, mean BMI 25.4 kg/m2) underwent 38 TTS-BAE procedures. Thirty-two percent of cases had a prior attempt at conventional enteroscopy which failed to reach the target site. The target was successfully reached in 23 (60.5%) cases. Of the 23 cases that reached the intended target, 22 (95.7%) achieved technical success and 21 (91.3%) achieved clinical success. The median procedure time was 43 min. Target, technical, and clinical success rates for TTS-BAE-assisted ERCP (n = 31) were 58.1, 54.8 and 54.8%. Seven self-expandable metallic stents (five biliary, two jejunal) were attempted, and all successfully deployed. Adverse events occurred in 4 (10.4%) cases, including one luminal perforation. CONCLUSION: TTS-BAE is an alternative to overtube-assisted enteroscopy that is comparable in safety in patients with surgically altered anatomies. Technical success in the instances where the target had been reached was excellent. TTS-BAE confers an advantage over overtube-assisted enteroscopy as it can facilitate the deployment of self-expandable metallic stents in the biliary tree and deep small bowel.

Comparison of adenoma detection and miss rates between a novel balloon colonoscope and standard colonoscopy: a randomized tandem study.

BACKGROUND AND STUDY AIMS: Although colonoscopy is the "gold standard" for colorectal cancer screening, a significant number of adenomas are still missed during standard colonoscopy, often because they are hidden behind colonic folds and flexures. The aim of this study was to assess the ability of a novel balloon colonoscope (G-EYE endoscope; Smart Medical Systems, Ra'anana, Israel) to increase adenoma detection and reduce the miss rate compared with standard colonoscopy. PATIENTS AND METHODS: This was a multicenter, randomized, prospective, controlled study in patients (age ≥ 40 years) undergoing colonoscopy for screening or diagnostic work-up (including surveillance). Patients underwent same-day, back-to-back tandem colonoscopy. Patients in Group A underwent standard colonoscopy followed by balloon colonoscopy, and patients in Group B underwent balloon colonoscopy followed by the standard technique. The adenoma detection and miss rates were compared between the two colonoscopy procedures. RESULTS: A total of 126 patients were enrolled and randomized into Group A (n = 60) or Group B (n = 66). The adenoma miss rate of balloon colonoscopy was significantly lower than that of standard colonoscopy (7.5 % vs. 44.7 %; P = 0.0002). The detection of additional adenomas by balloon colonoscopy was significant (81.0 %; P = 0.0002), in particular, the relative amount of adenomas detected in the ascending colon by balloon colonoscopy was 41 % versus 14 % for standard colonoscopy. CONCLUSIONS: A novel balloon colonoscopy technique detected significantly more adenomas than standard colonoscopy, and missed fewer adenomas. Balloon colonoscopy has the potential to increase the effectiveness of colorectal cancer screening and surveillance colonoscopy.

High-definition endoscopy with digital chromoendoscopy for histologic prediction of distal colorectal polyps.

BACKGROUND: Distal diminutive colorectal polyps are common and accurate endoscopic prediction of hyperplastic or adenomatous polyp histology could reduce procedural time, costs and potential risks associated with the resection. Within this study we assessed whether digital chromoendoscopy can accurately predict the histology of distal diminutive colorectal polyps according to the ASGE PIVI statement. METHODS: In this prospective cohort study, 224 consecutive patients undergoing screening or surveillance colonoscopy were included. Real time histology of 121 diminutive distal colorectal polyps was evaluated using high-definition endoscopy with digital chromoendoscopy and the accuracy of predicting histology with digital chromoendoscopy was assessed. RESULTS: The overall accuracy of digital chromoendoscopy for prediction of adenomatous polyp histology was 90.1 %. Sensitivity, specificity, positive and negative predictive values were 93.3, 88.7, 88.7, and 93.2 %, respectively. In high-confidence predictions, the accuracy increased to 96.3 % while sensitivity, specificity, positive and negative predictive values were calculated as 98.1, 94.4, 94.5, and 98.1 %, respectively. Surveillance intervals with digital chromoendoscopy were correctly predicted with >90 % accuracy. CONCLUSIONS: High-definition endoscopy in combination with digital chromoendoscopy allowed real-time in vivo prediction of distal colorectal polyp histology and is accurate enough to leave distal colorectal polyps in place without resection or to resect and discard them without pathologic assessment. This approach has the potential to reduce costs and risks associated with the redundant removal of diminutive colorectal polyps. TRIAL REGISTRATION: ClinicalTrials NCT02217449.

Acetic acid compared with i-scan imaging for detecting Barrett's esophagus: a randomized, comparative trial.

BACKGROUND: Traditional surveillance in patients with Barrett's esophagus (BE) has relied on random biopsies. Targeted biopsies that use advanced imaging modalities may significantly improve detection of specialized columnar epithelium (SCE). OBJECTIVE: We compared the efficacy of targeted biopsies that used i-scan or acetic acid to random biopsies in the detection of SCE. DESIGN: Patients with visible columnar lined epithelium or known BE were randomized at a 1:1 ratio to undergo acetic acid application or i-scan with targeted biopsies. SETTING: Targeted biopsies were performed based on surface architecture according to the Guelrud classification followed by 4-quadrant biopsies. PATIENTS: A total of 95 patients were randomized. INTERVENTION: A total of 46 patients underwent acetic acid staining, and 49 underwent i-scan imaging. Random biopsies were performed in 86 patients. MAIN OUTCOME MEASUREMENTS: The primary outcome was the yield of SCE as confirmed by histologic assessment. RESULTS: The diagnostic yield for SCE was significantly higher with targeted biopsies than with random biopsies in both groups combined (63% vs 24%; P = .0001). The yield of targeted biopsies was significantly greater with both i-scan (66% vs 21%; P = .009) and acetic acid (57% vs 26%; P = .012) technologies and did not differ between these groups. The accuracy for predicting SCE was 96% (k = .92) for i-scan and 86% (k = .70) for acetic acid analysis. LIMITATIONS: No dysplastic lesions were found. CONCLUSION: The i-scan or acetic acid-guided biopsies have a significantly higher diagnostic yield for identifying SCE, with significantly fewer biopsies, as compared with a protocol of random biopsies. Acetic acid and i-scan showed comparable results diagnosing SCE in our study. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01442506.).

Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

MAIN RECOMMENDATIONS: 1 ESGE suggests the routine use of high definition white-light endoscopy systems for detecting colorectal neoplasia in average risk populations (weak recommendation, moderate quality evidence). 2 ESGE recommends the routine use of high definition systems and pancolonic conventional or virtual (narrow band imaging [NBI], i-SCAN) chromoendoscopy in patients with known or suspected Lynch syndrome (strong recommendation, low quality evidence). 2b ESGE recommends the routine use of high definition systems and pancolonic conventional or virtual (NBI) chromoendoscopy in patients with known or suspected serrated polyposis syndrome (strong recommendation, low quality evidence). 3 ESGE recommends the routine use of 0.1 % methylene blue or 0.1 % - 0.5 % indigo carmine pancolonic chromoendoscopy with targeted biopsies for neoplasia surveillance in patients with long-standing colitis. In appropriately trained hands, in the situation of quiescent disease activity and adequate bowel preparation, nontargeted, four-quadrant biopsies can be abandoned (strong recommendation, high quality evidence). 4 ESGE suggests that virtual chromoendoscopy (NBI, FICE, i-SCAN) and conventional chromoendoscopy can be used, under strictly controlled conditions, for real-time optical diagnosis of diminutive (≤ 5 mm) colorectal polyps to replace histopathological diagnosis. The optical diagnosis has to be reported using validated scales, must be adequately photodocumented, and can be performed only by experienced endoscopists who are adequately trained and audited (weak recommendation, high quality evidence). 5 ESGE suggests the use of conventional or virtual (NBI) magnified chromoendoscopy to predict the risk of invasive cancer and deep submucosal invasion in lesions such as those with a depressed component (0-IIc according to the Paris classification) or nongranular or mixed-type laterally spreading tumors (weak recommendation, moderate quality evidence). CONCLUSION: Advanced imaging techniques will need to be applied in specific patient groups in routine clinical practice and to be taught in endoscopic training programs.

Hemospray application in nonvariceal upper gastrointestinal bleeding: results of the Survey to Evaluate the Application of Hemospray in the Luminal Tract.

BACKGROUND: Hemospray TM (TC-325) is a novel hemostatic agent licensed for use in nonvariceal upper gastrointestinal bleeding (NVUGIB) in Europe. GOALS: We present the operating characteristics and performance of TC-325 in the largest registry to date of patients presenting with NVUGIB in everyday clinical practice. METHODS: Prospective anonymized data of device performance and clinical outcomes were collected from 10 European centers using the multicentre SEAL survey (Survey to Evaluate the Application of Hemospray in the Luminal tract). TC-325 was used as a monotherapy or as second-line therapy in combination with other hemostatic modalities at the endoscopists' discretion. RESULTS: Sixty-three patients (44 men, 19 women), median age 69 (range, 21 to 98) years with NVUGIB requiring endoscopic hemostasis were treated with TC-325. There were 30 patients with bleeding ulcers and 33 with other NVUGIB pathology. Fifty-five (87%) were treated with TC-325 as monotherapy; 47 [85%; 95% confidence interval (CI), 76%-94%] of them achieved primary hemostasis, and rebleeding rate at 7 days was 15% (95% CI, 5%-25%). Primary hemostasis rate for TC-325 in patients with ulcer bleeds was 76% (95% CI, 59%-93%). Eight patients, who otherwise may have required either surgery or interventional radiology, were treated with TC-325 as second-line therapy after failure of other endoscopic treatments, all of whom achieved hemostasis following the adjunct of TC-325. CONCLUSIONS: This multicentre registry identifies potentially useful characteristics of Hemospray (TC-325) when used either as monotherapy or as a rescue therapy in a wide variety of ulcer and nonulcer NVUGIB.

To biopsy or not to biopsy: evaluation of a large German cohort of patients with abnormal liver tests of unknown etiology.

BACKGROUND AND AIMS: Despite increasingly sensitive and accurate blood tests to detect liver disease, liver biopsy remains very useful in patients with atypical clinical features and abnormal liver tests of unknown etiology. The aim was to determine those elevated laboratory liver parameters that cause the clinician to order a biopsy, and whether laboratory tests are associated with pathological findings on histology. METHODS: 504 patients with unclear hepatopathy, admitted to the outpatient clinic of a university hospital between 2007 and 2010, were analyzed with respect to laboratory results, clinical data, and the results of liver biopsies. RESULTS: Aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH) levels above the normal range significantly increased the likelihood of recommending a liver biopsy by 81% [OR with 95% CI 1.81 (1.21-2.71), p = 0.004] and 159% [OR with 95% CI 2.59 (1.70-3.93), p < 0.001], respectively. AST values above normal were associated with fibrosis (63 vs. 40% for normal AST, p = 0.010). Elevated ferritin levels pointed to a higher incidence of steatosis (48 vs. 10% for normal ferritin, p < 0.001) and inflammation (87 vs. 62% for normal ferritin, p = 0.004). CONCLUSIONS: Our results indicate that elevated AST and GLDH were associated with a greater likelihood of recommending liver biopsy. Elevated AST and ferritin levels were associated with steatosis, inflammation and fibrosis on liver biopsies. Thus, AST and ferritin may be useful non-invasive predictors of liver pathology in patients with unclear hepatopathy.

Gastrointestinal disorders and dabigatran.

Anticoagulants play an important role in the prevention and treatment of a variety of acute and chronic thromboembolic disorders such as primary prevention and treatment of venous thromboembolism or prevention of stroke and systemic embolism in atrial fibrillation just to name of few. Within recent years, a promising new oral anticoagulant, the direct thrombin inhibitor dabigatran etexilate (dabigatran) successfully underwent clinical development and has emerged as an alternative to vitamin K antagonists according to a variety of recently revised and updated international guidelines referring to the indication of stroke prevention in atrial fibrillation. Considering the intensive clinical use of vitamin K antagonists in the mentioned indication as well as the widespread and increasing therapeutic need on one hand and the likely availability of a more efficacious alternative with fewer limitations in clinical practice on the other, there is good reason to assume that the use of dabigatran may be broad within the general medical community in the near future. Based on what is currently published in the public domain and clinical trial data it is suggested that dabigatran etexilate is associated with higher rates of dyspeptic symptoms compared to warfarin. Therefore, it is the authors' intent to review and discuss this potential dyspeptic side effect profile of dabigatran and potential counter measures from a gastroenterologist's perspective.

Retrospective comparison of G-EYE balloon-colonoscopy with standard colonoscopy for increased adenoma detection rate and reduced polyp removal time.

Background and study aims The newly introduced G-EYE colonoscope (G-EYE) employs a balloon, installed at the bending section of a standard colonoscope (SC), for increasing adenoma detection and stabilizing the colonoscope tip during intervention. This retrospective work explores the effect of introducing G-EYE into an SC endoscopy room, in terms of adenoma detection and polyp removal time. Patients and methods This was a single-center, retrospective study. Historical data from patients who underwent colonoscopy prior to, and following, introduction of G-EYE into a particular endoscopy room were collected and analyzed to determine adenoma detection rate (ADR), adenoma per patient (APP), and polyp removal time (PRT), in each of the SC and G-EYE groups. Results Records of 1362 patients who underwent SC and 1433 subsequent patients who underwent G-EYE colonoscopy in the same endoscopy unit by the same endoscopists were analyzed. Following G-EYE introduction, overall ADR increased by 37.5 % ( P  < 0.0001) from 39.2 % to 53.9 %, the serrated adenoma rate increased by 47.3 % from 27.9 % to 41.1 % ( P  < 0.0001), and the APP increased by 50.6 % from 0.79 to 1.19 ( P  < 0.0001). The number of advanced adenomas increased by 32.7 %, from 19.6 % to 26.0 % of all adenomas ( P  < 0.0001). With G-EYE, average PRT was reduced overall by 29.5 % ( P  < 0.0001), and particularly for endoscopic mucosal resection (EMR) by 37.5 % for polyps measuring ≥ 5 mm to ≤ 20 mm ( P  < 0.0001) and by 29.4 % for large polyps > 20 mm ( P  < 0.0001). Conclusions Introduction of G-EYE to an SC endoscopy room yielded considerable increase in ADR and notable reduction in PRT, particularly with the EMR technique. G-EYE balloon colonoscopy might increase the effectiveness of colorectal cancer screening and surveillance colonoscopy, and can shorten the time of endoscopic intervention.

Antibodies against tumor necrosis factor (TNF) induce T-cell apoptosis in patients with inflammatory bowel diseases via TNF receptor 2 and intestinal CD14⁺ macrophages.

BACKGROUND & AIMS: The anti-tumor necrosis factor (TNF) antibodies infliximab, adalimumab, and certolizumab pegol have proven clinical efficacy in Crohn's disease. Here, we assessed the effects of anti-TNF antibodies on apoptosis in inflammatory bowel disease (IBD). METHODS: CD14(+) macrophages and CD4(+) T cells were isolated from peripheral blood and lamina propria mononuclear cells from patients with IBD and control patients. Cell surface markers and apoptosis were assessed by immunohistology and fluorescence-activated cell sorting techniques. RESULTS: Lamina propria CD14(+) macrophages showed significantly more frequent and higher membrane-bound TNF (mTNF) expression than CD4(+) T cells in IBD, whereas mTNF-dependent signaling proteins such as TNF receptor (TNFR) 2, TNFR-associated factor (TRAF) 2, and nuclear factor κB were induced in IBD mucosal CD4(+) T cells. Most anti-TNF antibodies did not induce T-cell apoptosis in purified peripheral or mucosal CD4(+) T cells. However, in contrast to etanercept, administration of all clinically effective anti-TNF antibodies resulted in a significant induction of T-cell apoptosis in IBD when lamina propria CD4(+) T cells expressing TNFR2(+) were cocultured with mTNF(+) CD14(+) intestinal macrophages. In contrast, no effects in control patients were noted. T-cell apoptosis in IBD occurred in vivo after treatment with adalimumab and infliximab, was critically dependent on TNFR2 signaling, and could be prevented via interleukin-6 signal transduction. Blockade of interleukin-6R signaling augmented anti-TNF-induced T-cell apoptosis in IBD. CONCLUSIONS: Clinically effective anti-TNF antibodies are able to induce T-cell apoptosis in IBD only when mucosal TNFR2(+) T cells are cocultured with mTNF-expressing CD14(+) macrophages. The finding that anti-TNF antibodies induce apoptosis indirectly by targeting the mTNF/TNFR2 pathway may have important implications for the development of new therapeutic strategies in IBD.

Confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in inflammatory bowel disease in vivo.

BACKGROUND AND OBJECTIVES: Interaction of bacteria with the immune system within the intestinal mucosa plays a key role in the pathogenesis of inflammatory bowel disease (IBD). The aim of the current study was to develop a fluorescein-aided confocal laser endomicroscopy (CLE) method to visualise intramucosal enteric bacteria in vivo and to determine the involved mucosal area in the colon and ileum in patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Initially, E coli strains expressing enhanced green fluorescent protein (pEGFP) were endomicroscopically imaged in mice. In addition, ex vivo and in vivo imaging of fluorescent human enteric bacteria was performed to specify the distinct endomicroscopic appearance of enteral bacteria. Targeted mucosal biopsies towards endomicroscopic identifiable intramucosal bacteria and negative mucosal areas were prospectively obtained during colonoscopy and correlated with bench-top fluorescence microscopy (FISH) to prove the endomicroscopic visualisation of intramucosal bacteria. Finally, a retrospective analysis as well as a prospective study was performed in patients with UC and CD to confirm the presence and distribution of intramucosal bacteria within the gut. RESULTS: Confocal endomicroscopy was able to identify intramucosal pEGFP E coli in mice and strains of enteric microflora in the mucosa of humans. Using FISH as the gold standard, evaluation of 21 patients showed that CLE had a sensitivity of 89% and specificity of 100% to identify intramucosal bacteria. In a retrospective study, 113 patients with CD and UC had intramucosal bacteria significantly more often than 50 control patients (66% vs 60% vs 14%, p<0.001). This result was confirmed in a prospective study in which 10 patients with CD and 10 with UC had a significantly wider distribution of involvement with intramucosal bacteria in the colon and terminal ileum compared with 10 controls (85.2% vs 75.9% vs 16.8%, p<0.0001). CONCLUSIONS: CLE is a new tool that can image intramucosal bacteria in vivo in patients with IBD. Intramucosal bacteria are found more frequently and with a wider distribution in patients with IBD than in patients with a normal intestine.

The transcription factor IFN regulatory factor-4 controls experimental colitis in mice via T cell-derived IL-6.

The proinflammatory cytokine IL-6 seems to have an important role in the intestinal inflammation that characterizes inflammatory bowel diseases (IBDs) such as Crohn disease and ulcerative colitis. However, little is known about the molecular mechanisms regulating IL-6 production in IBD. Here, we assessed the role of the transcriptional regulator IFN regulatory factor-4 (IRF4) in this process. Patients with either Crohn disease or ulcerative colitis exhibited increased IRF4 expression in lamina propria CD3+ T cells as compared with control patients. Consistent with IRF4 having a regulatory function in T cells, in a mouse model of IBD whereby colitis is induced in RAG-deficient mice by transplantation with CD4+CD45RB(hi) T cells, adoptive transfer of wild-type but not IRF4-deficient T cells resulted in severe colitis. Furthermore, IRF4-deficient mice were protected from T cell-dependent chronic intestinal inflammation in trinitrobenzene sulfonic acid- and oxazolone-induced colitis. In addition, IRF4-deficient mice with induced colitis had reduced mucosal IL-6 production, and IRF4 was required for IL-6 production by mucosal CD90+ T cells, which it protected from apoptosis. Finally, the protective effect of IRF4 deficiency could be abrogated by systemic administration of either recombinant IL-6 or a combination of soluble IL-6 receptor (sIL-6R) plus IL-6 (hyper-IL-6). Taken together, our data identify IRF4 as a key regulator of mucosal IL-6 production in T cell-dependent experimental colitis and suggest that IRF4 might provide a therapeutic target for IBDs.

Current Endoscopic Resection Techniques for Gastrointestinal Lesions: Endoscopic Mucosal Resection, Submucosal Dissection, and Full-Thickness Resection.

BACKGROUND: Endoscopic resection of dysplastic lesions in early stages of cancer reduces mortality rates and is recommended by many national guidelines throughout the world. Snare polypectomy and endoscopic mucosal resection (EMR) are established techniques of polyp removal. The advantages of these methods are their relatively short procedure times and acceptable complication rates. The latter include delayed bleeding in 0.9% and a perforation risk of 0.4-1.3%, depending on the size and location of the resected lesion. EMR is a recent modification of endoscopic resection. A limited number of studies suggest that larger lesions can be removed en bloc with low complication rates and short procedure times. Novel techniques such as endoscopic submucosal dissection (ESD) are used to enhance en bloc resection rates for larger, flat, or sessile lesions. Endoscopic full-thickness resection (EFTR) is employed for non-lifting lesions or those not easily amenable to resection. Procedures such as ESD or EFTR are emerging standards for lesions inaccessible to EMR techniques. SUMMARY: Endoscopic treatment is now regarded as first-line therapy for benign lesions. KEY MESSAGE: Endoscopic resection of dysplastic lesions or early stages of cancer is recommended. A plethora of different techniques can be used dependent on the lesions.

Mindfulness Training to Improve Nurse Clinical Performance: A Pilot Study.

Health care errors are a national concern. Although considerable attention has been placed on reducing errors since a 2000 Institute of Medicine report, adverse events persist. The purpose of this pilot study was to evaluate the effect of mindfulness training, employing the standardized approach of an eight-week mindfulness-based, stress reduction program on reduction of nurse errors in simulated clinical scenarios. An experimental, pre- and post-test control group design was employed with 20 staff nurses and senior nursing students. Although not statistically significant, there were numerical differences in clinical performance scores from baseline when comparing mindfulness and control groups immediately following mindfulness training and after three months. A number of benefits of mindfulness training, such as improved listening skills, were identified. This pilot study supports the benefits of mindfulness training in improving nurse clinical performance and illustrates a novel approach to employ in future research.

Computer-aided detection of colorectal polyps using a newly generated deep convolutional neural network: from development to first clinical experience.

AIM: The use of artificial intelligence represents an objective approach to increase endoscopist's adenoma detection rate (ADR) and limit interoperator variability. In this study, we evaluated a newly developed deep convolutional neural network (DCNN) for automated detection of colorectal polyps ex vivo as well as in a first in-human trial. METHODS: For training of the DCNN, 116 529 colonoscopy images from 278 patients with 788 different polyps were collected. A subset of 10 467 images containing 504 different polyps were manually annotated and treated as the gold standard. An independent set of 45 videos consisting of 15 534 single frames was used for ex vivo performance testing. In vivo real-time detection of colorectal polyps during routine colonoscopy by the DCNN was tested in 42 patients in a back-to-back approach. RESULTS: When analyzing the test set of 15 534 single frames, the DCNN's sensitivity and specificity for polyp detection and localization within the frame was 90% and 80%, respectively, with an area under the curve of 0.92. In vivo, baseline polyp detection rate and ADR were 38% and 26% and significantly increased to 50% (P = 0.023) and 36% (P = 0.044), respectively, with the use of the DCNN. Of the 13 additionally with the DCNN detected lesions, the majority were diminutive and flat, among them three sessile serrated adenomas. CONCLUSION: This newly developed DCNN enables highly sensitive automated detection of colorectal polyps both ex vivo and during first in-human clinical testing and could potentially increase the detection of colorectal polyps during colonoscopy.