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Background: Fundamental techniques and essential tools for performing "no scar" surgery still need to be developed. Our study was designed to evaluate the feasibility of performing small bowel resection by transcolonic NOTES(®) and transabdominal approach using rigid laparoscopic and flexible endoscopic instruments.Methods: One non survival and four survival experiments were performed using a porcine model. The endoscope with an overtube was advanced into the peritoneal cavity through the colotomy. Mini-laparoscopic instruments were placed through the abdominal wall under the endoscopic observation. The endoscope was replaced with a rigid linear stapler. The small bowel was identified. The segment of the small bowel was resected by firing the endo stapler, and extracted through the colon. The two limbs of the small bowel were approximated with two stay-sutures. An enterotomy was then created on the antimesenteric sides of each line. A side-to-side anastomosis was performed with another application of the endo stapler. The stapler was withdrawn. The enterotomy was closed by suturing. The colotomy was closed with endoclips and the endoscope was withdrawn. The mini-laparoscopic instruments were removed.Results: Small bowel resection was successfully performed in all animals. The surgery time was 70 minutes. There was no mortality or complications. The animals recovered uneventfully, and survived the 2 weeks postprocedure period. They remained healthy, and gained weight. Necropsy was performed 2 weeks after the surgery. On necropsy, evaluation of the abdominal skin revealed no scars. The peritoneal cavity was examined. No signs of infection, bleeding, perforations, and adhesions were noted. Endoscopic examination of the colotomy and anastomosis revealed complete healing that was confirmed by histopathology.Conclusions: The study has demonstrated the feasibility of small bowel resection using transcolonic NOTES(®) and transabdominal approach. Simultaneous use of flexible endoscopic and rigid laparoscopic instruments in NOTES(®) is not only feasible but has significant advantages and greatly facilitates the performance of the operation, yet leaves no scars. [ABSTRACT FROM AUTHOR]

BACKGROUND: Transgastric and transvaginal approaches in natural orifice transluminal endoscopic surgery (NOTES) are the most commonly used, although the transcolonic approach may have some advantages. OBJECTIVE: To develop a workable technique for transcolonic NOTES. DESIGN: A nonsurvival study followed by a survival study in a porcine model. Transcolonic peritoneoscopy was performed with the use of a novel intracolonic occlusion balloon. The colotomy was closed with endoclips. A necropsy and histologic evaluation were performed 2 weeks after surgery. SETTING: Academic hospital, health science research center. SUBJECTS: Fifteen female Yorkshire pigs (5 nonsurvival, 10 survival). INTERVENTIONS: A balloon-tipped catheter was placed proximal to the colotomy site. The balloon was inflated to occlude the colonic lumen. An endoscope was inserted through the anus. Colonic incision was created with an endoscopic needle-knife at 15 to 20 cm from the anal verge. Peritoneoscopy was performed. The colotomy was closed with endoclips. MAIN OUTCOME MEASUREMENTS: Rates of complications, survival, healing, and adhesions. RESULTS: Two initial experiments were complicated by bowel distension and contamination of the incision area by colonic content. In the remaining 13 pigs, the experiments were performed with the use of the intracolonic occlusion balloon. No complications were documented. Necropsies were performed 2 weeks after surgery. Gross and histologic evaluations demonstrated near complete healing. Minimal adhesions were identified in 4 of 10 pigs. LIMITATION: Imperfection of the prototype balloon. CONCLUSIONS: Excessive bowel distension and fecal contamination because of spillage from the proximal bowel may be barriers to performing transcolonic NOTES. Isolation of the operative area by splitting the bowel and sealing the colonic lumen with the balloon above the colonic incision may overcome these problems and optimize the technique. [ABSTRACT FROM AUTHOR]

BACKGROUND: The cardiovascular safety of testosterone-replacement therapy in middle-aged and older men with hypogonadism has not been determined. METHODS: In a multicenter, randomized, double-blind, placebo-controlled, noninferiority trial, we enrolled 5246 men 45 to 80 years of age who had preexisting or a high risk of cardiovascular disease and who reported symptoms of hypogonadism and had two fasting testosterone levels of less than 300 ng per deciliter. Patients were randomly assigned to receive daily transdermal 1.62% testosterone gel (dose adjusted to maintain testosterone levels between 350 and 750 ng per deciliter) or placebo gel. The primary cardiovascular safety end point was the first occurrence of any component of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, assessed in a time-to-event analysis. A secondary cardiovascular end point was the first occurrence of any component of the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization, assessed in a time-to-event analysis. Noninferiority required an upper limit of less than 1.5 for the 95% confidence interval of the hazard ratio among patients receiving at least one dose of testosterone or placebo. RESULTS: The mean (±SD) duration of treatment was 21.7±14.1 months, and the mean follow-up was 33.0±12.1 months. A primary cardiovascular end-point event occurred in 182 patients (7.0%) in the testosterone group and in 190 patients (7.3%) in the placebo group (hazard ratio, 0.96; 95% confidence interval, 0.78 to 1.17; P<0.001 for noninferiority). Similar findings were observed in sensitivity analyses in which data on events were censored at various times after discontinuation of testosterone or placebo. The incidence of secondary end-point events or of each of the events of the composite primary cardiovascular end point appeared to be similar in the two groups. A higher incidence of atrial fibrillation, of acute kidney injury, and of pulmonary embolism was observed in the testosterone group. CONCLUSIONS: In men with hypogonadism and preexisting or a high risk of cardiovascular disease, testosterone-replacement therapy was noninferior to placebo with respect to the incidence of major adverse cardiac events. [ABSTRACT FROM AUTHOR]

BACKGROUND Upadacitinib, an oral selective Janus kinase (JAK) inhibitor, is under investigation for the treatment of Crohn's disease. METHODS In two phase 3 induction trials (U-EXCEL and U-EXCEED), we randomly assigned patients with moderate-to-severe Crohn's disease to receive 45 mg of upadacitinib or placebo (2:1 ratio) once daily for 12 weeks. Patients who had a clinical response to upadacitinib induction therapy were randomly assigned in the U-ENDURE maintenance trial to receive 15 mg of upadacitinib, 30 mg of upadacitinib, or placebo (1:1:1 ratio) once daily for 52 weeks. The primary end points for induction (week 12) and maintenance (week 52) were clinical remission (defined as a Crohn's Disease Activity Index score of <150 [range, 0 to 600, with higher scores indicating more severe disease activity]) and endoscopic response (defined as a decrease in the Simple Endoscopic Score for Crohn's Disease [SES-CD; range, 0 to 56, with higher scores indicating more severe disease] of >50% from baseline of the induction trial [or for patients with an SES-CD of 4 at baseline, a decrease of >2 points from baseline]). RESULTS A total of 526 patients underwent randomization in U-EXCEL, 495 in U-EXCEED, and 502 in U-ENDURE. A significantly higher percentage of patients who received 45-mg upadacitinib than those who received placebo had clinical remission (in U-EXCEL, 49.5% vs. 29.1%; in U-EXCEED, 38.9% vs. 21.1%) and an endoscopic response (in U-EXCEL, 45.5% vs. 13.1%; in U-EXCEED, 34.6% vs. 3.5%) (P<0.001 for all comparisons). At week 52 in U-ENDURE, a higher percentage of patients had clinical remission with 15-mg upadacitinib (37.3%) or 30-mg upadacitinib (47.6%) than with placebo (15.1%), and a higher percentage had an endoscopic response with 15-mg upadacitinib (27.6%) or 30-mg upadacitinib (40.1%) than with placebo (7.3%) (P<0.001 for all comparisons). Herpes zoster infections occurred more frequently in the 45-mg and 30-mg upadacitinib groups than in the respective placebo groups, and hepatic disorders and neutropenia were more frequent in the 30-mg upadacitinib group than in the other maintenance groups. Gastrointestinal perforations developed in 4 patients who received 45-mg upadacitinib and in 1 patient each who received 30-mg or 15-mg upadacitinib. CONCLUSIONS Upadacitinib induction and maintenance treatment was superior to placebo in patients with moderate-to-severe Crohn's disease. [ABSTRACT FROM AUTHOR]

Background and Objective: Studies examining ambulatory blood pressure (BP) response to testosterone replacement therapy are needed owing to inconsistent prior findings across formulations. This study assessed testosterone gel 1.62% and 24-h ambulatory BP., Materials and Methods: Single-arm non-inferiority trial (NCT04274894) conducted at 36 US sites enrolled 246 men with hypogonadism (mean age, 57.6 years; mean office systolic/diastolic BP [SBP/DBP], 129.8/79.5 mm Hg) who were treated for 16 weeks with once-daily testosterone gel treatment (starting dose, 40.5 mg/day; min, max dose, 20.25, 81.0 mg/day) to achieve testosterone concentration of 350-750 ng/dL. Main outcome measures included mean change in 24-h average SBP (primary endpoint) and DBP from baseline to week 16. The non-inferiority threshold was a two-sided 95% confidence interval (CI) upper limit <3.0 mm Hg for 24-h average SBP., Results: Increase in mean ± SD serum testosterone concentration to a physiologic level (baseline, 244.4 ± 93.9 ng/dL; week 16, 502.5 ± 394.4 ng/dL) was associated with a 1.9-mm Hg mean change in 24-h average SBP observed in the primary analysis (baseline, 123.5 mm Hg; week 16, 125.4 mm Hg; 95% CI, 0.63-3.13 mm Hg; n = 169). As the upper CI limit modestly exceeded the non-inferiority margin (3 mm Hg), study drug effect on SBP could not be ruled out. Non-inferiority was observed in subgroups without hypertension or diabetes (95% CI, upper limit <3.0 mm Hg) and was not observed in those with hypertension or diabetes. Daytime SBP and DBP changes were larger compared with nighttime. No clear cardiovascular adverse events or new safety signals were identified., Discussion and Conclusions: While the effect of testosterone gel 1.62% on 24-h average SBP could not be ruled out based on the study's non-inferiority margin, the clinical relevance of the small-magnitude mean increase of 1.9 mm Hg is anticipated to be minimal considering the results of the TRAVERSE study of testosterone gel 1.62% and major adverse cardiac events., Clinical Trial Information: ClinicalTrials.gov identifier: NCT04274894 (registered February 17, 2020)., (© 2024 American Society of Andrology and European Academy of Andrology.)

Background & Aims: Upadacitinib, an oral Janus kinase inhibitor, achieved significantly higher rates of clinical remission and endoscopic response vs placebo during induction (U-EXCEL [NCT03345849], U-EXCEED [NCT03345836]) and maintenance (U-ENDURE [NCT03345823]) treatment in patients with moderate-to-severe Crohn's disease. Prior biologic failure is often associated with reduced responses to subsequent therapies. This post hoc analysis assessed upadacitinib efficacy by prior biologic failure status., Methods: Patients were randomized to placebo or upadacitinib 45 mg (UPA45) for 12 weeks (induction). UPA45 clinical responders were enrolled in U-ENDURE and rerandomized to placebo, upadacitinib 15 mg, or upadacitinib 30 mg (UPA30) for 52 weeks. Assessments were by prior biologic failure., Results: Of 1021 patients, 733 (71.8%) had prior biologic failure. Across outcomes and subgroups, upadacitinib-treated patients achieved higher rates vs placebo. During induction, upadacitinib had higher rates vs placebo for clinical remission based on stool frequency/abdominal pain score (without failure: 54.0% vs 28.3%; with failure: 42.2% vs 14.1%) and endoscopic response (without failure: 52.0% vs 16.2%; with failure: 35.7% vs 5.3%). In maintenance, the greatest treatment effect (upadacitinib vs placebo) was among patients with prior biologic failure treated with UPA30 (clinical remission without failure: 58.5% vs 32.7%; with failure: 42.5% vs 8.7%; endoscopic response without failure: 43.9% vs 17.9%; with failure: 38.9% vs 4.0%). Patients without vs with prior biologic failure had fewer adverse events., Conclusions: Upadacitinib led to higher absolutes rates of clinical and endoscopic outcomes in patients without vs with prior biologic failure. Patients treated with upadacitinib achieved greater rates of clinical and endoscopic improvements vs placebo, regardless of prior biologic exposure., Clinicaltrials: gov: NCT03345849, NCT03345836, NCT03345823., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background & Aims: Efficacy of upadacitinib, an oral Janus kinase inhibitor, for moderate-to-severe Crohn's disease was demonstrated in phase 3 induction (U-EXCEL, U-EXCEED) and maintenance (U-ENDURE) trials; this post hoc analysis evaluated upadacitinib outcomes in patients with fistulizing disease in these studies., Methods: Patients were randomized (2:1) to once daily upadacitinib 45 mg or placebo for 12 weeks. Upadacitinib 45 mg clinical responders were rerandomized (1:1:1) to upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 52 weeks. In patients with fistulas (any and perianal), resolution of drainage, closure of external openings, clinical remission, endoscopic response, and safety were assessed., Results: Of 1021 patients in U-EXCEL and U-EXCEED, 143 (14.0%) had any fistulas at baseline (66 draining); of these, most (n = 128) had perianal fistulas (56 draining). Greater proportions of patients receiving upadacitinib vs placebo achieved resolution of drainage of perianal fistulas at the end of induction (placebo: 5.6%, n/n = 1/18; upadacitinib 45 mg: 44.7%, n/n = 17/38; P = .003) and maintenance (placebo: 0%, n/n = 0/11; upadacitinib 15 mg: 28.6%, n/n = 4/14; P = .105; upadacitinib 30 mg: 23.1% n/n = 3/13; P = .223) and closure of perianal fistula external openings (for induction, placebo: 4.8%, n/n = 2/42; upadacitinib 45 mg: 22.1%, n/n = 19/86; P = .013; for maintenance, placebo: 0%, n/n = 0/30; upadacitinib 15 mg: 18.8%, n/n = 6/32; P = .024; upadacitinib 30 mg: 16.0%, n/n = 4/25; P = .037)., Conclusion: Patients with fistulizing disease (primarily perianal) treated with upadacitinib achieved higher rates of resolution of drainage, closure of external openings, clinical remission, and endoscopic response vs placebo., Clinicaltrials: gov, Numbers: NCT03345849 (U-EXCEL), NCT03345836 (U-EXCEED), NCT03345823 (U-ENDURE)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Testosterone exerts some effects on the cardiovascular system that could be considered beneficial; some other effects may potentially increase the risk of cardiovascular (CV) events. Neither the long-term efficacy nor safety of testosterone treatment has been studied in an adequately-powered randomized trial., Methods: The Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men (TRAVERSE) study is a randomized, double-blind, placebo-controlled, parallel group, non-inferiority, multicenter study. Eligible participants are men, 45 to 80 years, with serum testosterone concentration <300 ng/dL and hypogonadal symptoms, who have evidence pre-existing CV disease or increased risk of CV disease. Approximately 6,000 subjects will be randomized to either 1.62% transdermal testosterone gel or a matching placebo gel daily for an anticipated duration of up to 5 years. The primary outcome is CV safety defined by the major adverse CV event composite of nonfatal myocardial infarction, nonfatal stroke, or death due to CV causes. The trial will continue until at least 256 adjudicated major adverse CV event endpoints have occurred to assess whether the 95% (2-sided) upper confidence limit for a hazard ratio of 1.5 can be ruled out. Secondary endpoints include prostate safety defined as the incidence of adjudicated high grade prostate cancer and efficacy in domains of sexual function, bone fractures, depression, anemia, and diabetes., Results: As of July 1, 2021, 5,076 subjects had been randomized., Conclusions: The TRAVERSE study will determine the CV safety and long-term efficacy of testosterone treatment in middle-aged and older men with hypogonadism with or at increased risk of CV disease., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The Crohn's Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score for Crohn's Disease (SES-CD) are commonly used to assess Crohn's disease (CD) activity; however neither instrument is fully validated. We evaluated the responsiveness to change of the SES-CD and CDEIS using data from a trial of adalimumab, a drug therapy of known efficacy., Methods: Paired video recordings (N=112) of colonoscopies (baseline and week 8-12) obtained from patients with CD who participated in a trial of adalimumab therapy were reviewed in random order, in duplicate, by four central readers (56 pairs of videos by 2 groups of readers). Responsiveness of the SES-CD and the CDEIS was evaluated by comparing correlations between the observed and pre-specified predictions of change scores for these endoscopic indices with a global endoscopic evaluation of severity (GELS), a patient reported outcome (PRO2), and the Crohn's disease activity index (CDAI), and by calculation of the standardized effect size, and Guyatt's Responsiveness statistic (GRS) using 2 definitions of change; (1) treatment assignment and (2) an absolute change in total PRO2 of 50. The potential application of effect size estimates was demonstrated by calculating hypothetical sample sizes for comparing two independent groups. The impact of removing stenosis as an index item and adjusting for the number of segments observed was also assessed., Results: Changes in both endoscopic instruments and the GELS were highly correlated. The SES-CD displayed numerically higher effect sizes for both definitions of change. The standardized effect size and GRS estimates (95% confidence interval) for the SES-CD based on treatment assignment were 0.84 (0.53, 1.15) and 0.79 (0.48, 1.09). Corresponding values for the CDEIS were 0.72 (0.42, 1.02) and 0.75 (0.45, 1.06). The standardized effect size and GRS estimates for the SES-CD based on an absolute change in total PRO2 of 50 points or greater were 0.76 (0.49, 1.02) and 0.93 (0.64, 1.21). Corresponding values for CDEIS were 0.70 (0.44, 0.97), 0.83 (0.55, 1.10). Removal of stenosis as an index item and adjusting for observed segments did not improve responsiveness estimates., Conclusions: Although both the SES-CD and CDEIS are valid measures of endoscopic disease activity that are moderately responsive to changes in endoscopic disease activity, the SES-CD displayed numerically greater responsiveness in this data set.

Background and Aims: The Crohn's Disease Endoscopic Index of Severity [CDEIS] and Simplified Endoscopic Score for Crohn's Disease [SES-CD] demonstrate consistent overall intra- and inter-rater reliability. However, the reliability of some index items is relatively poor. We evaluated scoring conventions to improve the reliability of these items., Methods: Five gastroenterologists with no previous experience scoring the CDEIS or SES-CD were trained on their use. A total of 65 video recordings of colonoscopies were scored blindly by each gastroenterologist before and after additional training on index scoring conventions. Intra-class correlation coefficients [ICCs] assessed the effect of application of these conventions on the reliability of the CDEIS, SES-CD, and a Global Evaluation of Lesion Severity [GELS] score., Results: Following training on scoring conventions, inter-rater ICCs (95% confidence interval [CI]) for the total SES-CD score increased from 0.78 [0.71, 0.85] to 0.85 [0.79, 0.89]. The ICCs for the total CDEIS and GELS scores were not affected: corresponding inter-rater ICCs were 0.74 [0.65, 0.81] and 0.49, [0.38, 0.61] before and 0.73 [0.65, 0.81] and 0.53 [0.42, 0.64] following application of scoring conventions. Estimations of ulcer depth, surface area, anatomical location, and stenosis were important sources of variability., Conclusions: Use of scoring conventions previously developed by expert central readers enhanced the reliability of the SES-CD but did not similarly affect the CDEIS or GELS. As the SES-CD is more likely to be reliable than the CDEIS and can be optimised with targeted training, it is the preferred instrument for use in clinical trials., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The Crohn's Disease Endoscopic Index of Severity (CDEIS) and Simple Endoscopic Score for Crohn's Disease (SES-CD) are commonly used to assess Crohn's disease (CD) activity; however, neither instrument has been fully validated. We assessed intra-rater and inter-rater reliability of these indices., Design: Video recordings of colonoscopies obtained from 50 patients with CD who participated in an induction trial of a biological therapy were triplicated and reviewed in random order by four central readers. Data were used to assess intra-rater and inter-rater reliability for CDEIS, SES-CD and a global evaluation of lesion severity (GELS). Subsequently, readers participated in a consensus process that identified common sources of disagreement., Results: Intraclass correlation coefficients (ICCs) for intra-rater reliability for CDEIS, SES-CD and GELS (95% CIs) were 0.89 (0.86 to 0.93), 0.91 (0.89 to 0.95) and 0.81 (0.77 to 0.89), respectively, with standard error of measurement (SEM) of 2.10, 2.42 and 1.15. The corresponding ICCs for inter-rater reliability were 0.71 (0.63 to 0.76), 0.83 (0.75 to 0.88) and 0.62 (0.52 to 0.70), with SEM of 3.42, 3.07 and 1.63, respectively. Correlation between CDEIS and GELS was 0.75, between SES-CD and GELS was 0.74 and between CDEIS and SES-CD was 0.92. The most common sources of disagreement were interpretation of superficial ulceration, definition of disease site at the ileocolonic anastomosis, assessment of anorectal lesions and grading severity of stenosis., Conclusions: Central reading of CDEIS and SES-CD had 'substantial' to 'almost perfect' intra-rater and inter-rater reliability; however, the responsiveness of these instruments is yet to be determined., Trial Registration Number: Clinicaltrials.gov NCT01466374., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Crohn's disease (CD) is an idiopathic, chronic, transmural inflammatory disorder of the gastrointestinal tract. Because mucosal involvement is near-universal, endoscopic healing has emerged as an important aspect in improving outcome. However, resolution of histologic disease activity has potential to convey additional benefit beyond that attained with endoscopic healing alone. Validated scoring systems of histologic disease activity are required to further assess this possibility. The aim of this study was to systematically review the existing histologic disease activity indices (HDAI) for CD and to assess their operating properties and potential use as outcome measures in clinical trials., Methods: MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and Digestive Disease Week (DDW) abstracts were searched from 1981 to April 2013 for applicable studies to identify relevant studies for review and analysis., Results: In total, 3732 citations were screened to obtain 89 articles for inclusion. Sixty-six HDAIs were characterized as either stepwise or numerical instruments. These HDAIs were used for either assessment of response to medical therapy or for comparison with biomarkers or imaging tests. None of the HDAIs identified was developed according to currently accepted methods for developing evaluative instruments, and none have been formally validated., Conclusions: Measurement of histologic disease activity has potential value in CD; however, no validated measures are available. Additional research is needed to develop a methodologically rigorous instrument for use in clinical investigation and potentially for clinical practice.

Background: Crohn's disease (CD) is a chronic idiopathic inflammatory disorder of the gastrointestinal tract. Recently, mucosal healing has been proposed as a goal of therapy because clinical symptoms are subjective. Evaluative indices that measure endoscopic disease activity are required to define mucosal healing for clinical trials. The primary objective of this systematic review was to assess the existing evaluative indices that measure disease activity in CD and evaluate their role as outcome measures in clinical trials., Methods: A systematic literature review was performed using MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and DDW abstracts to identify randomized controlled trials and controlled clinical trials that used a relevant evaluative index from inception to February 2013. The data obtained from these trials were reviewed and summarized., Results: The initial literature searches identified 2300 citations. After duplicates were removed, 1454 studies remained. After application of the apriori inclusion and exclusion criteria, 109 articles were included and 3 were identified with handsearches. In total, 9 evaluative indices for CD were identified and reviewed. The Crohn's Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score in Crohn's Disease (SES-CD) are indices with the most extensively described operating properties., Conclusions: Both the endoscopic evaluative instrument selected and the definition chosen for mucosal healing affect the validity of assessing endoscopic disease activity during a clinical trial for CD. Currently, the CDEIS and SES-CD have the most data regarding operating properties; however, further validation is required.

Background: Assessment of endoscopic disease activity, as measured by various endoscopic evaluative instruments, is an essential part of quantifying disease activity in clinical trials in patients with ulcerative colitis (UC). Evaluative instruments have specific definitions and operating properties that influence the interpretation of clinical trial results. Our objective was to systematically review all endoscopic evaluative instruments that measure endoscopic disease activity in UC and to describe their definitions and operating characteristics (reliability, responsiveness, and predictive validity)., Methods: We performed a systematic review of evaluative instruments assessing endoscopic disease activity in UC. MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and Digestive Disease Week abstracts of clinical trials were searched from inception to January 2013., Results: In total, 5885 studies were identified and screened for inclusion criteria. Four hundred twenty-two studies involving 31 evaluative instruments were identified. Two types of indices were found, numerical scoring systems and stepwise grading scales., Conclusions: Both the endoscopic evaluative instrument selected and the definition chosen for mucosal healing affect the validity of assessing endoscopic disease activity during a clinical trial for UC. Currently, the sigmoidoscopic component of the Mayo Score and the ulcerative colitis endoscopic index of severity show the most promise as reliable evaluative instruments of endoscopic disease activity. However, further validation is required.

Introduction: Lasers 2-microm in wavelength offer efficient tissue cutting with limited thermal damage in biological tissue., Objective: To evaluate the dissection capabilities of a 2-microm continuous-wave laser for NOTES procedures., Methods and Procedures: We conducted 18 acute animal experiments. Group 1 (three animals): transcolonic access to the peritoneal cavity (15-W transcolonic laser puncture, balloon dilation over the laser probe). Group 2 (six animals): transcolonic access with needle-knife puncture and balloon dilation. Group 3 (three animals): transgastric access to the peritoneal cavity (similar technique as group 1) followed by laser-assisted dissection of the kidney. In one animal of group 3, a therapeutic target (hematoma) was created by percutaneous puncture of the kidney. Group 4 (six animals): transgastric access (similar to the technique of group 2)., Results: Translumenal access to the peritoneal cavity was achieved in 2-3 min in group 1 (significantly shorter than with the needle-knife-assisted technique, 4-5 min, p=0.02) and in 7-10 min in group 3 (compared to 6-17 min in group 4, p=0.88). In group 3, laser dissection of the parietal peritoneum and of perinephric connective tissue allowed access to the retroperitoneum with complete removal of a blood collection in the animal with puncture trauma. Laser dissection demonstrated good maneuverability, clean and rapid cutting, and excellent hemostasis. Peritoneoscopy and necropsy showed no damage of targeted tissue and surrounding organs., Conclusions: The 2-microm continuous-wave laser system showed promising capabilities for highly precise and safe dissection during NOTES procedures.

Background: A 65-year-old white Mediterranean male with a 10-year history of intermittent anemia, who was otherwise completely asymptomatic, was referred to our hospital in March 2004. He had a medical history of beta thalassemia and fecal occult blood tests had occasionally been positive., Investigations: Fecal occult blood test, laboratory investigations, esophagogastroduodenoscopy, colonoscopy with retrograde ileoscopy, mesenteric angiography, small-bowel series, CT scan of the abdomen and pelvis, Meckel's scan, and capsule endoscopy. Laparoscopic surgery followed by macroscopic and microscopic histopathologic examination of samples obtained during the procedure., Diagnosis: Crohn's disease of the small bowel., Management: Laparoscopic segmental small-bowel resection with end-to-end anastomosis. Postsurgical treatment with Pentasa 4 g a day.

Background and Aims: Capsule endoscopy (CE) has been increasingly used for diagnosing diseases of the small bowel. It is an attractive technique for assessing celiac disease (CD) because it is noninvasive and provides a close and magnified view of the mucosa of the entire small bowel. In this study, we evaluated the accuracy of CE and interobserver agreement in recognizing villous atrophy (VA) using histopathology as the reference. We also explored the extent of small bowel involvement with CD and the relationship between the length of the affected bowel and the clinical presentation., Methods: Ten CD patients with histologically proven VA and the same number of controls were subjected to CE. Four, blinded to histology findings, investigators (two with and two without prestudy CE experience) were asked to diagnose VA on CE images., Results: Based on assessment of all four investigators, the overall sensitivity, specificity, PPV, and NPV of CE in diagnosing VA were 70%, 100%, 100%, and 77%, respectively. The sensitivity and the specificity of the test was 100% when the reports of experienced capsule endoscopists only were analyzed. The interobserver agreement was perfect (kappa= 1.0) between investigators with prestudy CE experience and poor (kappa= 0.2) between the investigators who had limited prestudy exposure to CE. Celiac patients with extensive small bowel involvement had typical symptoms of malabsorption (diarrhea, weight loss) as opposed to mild and nonspecific symptoms in patients whose disease was limited to the proximal small bowel. CE was tolerated well by all study participants with 95% reporting absence of any discomfort., Conclusions: Although based on a small sample size, the study suggests that CE may be useful in assessing patients with CD. Familiarity with CE technology appears to be a critical factor affecting the accuracy of the test. Larger studies are warranted to more precisely define the advantages and limitations of CE in CD.

Background: Wireless capsule endoscopy (CE) is increasingly being used in the investigation of obscure gastrointestinal (GI) bleeding, but some studies have found that many of the bleeding lesions recognized by this technique are within the reach of conventional endoscopy., Methods: The results of CE performed in the authors' centre in a 12 month period for obscure GI bleeding were retrospectively reviewed., Results: Of the 46 patients with obscure GI bleeding, CE found a definite or probable cause in 19 (41%) and a possible cause in another 10 (22%), with an overall diagnostic yield of 63%. One of these lesions was found to be within reach of conventional gastroscopy, two were within reach of push enteroscopy, four were within reach of colonoscopy and one was within reach of retrograde enteroscopy through a stoma. The percentage of patients with a bleeding source within reach of routine endoscopy but missed during pre-CE endoscopy was significantly higher for those patients having endoscopy only in the community (30% [eight of 27]) versus in the authors' centre (0% [zero of 19])., Conclusions: CE was valuable for diagnosing bleeding lesions not only within the small bowel, but also in the stomach and colon. However, "second-look" endoscopy may be considered before ordering CE for obscure GI bleeding when local expertise is available.