Detecting host responses to microbial stimulation using primary epithelial organoids.

The intestinal epithelium is constantly exposed to microbes residing in the lumen. Traditionally, the response to microbial interactions has been studied in cell lines derived from cancerous tissues, e.g. Caco-2. It is, however, unclear how the responses in these cancer cell lines reflect the responses of a normal epithelium and whether there might be microbial strain-specific effects. To address these questions, we derived organoids from the small intestine from a cohort of healthy individuals. Culturing intestinal epithelium on a flat laminin matrix induced their differentiation, facilitating analysis of microbial responses via the apical membrane normally exposed to the luminal content. Here, it was evident that the healthy epithelium across multiple individuals (n = 9) demonstrates robust acute both common and strain-specific responses to a range of probiotic bacterial strains (BB-12Ⓡ, LGGⓇ, DSM33361, and Bif195). Importantly, parallel experiments using the Caco-2 cell line provide no acute response. Collectively, we demonstrate that primary epithelial cells maintained as organoids represent a valuable resource for assessing interactions between the epithelium and luminal microbes across individuals, and that these models are likely to contribute to a better understanding of host microbe interactions.

Optimizing Screening for Colorectal Cancer: An Algorithm Combining Fecal Immunochemical Test, Blood-Based Cancer-Associated Proteins and Demographics to Reduce Colonoscopy Burden.

BACKGROUND: Fecal Immunochemical Test (FIT) is widely used in population-based screening for colorectal cancer (CRC). This had led to major challenges regarding colonoscopy capacity. Methods to maintain high sensitivity without compromising the colonoscopy capacity are needed. This study investigates an algorithm that combines FIT result, blood-based biomarkers associated with CRC, and individual demographics, to triage subjects sent for colonoscopy among a FIT positive (FIT+) screening population and thereby reduce the colonoscopy burden. MATERIALS AND METHODS: From the Danish National Colorectal Cancer Screening Program, 4048 FIT+ (≥100 ng/mL Hemoglobin) subjects were included and analyzed for a panel of 9 cancer-associated biomarkers using the ARCHITECT i2000. Two algorithms were developed: 1) a predefined algorithm based on clinically available biomarkers: FIT, age, CEA, hsCRP and Ferritin; and 2) an exploratory algorithm adding additional biomarkers: TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, B2M and sex to the predefined algorithm. The diagnostic performances for discriminating subjects with or without CRC in the 2 models were benchmarked against the FIT alone using logistic regression modeling. RESULTS: The discrimination of CRC showed an area under the curve (AUC) of 73.7 (70.5-76.9) for the predefined model, 75.3 (72.1-78.4) for the exploratory model, and 68.9 (65.5-72.2) for FIT alone. Both models performed significantly better (P < .001) than the FIT model. The models were benchmarked vs. FIT at cutoffs of 100, 200, 300, 400, and 500 ng/mL Hemoglobin using corresponding numbers of true positives and false positives. All performance metrics were improved at all cutoffs. CONCLUSION: A screening algorithm including a combination of FIT result, blood-based biomarkers and demographics outperforms FIT in discriminating subjects with or without CRC in a screening population with FIT results above 100 ng/mL Hemoglobin.

Early detection of colorectal neoplasia: application of a blood-based serological protein test on subjects undergoing population-based screening.

BACKGROUND: Blood-based biomarkers used for colorectal cancer screening need to be developed and validated in appropriate screening populations. We aimed to develop a cancer-associated protein biomarker test for the detection of colorectal cancer in a screening population. METHODS: Participants from the Danish Colorectal Cancer Screening Program were recruited. Blood samples were collected prior to colonoscopy. The cohort was divided into training and validation sets. We present the results of model development using the training set. Age, sex, and the serological proteins CEA, hsCRP, TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, ferritin and B2M were used to develop a signature test to discriminate between participants with colorectal cancer versus all other findings at colonoscopy. RESULTS: The training set included 4048 FIT-positive participants of whom 242 had a colorectal cancer. The final model for discriminating colorectal cancer versus all other findings at colonoscopy had an AUC of 0.70 (95% CI: 0.66-0.74) and included age, sex, CEA, hsCRP, HE4 and ferritin. CONCLUSION: The performance of the biomarker signature in this FIT-positive screening population did not reflect the positive performance of biomarker signatures seen in symptomatic populations. Additional biomarkers are needed if the serological biomarkers are to be used as a frontline screening test.

Danish Society for Gastroenterology and Hepatology's clinical recommendations for colonoscopic surveillance for colorectal dysplasia and cancer in patients with inflammatory bowel disease.

OBJECTIVES: We aimed to produce clinical recommendations for colonoscopic surveillance for dysplasia and colorectal cancer in patients with inflammatory bowel diseases. MATERIALS AND METHODS: The Danish Society for Gastroenterology and Hepatology convened a committee to assess the literature on colorectal cancer in inflammatory bowel diseases and the effectiveness of colonoscopy surveillance, according to the Oxford Centre for Evidence Based Medicine levels of evidence. RESULTS: Clinical recommendations for the colonoscopic surveillance for dysplasia and colorectal cancer in patients with inflammatory bowel diseases were produced. These guidelines cover the risk stratification, entry, and follow-up of patients in the colonoscopy programme, the choice of image-enhanced colonoscopy modality, the investigation and treatment of lesions, and the management of special patient populations in the colonoscopy programme. CONCLUSIONS: Colonoscopic surveillance of inflammatory bowel disease is thought to be associated with a decreased risk of colorectal cancer and colorectal cancer-related mortality. Further evidence regarding the effectiveness of colonoscopic surveillance will contribute to understanding its role in the management of inflammatory bowel diseases. The Danish Society for Gastroenterology and Hepatology clinical guideline will aid gastroenterologists in the risk stratification of patients with inflammatory bowel disease, and the management of colorectal lesions. Gastroenterologists must inform and support patients with inflammatory bowel disease to decide whether to participate in the colonoscopic surveillance programme.

Personalized B cell response to the Lactobacillus rhamnosus GG probiotic in healthy human subjects: a randomized trial.

The specific effects of administering live probiotics in the human gut are not well characterized. To this end, we investigated the immediate effect of Lactobacillus rhamnosus GG (LGG) in the jejunum of 27 healthy volunteers 2 h after ingestion using a combination of global RNA sequencing of human biopsies and bacterial DNA sequencing in a multi-visit, randomized, cross-over design (ClinicalTrials.gov number NCT03140878). While LGG was detectable in jejunum after 2 h in treated subjects, the gene expression response vs. placebo was subtle if assessed across all subjects. However, clustering analysis revealed that one-third of subjects exhibited a strong and consistent LGG response involving hundreds of genes, where genes related to B cell activation were upregulated, consistent with prior results in mice. Immunohistochemistry and single cell-based deconvolution analyses showed that this B cell signature likely is due to activation and proliferation of existing B cells rather than B cell immigration to the tissue. Our results indicate that the LGG strain has an immediate effect in the human gut in a subpopulation of individuals. In extension, our data strongly suggest that studies on in vivo probiotic effects in humans require large cohorts and must take individual variation into account.

Pain perception during colonoscopy in relation to gender and equipment: a clinical study.

Objectives A trend for gender-related differences in pain perception during colonoscopies has previously been observed. No consecutive clinical studies have been conducted to confirm such a relation. We aimed to investigate gender-related differences during the colonoscopy procedure, and the impact of endoscopic equipment and psychological factors on pain management. Methods In a consecutive clinical study, 391 patients referred for colonoscopy reported pain perception on a 0-10 visual analogue scale (VAS) after the procedure. A sub-group of patients (n=38) were given alternate instructions expertly tailored by a psychologist and their VAS scores were compared with those from the main study population. Data from a previous study from the same specialist practice and same source patient population using previous-generation equipment was included for comparison. Results No overall gender-related difference in VAS reports was found. There was no reduction in VAS when alternate instructions were given. Female patients were, however, more likely to benefit from light sedation (p=0.012). When compared with previous-generation endoscopes, the current generation equipment resulted in a VAS drop of 1.9 points for women and 1.6 for men (p<0.009) and washed out a previously observed gender-related difference. Conclusion No overall gender-related differences were found for pain experience during the colonoscopy procedure. Access to up-to-date endoscopic equipment can reduce procedure-related patient discomfort considerably, even at the expert level of a consultant physician. Implications Gastroenterologists should consider utilizing high-end endoscopic equipment to improve pain management and reduce VAS to very acceptable levels.

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.).

Enteroendocrine K and L cells in healthy and type 2 diabetic individuals.

AIMS/HYPOTHESIS: Enteroendocrine K and L cells are pivotal in regulating appetite and glucose homeostasis. Knowledge of their distribution in humans is sparse and it is unknown whether alterations occur in type 2 diabetes. We aimed to evaluate the distribution of enteroendocrine K and L cells and relevant prohormone-processing enzymes (using immunohistochemical staining), and to evaluate the mRNA expression of the corresponding genes along the entire intestinal tract in individuals with type 2 diabetes and healthy participants. METHODS: In this cross-sectional study, 12 individuals with type 2 diabetes and 12 age- and BMI-matched healthy individuals underwent upper and lower double-balloon enteroscopy with mucosal biopsy retrieval from approximately every 30 cm of the small intestine and from seven specific anatomical locations in the large intestine. RESULTS: Significantly different densities for cells positive for chromogranin A (CgA), glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, peptide YY, prohormone convertase (PC) 1/3 and PC2 were observed along the intestinal tract. The expression of CHGA did not vary along the intestinal tract, but the mRNA expression of GCG, GIP, PYY, PCSK1 and PCSK2 differed along the intestinal tract. Lower counts of CgA-positive and PC1/3-positive cells, respectively, were observed in the small intestine of individuals with type 2 diabetes compared with healthy participants. In individuals with type 2 diabetes compared with healthy participants, the expression of GCG and PYY was greater in the colon, while the expression of GIP and PCSK1 was greater in the small intestine and colon, and the expression of PCSK2 was greater in the small intestine. CONCLUSIONS/INTERPRETATION: Our findings provide a detailed description of the distribution of enteroendocrine K and L cells and the expression of their products in the human intestinal tract and demonstrate significant differences between individuals with type 2 diabetes and healthy participants. TRIAL REGISTRATION: NCT03044860.

Impact of feedback and monitoring on colonoscopy withdrawal times and polyp detection rates.

BACKGROUND: Previous studies have shown colonoscopy withdrawal time (WT) to be a reliable surrogate indicator for polyp detection rate (PDR) and adenoma detection rate (ADR) in colonoscopy. Our aim was to assess the impact of feedback and monitoring of WT on PDR in routine colonoscopies with long-term follow-up. MATERIALS AND METHODS: A total of 307 colonoscopies were performed in three separate clinical scenarios. First, PDR and WT were recorded without the staff being aware of the specific objective of the study. Before the second scenario, the staff was given interventional information and feedback on WTs and PDRs from the first scenario and was encouraged to aim for a minimum WT of 8 min. Retention of knowledge gained was reassessed in the third scenario 1 year later. RESULTS: The PDR in the first two scenarios differed significantly (p<0.01), with a more than 90% increase in PDR after intervention from 22% to 42% (95% CI 1.44 to 4.95), although the mean WT did not change (6.8 vs 7.2 min; p>0.05). The increase in PDR between the first and second scenarios was retained in the third follow-up scenario 1 year later where the WT of both polyp-positive and polyp-negative colonoscopies was found to be longer. CONCLUSIONS: PDR almost doubled from the first to the second scenario of a real-life colonoscopy setting, indicating that awareness of WT is crucial. The knowledge gained from this intervention in routine practice was even retained after a year.

Protocol Outlines for Parts 1 and 2 of the Prospective Endoscopy III Study for the Early Detection of Colorectal Cancer: Validation of a Concept Based on Blood Biomarkers.

BACKGROUND: Programs for population screening of colorectal cancer (CRC) have been implemented in several countries with fecal immunochemical testing (FIT) as the preferred platform. However, the major obstacle for a feces-based testing method is the limited compliance that reduces the clinical sensitivity for detection of participants with non-symptomatic CRC. Therefore, research approaches have been initiated to develop screening concepts based on biomarkers in blood. Preliminary results show that protein, genetic, epigenetic, and metabolomic components may be valuable in blood-based screening concepts, particularly when combinations of the various components appear to lead to significant improvements. OBJECTIVES: The protocol described in this paper focuses on the validation of concepts based on biomarkers in blood in a major population screened by FIT. METHODS: In Part 1, participants will be identified and included through the Danish CRC Screening Program comprising initial FIT and subsequent colonoscopy to those with a positive result. Blood samples will be collected from 8000 FIT-positive participants, who are offered subsequent colonoscopy. Findings and interventions at colonoscopy together with personal data including co-morbidity will be recorded. Blood samples and data will also be collected from 6000 arbitrarily chosen participants with negative FIT. In Part 2, blood samples and data will be collected from 30,000 FIT-negative participants three times within 4 years. The blood samples will be analyzed using various in-house and commercially available manual and automated analysis platforms. RESULTS: We anticipate Part 1 to terminate late August 2016 and Part 2 to terminate late September 2022. The results from Parts 1 and 2 will be presented within 12 to 18 months from termination. CONCLUSIONS: The purpose of this study is to improve the efficacy of identifying participants with neoplastic bowel lesions, to identify false negative participants, to identify participants at risk of interval neoplastic lesions, to improve the compliance in screening sessions, and to establish guidelines for out-patient follow-up of at-risk participants based on combinations of blood-based biomarkers.

Biodegradable stents for the treatment of bowel strictures in Crohn's disease: technical results and challenges.

BACKGROUND AND STUDY AIMS: In patients with Crohn's disease, the idea of biodegradable stents for treatment of bowel strictures with limited effect of endoscopic balloon dilation is tempting and initial results have been promising. The aim of this study was to evaluate the technical and clinical success of biodegradable stents for treatment of inflamed Crohn's strictures refractory to endoscopic balloon dilatation. PATIENTS AND METHODS: Consecutive patients treated with biodegradable stents due to Crohn's disease and inflamed bowel strictures refractory to endoscopic balloon dilatation were included. Technical and clinical success were evaluated. RESULTS: Six patients were included in the study. Technical success was obtained in five patients (83 %). Clinical success was limited to one patient (20 %); failure was observed due to mucosal overgrowth (n = 2), stent migration (n = 1), and stent collapse (n = 1). CONCLUSIONS: In Crohn's disease, it is technically feasible to treat bowel strictures with biodegradable stents. However, we have stopped using biodegradable stents due to lack of clinical success and side effects such as mucosal overgrowth and stent collapse.

Confocal laser endomicroscopy in ulcerative colitis: a longitudinal study of endomicroscopic changes and response to medical therapy (with videos).

BACKGROUND AND AIMS: Confocal laser endomicroscopy enables real-time in vivo microscopy during endoscopy and can predict relapse in patients with inflammatory bowel disease in remission. However, little is known about how endomicroscopic features change with time. The aim of this longitudinal study was to correlate colonic confocal laser endomicroscopy (CLE) in ulcerative colitis with histopathology and macroscopic appearance before and after intensification of medical treatment. METHODS: Twenty-two patients with ulcerative colitis in clinical relapse and 7 control subjects referred for colonoscopy were enrolled. The colonic mucosa was examined with high-definition colonoscopy, histopathology, and CLE at 4 colonic sites. Subsequently, patients requiring medical treatment escalation were referred for repeat endoscopy with CLE after 6 to 8 weeks. RESULTS: The baseline frequency of fluorescein leakage (P < .001), microerosions (P < .001), tortuosity of the crypts (P = .001), distortion of the crypts openings (P = .001), presence of inflammatory infiltrates (P < .001), and decreased crypt density (P < .001) were significantly higher in active ulcerative colitis compared with inactive ulcerative colitis and control subjects. A decrease in histopathologic score after medical treatment escalation was correlated with improvement in crypt tortuosity (rs = .35, P = .016), distortion of crypt openings (rs = .30, P = .045), and decreased crypt density (rs = .33, P = .026) but not in other features. CONCLUSIONS: CLE is an emerging endoscopic technique that reproducibly identifies mucosal changes in ulcerative colitis. With the exception of crypt changes, endomicroscopic features appear to improve slowly with time after medical treatment. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01684514.).

Confocal laser endomicroscopy: a novel method for prediction of relapse in Crohn's disease.

BACKGROUND AND STUDY AIMS: Confocal laser endomicroscopy (CLE) has been shown to predict relapse in ulcerative colitis in remission, but little is currently known about its role in Crohn's disease. The aim of this study was to identify reproducible CLE features in patients with Crohn's disease and to examine whether these are risk factors for relapse. PATIENTS AND METHODS: This was a single-center prospective feasibility study of CLE imaging in patients with Crohn's disease. CLE imaging was performed in the terminal ileum and four colorectal sites, and was correlated with histopathology and macroscopic appearance. Clinical relapse, defined as the need for treatment escalation or surgical intervention, was recorded during follow-up. RESULTS: The study included 50 patients: 39 with Crohn's disease (20 in remission), and 11 controls. Ileal fluorescein leakage and microerosions were significantly more frequent in patients with endoscopically active Crohn's disease compared with patients with inactive Crohn's disease and controls (P = 0.005 and (P = 0.006, respectively). The same applied to colorectal fluorescein leakage and vascular alterations ((P = 0.043 and (P = 0.034, respectively). During a 12-month follow-up period, ileal fluorescein leakage and microerosions were significant risk factors for relapse in the subgroup of patients in remission (log rank (P = 0.009 and (P = 0.007, respectively) as well as in the entire group of patients with Crohn's disease (log rank (P = 0.006 and (P = 0.01, respectively). Inter- and intraobserver reproducibility was almost perfect (κ > 0.80) or substantial (κ > 0.60) for the majority of CLE parameters. CONCLUSIONS: CLE can identify reproducible microscopic changes in the terminal ileum that are risk factors for relapse in patients with otherwise inactive Crohn's disease. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01738529).

Serial intralesional injections of infliximab in small bowel Crohn's strictures are feasible and might lower inflammation.

BACKGROUND: Crohn's disease can cause strictures throughout the gastrointestinal tract. Endoscopic balloon dilatation is a well-established treatment, but recurrence is seen in up to three out of four cases. Infliximab is playing an increasingly important role in the modern systemic treatment of severe Crohn's disease. Combining the anti-inflammatory effects of infliximab with the proven effect of endoscopic balloon dilatation could possibly improve outcome. In small studies, intralesional injections in perianal fistulas have been effective and endoscopic injection therapy in colonic strictures is feasible. OBJECTIVE: We wanted to assess whether serial intralesional injection of infliximab in small bowel strictures is feasible and reduces local inflammation. METHODS: We included six patients with Crohn's disease and inflammatory small bowel strictures. They were treated with endoscopic serial balloon dilatation. Subsequent to each dilatation, 40 mg infliximab was injected submucosally. A modified simplified endoscopic score for Crohn's disease was used for the involved area before the initial treatment and at the final follow-up after six months. Complications and development of symptoms were registered. RESULTS: Balloon dilatation and serial injection of infliximab were accomplished in five out of six patients. One patient completed the serial balloon dilatations and follow-up but received only one infliximab injection. The modified simplified endoscopic score for Crohn's disease decreased in all patients. There were no adverse events registered and all patients described themselves as feeling well. CONCLUSIONS: Combining balloon dilatation of strictures with serial intralesional injection of infliximab in Crohn's disease of the small bowel is feasible and seems successful in reducing inflammation.

[Successful endoscopic dilatation of a stenosis in relation to an ileorectal anastomosis by acute ileus].

Endoscopic dilatation is a treatment option for patients with Crohns disease suffering from stenosis in relation to an ileorectal anastomosis. We present a case of a patient with Crohns disease who was admitted with acute obstructive symptoms due to a stensosis of the ileorectal anastomosis. The patient was septic. We performed a successful endoscopic dilatation in the acute phase and the patient was discharged few days after an uneventful recovery. Endoscopic dilatation of an ileorectal anastomsis in patients with Crohns disease is a treatment option in the acute setting when performed by experienced endoscopists.

The use of double-balloon enteroscopy in retrieving mucosal biopsies from the entire human gastrointestinal tract.

OBJECTIVE: The aim of this explorative study was to evaluate double-balloon enteroscopy (DBE) as a new tool for collecting mucosal biopsies from well-defined parts of the entire small and large bowel in patients with type 2 diabetes and in matched healthy subjects. MATERIAL AND METHODS: Twelve subjects with type 2 diabetes and 12 body mass index and age-matched healthy subjects underwent anterograde and retrograde DBE under nurse-administered propofol sedation on two separate days. We attempted to collect two mucosal biopsies from every 30 cm from pylorus to rectum. RESULTS: A mean of 21 biopsy sites were sampled in the diabetic group versus 25 in the healthy group. In 4 out of 24 patients (2 [17%] from each group) sampling from the entire gastrointestinal system was possible. Mean depth of maximal insertion (anterograde) was 478 ± 32 cm in patients with type 2 diabetes versus 465 ± 44 cm in healthy subjects (p = 0.81) and with retrograde access 230 ± 36 cm (type 2 diabetes) versus 207 ± 26 cm (healthy subjects). CONCLUSIONS: DBE is a minimally invasive way of collecting fresh biopsies from the entire gastrointestinal tract and, thus provides research and clinical communities with a new possibility to access hitherto unexplored human anatomy and physiology.

IBD medications during pregnancy and lactation.

IBD often affects patients during their peak reproductive years. Several drugs are available for the treatment of IBD and new drugs are continuously in the pipeline. As long-term administration of medications is often necessary, the safety of drug therapy during pregnancy and breast-feeding needs to be considered in daily clinical practice. The aim of this Review is to summarize the latest information concerning the safety of medications used to treat IBD during pregnancy and lactation, as well as their effect on fertility. Although only thalidomide and methotrexate are absolutely contraindicated during pregnancy and breast-feeding, alternatives to ciprofloxacin, natalizumab and sodium phosphate should also be considered for pregnant women. Breast-feeding is also discouraged while on treatment with ciclosporin, metronidazole and ciprofloxacin. However, therapy with 5-aminosalicylic acid preparations, glucocorticoids, thiopurines and TNF inhibitors are acceptable during pregnancy and lactation. Pregnant women who have symptomatic IBD or who require therapy should have the opportunity to discuss any associated risks to their pregnancy and infant with the appropriate consultants. By ensuring that the patient and her family are informed, the clinical outcome might be optimized.

Colonoscopy results are not enhanced by use of magnet endoguide in specialist practice.

INTRODUCTION: It is discussed whether the use of a magnetic positioning device (OLYMPUS; UPD (unit of magnetic positioning device)) enhances the success of the colonoscopic procedure. Concern for patient compliance and endoscopic efficiency has been voiced in connection with the implementation of colon cancer screening. UPD has been proposed as a tool for optimization of results and reduction of patient discomfort. In this study, we aimed to qualify the debate by examining the success rate and patient discomfort in an unselected colonoscopy population referred to specialist clinics with experienced investigators. Furthermore, the study assessed the effect of using a UPD. MATERIAL AND METHODS: A total of 1,068 consecutive patients referred for colonoscopy were enrolled and randomised for investigation with or without use of UPD. The evaluation endpoints were: success rate (coecum visualised, ileal intubation was carried out at the investigator's discretion), duration of procedure, and patient discomfort indicated by the patient as a visual analogue scale score. RESULTS: No significant differences between the two investigational procedures were demonstrated in relation to the chosen endpoints. CONCLUSION: UPD is convenient to have, but not a necessity for colonoscopy. FUNDING: The study was supported by the Danish Association of Medical Specialists. TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency, journal no. 2009-41-3716, the National Ethics Committee, journal no.: H-1-2009-80, and registered with ClinicalTrials.gov., protocol no: NCT01055782.

Endoscopic balloon dilatation for Crohn's strictures of the gastrointestinal tract is feasible.

INTRODUCTION: Despite optimized medical treatment, Crohn´s disease can cause gastrointestinal (GI) strictures, which requires surgical intervention. Lately, endoscopic balloon dilatation has been established as an alternative to surgery. In the following, we report our experiences with endoscopic dilatation of strictures in the gastrointestinal tract caused by Crohn´s disease. MATERIAL AND METHODS: From January 2005 to February 2011, 23 patients with Crohn´s disease were referred for endoscopic dilatation. Based on data derived from this cohort, a retrospective analysis was made. Patients with Crohn´s disease, obstructive GI symptoms and known bowel strictures were included. Their mean age was 39 years (20-59 years) and 65% were female. Prior to the procedure, all patients had been evaluated by barium small-bowel follow through, abdominal magnetic resonance imaging and/or endoscopy. RESULTS: Dilatation was performed in 19/23 (83%) patients. During a mean follow-up period of 21 months (range 1-47 months), relapse was observed in 14/19 patients (74%). Five patients (26%) were referred to surgery due to complications (n = 1) or multiple relapses (n = 4). A total of 54 endoscopic dilatations were performed during the study period. Only one complication (perforation) was experienced, which resulted in a complication rate of 1.9%. CONCLUSION: Endoscopic dilatation in patients with Crohn´s disease with obstructive GI symptoms seems safe. In three out of four patients, surgery was avoided during a mean follow-up of two years. Further optimisation of the procedure is needed to lower the rate of recurrence.

[Modest risk of phosphate nephropathy by bowel cleansing]. / Beskeden risiko for fosfatnefropati ved colonudrensning.

Acute phosphate nephropathy is a rare, but serious adverse event associated with the use of sodium phosphate for bowel cleansing. It may lead to permanent renal impairment and a need for dialysis. The aetiology is hyperphosphataemia caused by intestinal absorption of the cleanser. Risk factors include: advanced age, existing kidney disease, decreased intravascular volume, and medications affecting renal perfusion or function such as diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and possibly nonsteroidal anti-inflammatory drugs.