Factors associated with delayed bleeding after resection of large nonpedunculated colorectal polyps.

BACKGROUND: Delayed bleeding is the most common significant complication after piecemeal endoscopic mucosal resection (p-EMR) of large nonpedunculated colorectal polyps (NPCPs). Risk factors for delayed bleeding are incompletely defined. We aimed to determine risk factors for delayed bleeding following p-EMR. METHODS: Data were analyzed from a prospective tertiary center audit of patients with NPCPs ≥ 20 mm who underwent p-EMR between 2010 and 2012. Patient, polyp, and procedure-related data were collected. Four post p-EMR defect factors were evaluated for interobserver agreement and included in analysis. Delayed bleeding severity was reported in accordance with guidelines. Predictors of bleeding were identified. RESULTS: Delayed bleeding requiring hospitalization occurred after 22 of 330 procedures (6.7 %). A total of 11 patients required blood transfusion; of these, 4 underwent urgent colonoscopy, 1 underwent radiological embolization, and 1 required surgery. Interobserver agreement for identification of the four post p-EMR defect factors was moderate (kappa range 0.52 - 0.57). Factors associated with delayed bleeding were visible muscle fibers (P = 0.03) and the presence of a "cherry red spot" (P = 0.05) in the post p-EMR defect. Factors not associated with delayed bleeding were American Association of Anesthesiologists class, aspirin use, polyp size, site, and use of argon plasma coagulation. CONCLUSIONS: Visible muscle fibers and the presence of a "cherry red spot" in the resection defect were associated with delayed bleeding after p-EMR. These findings suggest evaluation and photodocumentation of the post p-EMR defect is important and, when considered alongside other patient and procedural factors, may help to reduce the incidence and severity of delayed bleeding.

Endoscopic mucosal ablation: a new argon plasma coagulation/injection technique to assist complete resection of recurrent, fibrotic colon polyps (with video).

BACKGROUND: Incomplete piecemeal EMR of large, sessile/flat colon polyps results in polyp recurrence, with massive submucosal scarring making subsequent attempts at endoscopic resection problematic. OBJECTIVE: We report our experience with a new endoscopic mucosal ablation (EMA) technique that can be used to complement the eradication of recurrent fibrotic colon polyps. DESIGN: Single-center, retrospective case series. SETTING: Tertiary-care referral academic endoscopy unit. PATIENTS: This study involved consecutive patients referred for endoscopic excision of recurrent benign colon polyps with severe submucosal fibrosis (>30% of the entire lesion). INTERVENTION: Application of high-power argon plasma coagulation (APC), preceded by injection of a submucosal fluid cushion (normal saline/diluted adrenaline and/or sodium hyaluronate solution) to protect the muscle layer, was performed to augment further piecemeal EMR and polyp eradication. MAIN OUTCOME MEASUREMENTS: Technical safety and success, complication and recurrence rates. RESULTS: Fourteen patients (mean age 73 years; 9 men, 5 women) with 15 recurrent colon adenomas (mean polyp size 30 mm, 9 proximal/6 distal) were included. EMA with a mean APC power setting of 55 W was applied. Complete polyp eradication was achieved in 9 of 11 patients (82%) at first or second completed follow-up. One patient needed laparoscopic colectomy because of cancer, and 1 underwent transanal endoscopic microsurgery for benign massive recurrence. The other 3 patients with small, easily treatable recurrence (≤3 mm) were followed by 1-year-surveillance. No perforations and no postpolypectomy syndrome were reported. LIMITATIONS: Single-center, nonrandomized case series with short duration follow-up. CONCLUSION: EMA appears to be a safe and easily applicable technique to assist the complete eradication of recurrent fibrotic colon polyps.

Expression of a splice variant of CXCR3 in Crohn's disease patients; indication for a lymphocyte--epithelial cell interaction.

BACKGROUND AND AIM: T-lymphocyte migration is implicated in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). CXC chemokines MIG, IP-10, and I-TAC act by binding to CXCR3 receptor on T-lymphocytes. We investigated the role of these chemokines and their receptor in patients with UC, CD, and normal controls (NC). METHODS: Chemokine expression and serum levels were examined in colonic biopsies from patients and NC using reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay. HT-29 and Caco2 colonic epithelial cells were studied following in vitro stimulation with proinflammatory (Th1) and Th2-derived cytokines. CXCR3 receptor expression was assessed in CD3+ peripheral blood lymphocytes (PBL) from patients and NC and in stimulated Jurkat leukaemia cells, using RT-PCR and flow cytometry. RESULTS: Full size CXCR3 mRNA (FS) expression was found in CD3+ PBL from controls and UC, but not from CD patients. In contrast, CD3+ PBL from CD patients showed a marked mRNA expression of the spliced variant CXCR3 (TV). This finding explains the high expression of CXCR3 on CD3+ PBL from CD patients in flow cytometry. Increased chemokine expression and production was found in colonic biopsies and serum from CD compared to UC patients and controls. Stimulation of epithelial cells with proinflammatory cytokines significantly induced chemokine production. The addition of Th2 cytokines had an inhibitory effect. Stimulation of Jurkat cells with cytokines and supernatant conditioned media from epithelial cells induced CXCR3TV expression. CONCLUSIONS: These data demonstrate that PBL from CD patients express a spliced variant of the CXCR3 receptor and suggest a role for the colonic epithelial cells in T-lymphocyte migration in intestinal inflammation.

A prospective randomised study comparing double-balloon colonoscopy and conventional colonoscopy in pre-defined technically difficult cases.

BACKGROUNDS AND AIM: Technically 'difficult' (TD) colonoscopy is associated with incomplete colonoscopy, discomfort and longer procedures. Double-balloon colonoscopy (DBC) may facilitate TD colonoscopy. The primary outcome was to compare the time taken to achieve caecal intubation during conventional colonoscopy (CC) and DBC in patient with a TD colon. METHODS: We performed a prospective, randomised study comparing DBC and CC for TD colonoscopy. Patients were screened for parameters predictive of TD colonoscopy using an original scoring system and randomised to DBC or CC. Pain, sedation dose, colonoscopy completeness, time taken for cecal intubation, procedure completion, recovery time and patient satisfaction were recorded. RESULTS: Forty-four patients were recruited (DBC=22; CC=22). DBC facilitated total colonoscopy in 22 cases whereas 9 CC procedures were incomplete (P=0.019). Median pre-procedure difficulty scores were equal for both groups (4.0 vs. 4.0). Mean patient discomfort, pain scores and recovery time were significantly lower for the DBC group (2.3 vs. 5.5, P=0.001; 2.0 vs. 5.9, P=0.005; 5 vs. 20min, P=0.014 respectively). Mean time taken for cecal intubation was similar (17.5 vs. 14min, P=0.18); CONCLUSION: DBC facilitates colonoscopy completion and may be a more comfortable alternative to CC for TD cases although the time taken to achieve caecal intubation was similar.

Dataset of the livability performance of the city of Birmingham, UK, as measured by its citizen wellbeing, resource security, resource efficiency and carbon emissions.

This data article presents the UK City LIFE1 data set for the city of Birmingham, UK. UK City LIFE1 is a new, comprehensive and holistic method for measuring the livable sustainability performance of UK cities. The Birmingham data set comprises 346 indicators structured simultaneously (1) within a four-tier, outcome-based framework in order to aid in their interpretation (e.g., promote healthy living and healthy long lives, minimize energy use, uncouple economic vitality from CO2 emissions) and (2) thematically in order to complement government and disciplinary siloes (e.g., health, energy, economy, climate change). Birmingham data for the indicators are presented within an Excel spreadsheet with their type, units, geographic area, year, source, link to secondary data files, data collection method, data availability and any relevant calculations and notes. This paper provides a detailed description of UK city LIFE1 in order to enable comparable data sets to be produced for other UK cities. The Birmingham data set is made publically available at http://epapers.bham.ac.uk/3040/ to facilitate this and to enable further analyses. The UK City LIFE1 Birmingham data set has been used to understand what is known and what is not known about the livable sustainability performance of the city and to inform how Birmingham City Council can take action now to improve its understanding and its performance into the future (see "Improving city-scale measures of livable sustainability: A study of urban measurement and assessment through application to the city of Birmingham, UK" Leach et al. [2]).

A prospective comparison of performance during back-to-back, anterograde manual spiral enteroscopy and double-balloon enteroscopy.

BACKGROUND: Spiral enteroscopy is a recently introduced technology alternative to balloon-assisted enteroscopy for examination of the small bowel. AIM: To compare small bowel insertion depths and procedure duration by spiral enteroscopy and double-balloon enteroscopy performed in the same cohort of patients, in immediate succession, using the same method of insertion depth estimation. METHODS: A prospective, back-to-back comparative study was performed in 15 patients. Spiral enteroscopy procedures were performed first and a tattoo was placed to mark the most distal point. RESULTS: Double-balloon enteroscopy passed the tattoo placed at spiral enteroscopy in 14/15 cases (93%). Median insertion depths for double-balloon enteroscopy and spiral enteroscopy were 265cm and 175cm, respectively (P=0.004). Median time to achieve maximal depth of insertion was significantly shorter for spiral enteroscopy compared with double-balloon enteroscopy (24min vs. 45min, respectively; P=0.0005). However, in 14 patients no differences were found in median time to reach the same insertion depth (P=0.28). CONCLUSION: Double-balloon enteroscopy achieved significantly greater small bowel insertion depth than spiral enteroscopy. Although overall double-balloon enteroscopy procedure duration was longer, the time taken to reach the same small bowel insertion depth by both spiral enteroscopy and double-balloon enteroscopy was similar.

How we can measure quality in colonoscopy?

Measuring quality is a current need of medical services either to assess their cost-effectiveness or to identify discrepancies requiring refinement. With the advent of bowel cancer screening and increasing patient awareness of bowel symptoms, there has been an unprecedented increase in demand for colonoscopy. Consequently, there is an expanding open-discussion on missed rates of cancer or precancerous polyps during diagnostic/screening colonoscopy and on the rate of adverse events related to therapeutic colonoscopy. Delivering a quality colonoscopy service is therefore a healthcare priority. Colonoscopy is a multi-step process and therefore assessment of all aspects of the procedure must be addressed. Quality in colonoscopy refers to a combination of many patient-centered technical and non-technical skills and knowledge aiming to patient's safety and satisfaction through a continuous effort for improvement. The benefits of this endless process are hiding behind small details which can eventually make the difference in colonoscopy. Identifying specific quality metrics help to define and shape an optimal service and forms a secure basis of improvement. Τhis paper does not aim to give technical details on how to perform colonoscopy but to summarize what to measure and when, in accordance with the current identified quality indicators and standards for colonoscopy.

Hepcidin is a key mediator of anemia of inflammation in Crohn's disease.

UNLABELLED: Anemia often complicates the course of Inflammatory Bowel Disease (IBD). Hepcidin, a liver-produced peptide hormone, is a key mediator of anemia of chronic disease (ACD). We hypothesized that hepcidin is significantly elevated in anemic CD patients and that hepcidin may cause iron restriction and, therefore, mediate ACD. METHODS: We enrolled 17 patients with CD and ACD recruited from the Cedars-Sinai IBD Center. Routine blood tests included hemoglobin (Hgb), hematocrit, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Anemia was defined as hemoglobin <12g/dL and <13.5g/dL, in men and women, respectively. ACD was diagnosed on the basis of a combination of the following: a) normal or elevated ferritin b) lowered serum iron and total iron binding capacity and c) normal percent iron saturation. Serum and urine hepcidin, as well as IL-6 levels were also measured. Patients with documented iron-deficiency anemia were excluded. RESULTS: There was an excellent correlation between urine (expressed as ng/mg of creatinine) and serum hepcidin levels expressed as ng/ml (r=0.853, p<0.001). We also found a strong positive correlation between serum hepcidin and ferritin levels (r=0.723, p=0.0015). There was a positive correlation between serum hepcidin and IL-6 levels (r=0.546, p=0.023). We found a strong negative correlation between serum hepcidin concentrations and Hgb levels (r=0.528, p=0.029). CONCLUSION: We demonstrate that ACD in CD is characterized by high serum IL-6 and hepcidin levels, which negatively correlate with Hgb levels. Our data support the hypothesis that IL-6-driven hepcidin production mediates ACD in patients with CD.

Proinflammatory cytokines induce crosstalk between colonic epithelial cells and subepithelial myofibroblasts: implication in intestinal fibrosis.

BACKGROUND AND AIMS: Colonic epithelial cells and adjacent subepithelial myofibroblasts are important counterparts in the pathogenesis of intestinal inflammation and fibrosis. We investigated the possible crosstalk between them, whilst focusing on the mucosal inflammation pathways that potentially trigger intestinal fibrosis. METHODS: We studied the effects of proinflammatory cytokines (IL-1α, TNF-α, IFN-γ) on human colonic epithelial cell lines and the effects of epithelial cell-conditioned media on primary human colonic subepithelial myofibroblasts isolated from normal controls or patients with inflammatory Crohn's disease along with the corresponding 18CO cell line. Readouts included production of TGF-ß and TIMP-1, total collagen synthesis, matrix metalloproteinases MMP-2 and MMP-9 and myofibroblast migration/mobility. RESULTS: Proinflammatory cytokines upregulated TGF-ß and TIMP-1 in colonic epithelial cells. Conditioned medium from these epithelial cell cultures induced production of MMP-9 and collagen and inhibited the migration/mobility of subepithelial myofibroblasts. MMP-9 production depended on endothelin receptor A signalling on responding myofibroblasts. Collagen up-regulation was independent of TGF-ß, CTGF, TF and endothelin. Subepithelial myofibroblasts isolated from Crohn's disease patients had similar responses to those isolated from normal controls, with the exception of higher basal collagen production. CONCLUSIONS: Our study indicates that colonic epithelial cells may respond to an inflammatory milieu by inducing myofibroblast functions similar to those observed during intestinal fibrosis.

Musculoskeletal manifestations of inflammatory bowel disease.

Extraintestinal manifestations develop in ≈25% of patients with inflammatory bowel disease (IBD). Musculoskeletal symptoms are the most common extraintestinal manifestations of IBD, often associated with colonic involvement, and present as either articular (arthritis) or periarticular inflammation including enthesitis, myositis, or soft tissue rheumatism (fibromyalgia). Musculoskeletal manifestations can precede or be synchronous with the development of bowel disease or develop following the diagnosis of IBD. Their clinical course often correlates with IBD activity but it can also be independent of the activity of bowel disease. Controlling intestinal inflammation remains the cornerstone therapeutic approach for the musculoskeletal manifestations of IBD.

Crohn's disease lymphadenopathy: MR imaging findings.

PURPOSE: To assess mesenteric lymph nodes in patients with different Crohn's disease subtypes identified on MR Enteroclysis. MATERIALS AND METHODS: Thirty-four patients, categorized into three different Crohn's disease subgroups, underwent MR Enteroclysis. A high resolution coronal true FISP sequence with fat saturation was applied to assess mesenteric lymph node anatomic distribution, size and shape. Their enhancement ratio (ER) was calculated by dividing signal intensity of each node to signal intensity of nearby vessel on T1 weighted FLASH images, acquired 75 s after intravenous administration of gadolinium. A one-way analysis of variance statistical test was applied to investigate any significant differences regarding mean ER among different disease subgroups. RESULTS: Two hundred and eighty-three mesenteric lymph nodes were assessed, 231 in patients with active inflammatory (AI) disease, 36 in patients with fibrostenotic (FS) and 16 in patients with fistulizing/perforating (FP) disease. Maximum and minimum diameters were 3.2 and 0.3 cm, respectively. 75% of the lymph nodes presented with an oval shape. The majority were identified as being ileocolic (34%) and paracolic (31%). AI subgroup lymph nodes presented with the highest mean ER (0.783+/-0.17) followed by FP (0.706+/-0.1) and FS subgroup (0.652+/-0.17) lymph nodes. The differences in mean values of ER of mesenteric lymph nodes between AI and FS subtypes were statistically significant (p<0.0001), while mean ER between nodes of FP and the other two subtypes did not present statistically significant differences. CONCLUSION: ER of mesenteric lymph nodes identified on MR Enteroclysis may vary across different subtypes of Crohn's disease. Such differences may be valuable in clinical practice.

Ciprofloxacin decreases survival in HT-29 cells via the induction of TGF-beta1 secretion and enhances the anti-proliferative effect of 5-fluorouracil.

BACKGROUND AND PURPOSE: Fluoroquinolones are potent anti-microbial agents with multiple effects on host cells and tissues. Previous studies have highlighted their pro-apoptotic effect on human cancer cells and an immunoregulatory role in animal models of inflammatory bowel disease. We examined the effect of ciprofloxacin on proliferation, cell cycle and apoptosis of HT-29 cells, a human colonic epithelial cell line sensitive to transforming growth factor (TGF)-beta1-mediated growth inhibition and its role in TGF-beta1 production. We also examined the effect of ciprofloxacin on proliferation of HT-29 cells in combination with 5-fluorouracil (5-FU), a well-established pro-apoptotic agent. EXPERIMENTAL APPROACH: Using subconfluent cultures of HT-29 and Caco-2 cells, we studied the effect of ciprofloxacin, TGF-beta1 and 5-FU on proliferation, apoptosis, necrosis and cell cycle. The effect of ciprofloxacin on TGF-beta1 mRNA expression and production was studied in RNA extracts and cell culture supernatants respectively, using confluent cultures. KEY RESULTS: Ciprofloxacin decreased proliferation of HT-29 cells in a concentration- and time-dependent manner. This was mediated by accumulation of HT-29 cells into the S-phase but without any effect on apoptosis or necrosis. Additionally, ciprofloxacin enhanced the antiproliferative effect of 5-FU. Interestingly, ciprofloxacin was found to up-regulate TGF-beta1 production by HT-29 cells and its anti-proliferative effect was abolished when TGF-beta1 was blocked. Confirming this mechanism further, ciprofloxacin had no effect on Caco-2, a human colonic epithelial cell line that lacks functional TGF-beta1 receptors. CONCLUSIONS AND IMPLICATIONS: We demonstrate a novel anti-proliferative and immunoregulatory effect of ciprofloxacin on human intestinal epithelial cells mediated via TGF-beta1.