Intestinal Conventional Ultrasonography, Contrast-Enhanced Ultrasonography and Magnetic Resonance Enterography in Assessment of Crohn's Disease Activity: A Comparison with Surgical Histopathology Analysis.

BACKGROUND AND AIMS: Contrast-enhanced ultrasonography (CEUS) is a potential interesting method for assessing accurately Crohn's disease (CD) activity. We compared the value of intestinal ultrasonography (US) coupled with contrast agent injection with that of magnetic resonance enterography (MRE) in the assessment of small bowel CD activity using surgical histopathology analysis as reference. METHODS: Seventeen clinically active CD patients (14 women, mean age 33 years) requiring an ileal or ileocolonic resection were prospectively enrolled. All performed a MRE and a US coupled with contrast agent injection (CEUS) less than 8 weeks prior to surgery. Various imaging qualitative and quantitative parameters were recorded and their respective performance to detect disease activity, disease extension and presence of complications was compared to surgical histopathological analysis. RESULTS: The median wall thickness measured by US differed significantly between patients with non-severely active CD (n = 5) and those with severely active CD (n = 12) [7.0 mm, IQR (6.5-9.5) vs 10.0 mm, IQR (8.0-12.0), respectively; p = 0.03]. A non-significant trend was found with MRE with a median wall thickness in severe active CD of 10.0 mm, IQR (8.0-13.7) compared with 8.0 mm, IQR (7.5-10.5) in non-severely active CD (p = 0.07). The area under the ROC curve (AUROC) of the wall thickness assessed by US and MRE to identify patients with or without severely active CD on surgical specimens were 0.85, 95% CI (0.64-1.04), p = 0.03 and 0.80, 95% CI (0.56-1.01), p = 0.07, respectively. Among the parameters derived from the time-intensity curve during CEUS, time to peak and rise time were the two most accurate markers [AUROC = 0.88, 95% CI (0.70-1.04), p = 0.02 and 0.86, 95% CI (0.68-1.04), p = 0.03] to detect patients with severely active CD assessed on surgical specimens. CONCLUSION: The accuracy of intestinal CEUS is close to that of conventional US to detect disease activity. A thickened bowel and shortened time to peak and rise time were the most accurate to identify CD patients with severe histological disease activity.

Fetal death in utero and miscarriage in a patient with Crohn's disease under therapy with ustekinumab: case-report and review of the literature.

BACKGROUND: Ustekinumab is a fully human monoclonal antibody against the p40 subunit of interleukin (IL) 12 and 23 which is involved in the pathogenesis of several inflammatory diseases. Ustekinumab is approved for psoriasis and psoriatic arthritis treatment and has been successfully evaluated in phase II and III trials for patients with Crohn's disease (CD). CASE PRESENTATION: We report here the case of a patient who became pregnant during treatment with ustekinumab for a refractory CD and which ended in miscarriage. CONCLUSION: Ustekinumab is a relatively new pharmacotherapy and in addition to this clinical case, we reviewed the published literature concerning the use of this treatment during pregnancy and its consequences on pregnancy and fetus outcome.

Patients with Peritoneal Carcinomatosis from Gastric Cancer Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Is Cure a Possibility?

BACKGROUND: Peritoneal carcinomatosis is an increasingly common finding in gastric carcinoma. Previously, patients were treated as terminal, and median survival was poor. The use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in this context is still highly debatable. OBJECTIVE: The aim of this study was to evaluate the long-term outcomes associated with CRS and HIPEC, and define prognostic factors for cure, if possible. PATIENTS AND METHODS: All patients with gastric carcinomatosis from five French institutions who underwent combined complete CRS and HIPEC and had a minimum follow-up of 5 years were included in this study. Cure was defined as a disease-free interval of more than 5 years from the last treatment until the last follow-up. RESULTS: Of the 81 patients who underwent CRS and HIPEC from 1989 to 2009, 59 had a completeness of cytoreduction score (CCS) of 0 (complete macroscopic resection), and the median Peritoneal Cancer Index (PCI) score was 6. Mitomycin C was the most commonly used drug during HIPEC (88 %). The 5-year overall survival (OS) rate was 18 %, with nine patients still disease-free at 5 years, for a cure rate of 11 %. All 'cured' patients had a PCI score below 7 and a CCS of 0. Factors associated with improved OS on multivariate analysis were synchronous resection (p = 0.02), a lower PCI score (p = 0.12), and the CCS (p = 0.09). CONCLUSION: The cure rate of 11 % for patients with gastric carcinomatosis who are deemed terminal emphasizes that CRS and HIPEC should be considered in highly selected patients (low disease extent and complete CRS).

Glycaemic fall after a glucose load. A population-based study.

BACKGROUND AND AIMS: A blood glucose (BG) fall after an oral glucose load has never been described previously at a population level. This study was aimed at looking for a plasma glucose trend after an oral glucose load for possible blood glucose fall if any, and for its impact on coronary mortality at a population level. METHODS AND RESULTS: In subjects from an unselected general population, BG and insulin were detected before and 1 and 2h after a 75-g oral glucose load for insulin sensitivity and ß-cell function determination. Blood pressure, blood examinations and left ventricular mass were measured, and mortality was monitored for 18.8±7.7 years. According to discriminant analysis, the population was stratified into cluster 0 (1-h BG < fasting BG; n=497) and cluster 1 (1-h BG ≥ fasting BG; n=1733). To avoid any interference of age and sex, statistical analysis was limited to two age-gender-matched cohorts of 490 subjects from each cluster (n=940). Subjects in cluster 0 showed significantly higher insulin sensitivity and ß-cell function, lower visceral adiposity and lower blood pressure values. Adjusted coronary mortality was 8 times lower in cluster 0 than 1 (p<0.001). The relative risk of belonging to cluster 1 was 5.40 (95% CI 2.22-13.1). CONCLUSION: It seems that two clusters exist in the general population with respect to their response to an oral glucose load, independent of age and gender. Subjects who respond with a BG decrease could represent a privileged sub-population, where insulin sensitivity and ß-cell function are better, some risk factors are less prevalent, and coronary mortality is lower.

Update: Role of surgery in acute necrotizing pancreatitis.

Acute necrotizing pancreatitis is a prevalent disease with high morbidity and mortality. The development of radiologic and endoscopic techniques to manage pancreatic necrosis commands a multidisciplinary approach, which has considerably decreased the need for laparotomy. The objective of this update is to define the role of surgery in the multidisciplinary approach to management of necrotizing acute pancreatitis.

Azathioprine dose reduction in inflammatory bowel disease patients on combination therapy: an open-label, prospective and randomised clinical trial.

BACKGROUND: Infliximab (IFX) combined with azathioprine (AZA) is more effective than IFX monotherapy in inflammatory bowel disease (IBD). AIM: To identify the AZA optimal dose that is required for efficacy when receiving combination therapy. METHODS: Patients with IBD in durable remission on combination therapy were enrolled in a 1-year, open-label, prospective trial after randomisation into three groups: AZA steady (2-2.5 mg/kg/day, n=28) vs AZA down (dose was halved 1-1.25 mg/kg/day, n=27) vs AZA stopped (n=26). Primary endpoint was failure defined as occurrence of a clinical relapse and/or any change in IBD therapy. RESULTS: Eighty-one patients were included. Five (17.9%), 3 (11.1%), and 8 (30.8%) patients experienced failure at 1 year in groups AZA steady, AZA down and AZA stopped, respectively (P=.1 across the groups). The median trough levels of IFX at inclusion were close to those measured at the end of follow-up in group AZA steady (3.65 vs 3.45 µg/mL, P=.9) and in group AZA down (3.95 vs 3.60 µg/mL, P=.5), whereas these levels dropped from 4.25 to 2.15 µg/mL (P=.02) in group AZA stopped. Four (14.3%), four (14.8%) and 11 (42.3%) patients experienced an unfavourable evolution of IFX pharmacokinetics in groups AZA steady, AZA down and AZA stopped, respectively. A threshold of 6-TGN <105 pmoles/8.108 RBC was associated with an unfavourable evolution of IFX pharmacokinetics. CONCLUSIONS: Under combination therapy, AZA dose reduction, but not withdrawal, appears to be as effective as continuation of AZA at full dose.

Association of Anti-glycan Antibodies and Inflammatory Bowel Disease Course.

BACKGROUND AND AIMS: The usefulness of anti-glycan antibodies alone or combined with anti-Saccharomyces cerevisiae [ASCA] or perinuclear antineutrophil cytoplasmic [pANCA] antibodies for diagnosis of inflammatory bowel disease [IBD], differentiation between Crohn's disease [CD] and ulcerative colitis [UC], disease stratification including IBD phenotype, and also for determination of the course of the disease, remain unclear. METHODS: A large panel of serological anti-glycan carbohydrate antibodies, including anti-mannobioside IgG antibodies [AMCA], anti-chitobioside IgA [ACCA], anti-laminaribioside IgG antibodies [ALCA], anti-laminarin [anti-L] and anti-chitine [anti-C] were measured in the serum from a cohort of 195 patients with IBD] [107 CD and 88 UC]. The respective accuracy of isolated or combined markers for diagnosis, disease differentiation, stratification disease phenotype, and severity of the disease course, defined by a wide panel of criteria obtained from the past medical history, was assessed. RESULTS: The positivity of at least one anti-glycan antibody was detected in a significant higher proportion of CD and UC compared with healthy controls [p < 0.0001 and p < 0.0007, respectively]. Whereas ASCA and ANCA antibody status had the highest efficacy to be associated with CD in comparison with UC (area under receiver operating characteristic curve [AUROC] = 0.70 for each], the adjunction of anti-laminarin antibody substantially improved the differentiation between CD and UC [AUROC = 0.77]. Titres of ACCA [> 51U/ml] and anti-laminarin [> 31U/ml] were significantly linked with a higher association with steroid dependency (odds ratio [OR] =2.0 [1.0-4.0], p = 0.03 and OR = 2.4 [1.1-5.2], p = 0.02, respectively]. We further defined the respective performance of anti-glycan antibodies to discriminate between patients with severe or not severe CD and UC course and determined the associated optimal cut-off values: severe CD course was significantly more likely in case of AMCA > 77U/ml [OR = 4.3; p = 0.002], ASCA > 63U/ml [OR = 3.5; p < 0.009] and at a lesser degree ACCA > 50U/ml [OR = 2.8; p < 0.02] and severe UC course was significantly associated with AMCA > 52U/ml [OR = 3.4; p = 0.04] and ACCA > 25U/ml [OR = 3.0; p < 0.04]. CONCLUSIONS: Anti-glycan antibodies are valuable serological markers, especially AMCA antibodies that may help clinicians to promptly classify patients into high risk for severe disease.

Effect of short-chain fatty acids and acidification on the phasic and tonic motor activity of the human colon.

BACKGROUND: The effects of bacterial fermentation on human colonic motor activity could be explained by colonic acidification or short-chain fatty acid (SCFA) production. We compared in healthy volunteers the colonic motor effects of intracolonic infusion of neutral or acidic saline solutions and then of neutral or acidic solutions containing an SCFA mixture. METHODS: 20 healthy volunteers swallowed a probe (with an infusion catheter, 6 perfused catheters and a balloon connected to a barostat) that migrated into the colon. Colonic motor activity was recorded in fasting basal state (1 h), during (3 h) and after (2 h) intracolonic infusion in a random order on two consecutive days of 750 mL of NaCl at pH 7.0 (neutral saline) or 4.5 (acidic saline) in 10 volunteers (first experiment) and of an SCFA mixture (acetic acid 66%, propionic acid 24% and butyric acid 10%; 100 mM) at pH 7.0 or 4.5 in 10 other volunteers (second experiment). We determined for each hour a global motility index (reflecting phasic activity recorded by all catheters), the mean balloon volume (reflecting tonic activity), and the mean number of high-amplitude-propagated contractions (HAPCs). KEY RESULTS: Intracolonic infusion of neutral or acidic solutions containing saline or an SCFA mixture did not change the global motility index, the barostat balloon volume, or the HAPC number compared with basal values. CONCLUSIONS & INFERENCES: Under our experimental conditions, these findings suggest that the stimulation of colonic motor activity induced by carbohydrate fermentation is not explained by the acidification of the colonic contents or the resulting production of SCFAs.

Urinary neopterin is a valuable tool in monitoring Crohn's disease activity.

BACKGROUND: The aim was to investigate the relation between urinary neopterin and the Crohn's Disease Activity Index (CDAI) and to compare its ability to discriminate active versus inactive CD with serum C-reactive protein (CRP). METHODS: In all, 217 urinary samples for neopterin measurement were obtained in a cohort of 93 consecutive patients with CD and 66 samples in 33 healthy volunteers. Clinical parameters were recorded and blood samples for CRP were collected as well. RESULTS: Whereas patients with inactive CD showed similar levels of urinary neopterin excretion than healthy volunteers (163 +/- 8 versus 142 +/- 7 nmol/mol of creatinine, respectively; P = 0.1), urinary neopterin excretion from mild to severe active CD was significantly higher (302 +/- 15 nmol/mol of creatinine; P < 0.001). Serum CRP levels were higher in active CD (14.8 +/- 2.1 mg/L) compared with inactive CD (5.6 +/- 0.8 mg/L; P < 0.001). Urinary neopterin excretion, and to a lesser degree CRP, were positively and significantly correlated with CDAI (r = 0.64 and 0.43, respectively, P < 0.001). Based on the cutoff of 183 nmol/mol of creatinine for urinary neopterin, the sensitivity and specificity of urinary neopterin to discriminate between active and inactive CD were 73% and 82%, respectively, and the positive and negative predictive values were 80% and 78%, respectively. CONCLUSIONS: Urinary neopterin excretion is an objective, valuable, simple, and noninvasive biomarker to detect and follow fluctuations of CD activity. Further work is warranted to study its clinical value and relation to mucosal healing.