Early Transmural Response Assessed Using Magnetic Resonance Imaging Could Predict Sustained Clinical Remission and Prevent Bowel Damage in Patients with Crohn's Disease Treated with Anti-Tumour Necrosis Factor Therapy.

BACKGROUND: Magnetic resonance imaging [MRI] is a promising tool to evaluate therapeutic efficacy in ileocolonic Crohn's disease [CD]. AIMS: We aimed to assess the feasibility of early MRI evaluation (week 12 [W12]) to predict corticosteroid-free remission [CFREM] at W52 and prevent long-term bowel damage. METHODS: All patients with active CD needing anti-tumour necrosis factor [anti-TNF] therapy were consecutively enrolled in this multicentre prospective study. MRI was performed before starting therapy, at W12 and W52. CFREM was defined as Crohn's Disease Activity Index < 150, C-reactive protein < 5 mg/L and faecal calprotectin < 250 µg/g, with no switch of anti-TNF agents, no bowel resection and no therapeutic intensification between W12 and W52. RESULTS: Among 46 patients, 22 [47.8%] achieved CFREM at W52. Anti-TNF agents were able to heal almost all CD lesions as soon as W12 [p < 0.05]. Early transmural response defined as a 25% decrease of either Clermont score (odds ratio [OR] = 7.7 [1.7-34.0], p < 0.001) or Magnetic Resonance Index of Activity (OR = 4.2 [1.3-13.3], p = 0.015) was predictive of CFREM at W52. Achieving at least two items on W12-MRI among ulceration healing, disappearance of enlarged lymph nodes or sclerolipomatosis, ΔADC [apparent diffusion coefficient] > +10% or ΔRCE [relative contrast enhancement] > -30% was associated with a likelihood of CFREM at W52 of 84.6% vs 37.5% in patients without transmural response [p < 0.001]. Early transmural response could prevent bowel damage progression over time using Clermont score (hazard ratio = 0.21 [0.0-0.9]; p = 0.037). CONCLUSION: Evaluation of early transmural response by MRI is feasible and is a promising end point to monitor therapeutic efficacy in patients with CD.

Migraine prevalence in inflammatory bowel disease patients: A tertiary-care centre cross-sectional study.

BACKGROUND: Inflammatory bowel diseases (IBD) are systemic, chronic inflammatory conditions that predominately affect the gastrointestinal tract and can induce abdominal pain. Besides, many IBD patients complain about headaches in daily practice. The objective was to assess the prevalence of headaches, including migraines and pain with neuropathic characteristics (NC), in IBD patients compared to historical controls from the general population. METHODS: Overall, 203 consecutive tertiary-care centre patients completed validated self-administered questionnaires and benefitted from a clinical evaluation performed by an IBD physician at the same time. RESULTS: In our cohort, 75% of the patients experienced pain in the previous 3 months. Migraine prevalence was two-fold higher in IBD patients compared to the general population (41% vs. 21.3%, p < 0.001). Migraine was associated with a younger age, female gender and higher depression scores. Although migraine impact was very important for 30% of the patients (61/203), specific acute therapeutics were prescribed in only 22% of cases (18/83). Chronic pain with NC was more frequent than in the general population (11.3% vs. 6.9%, p = 0.012) and was strongly associated with the presence of extra-intestinal manifestations (p < 0.001). Abdominal pain concerned 19% of the patients during the previous week and was, as expected, associated with disease activity. CONCLUSIONS: Migraine prevalence is strongly increased in IBD patients followed in tertiary care. A systematic screening for migraine should be done by IBD physicians in daily practice to provide adequate therapeutics. Further studies are needed to confirm whether migraine should be classified as IBD extra-intestinal manifestations. SIGNIFICANCE: Migraine prevalence was two-fold higher in IBD patients compared to the general population, was generally poorly treated and a systematic screening for migraine should be done by IBD physicians in daily practice to provide adequate therapeutics.

Colonic overexpression of the T-type calcium channel Cav 3.2 in a mouse model of visceral hypersensitivity and in irritable bowel syndrome patients.

BACKGROUND: Among the different mechanisms involved in irritable bowel syndrome (IBS) physiopathology, visceral hypersensitivity seems to play a key role. It involves sensitization of the colonic primary afferent fibers, especially through an overexpression of ion channels. The aims of this translational study were to investigate the colonic expression of Cav 3.2 calcium channels and their involvement in an animal model of colonic hypersensitivity, and to assess their expression in the colonic mucosa of symptomatic IBS patients. METHODS: This bench-to-bed study combined a preclinical experimental study on mice and a case-control clinical study. Preclinical studies were performed on wild-type and Cav 3.2-KO mice. Colonic sensitivity and Cav 3.2 expression were studied after a low-dose treatment of dextran sodium sulfate (DSS 0.5%). Regarding the clinical study, colonic biopsies were performed in 14 IBS patients and 16 controls during a colonoscopy to analyze the mucosal Cav 3.2 expression. KEY RESULTS: Wild-type, but not Cav 3.2-KO, mice developed visceral hypersensitivity without colonic inflammation, after 0.5% DSS treatment. A significant increase of Cav 3.2 mRNA (p = 0.04) was found in the colon of low-dose DSS-treated wild-type (WT) mice compared to their controls. In human colonic biopsies, the Cav 3.2 mRNA level was significantly higher in the IBS group compared to the control group (p = 0.01). The immunofluorescence staining revealed their protein expression in colonic mucosa, particularly in nerve fibers. CONCLUSIONS & INFERENCES: This translational study supports the involvement of the calcium channels Cav 3.2 in abdominal pain, as observed in IBS patients. It opens new therapeutic perspectives based on molecules specifically blocking these channels.

Faecal chitinase 3-like 1 is a reliable marker as accurate as faecal calprotectin in detecting endoscopic activity in adult patients with inflammatory bowel diseases.

BACKGROUND: Faecal biomarkers are emerging tools in the assessment of mucosal healing in inflammatory bowel diseases (IBDs). AIM: To evaluate the accuracy of faecal chitinase 3-like 1(CHI3L1) compared to calprotectin in detecting endoscopic activity in IBD. METHODS: Overall, 86 IBD adults underwent colonoscopy consecutively and prospectively, with Crohn's disease Endoscopic Index of Severity (CDEIS) or Mayo endoscopic subscore calculation for ulcerative colitis, and stool collection. Faecal calprotectin was measured using quantitative immunochromatographic testing. Faecal CHI3L1 was quantified by ELISA. CHI3L1 cut-off value was determined using a receiver-operating curve. RESULTS: In 54 Crohn's disease patients, faecal CHI3L1 (ρ = 0.70, P < 0.001) and calprotectin (ρ = 0.74, P < 0.001) levels correlated with CDEIS and were significantly increased in patients with endoscopic ulceration. In patients with ileal Crohn's disease, faecal CHI3L1 seemed to be better correlated with CDEIS than faecal calprotectin (ρ = 0.78 vs. ρ = 0.62, P < 0.001 for both). CHI3L1 > 15 ng/g detected endoscopic ulceration in Crohn's disease with a sensitivity of 100% and a specificity of 63.6%, compared to faecal calprotectin > 250 µg/g showing a sensitivity of 90.5% and a specificity of 59.1%. In 32 ulcerative colitis patients, faecal CHI3L1 and calprotectin levels correlated with Mayo endoscopic subscore (ρ = 0.44 and 0.61, respectively, P < 0.001 for both) and were significantly increased in ulcerative colitis patients with endoscopic activity. In ulcerative colitis patients, faecal CHI3L1 > 15 ng/g predicted endoscopic activity with a sensitivity of 81.8% and a specificity of 80.0%, compared to faecal calprotectin>250 µg/g showing a sensitivity of 86.4% and a specificity of 80.0%. CONCLUSION: Faecal CHI3L1 is a reliable biomarker in detecting endoscopic activity in IBD.

Biliary stenting is not a prerequisite to endoscopic placement of duodenal covered self-expandable metal stents.

BACKGROUND: Duodenal covered self-expandable metal stent (cSEMS) can be used in malignant or benign gastroduodenal obstruction. The need for biliary stenting in patients with no concomitant biliary stricture, before duodenal cSEMS placement, remains unknown. The aim of this study was to determine whether cSEMS placement is responsible for biliary obstruction. METHODS: This is a single-center, retrospective, case-controlled study, including 106 patients with symptomatic gastric outlet obstruction or duodenal fistula who received a covered nitinol duodenal stent by using through-the-scope/over-the-wire placement procedure. The main outcome measurement was the occurrence comparison of jaundice and bilirubin level, between patients with previous or concomitant biliary stenting (cSEMS + BS group), and patients with no biliary stent (cSEMS group) during an observational period of 90 days. RESULTS: Hundred and six patients underwent cSEMS placement between June 2005 and March 2014: 53 in the cSEMS group (58% male, mean age 66.4 ± 13.3 years) and 53 in cSEMS + BS group (60% male, mean age 70.4 ± 11.6 years). The obstruction was due to cancer in 45% in cSEMS group and 87% in cSEMS + BS group. No case of jaundice was reported in the cSEMS group or in the cSEMS + BS group. In cSEMS group, the mean bilirubin level (µmol/L ± SD) was 8.0 ± 4 at baseline and 8.5 ± 4.6 at day 10, while in the cSEMS + BS group it was 91.4 ± 108 at baseline and 35.3 ± 39 at day 10 (p < 0.01). Patients from the two groups were matched on age, gender and bilirubin level at baseline. Evolution of bilirubinemia was +0.98 ± 2.76 µmol/L in experimental group and +0.39 ± 522 µmol/L in the control group (p = 0.34). No significant difference was observed between the two groups in term of technical success, clinical effectiveness, migration and other complications. CONCLUSIONS: Previous biliary stenting is not required before endoscopic covered duodenal stent placement in patients with no associated biliary obstruction. Prospective studies are needed.

Endoscopic Factors Influencing Fecal Calprotectin Value in Crohn's Disease.

BACKGROUND AND AIMS: Fecal calprotectin [fcal] is a biomarker of Crohn's disease [CD] endoscopic activity. Identifying the endoscopic situations in which fcal is less reliable remains unexplored. We aimed to determine the endoscopic factors influencing fcal level in CD. METHODS: Overall, 53 CD patients consecutively and prospectively underwent colonoscopy, with CD Endoscopic Index of Severity [CDEIS] calculation and stool collection. Fcal was measured using a quantitative immunochromatographic test. Correlation analysis was done with Pearson statistics. RESULTS: Fcal was correlated with CDEIS [0.66, p < 0.001]. In univariate analysis, fcal was correlated with the affected surface [0.65, p < 0.001] and the ulcerated surface [0.47, p < 0.001]. Fcal was significantly associated with ulceration depth, with median fcal of 867.5 µg/g, 1251.0 µg/g, and 1800.0 µg/g, in patients presenting with non-ulcerated lesions, superficial ulcerations [SU], and deep ulcerations [DU], respectively. Lesion locations did not influence fcal. In multivariate analysis, fcal was associated with affected surface [p = 0.04] and the presence of CD lesions. Moreover, fcal increased with the ulceration depth [p = 0.03]. However, ulcerated surface and CD location did not affect fcal. Using a receiver operating characteristic [ROC] curve, we showed that fcal of 400 µg/g was the best compromise between sensitivity [0.76] and specificity [0.77], whereas fcal ≥ 200 µg/g was highly sensitive [0.86] to detect SU or DU. CONCLUSIONS: Fcal is a very reliable biomarker to detect endoscopic ulcerations in CD. We suggest repeating measurement in case of intermediary results [200-400 µg/g] in daily practice. Fcal level is mostly influenced by the presence of CD lesions [even non-ulcerated], in a depth-related manner and by the affected surface.

Diffusion-weighted magnetic resonance imaging is effective to detect ileocolonic ulcerations in Crohn's disease.

BACKGROUND: Magnetic resonance entero-colonography enables accurate assessment of ileocolonic Crohn's disease, but the need for bowel cleansing and rectal enema limits considerably its use in daily practice. AIM: We evaluated the accuracy of diffusion-weighted magnetic resonance entero-colonography with neither bowel cleansing nor rectal enema to assess endoscopic activity. METHODS: Forty-four Crohn's disease patients underwent prospectively and consecutively diffusion-weighted magnetic resonance entero-colonography [with apparent diffusion coefficient (ADC) and Clermont score calculation] and ileocolonoscopy [with Crohn's Disease Endoscopic Index of Severity (CDEIS) and Simplified Endoscopic score for Crohn's Disease (SES-CD) calculation]. RESULTS: Mean ADC was inversely correlated with total CDEIS (ρ = -0.40; P = 0.0067) and total SES-CD (ρ = -0.33; P = 0.032). Considering the 194 segments, ADC was inversely correlated with segmental CDEIS (-0.48; P < 0.001) and segmental SES-CD (-0.44; P < 0.001). ADC values were lower in segments with deep ulcers (1.30 ± 0.23) or superficial ulcerations (1.75 ± 0.64) than in non-ulcerated segments (2.15 ± 0.5) (P = 0.001). Using a receiver operating curve, we determined that segmental ADC <1.42 detected endoscopic deep ulcerations with sensitivity = 0.91 and specificity = 0.83 (Area under the curve = 0.84; P < 0.001). Segmental ADC <1.88 detected endoscopic superficial ulcerations with sensitivity = 0.64 and specificity = 0.75. The segmental ADC values decreased when the ulcerations size increased (P = 0.0001). Clermont score correlated with ileal CDEIS (0.63; P < 0.05) and ileal SES-CD (0.58; P < 0.05). Clermont score was higher in ulcerated segments (23.3 ± 8.4) than in non-ulcerated segments (12.4 ± 10.0) (P = 0.006) and increased with ulcers size (P = 0.012). Clermont score >18.9 detected ulcerations with sensitivity = 0.79 and specificity = 0.73. CONCLUSION: Diffusion-weighted magnetic resonance entero-colonography using apparent diffusion coefficient and Clermont score was effective to indirectly detect endoscopic ulcerations in ileocolonic Crohn's disease.

An oropharyngeal pH monitoring device to evaluate patients with chronic laryngitis.

BACKGROUND: Diagnostics for gastro-esophageal reflux disease (GERD) are suboptimal because of limited sensitivity. We performed in vitro and in vivo studies to systematically assess the performance characteristics of an oropharyngeal pH probe. METHODS: In vitro studies compared the oropharyngeal probe with a standard pH catheter in liquid and aerosolized solutions, pH 1-7. The accuracy of measurements, deviation from target pH, and time to equilibrium pH were determined. Simultaneous distal esophageal pH measurements were obtained in 11 patients with GERD. Oropharyngeal and distal esophageal reflux parameters were measured for controls (n = 20), patients with GERD (n = 17), and patients with chronic laryngitis (n = 10). KEY RESULTS: In the liquid phase, at pH 4-5, the oropharyngeal probe had less deviation from the target value than the standard catheter; deviation in the vapor phase was similar (0.4 pH units). Median (interquartile) time to reach equilibrium pH was significantly (P < 0.001) faster with the oropharyngeal than the standard probe. In comparing simultaneous distal esophageal pH characteristics, 96% of recordings with the new and standard probes were in agreement to within ± 1.0 pH unit; 71% of recordings were in agreement within ± 0.5 pH units. Patients with chronic laryngitis had significantly higher levels of oropharyngeal acid exposure at pH <4, <5, and <6, in the upright position than patients with GERD or controls (P < .001). CONCLUSIONS & INFERENCES: Oropharyngeal pH monitoring appears to be more sensitive than traditional pH monitoring in evaluation of patients with extraesophageal reflux. It is a promising tool in evaluation of this difficult group of patients.

Dilated intercellular space in chronic laryngitis and gastro-oesophageal reflux disease: at baseline and post-lansoprazole therapy.

BACKGROUND: Dilation of intercellular spaces is reported to be an early morphological marker in gastro-oesophageal reflux. It remains unknown if this marker is useful in diagnosing reflux-related chronic laryngitis. AIM: To determine histopathology and electron microscopic changes in oesophageal and laryngeal epithelium in chronic laryngitis. METHODS: In this prospective blinded study, we enrolled 53 participants: 15 controls, 20 patients with GERD and 18 patients with chronic laryngitis. The latter two groups were subsequently treated with lansoprazole 30 mg bid for 12-weeks. Baseline and postacid suppressive therapy biopsies were obtained from distal oesophagus and laryngeal postcricoid areas. Biopsy specimens were evaluated for histopathology and dilated intercellular space changes. RESULTS: There was no significant increase in oesophageal or laryngeal epithelium intercellular spaces among GERD or laryngitis patients compared with controls at baseline or postacid suppressive therapy. Only patients with GERD had significantly (P = 0.03) higher proportion of moderate-to-severe oesophageal spongiosis and basal cell hyperplasia, which normalized postacid suppressive therapy. CONCLUSIONS: There was no increase in the width of intercellular spaces in the oesophagus or larynx in GERD or chronic laryngitis at baseline or postacid suppressive therapy. Our findings question the uniform presence of dilated intercellular space in patients with GERD.

Relationship between nutritional status and quality of life in patients with cancer.

Patients with cancer frequently suffer a deteriorated quality of life and this is an important factor in the therapeutic decision. The correlation between quality of life and malnutrition seems obvious and bidirectional. The aim of our study was to describe the global quality of life and its various dimensions in patients with cancer, as a function of the nutritional status. A transversal observational study was performed in wards in hospitals in Clermont-Ferrand and Saint Etienne on 907 patients. The EORTC questionnaire, QLQ-C30, was used to assess the quality of life. The mean global quality of life score was 48.8 for patients who had a weight loss of more than 10% since the beginning of their illness, compared with 62.8 for the other patients (p<0.001). A significant association with weight was observed for the main dimensions of the quality of life: physical, functional, cognitive, social, fatigue, nausea, pain, loss of appetite, constipation and diarrhoea. This strong relation between quality of life and weight loss shows the importance of dietary management in patients with cancer.