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In patients with clinical signs that may indicate a colorectal cancer, physicians may interpret the presence of a comorbid depressive mood as either increasing or decreasing the likelihood of cancer diagnosis. This study examined the association between depressive mood in candidates for a colonoscopy and subsequent diagnosis of cancer.Ninety-four outpatients [35 men, mean age ± standard deviation (SD) = 56.2 ± 9.8 years, 59 women, mean age ± SD = 54.2 ± 12.9 years] were given the 13-item Beck depression inventory to assess depressive mood before undergoing a colonoscopy. Additional psychological, demographic, and clinical data were collected prior to the colonoscopy.The colonoscopy found a cancer in 18 patients (19.1%). Cancer patients were older (P = 0.015) and more likely to present with anemia (P0.001) and unexplained weight loss (P = 0.046). Depressive mood was associated with a subsequent diagnosis of cancer in women (P = 0.007), but not in men (P = 0.985). This association remained significant after adjustment for potential confounders in women (i.e., anemia and unexplained weight loss) (P = 0.014).In women with clinical signs that warrant a colonoscopy, comorbid depressive mood may be associated with an increased likelihood of colorectal cancer and should not delay the receipt of a guideline-based diagnosis procedure.

Introduction La resection muqueuse endoscopique (EMR) est un traitement curatif des cancers epidermoides (SCC) superficiels de l’œsophage. L’objectif de cette etude etait d’evaluer l’evolution a long terme et la survie des patients traites par EMR.

BACKGROUND: Surveillance colonoscopy is recommended for inflammatory bowel disease (IBD) patients with longstanding extensive colitis (LEC). AIMS: To assess modalities and results of colonoscopic surveillance in a subset of CESAME cohort patients at high risk of colorectal cancer (CRC) and followed in university French hospitals. METHODS: Among 910 eligible patients with more than a 7-year history of extensive colitis at CESAME enrolment, 685 patients completed a questionnaire on surveillance colonoscopy and 102 were excluded because of prior proctocolectomy. Finally, 583 patients provided information spanning a median period of 41months (IQR 38-43) between cohort enrolment and the end of follow-up. Details of the colonoscopic procedures and histological findings were obtained for 440 colonoscopies in 270 patients. RESULTS: Only 54% (n=312) of the patients with LEC had at least one surveillance colonoscopy during the study period, with marked variations across the nine participating centres (27% to 70%, P≤0.0001). Surveillance rate was significantly lower in Crohn's colitis than in ulcerative colitis (UC) (48% vs. 69%, P≤0.0001). Independent predictors of colonoscopic surveillance were male gender, UC IBD subtype, longer disease duration, previous history of CRC and disease management in a centre with large IBD population. Random biopsies, targeted biopsies and chromoendoscopy were performed during respectively 71%, 27 and 30% of surveillance colonoscopies. Two cases of high-grade dysplasia were detected in patients undergoing colonoscopic surveillance. Two advanced-stage CRC were diagnosed in patients who did not have colonosocopic surveillance. CONCLUSIONS: Colonoscopic surveillance rate is low in IBD patients with longstanding extensive colitis.

We report on a 32-year-old man with a history of chronic lower abdominal pain and urogenital symptoms, leading to the diagnosis of coloseminal fistula complicating diverticular disease. We reviewed the literature on this rare clinical entity and would like to stress the role of pelvic imaging with rectal contrast to investigate complicated forms of diverticular disease.

Background & Aims Little is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohn's disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohn's perianal disease followed up in the Cancers Et Surrisque Associe aux Maladies Inflammatoires Intestinales En France (CESAME) cohort. Methods We collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohn's disease. Subjects were followed up for a median time of 35 months (interquartile range, 29–40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex. Results Among the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohn's lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistula–related adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistula–related adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohn's disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18-551.51; P = .03). Conclusions In an analysis of data from the CESAME cohort in France, patients with anal and/or perianal Crohn's disease have a high risk of anal cancer, including perianal fistula–related cancer, and a high risk of rectal cancer.

During the 20th century, gastro-esophageal reflux moved from the status of a rare and severe disease to that of a frequent disease occurring mostly, in the absence of any significant lesions. Proton pump inhibitors (PPIs) are the mainstay of its therapy and are prescribed mainly in an empirical way. Extradigestive manifestations require more accurate diagnostic tests and therapeutic management. The modalities of prescription of the PPIs quickly progressed toward the on-demand therapy and over-the-counter PPIs should become widespread. The relative failures of PPIs led to a profusion of new antisecretory agents but clinical improvements are presently disappointing and the rationale of this escalation is questionable. The concept of non acid gastro-esophageal reflux opens more innovative diagnostic and therapeutic perspectives which, however, must be validated. In this respect, endoscopic treatment needs more reliable techniques and more rigorous trials. Gastro-esophageal reflux refractory to PPIs corresponds mainly to functional esophageal disorders that need diagnostic and therapeutic improvements. Barrett's esophagus constitutes a major challenge for the next few years. Its screening and its prevention seem, for the moment, inaccessible. Its survey and the prevention of its complications should benefit from progress of diagnostic and interventional endoscopy.

Objectives CX3CR1, the receptor of CX3CL1/fractalkine, is involved in regulation of inflammatory response and the CX3CR1-I249-M280 naturally occurring mutants are associated with altered binding to the ligand. Our aim was to evaluate the frequency of CX3CR1 V249I and T280M polymorphisms and NOD2/CARD15 mutations in Crohn's disease patients and to search for a relationship with phenotype. Methods Clinical data were retrospectively collected. V249I and T280M polymorphisms of CX3CR1 gene and NOD2/CARD15 mutations (R702W, G908R, 3020InsC) were identified. Results Two hundred and thirty-nine patients (140 females, 39.7±14.1 years) were included. About 37.4% were heterozygous and 8.8% were homozygous for the V249I CX3CR1 polymorphism, 18.1% were heterozygous and 1.3% homozygous for the T280M CX3CR1 polymorphism and 35.9% had at least one of the three mutations of NOD2/CARD15. The T280M CX3CR1 polymorphism was not associated with any phenotype. In univariate analysis, stenosis was significantly associated with both V249I CX3CR1 polymorphism and 3020InsC NOD2/CARD15 mutations. In smoker patients carrying the CX3CR1 allele I249, there was a significant increase in the frequency of fibrostenosing disease [P=0.005, odds ratio (OR): 3.25] whereas this relationship disappeared in the group of nonsmokers (P=0.72). In multivariate analysis, 3020InsC NOD2/CARD15 mutations and the V249I CX3CR1 polymorphism were independent risk factors for intestinal stenosis (P=0.046, OR: 1.8 and P=0.044, OR: 2.4, respectively). Conclusion In Crohn's disease, V249I CX3CR1 polymorphism is associated with intestinal strictures, particularly in smokers. This association is independent of CARD15 mutations.

Summary Background Lactulose and polyethylene glycol are osmotic agents used to treat idiopathic chronic constipation. Aim To compare the effects of low doses of lactulose and PEG 4000 on transit time measured by scintigraphy in normal subjects. Methods For 5 days, 10 healthy subjects received either 10 g b.d. of lactulose or PEG 4000 in a randomized, double-blind, crossover study. On the evening of day 4, they took a capsule containing Amberlite resin pellets labelled with 111In. On day 5, after a 1000 kcal test meal labelled with 99Tcm, gastric, small bowel and colonic transits were measured. Results Gastric emptying and small bowel transit time were not different. Ascending colon emptying curve was significantly accelerated with lactulose in comparison with polyethylene glycol (P = 0.001) and, respectively, 50 ± 18% vs. 35 ± 18% of the radioactivity had left the ascending colon at the end of the study (P

Summary Objective The aim of the present study was to describe the management of gastro-esophageal reflux disease(GERD) by primary care physicians (PCPs). Methods This prospective survey was conducted in patients with suspected or previously diagnosed GERD. PCPs completed questionnaires at first consultation (M0) and at a 3-month follow-up visit (M3). Results 2 474 patients were available for analysis at M0 and 1 993 at M3. GERD was the reason for consultation in 84% of patients; 33% were consulting about reflux symptoms for the first time. Symptoms occurred once daily in 55% of patients and were considered very disruptive or incapacitating by 51%. Upper gastrointestinal endoscopy was performed at any time in 57% of patients and at M0 in 20%. Only 48% of demands for endoscopy agreed with current recommendations and this rate was not influenced by PCP training in the previous 6 months. Lifestyle measures were recommended in 95% of patients at M0. Proton pump inhibitors were prescribed in 98%, to be taken “on-demand” in 22-57% depending on symptom frequency. Therapeutic management was considered as very satisfactory by 81% of patients. Conclusions GERD managed in primary care is severe, leading to expensive, but effective diagnostic investigations and treatments. Agreement with recommendations for endoscopy is poor.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and platelet dysfunction. A subset of patients also show ceroid deposition, which can result in pulmonary fibrosis or granulomatous colitis. Whether this colitis may be considered Crohn's disease is under debate. We report a case of a patient with HPS associated with inflammatory bowel disease which affected the distal small bowel but not the colon. Ileitis was severe, and recurred rapidly after surgery. Search for mutations in HPS1, ADTB3A, HPS3, HPS4 and for CARD15 were negative. Symptoms and ileal ulcerations which recurred after surgery were successfully treated with azathioprine and infliximab.

Lactulose (10-20 g day(-1)) is used to treat constipation. At this therapeutic dose, its effects on colonic motility remain unknown. Twenty-two healthy subjects swallowed a probe with an infusion catheter, six perfused catheters and a balloon connected to a barostat. Colonic phasic and tonic motor activity was recorded in fasting state. In group 1, four volunteers ingested 15 g lactulose and motility was recorded for 5 h after entry of lactulose into the caecum; in group 2, motility was recorded during (3 h) and 2 h after intracolonic infusion of isoosmotic and isovolumetric solutions containing sodium chloride alone (n = 9) or with 15 g lactulose (n = 9). In a last group of volunteers, isotopic colonic transit after ingestion of lactulose (10 g,n = 9) was assessed and compared with a control group (n = 17). Ingestion or intracolonic infusion of 15 g lactulose significantly decreased barostat bag volume (maximal decrease: 45 +/- 12% and 35 +/- 9% of basal value respectively). Phasic contractions remained unchanged. Tonic and phasic motility was unchanged by the isotonic and isovolumetric infusion of saline. Ingestion of lactulose significantly accelerated isotopic colonic transit time compared with the control group. We conclude that in healthy humans, 10-15 g ingestion or intracaecal infusion of lactulose produces a prolonged tonic contraction that may be involved in the laxative effect of lactulose.

Background & Aims: In hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, flat and small adenomas are particularly prone to malignant transformation but might be missed by standard colonoscopy. We prospectively studied the diagnostic yield of high-resolution colonoscopy coupled with chromoendoscopy for preneoplastic and neoplastic colorectal lesions in patients with HNPCC syndrome. Methods: Thirty-six consecutive asymptomatic patients (mean age, 42 years) belonging to HNPCC families and receiving genetic counseling were enrolled in this prospective study. Colonoscopy was performed in 2 steps. Conventional colonoscopy was performed first, followed by a second colonoscopy with chromoendoscopy with indigo carmine (.4%) dye sprayed onto the entire proximal colon. Results: Conventional colonoscopy identified 25 lesions (mean size, 4 ± 3 mm) in 13 patients. Seven lesions, detected in 5 patients, were adenomas, 3 of which were located in the proximal colon. Chromoendoscopy identified additional 45 lesions (mean size, 3 ± 1 mm) in 20 patients; most of these lesions were flat and hyperplastic. Eleven additional adenomas were detected in the proximal colon of 8 patients, and 8 of these 11 lesions were flat. The use of chromoendoscopy significantly increased the detection rate of adenomas in the proximal colon, from 3 of 33 patients to 10 of 33 patients (P = .045). Conclusion: Relative to conventional colonoscopy, high-resolution colonoscopy with chromoendoscopy markedly improves the detection of adenomas in patients with HNPCC syndrome and might help to prevent colorectal carcinoma in these patients with a very high risk of colorectal cancer.

International audience; BACKGROUND: The mucosa-associated microbiota, being very close to the inflammatory process associated with inflammatory bowel disease (IBD), may have a pathogenic role. We used a culture-independent method to analyze the mucosa-associated microbiota in IBD patients at various points of the distal digestive tract. METHODS: Thirty-five patients (20 with Crohn's disease, 11 with ulcerative colitis, and 4 controls) underwent colonoscopy. Biopsies (n = 126) were taken from 4 sites: the ileum, right colon, left colon, and rectum. Fecal samples were also obtained from 7 individuals. Temporal temperature gradient gel electrophoresis (TTGE) of 16S rDNA was used to evaluate dominant species diversity. TTGE profiles were compared using software that measures the degree of similarity. RESULTS: In a given individual, the overall similarity percentage between the 4 segments of the distal digestive tract was 94.7 +/- 4.0%, regardless of clinical status. The average similarity of all profiles for a given segment was 59.3 +/- 18.3% in the overall population. Dendrogram analysis showed that TTGE profiles did not cluster with clinical status. Differences were observed between the dominant fecal microbiota and the mucosa-associated microbiota of all 4 sites, with similarity percentages less than 92%. CONCLUSIONS: These results confirm that the dominant species differ between the mucosa-associated and fecal microbiota. They also show that, in a given individual, the microbiota is relatively stable along the distal digestive tract, showing a slight evolution in dominant species diversity from the ileum to the rectum, in both healthy subjects and patients with IBD.

Purpose: The target enzyme for 5-fluorouracil (5-FU) is thymidylate synthase (TS). The TYMS gene encoding this enzyme is polymorphic, having either double (2R) or tri-tandem (3R) repeats of a 28-bp sequence in the promoter region and a 6-bp variation in the 3′-untranslated region (3′-UTR). TS expression predicts response to 5-FU-based chemotherapy, and the expression seems to be determined by the TYMS gene promoter. The aim of this study was to investigate the utility of determining these two TYMS gene polymorphisms to predict the toxicity and efficacy of 5-FU treatment in patients with colorectal cancer. Experimental Design: The determination of TYMS genotypes was performed in tumor and normal tissues by PCR amplification from 90 patients with colorectal cancer who were treated with adjuvant or palliative 5-FU-based chemotherapy. Associations between polymorphisms in the TYMS promoter and in the 3′-UTR gene and clinical outcome of these 90 patients treated with 5-FU based chemotherapy were evaluated individually. The linkage between TYMS promoter and TYMS 3′-UTR region polymorphisms was evaluated and a haplotype analysis was performed. Results: Individuals who were homozygous for the double repeat in the TYMS promoter region had more severe side effects to 5-FU. Patients with a 2R/2R, a 2R/3R, or a 3R/3R genotype had a grade 3 or 4 toxicity rate of 43, 18, and 3% respectively (P < 0.01). The TYMS promoter and TYMS 3′-UTR polymorphisms were in linkage disequilibrium, and the haplotype 2R/ins 6-bp was significantly associated with a high risk of severe side effects to 5-FU. The TYMS promoter and TYMS 3′-UTR polymorphisms were not associated with a response to 5-FU and survival of patients who received palliative 5-FU-based chemotherapy. Conclusions: This study demonstrated that TYMS genotyping could be of help in predicting toxicity to 5-FU-based chemotherapy. TYMS genotyping might make it possible to individualize treatment for patients with colorectal cancer.

Hypersensitivity during rectal distension has been demonstrated in irritable bowel syndrome (IBS). Studies performed in animals and indirect data in humans suggest that cholecystokinin (CCK) could modulate visceral sensations. The aim of this study was to assess the effects of i.v. infused sulphated cholecystokinin octapeptide (CCK-OP) on rectal sensitivity in response to distension. In eight healthy subjects, rectal sensitivity and compliance were determined during a randomized double-blind study, with four sessions each separated by 7 days. Sensory thresholds and rectal compliance were assessed during slow-ramp (40 mL min-1) and rapid-phasic distensions (40 mL s-1, 5 mmHg stepwise, 1-min duration), and were compared before and during continuous infusion of either saline or CCK-OP at 5, or 20 or 40 ng kg-1 h-1. During rapid phasic distension but not during slow ramp distension, CCK-OP at 40 ng kg-1 h-1 produced a significant decrease in sensory thresholds compared with the basal period. Rectal compliance was not modified by any infusion. At pharmacological doses, CCK-OP decreases sensory thresholds during rapid phasic distension that may preferentially stimulate serosal mechanoreceptors, but has no effect on mucosal mechanoreceptors stimulated during slow ramp distensions. Modulation of rectal sensitivity by CCK could be implicated in the pathogenesis of the rectal hypersensitivity observed in IBS.

OBJECTIVE: Prediction of the clinical course of Crohn’s disease (CD) is difficult in the long term. Our aim was to determine whether the presence of severe endoscopic lesions (SELs) may predict a higher risk of colectomy and penetrating complications. METHODS: All patients at our institution with active ileocolonic CD who had colonoscopies between 1990 and 1996 were included in the study. SELs were defined as extensive and deep ulcerations covering more than 10% of the mucosal area of at least one segment of the colon. RESULTS: Among the 102 patients included, 53 had SELs at index colonoscopy. During the follow-up (median = 52 months), 37 patients underwent colonic resection. Probabilities of colectomy at 1, 3, and 8 yr were 20%, 26%, and 42%. Risk of colectomy was independently affected by the presence of SELs at index colonoscopy (relative risk [RR] = 5.43, 95% CI = 2.64–11.18), a Crohn’s Disease Activity Index level greater than 288 (RR = 2.21, 95% CI = 1.09–4.47), and the absence of immunosuppressive therapy during the follow-up (RR = 2.44, 95% CI = 1.20–5.00). Probabilities of colectomy were, respectively, 31% and 6% at 1 yr, 42% and 8% at 3 yr, and 62% and 18% at 8 yr in patients with and without SELs. We performed a second analysis excluding the 14 patients operated on within the 3 months after the index colonoscopy: presence of SELs remained the only significant factor predictive of colectomy (RR = 6.72, 95% CI = 2.26–20.03). All six patients with penetrating complications during the follow-up had SELs at index colonoscopy. CONCLUSIONS: Patients with CD exhibiting deep and extensive ulcerations at colonoscopy have a more aggressive clinical course with an increased rate of penetrating complications and surgery.

The origin and mechanisms of symptoms in sugar intolerance were studied in 8 healthy volunteers. For two test periods, volunteers swallowed a probe with perfused catheters and an infusion catheter which migrated into the colon. A meal containing 40 g lactulose or 40 g sucrose was ingested; the sucrose meal was followed by colonic infusion of 40 g lactulose in order to bypass the small intestine. Recordings of small intestinal and colonic motility were performed. Abdominal pain, bloating, borborygmi, and flatulence were similar during both periods. Both meals increased small intestinal and colonic motility. Only 37% of the symptoms coincided in time with colonic motor events. Symptoms were not related to a specific motor event and were not correlated with breath hydrogen excretion. In conclusion, symptoms of sugar intolerance originate from the colon. They are not related to specific phasic motor events or to breath hydrogen excretion.

Smart manufacturing has increasingly become a prominent research topic across the academia and industry during recent years. However, in the real world, most factories' conditions are normally insufficient for implementing full scale smart manufacturing. In order to increase smartness for manufacturing systems under different situations, one may observe that computational reasoning and learning, including latest machine learning methodology and traditional rule based systems, are able to offer potential powerful theoretical foundations as well as technical tools for enabling such smarter systems. Unfortunately, few studies exist to propose a practical yet systematic procedure that implements computational reason and learning to implement smartness for typical manufacturing systems. This paper proposes a general computational reasoning and learning framework to describe the key functions in smart manufacturing under the "three Fs in one" system framework, namely a system of interconnected data, integrated automation, and intelligent information. Among three Fs, the intelligent information plays the most important role in working towards smartness by connecting the other two Fs. Furthermore, to achieve it, a learning enabled comprehensive multi-agent decision model is developed. In particular, we first design a computational learning based architecture for analyzing support information for manufacturing processes. Then we provide an optimization architecture that enables realtime learning for a manufacturing process. At last, we employ a rule based learning system to integrate these two architectures to facilitate self-evolution of the manufacturing system. The advantages of our procedure include adaptive responses to dynamic environment, efficient computations, and abilities to fulfill complex manufacturing processes, which are demonstrated by a specific modeling procedure.

International audience; BACKGROUND:: Crohn's disease (CD)-associated dysbiosis could predispose patients to relapse. Gut microbiota composition of patients from the prospective cohort study designed to identify predictive factors of clinical relapse after infliximab discontinuation (STORI Study) was investigated to determine the impact of dysbiosis in CD relapse. METHODS:: Fecal samples from 33 patients with CD in this cohort were collected at baseline, 2 months, 6 months, and at the end of the follow-up period (19 relapsers and 14 nonrelapsers). Healthy volunteers subjects (n = 29) were used as a control group. The fecal microbiota composition was assessed using quantitative PCR, and comparisons between the patient groups were made at different time points using the Wilcoxon test. The analysis of the time-to-relapse was performed according to the baseline median level of each bacterial signal. RESULTS:: Dysbiosis was observed in patients with CD compared with healthy subjects, and it was characterized by low mean counts of Firmicutes (Clostridium coccoides [P = 0.0003], C. leptum [P < 0.0001], and Faecalibacterium prausnitzii [P = 0.003]). Lower rates of Firmicutes were seen in relapsers compared with nonrelapsers. Moreover, a low rate of F. prausnitzii (P = 0.014) and a low rate of Bacteroides (P = 0.030) predicted relapse independently from high C reactive protein level (P = 0.0001). CONCLUSIONS:: In this work, we report that CD-associated dysbiosis, characterized by a decrease in Firmicutes, correlates with the time-to-relapse after infliximab withdrawal. A deficit in some bacterial groups or species, such as F. prausnitzii, may represent a predictive factor for relapse. Restoring normobiosis in CD could be a new goal for optimal CD management.

Background We have assessed the long-term efficacy and safety of a combination therapy of interferon alpha-2b (IFN) and ribavirin (RBV) for the treatment of severe chronic hepatitis C in co-infected HIV-seropositive patients in an open prospective study. Methods Fifty-one patients were treated for 12 months. Mean baseline CD4 cell count, alanine aminotransferase and aspartate aminotransferase were 412 +/- 232 x 106/l, 113 +/- 75 IU/l and 111 +/- 84 IU/l respectively. The mean Knodell score was 11.5 +/- 2.1 with 28 patients (55%) exhibiting histological evidence of active cirrhosis. Results Fifteen (29%) patients discontinued the treatment prematurely because of adverse events. An end of treatment response (ETR) as defined by the lack of detectable hepatitis C virus (HCV) RNA in plasma at the end of treatment was achieved in 15 patients (29%). A sustained virological response (SVR), defined by the lack of detectable HCV RNA in plasma 6 months after completion of combination therapy, was achieved in 11 patients (21%). The HCV genotype 3a was associated with ETR and SVR (P = 0.002 and P = 0.003, respectively). HCV viraemia at baseline was lower in patients who achieved SVR and ETR than in those who did not (6.7 +/- 7.8 versus 24 +/- 26.7 x 10(6) genome equivalents/ml, P = 0.03 and 14.3 +/- 28.7 versus 22.5 +/- 23, P = 0.05, respectively). Conclusion Our results indicate that combination therapy with IFN and RBV is effective in approximately 20% of co-infected patients with severe liver disease.

Somatostatin analogs are the first-line drugs for controlling hormone-mediated symptoms of carcinoid tumors. Prospective and retrospective studies have suggested that somatostatin analogs also have antiproliferative activity. The octapeptide lanreotide is available in sustained-release form, obviating the need for daily injections.A total of 46 patients were enrolled in this open, prospective, phase II trial. They received lanreotide 30 mg i.m. every 14 days for 6 months when they had symptomatic carcinoid tumors, and lanreotide 30 mg i.m. every 10 days if they had nonsymptomatic tumors. Nonsymptomatic tumors were progressive before the start of the study. Tumor size was assessed every 3 months by means of computed tomography. The assessment was centralized and was made by an external panel.In all, 30 patients had symptomatic neuroendocrine tumors and 16 had asymptomatic neuroendocrine tumors. Five patients in the group with symptomatic tumors and two in the group with nonsymptomatic tumors were considered not to be evaluable. The mean duration of treatment was 12 months in the group with symptomatic tumors and 13 months in the other group. Among the 39 evaluable patients, two objective responses were obtained, giving an objective response rate of 5% (one in the group with symptomatic tumors and one in the other group). Nineteen patients had no significant increase in their tumor size for a mean of 9.5 months.Lanreotide is safe and well tolerated in patients with carcinoid tumors. It seems to have both symptomatic and antitumoral effects in this setting.

The aim of this study was to assess in nine healthy subjects the effects of CCK octapeptide (CCK-8) on colonic tonic activity, measured by a barostat, and phasic activity, measured by manometry. On 2 consecutive days, recordings were performed in the unprepared proximal and distal colons during intravenous infusion of saline and CCK-8 at 5, 20, and 40 ng ⋅ kg−1⋅ h−1. In the proximal colon CCK-8 induced, at the 20 and 40 ng ⋅ kg−1⋅ h−1doses, a tonic relaxation with an increase in barostat bag volume to 156 ± 25 and 157 ± 19% of basal ( P < 0.01) and a decrease in phasic activity to 72 ± 7 and 76 ± 7% of basal ( P < 0.01). In the distal colon, CCK-8 induced, at the 20 and 40 ng ⋅ kg−1⋅ h−1doses, a tonic relaxation (increase in intrabag volume to 133 ± 12 and 149 ± 15%, respectively; P< 0.01), whereas phasic activity increased (128 ± 8 and 132 ± 6%, respectively; P < 0.01). Effects of CCK-8 on tonic and phasic activities are different according to the colonic segment. Because meals induce colonic tonic contraction, our results suggest that CCK, as a hormone, is not an important mediator of the response of the colon to feeding in humans.

A 67-year-old woman with end-stage renal disease (ESRD) was referred with chronic diarrhoea, severe hypokalaemia and recurrent colonic pseudo-obstructions following haemorrhagic shock. The cause of secretory diarrhoea was uncertain, but an ileostomy identified the colon as the source of the watery diarrhoea and potassium (K(+)) losses, and symptoms only resolved after colectomy. Immunohistochemistry of the colon revealed over-expression of high conductance K(+) (BK) channel protein in surface colonocytes and crypt cells compared with controls and other patients with ESRD. We hypothesize that colonic ischaemia during haemorrhagic shock led to increased BK channel expression and thus enhanced colonic K(+) and water secretion, resulting in severe hypokalaemia and colonic pseudo-obstruction.

We previously showed that gastric distension inhibits the somatic nociceptive flexion RIII reflex. To explore further the viscerosomatic interactions, we tested in the present study the effects of rectal distensions on RIII reflexes. Rapid and slow-ramp rectal distensions were performed in 10 healthy volunteers with an electronic barostat. The RIII reflex was continuously recorded from the lower limb during both types of distension and from the upper limb during rapid distensions. The visceral sensations were scored on a graded questionnaire. Rapid distensions facilitated the RIII reflex recorded from the lower limb, but at the highest distension level, facilitation was followed by inhibition. Slow-ramp distension induced gradual inhibition of the RIII reflex, which correlated with both distension volume and visceral sensation. RIII reflex recorded from the upper limb was also inhibited by rapid rectal distensions. Reflex inhibitions were probably related to the activation of pain modulation systems. One plausible explanation for the facilitatory effects, observed only at the lower limb, is the convergence of rectal and reflex afferents at the same levels of the spinal cord. The differential effects of rapid and slow-ramp distensions suggest the activation of two distinct populations of mechanoreceptors by these two modes of distension.

In healthy humans, meals stimulate phasic and tonic motor activity in the unprepared distal colon. The response of the proximal colon remains unknown. In this study, we assessed the effect of a liquid meal on proximal and distal colonic motor activity. In 12 healthy volunteers, colonic tone and phasic motility were simultaneously recorded by using an electronic barostat and perfused catheters in the fasting state and in response to a 1,000-kcal meal. The meal significantly increased the phasic activity in the distal colon (230 ± 46% of the basal value; P = 0.02) but not in the proximal colon (138 ± 25% of the basal value; P = 0.2). The intrabag volume of the barostat was significantly more reduced in the distal than in the proximal colon (74 ± 11 vs. 50 ± 9% of the basal values, respectively; P = 0.04). We conclude that the postprandial response of the unprepared proximal colon is an immediate tonic contraction that is less pronounced than in the distal colon.

We previously showed that a meal induced, in the human terminal ileum, a delayed tonic relaxation, which could be related to the ileal delivery of meal residues and/or endogenous secretions released by a meal. In this study, we assessed the effects of some components of the ileal contents on its motor activity. In six healthy subjects, we studied ileal tonic and phasic motility in response to the infusion into the terminal ileum of different isotonic solutions: saline, glycochenodeoxycholic acid (GDCA), triglycerides, and short-chain fatty acids (SCFA). Tonic activity was not modified by saline, whereas it was significantly decreased by GDCA and triglycerides (maximal increase in intrabag volume 139 +/- 7% and 152 +/- 16%, respectively, P < 0.01), and significantly increased by SCFA (maximal decrease in intrabag volume 72 +/- 4%, P < 0.01). No significant change of phasic activity was evidenced with either solution. We conclude that 1) bile acids and triglycerides not absorbed in the more proximal gut could be involved in the ileal relaxation occurring after eating and 2) local stimulation of chemoreceptors is of importance in the regulation of ileal motility.

A 24-year-old woman (53 kg) with a 5-year history of steroid-dependent ulcerative colitis with mild and extensive ulcerations presented to the gastroenterology clinic for symptom recurrence. She was given 100 mg/day (1.9 mg · kg−1 · day−1) azathioprine (AZA)5 for 1 month, after which the dose was increased to 125 mg/day (2.3 mg · kg−1 · day−1). Four months later, the patient was tapered off steroid therapy. Her symptoms persisted after 7 months of AZA therapy, however, and she experienced gastrointestinal side effects. The patient was switched to another thiopurine drug, 6-mercaptopurine (6-MP), at 75 mg/day (1.4 mg · kg−1 · day−1), which was well tolerated but similarly ineffective (8 stools daily). A brief course of steroid therapy rapidly produced a substantial but short-lived clinical improvement. To understand this patient's unresponsiveness to 2 thiopurine agents, we quantified thiopurine metabolites (1) 1 year after initiating AZA therapy. Intraerythrocyte concentrations of 6-thioguanine nucleotides (6-TGNs) were low (132 pmol/8 · 108 erythrocytes; therapeutic interval, 230–400 pmol/8 · 108 erythrocytes), and 6-methylmercaptopurine ribonucleotides (6-MMPRs) were very high (11 666 pmol/8 · 108 erythrocytes; therapeutic interval

BACKGROUND: Somatostatin analogues effectively control flushing and diarrhoea in patients with the carcinoid syndrome. The octapeptide lanreotide is available in slow release form, which could eliminate the necessity of twice a day injections as with octreotide. PATIENTS AND METHODS: 39 patients with carcinoid syndrome were included in a prospective multicentre study. Patients received lanreotide 30 mg intramuscularly every 14 days for six months. The number and intensity of flushing episodes and bowel movements, urinary 5 hydroxy-indolacetic acid (5 HIAA) concentrations, and variations of tumour mass were recorded. RESULTS: After one month of treatment, flushing episodes (median (range)) decreased significantly (3 (0.3-24) episodes per day v 1 (0-15), p = 0.04) and completely resolved in 39% of the patients. A significant decrease was seen in the number of bowel movements and discomfort related to diarrhoea. Urinary 5 HIAA concentrations were unchanged in 57% of the patients and decreased in 18%. After six months of treatment, the actuarial proportions of patients with at least a 50% decrease in the number of flushing episodes and bowel movements were 54% and 56%, respectively. Forty two per cent of the patients who were treated for six months had at least a 50% reduction in 5 HIAA values. No clear signs of regression of tumours were seen in any of the patients. Lanreotide was well tolerated despite transient mild pain or erythema at the injection site in 25% of the patients. Biliary lithiasis appeared in two patients after six months of lanreotide. CONCLUSION: Lanreotide, 30 mg intramuscularly every other week, is an effective and convenient treatment in patients with the carcinoid syndrome.

Introduction Prognosis of enteropathy-associated T cell lymphoma is poor but predictors of survival remain ill-defined. How clinical presentation, pathological features and therapies influence outcome was evaluated in 37 thoroughly characterized patients with celiac disease and T-cell lymphoma. Patients and methods Medical files were studied retrospectively. Lymphoma and intestinal mucosa were analysed by histopathology, multiplex PCR and intestinal intraepithelial lymphocytes phenotyping. Survival and prognostic factors were analysed using Kaplan–Meier curves with Logrank test and Cox Model. Results Lymphoma complicated non clonal enteropathy, celiac disease (n = 15) and type I refractory celiac disease (n = 2) in 17 patients and clonal type II refractory celiac disease in 20 patients. Twenty-five patients underwent surgery with resection of the main tumour mass in 22 cases. In univariate analysis, non clonal celiac disease, serum albumin level > 21.6 g/L at diagnosis, chemotherapy and surgical resection predicted good survival (p = 0.0007, p 21.6 g/L, chemotherapy and reductive surgery were all significantly associated with increased survival (p

The effect of the energy density of a meal on gastric emptying and satiety was assessed in nine volunteers. They ingested, in randomized order, a diluted (2671 kJ/L, 950 mL) and a concentrated (7452 kJ/L, 350 mL) test meal of 2500 kJ each (80% as solids). Half-emptying times of solids and liquids were not significantly different for the diluted and concentrated meal (solids: 145 +/- 18 and 156 +/- 16 min, respectively; liquids: 76 +/- 10 and 84 +/- 10 min, respectively), and consequently, pyloric outputs of energy were identical. Neither the intensity and duration of satiety, nor the amount of energy ingested, ad libitum, 6 h after the test meal, were significantly affected by energy density of the food ingested. Both the intensity and duration of satiety correlated significantly with the gastric emptying time for solids (r = 0.60 and 0.67, respectively, P < 0.01). These results show that satiety depends on gastric emptying of energy and is not affected by the energy density of food intake.

Background & Aims It is important to determine whether infliximab therapy can be safely interrupted in patients with Crohn's disease who have undergone a period of prolonged remission. We assessed the risk of relapse after infliximab therapy was discontinued in patients on combined maintenance therapy with antimetabolites and identified factors associated with relapse. Methods We performed a prospective study of 115 patients with Crohn's disease who were treated for at least 1 year with scheduled infliximab and an antimetabolite and had been in corticosteroid-free remission for at least 6 months. Infliximab was stopped, and patients were followed up for at least 1 year. We associated demographic, clinical, and biologic factors with time to relapse using a Cox model. Results After a median follow-up period of 28 months, 52 of the 115 patients experienced a relapse; the 1-year relapse rate was 43.9% ± 5.0%. Based on multivariable analysis, risk factors for relapse included male sex, the absence of surgical resection, leukocyte counts >6.0 × 10 9 /L, and levels of hemoglobin ≤145 g/L, C-reactive protein ≥5.0 mg/L, and fecal calprotectin ≥300 μg/g. Patients with no more than 2 of these risk factors (approximately 29% of the study population) had a 15% risk of relapse within 1 year. Re-treatment with infliximab was effective and well tolerated in 88% of patients who experienced a relapse. Conclusions Approximately 50% of patients with Crohn's disease who were treated for at least 1 year with infliximab and an antimetabolite agent experienced a relapse within 1 year after discontinuation of infliximab. However, patients with a low risk of relapse can be identified using a combination of clinical and biologic markers.

Sensory and pressure responses to gastric distension were evaluated in 24 consecutive patients suffering from chronic idiopathic dyspepsia and 20 healthy subjects. A latex balloon was placed in the proximal stomach and inflated by increments of 100 ml of air up to a maximal volume of 800 ml. Symptom response and intragastric pressure-volume curve were recorded during the gradual balloon distension. Thirteen of the 24 patients experienced pain at a distension volume less than or equal to 400 ml of air, but only one of the 20 controls (P less than 0.001). Intragastric pressure-volume curves were similar in patients and controls, and in patients with and without abnormal pain threshold, suggesting that a compliance defect was not the cause of the sensory anomaly. Gastric emptying of solids and liquids was measured in 20 of the 24 patients using a dual isotopic technique; psychological status was also evaluated in 18 patients using the Mini-Mult test. The frequency of the sensory anomaly was not different in patients with (7/14) or without (4/6) gastric stasis, but was lower in patients with (5/13) than in those without psychological disturbances (5/5, P less than 0.01). Thus, a primary visceral sensory anomaly, either alone or in conjunction with motility disturbances, can play an important role in chronic idiopathic dyspepsia and must be taken in account for further therapeutic research.