Xavier Dray

Pregnancy outcome in patients with inflammatory bowel disease treated with thiopurines: cohort from the CESAME Study

Background and aims Few studies have been conducted addressing the safety of thiopurine treatment in pregnant women with inflammatory bowel disease (IBD). The aim of this study was to evaluate the pregnancy outcome of women with IBD who have been exposed to thiopurines. Methods 215 pregnancies in 204 women were registered and documented in the CESAME cohort between May 2004 and October 2007. Physicians documented the following information from the women: last menstrual date, delivery term, details of pregnancy outcome, prematurity, birth weight and height, congenital abnormalities, medication history during each trimester, smoking history and alcohol ingestion. Data were compared between three groups: women exposed to thiopurines (group A), women receiving a drug other than thiopurines (group B) and women not receiving any medication (group C). Results Mean age at pregnancy was 28.3 years. 75.7% of the women had Crohns disease and 21.8% had ulcerative colitis, with a mean disease duration of 6.8 years at inclusion. Of the 215 pregnancies, there were 138 births (142 newborns), and the mean birth weight was 3135 g. There were 86 pregnancies in group A, 84 in group B and 45 in group C. Interrupted pregnancies occurred in 36% of patients enrolled in group A, 33% of patients enrolled in group B, and 40% of patients enrolled in group C; congenital abnormalities arose in 3.6% of group A cases and 7.1% of group B cases. No significant differences were found between the three groups in overall pregnancy outcome. Conclusions The results obtained from this cohort indicate that thiopurine use during pregnancy is not associated with increased risks, including congenital abnormalities.

Distal intestinal obstruction syndrome in adults with cystic fibrosis

BACKGROUND & AIMS With the improved survival of patients with cystic fibrosis (CF), gastrointestinal complications become more evident in adults with this condition. The aims of this study were to determine the prevalence and clinical features of distal intestinal obstruction syndrome (DIOS) and its relationship with the cystic fibrosis transmembrane conductance regulator (CFTR) genotype in an adult CF population. METHODS Cross-sectional study was conducted in an adult CF cohort. RESULTS Among 171 adults with CF (mean age, 28.9 years), 27 patients (15.8%) reported 43 episodes of DIOS. No significant association was found between DIOS and a history of meconium ileus. The first episode of DIOS occurred in adulthood in 21 cases (77.8%). DIOS recurred in 13 patients (48.1%). All patients who developed DIOS had pancreatic insufficiency. Pulmonary function was significantly more altered in patients with DIOS than in the other patients, but pancreatic insufficiency and age might act as confounding factors. DIOS occurred in 21.9% of patients with a severe CFTR genotype and in only 2.4% of patients with a mild CFTR genotype (P < 0.005). CONCLUSIONS DIOS is frequent in adults with CF with a severe CFTR genotype and/or advanced-stage pulmonary disease. The relative contributions of malabsorption and impaired intestinal secretion in the development of DIOS are discussed.

Tube Feeding Improves Intestinal Absorption in Short Bowel Syndrome Patients

BACKGROUND & AIMS Tube feeding, recommended for patients with short bowel syndrome in only the postoperative period, has not been compared with oral feeding for absorption. We studied whether tube feeding increased absorption in patients with short bowel syndrome following the postoperative period. METHODS A randomized crossover study compared absorption between isocaloric tube feeding and oral feeding in 15 short bowel syndrome patients more than 3 months after short bowel constitution. An oral feeding period combined with enriched (1000 kcal * day(-1)) tube feeding was also tested. We measured the net intestinal absorption rates of proteins, lipids, and total calories using elemental nitrogen, Van de Kamer, and bomb calorimetry methods, respectively. RESULTS Tube feeding increased the mean (+/-SD) percent absorption (P < .001) of proteins (72% +/- 13% vs 57% +/- 18%), lipids (69% +/- 25% vs 41% +/- 27%), and energy (82% +/- 12% vs 65% +/- 16%) compared with oral feeding. In the group given the combined feedings (n = 9), the total enteral intake and net percent absorption increased (P < .001) for proteins (67% +/- 10%), lipids (59% +/- 19%), and total energy (75% +/- 8%) compared with oral feeding. Absorption (kcal * day(-1)) was greater (P < .001) with tube (2225 +/- 457) and combined feedings (2323 +/- 491) than with oral feeding (1638 +/- 458). CONCLUSIONS In patients with short bowel syndrome, continuous tube feeding (exclusively or in conjunction with oral feeding) following the postoperative period significantly increased net absorption of lipids, proteins, and energy compared with oral feeding.

Factors associated with septic shock and mortality in generalized peritonitis: comparison between community-acquired and postoperative peritonitis.

IntroductionThe risk factors associated with poor outcome in generalized peritonitis are still debated. Our aim was to analyze clinical and bacteriological factors associated with the occurrence of shock and mortality in patients with secondary generalized peritonitis.MethodsThis was a prospective observational study involving 180 consecutive patients with secondary generalized peritonitis (community-acquired and postoperative) at a single center. We recorded peri-operative occurrence of septic shock and 30-day survival rate and analyzed their associations with patients characteristics (age, gender, SAPS II, liver cirrhosis, cancer, origin of peritonitis), and microbiological/mycological data (peritoneal fluid, blood cultures).ResultsFrequency of septic shock was 41% and overall mortality rate was 19% in our cohort. Patients with septic shock had a mortality rate of 35%, versus 8% for patients without shock. Septic shock occurrence and mortality rate were not different between community-acquired and postoperative peritonitis. Age over 65, two or more microorganisms, or anaerobes in peritoneal fluid culture were independent risk factors of shock. In the subgroup of peritonitis with septic shock, biliary origin was independently associated with increased mortality. In addition, intraperitoneal yeasts and Enterococci were associated with septic shock in community-acquired peritonitis. Yeasts in the peritoneal fluid of postoperative peritonitis were also an independent risk factor of death in patients with septic shock.ConclusionsUnlike previous studies, we observed no difference in incidence of shock and prognosis between community-acquired and postoperative peritonitis. Our findings support the deleterious role of Enterococcus species and yeasts in peritoneal fluid, reinforcing the need for prospective trials evaluating systematic treatment against these microorganisms in patients with secondary peritonitis.

Plexitis as a predictive factor of early postoperative clinical recurrence in Crohn’s disease

Background and aims: A previous study suggested that the presence of myenteric plexitis in the proximal resection margins could be predictive of early endoscopic recurrence after ileocolonic or ileal resection for Crohn9s disease (CD). Our aim was to assess the predictive value of plexitis for early clinical CD recurrence. Methods: All consecutive patients with ileocolonic or ileal resection for active CD in Lariboisiere hospital (Paris) between 1995 and 2006 were included. Clinical, surgical, histological and follow up data were extracted from medical charts. Early clinical recurrence was defined as the reappearance of CD clinical manifestations requiring a specific treatment within two years post surgery. Proximal resection margin was analyzed using haematein eosin saffron (HES) staining and immunochemistry targeting mastocytes (anti-CD117 antibody) and lymphocytes (anti-CD3 antibody). Eosinophils were detected by HES staining. Ten cases of ileocolonic resections for cecal carcinoma served as controls. Results: Data were available from 171 postoperative follow up periods in 164 patients with CD. Early clinical recurrence of CD occurred in 28.1%. In multivariate analysis, factors associated with post operative recurrence were active smoking (HR= 1.94; IC95% [1.06; 3.60] ; p= 0.033), submucosal plexitis with ≥3 mastocytes (HR= 1.87; IC95% [1.00; 3.46] ; p= 0.048) and a disease-free resection margin Conclusions: Submucosal plexitis is associated with early clinical recurrence and could be taken into account in studies searching for new treatments strategies in the immediate postoperative period.

Reliable gastric closure after natural orifice translumenal endoscopic surgery (NOTES) using a novel automated flexible stapling device

BackgroundReliable closure of the translumenal incision is one of the main challenges facing natural orifice translumenal endoscopic surgery (NOTES). This study aimed to evaluate the use of an automated flexible stapling device (SurgASSIST) for closure of the gastrotomy incision in a porcine model.MethodsA double-channel gastroscope was advanced into the stomach. A gastric wall incision was made, and the endoscope was advanced into the peritoneal cavity. After peritoneoscopy, the endoscope was withdrawn into the stomach. The SurgASSIST stapler was advanced orally into the stomach. The gastrotomy edges were positioned between the opened stapler arms using two endoscopic grasping forceps. Stapler loads with and without a cutting blade were used for gastric closure. After firing of the stapler to close the gastric wall incision, x-ray with contrast was performed to assess for gastric leakage. At the end of the procedure, the animals were killed for a study of closure adequacy.ResultsFour acute animal experiments were performed. The delivery and positioning of the stapler were achieved, with technical difficulties mostly due to a short working length (60 cm) of the device. Firing of the staple delivered four rows of staples. Postmortem examination of pig 1 (when a cutting blade was used) demonstrated full-thickness closure of the gastric wall incision, but the cutting blade caused a transmural hole right at the end of the staple line. For this reason, we stopped using stapler loads with a cutting blade. In the three remaining animals (pigs 2–4), we were able to achieve a full-thickness closure of the gastric wall incision without any complications.ConclusionsThe flexible stapling device may provide a simple and reliable technique for lumenal closure after NOTES procedures. Further survival studies are currently under way to evaluate the long-term efficacy of gastric closure with the stapler after intraperitoneal interventions.

Obscure gastrointestinal bleeding: preliminary comparison of 64-section CT enteroclysis with video capsule endoscopy

ObjectiveTo retrospectively compare the diagnostic capabilities of 64-section CT enteroclysis with those of video capsule endoscopy (VCE) to elucidate the cause of obscure gastrointestinal bleeding.MethodsThirty-two patients who had 64-section CT enteroclysis and VCE because of obscure gastrointestinal bleeding were included. Imaging findings were compared with those obtained at double balloon endoscopy, surgery and histopathological analysis, which were used as a standard of reference.ResultsConcordant findings were found in 22 patients (22/32; 69%), including normal findings (n = 13), tumours (n = 7), lymphangiectasia (n = 1) and inflammation (n = 1), and discrepancies in 10 patients (10/32; 31%), including ulcers (n = 3), angioectasias (n = 2), tumours (n = 2) and normal findings (n = 3). No statistical difference in the proportions of abnormal findings between 64-section CT enteroclysis (11/32; 34%) and VCE (17/32, 53%) (P = 0.207) was found. However, 64-section CT enteroclysis helped identify tumours not detected at VCE (n = 2) and definitely excluded suspected tumours (n = 3) because of bulges at VCE. Conversely, VCE showed ulcers (n = 3) and angioectasias (n = 2) which were not visible at 64-section CT enteroclysis.ConclusionOur results suggest that 64-section CT enteroclysis and VCE have similar overall diagnostic yields in patients with obscure gastrointestinal bleeding. However, the two techniques are complementary in this specific population.

Long-term randomized controlled trial of a novel nanopowder hemostatic agent (TC-325) for control of severe arterial upper gastrointestinal bleeding in a porcine model

BACKGROUND AND STUDY AIM Endoscopic therapy of brisk upper gastrointestinal bleeding remains challenging. A proprietary nanopowder (TC-325) has been proven to be effective in high pressure bleeding from external wounds. The efficacy and safety of TC-325 were assessed in a survival gastrointestinal bleeding animal model. METHOD 10 animals were randomized to treatment or sham. All animals received intravenous antibiotics, H2-blockers and heparin (activated clotting time 2 × normal). In a sterile laparotomy the gastroepiploic vessels were dissected, inserted through a 1-cm gastrotomy, and freely exposed in the gastric lumen, and the exposed vessel lacerated by needle knife. The treatment group received TC-325 by a modified delivery catheter while the sham group received no endoscopic treatment. Time to hemostasis, and mortality at 60 minutes, 24 hours, 48 hours, and 7 days were noted. Necropsy was performed in all animals. RESULTS Spurting arterial bleeding was achieved in all animals. No control animal showed hemostasis within the first hour compared with 100 % (5 / 5) in the treatment arm (mean 13.8 minutes, P < 0.0079). Durable hemostasis was achieved with no evidence of rebleeding after 1 and 24 hours in 80 % (4 / 5) of the treated animals compared with none in the control group ( P < 0.0098). None of the control animals survived more than 6 hours. Necropsy at 1 week in treated animals revealed healed gastrotomy without foreign body granuloma or embolization to the lung or brain. CONCLUSION TC-325 is safe and highly effective in achieving hemostasis in an anticoagulated severe arterial gastrointestinal bleeding animal model.

Suspected Anastomotic Recurrence of Crohn Disease after Ileocolic Resection: Evaluation with CT Enteroclysis

PURPOSE To determine the utility of computed tomographic (CT) enteroclysis for characterization of the status of the anastomotic site in patients with Crohn disease who had previously undergone ileocolic resection. MATERIALS AND METHODS Written informed consent was prospectively obtained from all patients, and the institutional review board approved the study protocol. CT enteroclysis findings in 40 patients with Crohn disease who had previously undergone ileocolic resection were evaluated independently by two readers. Endoscopic findings, histopathologic findings, and/or the Crohn disease activity index was the reference standard. Interobserver agreement between the two readers was calculated with kappa statistics. Associations between CT enteroclysis findings and anastomotic site status were assessed at univariate analysis. The sensitivity, specificity, and accuracy of CT enteroclysis, with corresponding 95% confidence intervals (CIs), for the diagnosis of normal versus abnormal anastomosis and the diagnosis of anastomotic recurrence versus fibrostenosis were estimated. RESULTS Interobserver agreement regarding CT enteroclysis criteria was good to perfect (kappa = 0.72-1.00). At univariate analysis, stratification and anastomotic wall thickening were the two most discriminating variables in the differentiation between normal and abnormal anastomoses (P < .001). Stratification (P < .001) and the comb sign (P = .026) were the two most discriminating variables in the differentiation between anastomotic recurrence and fibrostenosis. In the diagnosis of anastomotic recurrence, severe anastomotic stenosis was the most sensitive finding (95% [20 of 21 patients]; 95% CI: 76.18%, 99.88%), both comb sign and stratification had 95% specificity (18 of 19 patients; 95% CI: 73.97%, 99.87%), and stratification was the most accurate finding (92% [37 of 40 patients]; 95% CI: 79.61%, 98.43%). In the diagnosis of fibrostenosis, both severe anastomotic stenosis and anastomotic wall thickening were 100% sensitive (eight of eight patients; 95% CI: 63.06%, 100.00%), and using an association among five categorical variables, including severe anastomotic stenosis, anastomotic wall thickening with normal or mild mucosal enhancement, absence of comb sign, and absence of fistula, yielded 88% sensitivity (seven of eight patients; 95% CI: 47.35%, 99.68%), 97% specificity (31 of 32 patients; 95% CI: 83.78%, 99.92%), and 95% accuracy (38 of 40 patients; 95% CI: 83.08%, 99.39%). CONCLUSION CT enteroclysis yields objective and relatively specific morphologic criteria that help differentiate between recurrent disease and fibrostenosis at the anastomotic site after ileocolic resection for Crohn disease. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09091165/-/DC1.

Factors Associated With Diagnosis of Obscure Gastrointestinal Bleeding by Video Capsule Enteroscopy

BACKGROUND & AIMS Capsule enteroscopy (CE) is the best noninvasive tool to explore the entire small bowel of patients with obscure gastrointestinal bleeding (OGIB); it has a diagnostic yield of 40%-80%. However, little is known about the factors associated with a diagnosis of OGIB by CE. METHODS We analyzed data from 911 consecutive patients who underwent CE for OGIB from January 2004 to January 2010. Results from upper and lower gastrointestinal endoscopy examinations were negative in all patients. CE findings were recorded. Features of patients that were associated with diagnosis of OGIB by CE were identified by using logistic regression. RESULTS Based on CE, 509 patients (56%) had a confirmed lesion responsible for the OGIB: 203 had disease of the small bowel (22%), 88 had ulcerations (10%), 70 had tumors (8%), 24 had varices (2%), 6 had diverticula (0.5%), and 118 had what appeared to be bleeding lesions of the esophagus or stomach (10.6%) or colon (2%). Factors independently associated with a diagnosis of OGIB by CE were age >60 years (odds ratio [OR], 1.2), male sex, history of overt bleeding (OR, 3.8), and current hospitalization (OR, 1.4). Women were less likely to be diagnosed with OGIB by CE (OR, 0.7). CONCLUSIONS A history of overt bleeding is the factor most strongly associated with a diagnosis of OGIB by CE. Male sex, age >60 years, and inpatient status were also independent predictors of positive diagnosis by CE.