Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study.

UNLABELLED: Data on the natural history of elderly-onset inflammatory bowel disease (IBD) are scarce. METHODS: In a French population-based cohort we identified 841 IBD patients >60 years of age at diagnosis from 1988 to 2006, including 367 Crohn's disease (CD) and 472 ulcerative colitis (UC). RESULTS: Median age at diagnosis was similar for CD (70 years (IQR: 65-76)) and UC (69 years (64-74)). Median follow-up was 6 years (2-11) for both diseases. At diagnosis, in CD, pure colonic disease (65%) and inflammatory behaviour (78%) were the most frequent phenotype. At maximal follow-up digestive extension and complicated behaviour occurred in 8% and 9%, respectively. In UC, 29% of patients had proctitis, 45% left-sided and 26% extensive colitis without extension during follow-up in 84%. In CD cumulative probabilities of receiving corticosteroids (CSs), immunosuppressants (ISs) and anti tumor necrosis factor therapy were respectively 47%, 27% and 9% at 10 years. In UC cumulative probabilities of receiving CS and IS were 40% and 15%, respectively at 10 years. Cumulative probabilities of surgery at 1 year and 10 years were 18% and 32%, respectively in CD and 4% and 8%, respectively in UC. In CD complicated behaviour at diagnosis (HR: 2.6; 95% CI 1.5 to 4.6) was associated with an increased risk for surgery while CS was associated with a decreased risk (HR: 0.5; 0.3 to 0.8). In UC CS was associated with an increased risk (HR: 2.2; 1.1 to 4.6) for colectomy. CONCLUSIONS: Clinical course is mild in elderly-onset IBD patients. This information would need to be taken into account by physicians when therapeutic strategies are established.

Mortality and cancer in pediatric-onset inflammatory bowel disease: a population-based study.

OBJECTIVES: Although the incidence of pediatric inflammatory bowel disease (IBD) continues to rise in Northern France, the risks of death and cancer in this population have not been characterized. METHODS: All patients <17 years, recorded in EPIMAD registry, and diagnosed between 1988 and 2004 with Crohn's disease (CD) or ulcerative colitis (UC) were included. The observed incidences of death and cancer were compared with those expected in the regional general population obtained by French Statistical Institute (INSEE) and the cancer Registry from Lille. Comparisons were performed using Fisher's exact test and were expressed using the standardized mortality ratios (SMRs) and standardized incidence ratios. RESULTS: A total of 698 patients (538 with CD and 160 with UC) were identified; 360 (52%) were men, the median age at IBD diagnosis was 14 years (12-16) and the median follow-up time was 11.5 years (7-15). During follow-up, the mortality rate was 0.84% (6/698) and did not differ from that in the reference population (SMR=1.4 (0.5-3.0); P=0.27). After a median follow-up of 15 years (10-17), 1.3% of patients (9/698) had a cancer: colon (n=2), biliary tract (cholangiocarcinoma; n=1), uterine cervix (n=1), prepuce (n=1), skin (basal cell carcinoma (n=2), hematological (acute leukemia; n=1), and small bowel carcinoid (n=1). There was a significantly increased risk of cancer regardless of gender and age (standardized incidence ratio=3.0 (1.3-5.9); P<0.02). Four out of nine patients who developed a cancer had received immunosuppressants or anti-tumor necrosis factor-α therapy (including combination therapy in three patients). CONCLUSIONS: In this large pediatric population-based IBD cohort, mortality did not differ from that of the general population but there was a significant threefold increased risk of neoplasia.

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 Crohn's 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.

Nutritional status and growth in pediatric Crohn's disease: a population-based study.

OBJECTIVES: Growth retardation and malnutrition are major features of pediatric Crohn's disease (CD). We examined nutritional and growth parameters from diagnosis to maximal follow-up in a population-based pediatric cohort, and we determined predictive factors. METHODS: A total of 261 patients (156 boys, 105 girls) with onset of CD before the age of 17 were identified from 1988 to 2004 through the EPIMAD registry (Registre des Maladies Inflammatoires Chroniques de l'Intestin) in northern France. Median age at diagnosis was 13 years (11.2-15.4) and median follow-up was 73 months (46-114). Z-scores of height/age, weight/age, and body mass index (BMI)/age were determined. Multivariate stepwise regression analysis identified predictive factors for malnutrition and growth retardation at maximal follow-up. RESULTS: At diagnosis, 25 children (9.5%) showed height less than -2 s.d., 70 (27%) weight less than -2 s.d., and 84 (32%) BMI less than -2 s.d. At maximal follow-up, growth retardation was present in 18 children (6.9%), whereas 40 (15%) had malnutrition. Nutritional status was more severely impaired in children with stricturing disease. Growth and nutritional retardation at diagnosis, young age, male gender, and extraintestinal manifestations at diagnosis were indicators of poor prognosis. A significant compensation was observed for weight and BMI in both genders and for height in girls. No treatment was associated with height, weight, or BMI at maximal follow-up. CONCLUSIONS: In our pediatric population-based study, growth retardation and severe malnutrition were still present at maximal follow-up in 6.9 and 15% of CD children, respectively. Young boys with substantial inflammatory manifestations of CD have a higher risk of subsequent growth failure, especially when growth retardation is present at diagnosis.

Azathioprine withdrawal in patients with Crohn's disease maintained on prolonged remission: a high risk of relapse.

BACKGROUND & AIMS: Azathioprine (AZA) withdrawal in Crohn's disease after long-term remission under treatment is controversial. In a Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif randomized, double-blind, placebo-controlled trial, the hypothesis that AZA withdrawal was not inferior to AZA continuation in patients in prolonged clinical remission could not be shown. METHODS: A cohort of 66 patients in prolonged remission while being treated with AZA who stopped AZA, during or at the end of the randomized controlled trial, underwent long-term follow-up evaluation. The primary end point was clinical relapse. Prognostic factors of relapse were looked for through a proportional hazards model. RESULTS: Median durations of AZA therapy and of clinical remission were 68.4 months (interquartile range, 52.8-85.2 mo) and 63.6 months (interquartile range, 48.0-55.7 mo), respectively. The median follow-up time after AZA interruption was 54.5 months; 32 of 66 patients had a relapse. The cumulative probabilities +/- SE of relapse at 1, 3, and 5 years were 14.0% +/- 4.3%, 52.8% +/- 7.1%, and 62.7% +/- 7.2%, respectively. C-reactive protein concentration of 20 mg/L or greater (risk, 58.6; 95% confidence interval, 7.5-457; P = .002), hemoglobin level less than 12 g/dL (risk, 4.8; 95% confidence interval, 1.7-13.7; P = .04), and neutrophil count 4 x 10(9)/L or greater (risk, 3.2; 95% confidence interval, 1.6-6.3; P = .003) were associated independently with an increased risk of relapse. Among the 32 relapsing patients, 23 were retreated by AZA alone, all but 1 up to successful remission. CONCLUSIONS: Our results confirm that AZA withdrawal is associated with a high risk of relapse, whatever the duration of remission under this treatment. These data suggest that if AZA is well tolerated, it should not be interrupted.

Natural history of pediatric Crohn's disease: a population-based cohort study.

BACKGROUND & AIMS: The natural history of pediatric Crohn's disease and risk factors necessitating surgery have not been thoroughly described. METHODS: In a geographically derived incidence cohort diagnosed from 1988 to 2002, we identified 404 Crohn's disease patients (ages, 0-17 years at diagnosis) with a follow-up time >or=2 years. RESULTS: Median follow-up time was 84 months (range, 52-124 months). The most frequent disease location at diagnosis was the terminal ileum/colon (63%). Follow-up was characterized by disease extension in 31% of children. Complicated behavior was observed in 29% of children at diagnosis and 59% at follow-up. Kaplan-Meier survival estimates of the cumulative incidence of surgery were 20% at 3 years and 34% at 5 years from diagnosis. Multivariate Cox models showed that both structuring behavior at diagnosis (hazard ratio [HR], 2.54; 95% confidence interval [CI]: 1.58-4.01) and treatment with corticosteroids (HR, 2.98; 95% CI: 1.64-5.41) were associated with increased risk for surgery, whereas treatment with azathioprine (HR, 0.51; 95% CI: 0.33-0.78) was associated with decreased risk. Azathioprine was introduced earlier in the course of disease in patients not undergoing surgery than in patients requiring surgery. CONCLUSIONS: Pediatric Crohn's disease was characterized by frequent occurrence, with time, of a severe phenotype with extensive, complicated disease. Immunosuppressive therapy may improve the natural history of this disease and decrease the need for performing surgery.

The natural history of pediatric ulcerative colitis: a population-based cohort study.

OBJECTIVES: The natural history of ulcerative colitis (UC) has been poorly described in children. METHODS: In a geographically derived incidence cohort diagnosed from 1988 to 2002, we identified 113 UC patients (age 0-17 years at diagnosis) with a follow-up of at least 2 years. The cumulative risk of colectomy was estimated by the Kaplan-Meier method. Risk factors for disease extension were assessed with logistic regression models, and risk factors for colectomy with Cox hazards proportional models. RESULTS: Median follow-up time was 77 months (46-125). At diagnosis, 28% of patients had proctitis, 35% left-sided colitis, and 37% extensive colitis. Disease course was characterized by disease extension in 49% of patients. A delay in diagnosis of more than 6 months and a family history of inflammatory bowel disease were associated with an increased risk of disease extension, with odds ratios of 5.0 (1.2-21.5) and 11.8 (1.3-111.3), respectively. The cumulative rate of colectomy was 8% at 1 year, 15% at 3 years, and 20% at 5 years. The presence of extra-intestinal manifestations (EIMS) at diagnosis was associated with an increased risk of colectomy (hazard ratio (HR)=3.5 (1.2-10.5)). Among the patients with limited disease at diagnosis, the risk of colectomy was higher in those who experienced disease extension than in those who did not (HR=13.3 1.7-101.7). CONCLUSIONS: Pediatric UC was characterized by widespread localization at diagnosis and a high rate of disease extension. Twenty percent of children had their colon removed after 5 years. The colectomy rate was influenced by disease extension and was associated with the presence of EIMS at diagnosis.

Predicting factors of fistula healing and clinical remission after infliximab-based combined therapy for perianal fistulizing Crohn's disease.

UNLABELLED: Perianal fistulizing Crohn's disease (PFCD) treatment is based on fistula drainage, antibiotics, immunosuppressant (IS) drugs, and infliximab. Our aim was to study the effectiveness of combination therapy on PFCD and to search for clinical or imaging features associated with the initial complete clinical response and its stability overtime. PATIENTS AND METHODS: All patients with PFCD treated in our tertiary center between 2000 and 2005 by infliximab in combination with seton placement and/or IS and evaluated by MRI before treatment were included in the study. Basal clinical and MRI characteristics were recorded. Response to treatment was evaluated after the infliximab induction regiment and at the end of the follow-up. RESULTS: Twenty-six patients were included and followed-up for an average 4.9 years. A complex fistula was present in 69% (18/26 patients) of cases and eight (8/26 patients) had an ano-vaginal fistula. After infliximab induction therapy, 13 patients (50%) achieved a complete clinical response. The initial clinical response was significantly associated with the absence of both, active intestinal disease (54% vs. 8%, P = 0.03) and active proctitis (77% vs. 23%, P = 0.01). No initial MRI characteristics were linked to the initial response. In multivariate analysis, only the presence of active proctitis was associated with the lack of response (P = 0.047). At the end of the follow-up, 42% of the patients remained in clinical remission. No clinical characteristics were associated to sustained response when among long-standing responders two exhibited a normal post-treatment MRI. CONCLUSION: An initial complete response of PFCD was observed in half of the patients after combined therapy including infliximab that decreased to 42% later on. Complete healing of fistulas on MRI was possible but unusual. The initial response seemed related to the absence of active intestinal disease, especially in the rectum, when the long-term response could not be predicted by the basal characteristics of patients.

Nonoperable patients with superficial esophageal cancer treated by photodynamic therapy after chemoradiotherapy have more severe complications than patients treated in primary intent.

INTRODUCTION: Photodynamic therapy (PDT) is a therapeutic option in patients with a superficial esophageal cancer. Recently, PDT was shown to be effective as a salvage therapy for a local recurrence after chemoradiotherapy (CRT). AIM: To compare retrospectively the results and the complications rate of PDT between consecutive patients treated in primary intent for a superficial esophageal cancer versus patients treated by PDT for a local recurrence after CRT. METHODS: Between 1999 and 2007 in a single center, 40 consecutive patients were treated by PDT for a superficial esophageal cancer, 25 (group 1) in primary intent and 15 (group 2) for a local recurrence after CRT. Two days after intravenous (IV) Photofrin (2 mg/kg), the phototherapy was performed with a dye laser. The treatment response and severe complications, defined as perforation and stricture requiring endoscopic dilation, were compared between the two groups. RESULTS: The patient and tumor characteristics were not different between the two groups. In group 1, 19 out of 25 patients (76%) were successfully treated versus 8 out of 15 patients (53%) in group 2 (P= 0.17). Severe complications occurred more frequently in patients with a prior CRT (8%vs 46.7%, P= 0.008) and included two perforations and five strictures requiring endoscopic dilation, while only two strictures occurred in group 1. A prior CRT was an independent risk factor of severe complications (odds ratio [OR] 8.05; 95% confidence interval [CI]1.22-43.0). CONCLUSIONS: Severe complications were significantly more frequent in patients treated after a prior CRT. PDT as a salvage therapy in patients with a local recurrence after CRT for esophageal cancer tended to be less efficient than in first-line treatment.

Combined glutamine and arginine decrease proinflammatory cytokine production by biopsies from Crohn's patients in association with changes in nuclear factor-kappaB and p38 mitogen-activated protein kinase pathways.

Glutamine (Gln) and arginine (Arg) are conditionally essential amino acids with immunomodulatory properties. The aim of the study was to assess the effects of Gln and Arg alone or in combination on cytokine release by cultured colonic biopsies from patients with active Crohn's disease (CD). Ten consecutive patients [mean (range) age 26 (18-39) y] with active colonic CD (mean CD activity index: 383.7 +/- 129.8) were prospectively included in the study. Eight colonic biopsies were obtained via a colonoscopy and incubated during 18 h with low (physiological) or high (pharmacological) doses of Arg (0.1 or 2 mmol/L designated as Arg(low) or Arg(high), respectively) and Gln (0.6 or 10 mmol/L designated as Gln(low) or Gln(high), respectively). The concentrations of cytokines [interleukin (IL)-4, IL-10, IL-8, IL-6, tumor necrosis factor-alpha (TNFalpha), IL-1beta, interferon-gamma) were assessed by ELISA, and nitric oxide (NO) production was evaluated by Griess assay. Nuclear factor (NF)-kappaB p65 subunit, inhibitor of NFkappaB-alpha, and p38 mitogen-activated protein kinase (MAPK) were assessed by immunoblotting. Arg(high)/Gln(high) decreased the production of TNFalpha, IL-1beta, IL-8, and IL-6 (each P < 0.01). Arg(low)/Gln(high) decreased IL-6 and IL-8 production (both P < 0.01), whereas Arg(high)/Gln(low) did not affect cytokine and NO production. Arg(low)/Gln(high) and Arg(high)/Gln(high) decreased NF-kappaB p65 subunit expression, whereas p38 MAPK was decreased only by Arg(high)/Gln(high). Combined pharmacological doses of Arg and Gln decreased TNFalpha and the main proinflammatory cytokines release in active colonic CD biopsies via NF-kappaB and p38 MAPK pathways. These results could be the basis of prospective studies evaluating the effects of enteral supply of combined Arg and Gln during active CD.

Value of wireless capsule endoscopy in patients with indeterminate colitis (inflammatory bowel disease type unclassified).

BACKGROUND: Wireless capsule endoscopy (WCE) can identify small bowel mucosal lesions not seen with other imaging modalities. This technique can therefore play an important diagnostic role in the evaluation of patients with inflammatory bowel disease type unclassified (IBDU). We report on a multicentric study whose objective was to evaluate the value of WCE to increase diagnostic accuracy in categorizing IBDU. METHODS: Thirty patients with IBDU and negative serology were included. WCE was performed with a standard Pillcam capsule. Outcome measures were classified as suggestive of Crohn's disease (CD) when -3 ulcerations were present. RESULTS: WCE displayed endoscopic features suggestive for CD in 5 patients. In 6 other patients, WCE was negative, but repeated ileocolonoscopy with biopsies performed during follow-up evaluation revealed CD in 5 and ulcerative colitis (UC) in 1 patient. UC was found in a seventh case at colectomy performed just after WCE. Eighteen patients remained with a diagnosis of IBDU 16 months on average after WCE. CONCLUSIONS: WCE is a potentially clinically useful technique for categorizing a subgroup of patients with IBDU, although negative WCE does not exclude further diagnosis of CD. Patients with negative WCE who remain IBDU at follow-up evaluation may belong to an original subgroup of IBD.

Pregnancy is possible on long-term home parenteral nutrition in patients with chronic intestinal failure: Results of a long term retrospective observational study.

BACKGROUND & AIMS: Home parenteral nutrition (HPN) improves survival and quality of life in patients with chronic intestinal failure (IF). Few cases of pregnancy on HPN have been published. The aim of this study was to report pregnancy cases on long-term HPN in benign IF. METHODS: This retrospective study included all pregnant patients on HPN from 4 HPN referral centers. Data on demographics, ongoing pathology, HPN type, maternal and newborn complications were collected. RESULTS: From 1984 to 2014, 21 pregnancies occurred in 15 patients (short bowel syndrome (n = 11), motility disorders (n = 3), mucosal disease (n = 1)) of whom 14 occurred after 2010. Median follow-up was 12 years. Median HPN duration before pregnancy was 8 years. HPN was adapted monthly during pregnancy, with close monitoring and supplementations. Energy intake was regularly increased and median maternal weight gain was 10 kg. Median age at the first pregnancy was 27 years. In 55% of cases, the newborn was preterm. Maternal complications occurred in 67% of cases (mainly due to underlying disease or HPN complications). There were 3 post-partum hemorrhages and 6 hypotrophic newborns. Eighteen infants were healthy and 2 chronic intestinal pseudo-obstruction (CIPO) were suspected. CONCLUSION: Our series, the largest reported to date, shows that pregnancy is possible in HPN patients but the complication rate is high. A specific support is necessary, particularly in CIPO patients. As pregnancies have increased over the last 15 years, physicians practicing in HPN referral centers should be aware of the need for implementing a specific multidisciplinary monitoring in HPN patients considering pregnancy.

Detection of a large genomic deletion in the pancreatic secretory trypsin inhibitor (SPINK1) gene.

Mutations and polymorphisms in the SPINK1 gene, which encodes trypsin's physiological inhibitor, pancreatic secretory trypsin inhibitor, have been found to be associated with chronic pancreatitis. However, to date, all currently reported SPINK1 variants are either single-nucleotide substitutions or microinsertions/deletions. It is possible that large genomic rearrangements at this locus may underlie certain cases of chronic pancreatitis. However, such events, if indeed they exist, may have been overlooked by conventional PCR-based techniques. Here we attempted to screen all four exons as well as the promoter region of the SPINK1 gene for large genomic deletions by means of quantitative high-performance liquid chromatography analysis. Of the 47 pancreatitis families (not carrying any known PRSS1, SPINK1 and CFTR variants/mutations after screening the coding regions by our previously established denaturing high-performance liquid chromatography methods), one family was suggested to carry a large genomic deletion in the SPINK1 gene. The aberrant chromosomal junction was encapsulated by long-range PCR and the breakpoints were determined by direct sequencing of the rearranged fragment. A 2-bp short direct repeat was present at the deletion breakpoints; this simple deletion (c.1-320_c.55+961del1336 bp) can thus in principle be explained by replication slippage. Identification of this lesion has not only expanded the SPINK1 mutational spectrum but also served to identify a novel mutational mechanism causing chronic pancreatitis.

Costs of Crohn's Disease According to Severity States in France: A Prospective Observational Study and Statistical Modeling over 10 Years.

BACKGROUND: To describe the medico-economic characteristics of Crohn's disease (CD), we implemented a multicenter study in France. METHODS: From 2004 to 2006, disease severity states, direct (hospital and extra hospital) and indirect costs were prospectively collected over 1 year in patients with CD naive from anti-tumor necrosis factor alpha (infliximab) at inclusion. Economic valorization was performed from the French Social Insurance perspective, and a statistical modeling over 10 years was performed. RESULTS: In 341 patients, the mean total costs of management were &OV0556;6024 per year (&OV0556;4675 for direct costs). As compared to patients in remission, costs were 4 to 6 times higher in patients in an active period and 19 times higher for patients requiring surgery (SURG). The most important expense items were medical and surgical hospitalizations (56% of total costs), including cost of infliximab (36% of hospitalization costs, i.e., 20% of total costs), indirect costs (22%), and drugs (11%). The statistical modeling over 10 years showed that most of the clinical course was spent in drug-responsive state (54%) with 26% of costs or in remission (32%) with 11% of costs; time spent in a SURG state was small (3.2%) but generated 48% of total costs. CONCLUSIONS: Before the introduction of self-injectable anti-tumor necrosis factor alpha, the most important expenses were supported by hospitalizations, explaining why the most costly states were for patients requiring SURG or dependent on inhospital administrated drugs. Projected data show that most time is spent in a stabilized state with appropriate treatments or in remission, and that costs associated with SURG are high.

Postoperative Complications in Pediatric Inflammatory Bowel Disease: A Population-based Study.

BACKGROUND: We describe, in a population-based cohort, the incidence of and factors associated with postoperative complications (POCs) in pediatric-onset inflammatory bowel disease. METHODS: Using the pediatric population-based EPIMAD Cohort (1988-2004), among 692 incident inflammatory bowel disease cases, 128 patients with Crohn's disease (CD) and 25 with ulcerative colitis (UC) (22%) had undergone at least 1 major abdominal surgery at a median age of 16 years [interquartile range, Q1-Q3 = 14-17]. Factors associated with POC were assessed using Cox models. RESULTS: After a median postoperative follow-up of 8 years (3-12), 76 (49.7%) patients had experienced at least 1 POC with a total of 113 complications. The frequency of severe POC (grade >2) was similar in CD and UC (28% of all complications versus 27%, P = 0.95). A total of 64 early POCs (within 30 d of surgery) were observed in 47 patients (31%), with 33 being infectious and 31 noninfectious, higher in UC than in CD (25% of patients with CD versus 60% of patients with UC, P < 0.001). Forty-nine late POCs (≥30 d) were observed in 37 patients (24%). The occurrence of late POC was similar in UC and CD. The cumulative probability of POC was 31% (95% confidence interval, 24-39) at 1 month, 46% (38-54) at 1 year, and 48% (41-57) at 5 years. Multivariate analysis found that the UC type was the only factor associated with early POC (hazard ratio = 2.9; 95% confidence interval, 1.6-5.4). CONCLUSIONS: One-half of the children with inflammatory bowel disease had experienced at least 1 POC. Only UC relative to CD was significantly associated with an increased risk of early POC.

Changes in characteristics and outcome of acute upper gastrointestinal haemorrhage: a comparison of epidemiology and practices between 1996 and 2000 in a multicentre French study.

OBJECTIVE: To evaluate the main changes in characteristics, practices and outcome between 1996 and 2000 in patients admitted for an acute upper gastrointestinal haemorrhage (AUGIH). PATIENTS AND METHODS: All consecutive patients (n=1165) admitted for an AUGIH in four French administrative areas were entered into two separate 6-month studies conducted in 1996 (n=712) and 2000 (n=453). Epidemiological and biological characteristics, endoscopic haemostatic procedures and outcomes were compared. RESULTS: Patient characteristics remained unchanged between the two studies; the two main bleeding lesions were peptic ulcer and oesophagogastric varices (30.2 versus 31.1% and 22.5 versus 20.3%). The use of non-steroidal anti-inflammatory drugs or aspirin was more frequent in 2000 (26.5 versus 32.6%; P<0.03). Proton pump inhibitor preventative therapy was administered in less than 15% of patients with a high risk of peptic ulcer bleeding in each period. In patients admitted for varices bleeding, the use of endoscopic haemostatic ligation increased (17.1 versus 40%; P<0.001), with a concomitant decrease in endoscopic sclerotic therapy (76.1 versus 37.5%; P<0.001). We observed a significant decrease in AUGIH mortality in the whole group (11.7 versus 7.2%; P=0.03), and particularly in the subgroup of cirrhotic patients (19.5 versus 11.1%; P=0.05) whatever the source of their bleeding. CONCLUSION: Our time-trend evaluation of changes in AUGIH characteristics revealed that peptic ulcer and varices were still the two most frequent bleeding lesions. In patients with varices bleeding, endoscopic ligation became the routine standard treatment instead of varices sclerosis. The mortality rate decreased significantly over the 5-year study period in the whole group and particularly in the subgroup of cirrhotic patients.

Palliative esophageal stent placement using endoscopic guidance without fluoroscopy.

AIMS: Fluoroscopy is not available in every endoscopic unit. This situation leads to delays in treatment or to transfer of patients to other centres for stent insertion. We assessed safety and effectiveness of expandable esophageal metal stent placement under endoscopic control without fluoroscopy using a thin gastroscope. PATIENTS AND METHODS: From October 2002 to June 2004, thirty-three consecutive patients have been included for esophageal stent placement under endoscopic control alone with a nasogastroscope (5.9 mm). A proximal release covered stent (Ultraflex; Boston Scientific Microvasive) was used. Indications were malignant esophageal stricture (N = 26), malignant extrinsic compression (N = 2 ) and esophago-respiratory neoplastic fistulae (N = 5). RESULTS: Stent placement using endoscopic control alone was successful in 30/33 (90%) patients. Complications occurred in 11 patients. Early complications (<7 days) included one death from pulmonary embolism, severe retrosternal pain needing transient morphinic treatment (N = 2) and GERD despite antisecretory therapy (N = 1). Late complications included: food impaction (N = 1), tumour overgrowth-related obstruction of the stent (N = 5) and one late esophago-respiratory fistula at 4 months at the proximal end of the stent. Relief of dysphagia was obtained for all patients at 48 hours and dysphagia score decreased from 3.1 before stent to 1.2 at 1 month (P < 0.05). CONCLUSION: Expandable esophageal stents can be accurately and safely placed using endoscopy with a thin gastrosocope. This method obviates the requirement of fluoroscopic access, lacking in many centres, and avoids exposure to X-ray.

Acute hepatitis due to buprenorphine administration.

BACKGROUND: Buprenorphine, a synthetic molecule derived from thebaine, has been commercialized in France since 1987 as a substitute treatment for pharmacodependence on opiates. Hepatotoxicity is poorly documented, since only few cases of hepatic injury have been reported. METHODS: We report seven cases of acute cytolytic hepatitis due to buprenorphine. All patients were former drug addicts by the parenteral route and had been receiving withdrawal therapy with buprenorphine for an average of 91 days at a daily dosage ranging from 2 to 12 mg. Liver tests, complete viral screening and an abdominal computerized tomography scan were performed in each patient. RESULTS: Five out of seven subjects presented with acute icteric hepatitis without abdominal pain or fever. Average alanine aminotransferase levels were 39 times the normal rate. There was no sign of liver failure. All patients had anti-hepatitis C virus-positive serology and two had positive hepatitis C virus-RNA. Although no specific treatment was administered, buprenorphine doses were reduced whenever possible. Cytolysis and jaundice resolved rapidly in all cases, although treatment was continued at the same doses in four cases and the dosage was reduced by 50% in three other cases. CONCLUSIONS: Although buprenorphine hepatitis is uncommon and has spontaneously good evolution, we suggest better monitoring of hepatic profiles in patients whose mitochondrial function is already impaired by viral infections or other toxic factors.

[Assessment of the quality and psychological impact of information delivered using official consent forms in digestive endoscopy]. / Evaluation de la qualité et de l'impact de l'information transmise par les fiches d'endoscopie digestive élaborées par les sociétés savantes.

AIM: To test the impact of information brochures and informed consent forms in patients undergoing digestive endoscopy procedures. METHOD: All patients undergoing digestive endoscopy procedures during a two-month period were given information about the procedure to be performed by delivery of an information form produced by the French Endoscopy and Gastroenterology Societies. The patients were then asked to sign an inform consent form. A questionnaire about the informed consent form and the consent experience was given to all patients after the endoscopic procedure. RESULTS: The questionnaire was completed by 108 consecutive patients. The informed consent form was completely read by 96.3% and understood by 95%. Sixteen percent asked for complementary information, all about complications. Twenty percent were distressed by the explanations. Receiving written information was surprising for 22.2% of the patients, and distressing for 18.5% mainly when endoscopy was planned without general anesthesia (P=0.01 versus general anesthesia). Obtaining informed consent was qualified as a normal procedure for 47.2%, but distressing for 19.4%. It was considered by 41.1% as a way for doctors to be discharged from their obligations. CONCLUSION: The informed consent forms written by scientific societies are easy to understand. One third of the patients were distressed or surprised to be given oral or written information. To sign a written consent form before an endoscopy procedure is considered to be a means of discharging practitioners from their responsibilities for 30% of the patients.

Diagnostic yield and therapeutic implications of capsule endoscopy in obscure gastrointestinal bleeding.

AIM: The main aim of this study was to evaluate efficacy and therapeutic impact of capsule endoscopy (CE) in obscure gastrointestinal bleeding (OGIB). In addition, we evaluated the software of automatic detection of red zones (SBI, Given Imaging). PATIENTS AND METHODS: From June 2002 to June 2003, thirty-five patients with OGIB underwent capsule endoscopy after negative upper and lower digestive endoscopy. Capsule endoscopy was performed following a 12-hour fasting period and some received 2 L of PEG the night before for bowel preparation. RESULTS: CE was performed for occult (N=18) or overt (N=17) OGIB. Potentially bleeding lesions were found in 16/35 patients (45.7%). Lesions were angiodysplasias (N=8), ulcerations (N=4), tumors (N=2) and active bleeding without visible lesion (N=2). Lesions were located in gastric antrum (N=1), duodenum (N=2) and jejuno-ileum (N=13). Endoscopic (N=10), surgical (N=2) or medical (N=1) treatments were performed in 13/35 (37%). SBI was retrospectively evaluated in 24 patients with sensitivity, specificity, positive and negative predictive value of respectively 45%, 73%, 50% and 69%. CE retention during 10 days occurred in a patient with a small bowel NSAID-induced stricture. CONCLUSION: CE is a safe and effective procedure in the management of OGIB and had a therapeutic impact in more than one third of patients.