Low prevalence of colonoscopic surveillance of inflammatory bowel disease patients with longstanding extensive colitis: a clinical practice survey nested in the CESAME cohort.

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.

Association between entero-hepatic Helicobacter species and Crohn's disease: a prospective cross-sectional study.

BACKGROUND: The pathogenesis of Crohn's disease (CD) involved microbial factors. Some Helicobacter species, the so-called entero-hepatic Helicobacters (EHH), can naturally colonize the intestinal surface and have been detected in humans. Aim To look for an association between CD and the presence of EHH DNA in intestinal biopsies. METHODS: Two groups of patients were included prospectively in a multicentre cross-sectional study: CD patients with an endoscopic post-operative recurrence within 2 years following a surgical resection and controls screened for colorectal polyps or cancer. Intestinal biopsies were taken for Helicobacter culture and Helicobacter 16S DNA detection. If positive, the EHH species were identified with specific PCRs, sequencing and denaturing gradient gel electrophoresis. RESULTS: In the 165 included patients (73 CD and 92 controls), Helicobacter cultures were negative. PCR was positive in 44% of CD and 47% of controls. After age-adjustment, CD was significantly associated with EHH in intestinal biopsies (OR = 2.58; 95%CI: 1.04-6.67). All EHH species detected were identified as Helicobacter pullorum and the closely related species Helicobacter canadensis. CONCLUSION: Crohn's disease is associated with the presence of EHH species DNA in intestinal biopsies after adjustment for age. Whether these species play a role in the pathophysiology of CD remains to be determined.

Infliximab treatment for symptomatic Crohn's disease strictures.

BACKGROUND: Some reports have suggested that infliximab may induce obstructive symptoms and, although there is no firm evidence, it is usually contra-indicated in-patients with Crohn's disease (CD) and strictures. AIMS: To evaluate the effect of infliximab on symptomatic strictures of the small intestine in CD and to identify predictive factors of clinical response. METHODS: This retrospective study included symptomatic patients treated with infliximab after conventional treatment had failed. The short-term (week 8) and long-term results were classified according to predefined criteria as complete, partial response, or failure. RESULTS: Before infliximab, 18 patients had complete obstruction or intermittent chronic abdominal pain. Fourteen patients were treated by corticosteroids and 13 received immunosuppressive drugs. At week 8, complete, partial response and failure were observed in 10, 7 and 1 patients, respectively. Fourteen patients continued maintenance infliximab treatment after week 8. During the most recent evaluation (median follow-up: 18 months), 8 patients were on maintenance infliximab treatment; only eight were still on prednisone; there were five complete responses, 10 partial responses and three failures. Initiating prednisone or increasing its dosage was the only factor associated with a short-term complete response. CONCLUSIONS: Infliximab may be effective in patients with symptomatic strictures from CD, and should be tested before considering surgery.

Ineffectiveness of Lactobacillus johnsonii LA1 for prophylaxis of postoperative recurrence in Crohn's disease: a randomised, double blind, placebo controlled GETAID trial.

BACKGROUND AND AIMS: Early endoscopic recurrence is frequent after intestinal resection for Crohn's disease. Bacteria are involved, and probiotics may modulate immune responses to the intestinal flora. Here we tested the probiotic strain Lactobacillus johnsonii LA1 in this setting. PATIENTS AND METHODS: This was a randomised, double blind, placebo controlled study. Patients were eligible if they had undergone surgical resection of <1 m, removing all macroscopic lesions within the past 21 days. Patients were randomised to receive two packets per day of lyophilised LA1 (2 x 10(9) cfu) or placebo for six months; no other treatment was allowed. The primary endpoint was endoscopic recurrence at six months, with grade >1 in Rutgeerts' classification or an adapted classification for colonic lesions. Endoscopic score was the maximal grade of ileal and colonic lesions. Analyses were performed primarily on an intent to treat basis. RESULTS: Ninety eight patients were enrolled (48 in the LA1 group). At six months, endoscopic recurrence was observed in 30/47 patients (64%) in the placebo group and in 21/43 (49%) in the LA1 group (p = 0.15). Per protocol analysis confirmed this result. Endoscopic score distribution did not differ significantly between the LA1 and placebo groups. There were four clinical recurrences in the LA1 group and three in the placebo group. CONCLUSION: L johnsonii LA1 (4 x 10(9) cfu/day) did not have a sufficient effect, if any, to prevent endoscopic recurrence of Crohn's disease.

Osteoporosis in inflammatory bowel disease: effect of calcium and vitamin D with or without fluoride.

BACKGROUND: Previous data have indicated low bone formation as a mechanism of osteoporosis in inflammatory bowel disease. Fluoride can stimulate bone formation. AIM: To assess the effect of fluoride supplementation on lumbar spine bone mineral density in osteoporotic patients with inflammatory bowel disease treated in parallel with calcium and vitamin D. METHODS: In this prospective, randomized, double-blind, parallel and placebo-controlled study, 94 patients with inflammatory bowel disease (lumbar spine T score below - 2 standard deviations, normal serum 25OH vitamin D), with a median age of 35 years, were included. Bone mineral density was measured by dual-energy X-ray absorptiometry. Patients were randomized to receive daily either sodium monofluorophosphate (150 mg, n=45) or placebo (n=49) for 1 year, and all received calcium (1 g) and vitamin D (800 IU). The relative change in bone mineral density from 0 to 12 months was tested in each group (fluoride or placebo) and compared between the groups. RESULTS: Lumbar spine bone mineral density increased significantly in both groups after 1 year: 4.8 +/- 5.6% (n=29) and 3.2 +/- 3.8% (n=31) in the calcium-vitamin D-fluoride and calcium-vitamin D-placebo groups, respectively (P < 0.001 for each group). There was no difference between the groups (P=0.403). Similar results were observed according to corticosteroid intake or disease activity. CONCLUSIONS: Calcium and vitamin D seem to increase lumbar spine density in osteoporotic patients with inflammatory bowel disease; fluoride does not provide further benefit.

Can laparoscopy reduce hospital stay in the treatment of Crohn's disease?

PURPOSE: The aim of this article was to investigate the safety, outcome, length of stay, and cost of hospital admission in patients with Crohn's disease who underwent laparoscopy compared with open surgery. METHODS: Among 51 consecutive patients with inflammatory bowel disease (1996-2000), 46 with Crohn's disease were included in this nonrandomized prospective study. Of these, 20 patients underwent laparoscopic surgery and 26 underwent open surgery. Data collected included the following information: age, gender, body mass index, diagnosis, duration of disease, preoperative medical treatment, previous abdominal surgery, present indication for surgery, and procedure performed (comparability measures), as well as conversion to open surgery, operating time, time to resolution of ileus, morbidity, duration of hospital stay, and cost of hospital admission (outcome measures). RESULTS: There was no significant difference with respect to comparability measures between the laparoscopic and the open-surgery groups. There was no mortality. There was no intraoperative complication in either group and no conversion in the laparoscopic group. Operating time was significantly longer in the laparoscopic group (302 minutes) vs. the open group (244.7 minutes) (P < 0.05), but this difference disappeared when data were adjusted for the extra time required to perform the laparoscopic hand-sewn anastomoses (288.2 minutes vs. 244.7 minutes). Bowel function returned more quickly in the laparoscopic group vs. the open group in terms of passage of flatus (3.7 vs. 4.7 days) (P < 0.05) and resumption of oral intake (4.2 vs. 6.3 day) (P < 0.01). There were significantly fewer postoperative complications in the laparoscopic group (9.5 percent) vs. the open group (18.5 percent) (P < 0.05); the length of stay was significantly shorter in the laparoscopic group (8.3 days) vs. the open group (13.2 days) (P < 0.01); and the cost of hospital admission was significantly lower in the laparoscopic group ($6106, United States dollars) vs. the open group ($9829, United States dollars) (P < 0.05). CONCLUSION: There is a reduction in the postoperative ileus, length of stay, cost of hospital admission, and postoperative complication rate in the laparoscopic group. Laparoscopic surgery for Crohn's disease is safe, and it is potentially more cost-effective than traditional open surgery.

[Clinical and biological syndrome of intestinal malabsorption: diagnostic tests]. / Syndrome clinique et biologique de malabsorption intestinale: explorations fonctionnelles.

Malabsorption has miscellaneous clinical and biological presentations. They may vary according to the site of the absorption abnormality (luminal, parietal, vascular transport), its type and severity. The problem of the physician is to become alerted to the possibility of malabsorption in patients who present with signs and symptoms which may be the concern of almost any specialist beside gastroenterologists. Patient history, type of signs and symptoms, physical examination and simple biochemical and haematological parameters may be of major interest in this regard and will help in the choice of the functional tests to perform. They will confirm the presumed malabsorption, precise its type and severity and may guide towards its aetiology, the precise diagnosis of which will usually require other investigations.

Hepatocellular carcinoma in patients with acute hepatic porphyria: frequency of occurrence and related factors.

BACKGROUND/AIMS: Previous retrospective studies have suggested an association between hepatocellular carcinoma and acute hepatic porphyrias. The incidence, the relative risk, the characteristics and the outcome of primary liver cancer were prospectively evaluated in patients with acute hepatic porphyrias; the molecular mechanism of carcinogenesis in these patients was also pointed out. METHODS: A cohort of 650 patients with acute hepatic porphyria was followed over 7 years. Standardized rate ratio was used to measure the relative risk of primary liver cancer after indirect standardization. Morphological and clinical aspects of primary liver cancer were investigated, and survival rates were calculated using the Kaplan-Meier method. Common etiological factors involved in liver carcinogenesis were screened. Excretion rates of porphyrin precursors, serum melatonin levels and mutations in the genes encoding for heme biosynthetic enzymes were studied. RESULTS: Hepatocellular carcinoma was found in four symptomatic and three asymptomatic patients (four female, three male). The overall standardized rate ratio was 36 (95% CI: 14-74). The 5-year disease-free survival was 43% in patients with hepatocellular carcinoma. Usual risk factors for primary liver cancer were not confounding factors. Hepatocellular carcinoma was not related to specific heme biosynthesis gene mutations. Heme precursors were significantly increased in porphyric patients with hepatocellular carcinoma, and serum melatonin levels were low. CONCLUSIONS: Acute hepatic porphyrias are risk factors for hepatocellular carcinoma. Hepatic porphyrias should be sought in patients with hepatocellular cancer without obvious etiology, and a periodic screening for hepatocellular carcinoma should be evaluated in these patients. Genes encoding for heme biosynthetic pathway may not act as tumor suppressor genes. Chronic increased levels of delta aminolevulinic acid could lead to the generation of free radicals and subsequently to hepatic carcinogenesis.

Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy.

BACKGROUND & AIMS: Myelosuppression in patients with Crohn's disease (CD) treated with azathioprine has been attributed to low activity of thiopurine S-methyltransferase (TPMT). Allelic variants of the TPMT gene responsible for changes in the enzyme activity have been characterized. We investigated the distribution of mutant alleles associated with TPMT deficiency in patients with CD and myelosuppression during azathioprine/6-mercaptopurine therapy. METHODS: Forty-one patients with CD were included. They developed leukopenia or thrombocytopenia during azathioprine or 6-mercaptopurine treatment. Polymerase chain reaction-based methods were used to search for mutations associated with TPMT deficiency. RESULTS: Four patients (10%) had 2 mutant alleles associated with TPMT deficiency, 7 (17%) had 1 mutant allele, and 30 (73%) had no known TPMT mutation. The delay between administration of the drug and occurrence of bone marrow toxicity was less than 1.5 months in the 4 patients with 2 mutant alleles, and ranged from 1 to 18 months in patients with 1 mutant allele and from 0.5 to 87 months in patients with normal genotype. CONCLUSIONS: Twenty-seven percent of patients with CD and myelosuppression during azathioprine therapy had mutant alleles of the TPMT gene associated with enzyme deficiency. Myelosuppression is more often caused by other factors. Continued monitoring of blood cell counts remains mandatory in patients treated with azathioprine.

Amantadine for chronic hepatitis C: pilot study in 14 patients.

BACKGROUND: Amantadine, a widely available antiviral drug, has been previously reported to be effective in patients with chronic hepatitis C who failed to respond to interferon-alpha therapy. Nevertheless, its efficacy has not been fully studied, particularly in naive patients. OBJECTIVE AND DESIGN: We conducted a pilot study to determine the efficacy and the safety of amantadine as initial therapy in patients with chronic hepatitis C. METHODS AND PARTICIPANTS: Fourteen consecutive patients (mean age, 40 years; M/F ratio, 9/5) with chronic hepatitis C, elevated alanine aminotransferase (ALT) and without cirrhosis were treated with a 6-month course of amantadine, 100 mg orally twice daily. Main outcome measures were ALT concentrations and serum hepatitis C virus-RNA (HCV-RNA) levels at the end of therapy. RESULTS: All adverse events were mild or moderate and were not treatment limiting. At the end of treatment, all patients had detectable serum HCV-RNA and only one patient had a normal ALT level. The serum HCV-RNA median level and the ALT median level were not significantly different at the end of treatment as compared to baseline levels. CONCLUSIONS: Our results show that amantadine alone cannot be recommended as an alternative therapy in patients with chronic hepatitis C.

[Bronchogenic cyst of the right hemidiaphragm mimicking a hydatic cyst of the liver].

Ectopic subdiaphragmatic development of a bronchogenic cyst is rare. We report the case of a 28-year-old woman with a symptomatic bronchogenic cyst of the right hemidiaphragm simulating a hydatic cyst of the liver on ultrasonography and CT scan. Diagnosis of a diaphragmatic lesion was made during laparotomy, and complete resection was successful. Final diagnosis was done on pathology.

[Clinical course of symptomatic duodeno-jejunal Crohn's disease]. / Aspects cliniques et évolutifs de la maladie de Crohn duodéno-jéjunale symptomatique.

AIMS: To describe retrospectively the characteristics of inaugural, symptomatic Crohn's disease of the upper gastrointestinal tract. METHODS: Eighteen patients (12 male and 6 female) with symptomatic Crohn's disease of the upper intestinal tract and without previous distal localisation were studied. RESULTS: Mean age of patients at diagnosis (21.3 years) was less than that usually reported in Crohn's disease. The time elapsed from first symptoms to diagnosis (mean = 29.8 months) was remarkably long for some patients, mainly as a result of an unusual clinical presentation. Abdominal pain and weight loss were the most common presenting features; diarrhea was rarely the main symptom. Persistent anorexia and weight loss without digestive symptoms had led to a diagnosis of anorexia nervosa in 4 patients. Zollinger-Ellison syndrome was the initial diagnosis in 3 other patients. Sixteen patients were followed during at least 2 years. All were treated with steroids for their first attack and 75 % required immunosuppressive therapy for steroid dependence. At the end of follow-up, 6 patients only were in remission without treatment or under mesalamine. CONCLUSION: Crohn's disease with initial symptomatic lesions of the upper gastrointestinal tract occurs mainly in young male patients. The clinical presentation may be very unusual, leading to misdiagnosis. The clinical course is close to that of diffuse jejunoileitis.

Epidemiology of hepatitis C and G in sporadic and familial porphyria cutanea tarda.

From 1995 to 1997, we prospectively evaluated the prevalence of hepatitis C virus (HCV) RNA in 124 patients with porphyria cutanea tarda (PCT) from Northern France (83 sporadic and 41 familial PCT). Serum samples were analyzed for ferritin, transaminases, HCV antibodies, and HCV RNA. In addition, genotyping of HCV and searches for HCV infection risk factors (blood transfusion, iv drug abuse, and surgical intervention) were performed. Twenty-six of 124 patients (21%; 95% CI: 13.9-28) were positive for serum HCV antibodies. All of them were also positive for HCV RNA. The prevalence of HCV infection was higher in the sporadic PCT group (26.5%, 22 out of 83) than in the familial PCT group (9.7%, 4 out of 41). Risk factors for hepatitis C infection were found to be significantly increased in the HCV-positive group when compared with the HCV-negative PCT group. In all HCV-positive patients with a risk factor, the suspected date of exposure to the virus always preceded the clinical onset of PCT. The HCV genotype pattern in PCT patients was similar to that observed in nonporphyric HCV patients in western European countries. Serum ferritin level was increased in both HCV-positive and HCV-negative porphyric patients. Transaminase levels were significantly higher in HCV-infected PCT patients. Sixty-seven out of 124 patients were retrospectively studied for hepatitis G virus (HGV) infection. Six of these 67 patients (8.9%; 95% CI: 2.1-15.8) were positive for HGV RNA. None of the six HGV-infected patients were positive for HCV RNA. The HGV-infected patients did not differ statistically from those without HGV infection with regard to age, ferritin, transaminase levels, and PCT treatment. These results support the view that sporadic cases of HGV infection may occur frequently. This study of a large cohort of HCV and PCT patients further documents an increasing gradient in HCV prevalence from northern to southern Europe, and shows that HCV infection acts as a triggering factor of PCT. Finally, the HGV prevalence found in the PCT patients was comparable with that found in French blood donors, suggesting that HGV is not a PCT triggering factor.

Gastro-oesophageal reflux prevalence and relationship with bronchial reactivity in asthma.

The relationship between asthma and gastro-oesophageal reflux (GER) is controversial. In an allergy department, GER prevalence was evaluated in asthmatics, with a view to judging the potential influence of GER on asthma. One hundred and five asthmatics were recruited and co-investigated for GER and lung function. Descriptive analysis was performed, patients with (GER+) and without (GER-) GER were then compared, and finally, stepwise regression analysis was used. GER prevalence was 32%. Lung parameters did not differ between GER+ and GER- patients. When restricting analysis to GER+ patients, bronchial reactivity was closely correlated to the number of reflux episodes (NRE) (r=0.983; p=0.001). When comparing patients with more than 15 reflux episodes x day(-1) (n=50), with those having less (n=43), no differences were found in lung function and GER parameters. However, there was a positive correlation between the provocative dose of methacholine causing forced expiration volume to fall 20% from the baseline and NRE in patients with NRE>15 (r=0.561; p=0.05). In conclusion, gastro-oesophageal reflux was observed in a third of the asthma patients studied. These data do not support a firm aetiological relationship between gastro-oesophageal reflux and asthma, but do suggest an association between the number of reflux episodes and bronchial hyperresponsiveness.

[Gastroesophageal reflux (II). Major medical therapeutics: efficacy and risks]. / Reflux gastro-oesophagien (II). Les thérapeutiques médicales majeures: efficacité et risques.

REFERENCE DATA FOR THE THERAPEUTIC MANAGEMENT OF GASTROESOPHAGEAL REFLUX (GOR): The natural history of the disease; the short- and long-term efficiency of the various therapies and their potential risks; patient-related factors (age, associated disorders, personal preference, duration and severity of his reflux disease). First line therapy will be medical in all cases. POTENTIAL CANDIDATES FOR SURGERY: Only patients with proven GOR, with or without esophagitis but who have required proton-pump inhibitors (PPI) are potential candidates for surgery; if their esophagitis is not healed after a 8-week PPI regimen, especially, if they remain symptomatic; if they relapse shortly after treatment withdrawal and require either frequent intermittent courses or long-term continuous treatment with PPI; moreover if they relapse while continuously taking PPI at usual dosage. LONG-TERM TREATMENT WITH PPI: It looks safe. However there still is some concern about the complete safety of extremely prolonged treatments started in young patients.

[Gastroesophageal reflux (II). Surgical interventions: results and indications]. / Reflux gastro-oesophagien (II). Les interventions chirurgicales: résultats et indications.

ANTIREFLUX SURGERY: Peri and postoperative morbidity is higher with Nissen fundoplication than with a 180 degrees posterior fundoplasty (Toupet procedure) which carries the risk of a compromised result with time. Although a 270 degrees posterior gastric valve may be the best technique, the surgeon's skill looks more important than the procedure used, especially for laparoscopic surgery. Its advantages include reduced postoperative pain, shorter hospital stay and convalescent time. INDICATIONS FOR SURGERY: Surgery must only be entertained in patients with severe GOR disease, especially those who require continuous PPI treatment. Excluding cases of esophagitis with deep ulcers and/or stenosis, severity criteria to be taken into account are mainly symptomatic and not anatomical. Age is an important decision-making factor. IN CLINICAL PRACTICE: Patients over 60 years of age or with any surgical risk and patients with associated severe motor disorders such as sclerodermia should be given drug therapy unless high-dose PPI are unsuccessful. Conversely, laparoscopic surgery performed by a skilled surgeon should be preferred in younger subjects, especially under 40. In the intermediate age range, patients should be informed about the advantages and drawbacks of the various methods as patient participation is essential in the decision making process.

Occurrence of hepatocellular carcinoma in a case of hereditary coproporphyria.

An association between two types of acute hepatic porphyria (porphyria variegata and acute intermittent porphyria) and hepatocellular carcinoma has previously been reported. In these studies, etiological factors for hepatocellular carcinoma were not completely sought. We report here the first case of an association between hepatocellular carcinoma and hereditary coproporphyria, the third type of acute hepatic porphyria. A 58-yr-old woman with hereditary coproporphyria presented with a 3.5-cm-diameter hepatocellular carcinoma. Results of exhaustive investigation of etiological factors for hepatocellular carcinoma were negative. Results of microscopic histological analysis of the nontumorous liver were normal. Five years after surgical resection, the patient had no evidence of tumor recurrence.