Long-term follow-up of patients undergoing capsule and double-balloon enteroscopy for identification and treatment of small-bowel vascular lesions: a prospective, multicenter study.

BACKGROUND AND STUDY AIMS: Few data are available concerning the long-term outcome of patients treated endoscopically for bleeding small-bowel vascular lesions (SBVL). The aim of this study was to evaluate the risk of rebleeding after endoscopic therapy for SBVLs detected by video capsule enteroscopy (VCE). The secondary aim was to assess risk factors for rebleeding. PATIENTS AND METHODS: A prospective, multicenter study (15 centers) was conducted, involving patients with obscure gastrointestinal bleeding and SBVL on VCE who were treated during double-balloon enteroscopy (DBE). The likelihood of bleeding was defined according to VCE findings, as high or low. RESULTS: A total of 183 patients underwent endotherapy during DBE, and 64 (35 %) had rebleeding during the 1 year follow-up period. Multivariate analysis indicated that cardiac disease (hazard ratio [HR] 2.04, 95 % confidence interval [CI] 1.20 - 3.48; P < 0.01) and the presence of overt bleeding (HR 1.78, 95 %CI 1.07 - 2.97; P = 0.03) at presentation were associated with the risk of rebleeding. The association between chronic renal failure and the risk of rebleeding was close to statistical significance (HR 1.77, 95 %CI 0.94 - 3.33; P = 0.08). Kaplan-Meier analysis suggested that patients treated during DBE for a lesion with low likelihood of bleeding on VCE had higher rebleeding rates than those with a high likelihood of bleeding (HR 1.87, 95 %CI 0.94 - 3.37; P = 0.07). CONCLUSION: Despite long-term remission in most patients, about one-third had rebleeding at 1 year. Independent risk factors for rebleeding were cardiac disease and overt bleeding at original presentation. The lesion characteristics on VCE may be useful to evaluate the bleeding potential of the lesion and may be used for better selection of patients for DBE.

Genomes of two chronological isolates (Helicobacter pylori 2017 and 2018) of the West African Helicobacter pylori strain 908 obtained from a single patient.

The diverse clinical outcomes of colonization by Helicobacter pylori reflect the need to understand the genomic rearrangements enabling the bacterium to adapt to host niches and exhibit varied colonization/virulence potential. We describe the genome sequences of the two serial isolates, H. pylori 2017 and 2018 (the chronological subclones of H. pylori 908), cultured in 2003 from the antrum and corpus, respectively, of an African patient who suffered from recrudescent duodenal ulcer disease. When compared with the genome of the parent strain, 908 (isolated from the antrum of the same patient in 1994), the genome sequences revealed genomic alterations relevant to virulence optimization or host-specific adaptation.

Prospective, randomized comparison of two small-bowel capsule endoscopy systems in patients with obscure GI bleeding.

BACKGROUND: Video capsule endoscopy is the first-intention examination in patients with obscure GI bleeding. The new MiroCam capsule, when using electric-field propagation for transmission, has been poorly evaluated in a clinical setting, in contrast with the PillCam SB2 capsule. OBJECTIVE: To evaluate the diagnostic concordance (κ value) between PillCam SB2 and MiroCam capsule examinations performed in the same patients. DESIGN AND SETTING: Prospective, randomized study in 7 endoscopy units. PATIENTS AND INTERVENTION: Eighty-three consecutive patients, ingesting the 2 capsules at a 1-hour interval. RESULTS: Seventy-three patients were analyzed (10 technical issues). There were 31 concordant negative cases (42.4%) and 30 concordant positive cases (41.1%). The study showed satisfactory diagnostic concordance between the 2 systems (κ = 0.66). In 12 patients (16.4%), the final diagnosis was different: 9 patients had positive findings on MiroCam examination but no image detected with PillCam SB2, 2 had positive findings on PillCam examination only, and 1 patient had 2 different diagnoses. A positive diagnosis was obtained in 46.6% and 56.2% of patients with PillCam SB2 and MiroCam capsule, respectively, so that the procedures identified 78.6% and 95.2% of positive cases, respectively (P = .02). Small-bowel transit time and capsule reading time were significantly longer in MiroCam procedures. LIMITATIONS: Technical failures possibly related to capsule interference. CONCLUSION: This study shows at least comparable efficiency of the MiroCam compared with the PillCam SB2 capsule system for the diagnosis of obscure GI bleeding.

Effects of Helicobacter pylori infection on gut appetite peptide (leptin, ghrelin) expression in elderly inpatients.

The aim of the study was to investigate the relationship between gastritis and leptin and ghrelin in elderly patients. Patients older than 75 years undergoing an endoscopy were included. We reported data on nutritional status and Helicobacter pylori infection diagnosis (serology, 13C-urea breath test, culture, histology, and polymerase chain reaction on gastric biopsies). Gastric messenger RNA expression of leptin and ghrelin were quantified by real-time polymerase chain reaction. Sixty-two patients were included (84.7 +/- 5.2 years). H. pylori infection was associated with decreased gastric expression of leptin (p = .021), ghrelin (p =.002), and plasma ghrelin levels (p = .018). Atrophy was associated with decreased gastric leptin (p = .007) and ghrelin (p = .02). H. pylori infection correlated negatively with patient energy intake (r = -0.36; p = .001) and body mass index (r = -0.34; p = .018). The negative association between ghrelin and H. pylori infection may be related to a higher prevalence of atrophy and raises the possibility that H. pylori may be contributing to undernutrition in some older people.

Temporary placement of fully covered self-expandable metal stents for the treatment of benign biliary strictures.

BACKGROUND: Endoscopic treatment of benign biliary strictures (BBS) can be challenging. OBJECTIVE: To evaluate the efficacy of fully covered self-expandable metal stents (FCSEMS) in BBS. METHODS: Ninety-two consecutive patients with BBS (chronic pancreatitis (n = 42), anastomotic after liver transplantation (n = 36), and post biliary surgical procedure (n = 14)) were included. FCSEMS were placed across strictures for 6 months before endoscopic extraction. Early success rate was defined as the absence of biliary stricture or as a minimal residual anomaly on post-stent removal endoscopic retrograde cholangiopancreatography (ERCP). Secondary outcomes were the final success and stricture recurrence rates as well as procedure-related morbidity. RESULTS: Stenting was successful in all patients. Stenting associated complications were minor and occurred in 22 (23.9%) patients. Migration occurred in 23 (25%) patients. Stent extraction was successful in all but two patients with proximal stent migration. ERCP after the 6 months stenting showed an early success in 84.9% patients (chronic pancreatitis patients: 94.7%, liver transplant: 87.9%, post-surgical: 61.5%) (p = 0.01). Final success was observed in 57/73 (78.1%) patients with a median follow-up of 12 ± 3.56 months. Recurrence of biliary stricture occurred in 16/73 (21.9%) patients. CONCLUSIONS: FCSEMS placement is efficient for patients with BBS, in particular for chronic pancreatitis patients. Stent extraction after 6 months indwelling, although generally feasible, may fail in a few cases.

Efficacy of intravenous cyclosporin in moderately severe ulcerative colitis refractory to steroids.

OBJECTIVE: The efficacy of intravenous cyclosporin (CSA) in acute severe ulcerative colitis (UC) is well established. The aim of this study was to evaluate its efficacy in moderately severe colitis refractory to steroids. METHODS: Twenty-six patients (17 men, mean age 41 +/- 14 yr) with UC refractory to steroids treated with CSA were included in this study. Severity was defined according to Truelove criteria. A clinical activity score below 10 during 2 consecutive days defined clinical response. RESULTS: According to Truelove criteria, all patients had moderate UC. CSA was administered IV at a mean daily dose of 3.7 +/- 0,5 mg/kg until response and then orally for 3.5 +/- 2.6 months. A clinical response was achieved in 20/26 patients (76,9%) within 5.7 +/- 2.8 days (5/6 failures were treated by proctocolectomy). During a follow-up of 27.8 +/- 20.8 months, relapse rate was 60% (12/20): 7 patients underwent proctocolectomy and 5 had clinical remission with CSA retreatment (N=4) and steroids (N=1). At the end of follow-up, 12 patients (46%) were in clinical remission, 12 (46%) required colectomy, 1 had chronic active UC and 1 was lost of follow-up. The probability to avoid surgery was 52% at 78 months. The only factor associated with avoidance of surgery was concomitant treatment with azathioprine (P=0.007). Ten reversible adverse events occurred in 9 patients. CONCLUSION: This study shows that CSA is safe and effective in moderately severe steroid resistant UC. Concomitant treatment with azathioprine significantly decreases the rate of subsequent surgery. CSA may act as a "bridge" until the therapeutic action of azathioprine is achieved for maintenance treatment. These results should be further confirmed by a prospective controlled study.

Predictors of response to infliximab in luminal Crohn's disease.

AIMS: To identify predictive factors of response to infliximab in luminal Crohn's disease (CD). PATIENTS AND METHODS: All consecutive patients with luminal CD treated with infliximab between October 1999 and March 2003 in Bordeaux's referral centers were included. All had at least 3 months follow-up post infliximab infusion and no prior treatment with infliximab. Response rates were determined 2 and 8 weeks after infusion according to Crohn's Disease Activity Index (CDAI) (remission=CDAI<150 and response=CDAI decrease more than 100). RESULTS: Among 44 patients (33 female; mean age 35 +/- 14 yr.), 39 (88%) had a clinical response 2 weeks after infusion (79% in remission). At week 8, the rate of response was 61.4% and exclusive colonic involvement predicted sustained response to treatment (P=0.03). The probability of remission at 56 weeks was 21.4%. Multivariate analysis demonstrated that the only factor associated with response duration was initiating immunosuppressive (IS) therapy in women (RR=3.61 95%CI[1.25-10.41], P=0.017). CONCLUSION: Exclusive colonic involvement is the only predictive factor of sustained response to infliximab in luminal CD. At the time of infliximab infusion, initiation or modification of IS therapy may favor sustained response, at least in women.

Value of microsatellite instability typing in detecting hereditary non-polyposis colorectal cancer. A prospective multicentric study by the Association Aquitaine Gastro.

AIM OF THE STUDY: To detect hereditary non-polyposis colorectal cancer (HNPCC) patients with a strategy combining clinical selection (patient age at onset of cancer less than 50 years or family history of HNPCC tumors) and microsatellite instability typing plus immunohistochemistry, leading to mismatch repair (MMR) germline mutation analysis. METHODS: Tumors were screened for microsatellite instability (MSI) and for hmlh1 and hmsh2 immunohistochemical expression. Germline mutation analysis was performed to search for MLH1 and MSH2 mutations in patients with MSI-High and MSI-Low tumors. RESULTS: 197 adenocarcinomas were studied: 164 patients were< or =50 years old, 33 were older than 50 years but had a family history of HNPCC tumors. Fifty tumors (25.4%) were MSI-High, 10 were MSI-Low (5.1%), and 130 were MS-Stable (66%). MSI typing was inconclusive in 7 (3.5%). Immunohistochemistry screening was performed on 165 tumors: sensitivity was 63.6%, specificity was 99%. Germline mutation analysis was performed in 33/60 MSI-High or Low tumors: 23 mutations were noted (70% of the tested patients). CONCLUSION: This proposed strategy of determining microsatellite instability in young colorectal cancer patients or in patients with a family history of HNPCC tumors led to an increased frequency in the detection of MMR germline mutations.

[Villo-glandular adenoma or polypoid dysplasia of esophagus: a case report]. / Polype tubulo-villeux ou dysplasie polypoïde de l'oesophage: une observation.

Gastrointestinal adenomas are neoplasms of glandular epithelium containing dysplasia of varying degrees. They are rare in esophagus. A case of villous tumor of the esophagus in a 71-year-old man is described. Histologically, this polypoid, villous lesion was developed on Barrett's esophagus and contained dysplastic epithelium and small adenocarcinomatous foci. This case illustrates that esophagus adenoma may be a premalignant lesion like other adenomas of the gastrointestinal tract. The term of polypoid dysplasia has therefore been recommended. This lesion, usually developed in gastric heterotopy or Barrett's esophagus, is often associated with high-grade dysplasia or carcinoma.

Comparison of a standard fully covered stent with a super-thick silicone-covered stent for the treatment of refractory esophageal benign strictures: A prospective multicenter study.

BACKGROUND: Some esophageal strictures resist endoscopic treatments. There is a need for new treatments, such as specifically designed stents. OBJECTIVE: Our study sought to compare the results achieved with a standard, fully covered metallic stent (FCMS) and those achieved using a stent designed specifically for benign strictures (BS-FCMS). PATIENTS AND METHODS: The study used a prospective, multicenter, controlled design, with patients recruited from tertiary referral centers. Patients with refractory esophageal strictures were included. Standard FCMS were used in group 1 (N = 24), and BS-FCMS were used in group 2 (N = 17). Patients were followed for 24 months after stent removal. The main outcomes measured were stricture resolution rate, 24 months' recurrence rate and stent-related morbidity. RESULTS: Early stent migrations occurred in one (4.1%) patient from group 1 and five (29.4%) from group 2 (p < 0.05). During esophageal stenting, complications occurred in six patients (25%) in group 1 and six patients (35.3%) in group 2 (p = 0.47), respectively. Fifty percent of complications were attributed to migration. There was no procedure-related morbidity associated with the extraction of the stent. The stricture resolution rate was, respectively, 95.2% in group 1 and 87.5% in group 2 (the difference between the two groups is not significant). During follow-up, stricture recurrence occurred in 15/19 patients (group 1, 79%) and 7/8 patients (group 2, 87.5%; p = 1.0). The median time to recurrence of esophageal stricture was 1.7 months (group 1, 0.6-12 months) and 1 month (group 2, 0.1-6 months). Study limitations include its nonrandomized design. CONCLUSION: The stricture resolution rate was high at the end of the stenting period for both types of stents without any statistical difference between the two groups, but the long-term results were disappointing, with stricture recurring frequently and rapidly in both groups.

Microevolution of Helicobacter pylori type IV secretion systems in an ulcer disease patient over a ten-year period.

Helicobacter pylori cagA and vacA genotypes have been used for almost a decade as stable entities to link the severity of gastritis and ulcer disease. We describe here microevolution of the two genomic islands, cag pathogenicity island (cagPAI; 40 kb) and tfs3 (16 kb) from isolates obtained at inclusion (one subclone) and after a 10-year period (two subclones) from a duodenal ulcer patient. Our results indicate microevolution in cagA, cagE, and cag7 genes of the cagPAI and open reading frames G, P, and L in tfs3, which possibly leads to inactivation or pseudogenization of these genes. Interestingly, no significant reduction in the severity of gastroduodenal pathology was found. These results point to an obvious difficulty in correlating the continuously evolving virulence factors such as the cagPAI genes with disease characteristics that appear to remain stable.

Repeated pneumatic dilations as long-term maintenance therapy for esophageal achalasia.

INTRODUCTION: In esophageal achalasia, pneumatic dilations (PD) provide short-term and long-term remission rates of 60-90% and 40-50%, respectively. The aim of this study was to evaluate the long-term efficacy of repeated PD as long-term maintenance therapy. PATIENTS AND METHODS: From 1992 to 2004, 150 patients with esophageal achalasia treated by PD were included in this retrospective study (78 males, mean age 57 +/- 20 yr). PD were performed until remission was achieved (symptom score < or = 3, each item < 2) and subsequently when symptomatic recurrence occurred. A standardized symptoms questionnaire was sent to patients lost to follow-up. Results are expressed as mean +/- SD. RESULTS: Initial remission was achieved in 137 of 150 (91.3%) patients with 2.67 +/- 1.59 dilations [range 1-12]. Failure and perforation rates were 7.3% (n = 11) and 1.3% (n = 2), respectively. After initial remission, 48 of 137 (35%) patients had recurrent symptoms; the probability to be in remission at 5 and 10 yr was 67% and 50%, respectively. At the end of follow-up (45 +/- 38 months, ext. 2-144) 108 of 137 (78.8%) patients were in remission. Among 112 patients whose symptoms could be treated by repeated PD (per protocol analysis), 108 (96.4%) were in remission (3.5 +/- 2.1 PD, ext. 2-12). In this group, the probability of being in remission after repeated PD at 5 and 10 yr was 96.8% and 93.4%, respectively. No pretherapeutic factor influenced long-term remission rate. The overall prevalence of gastroesophageal reflux was 34.7%. CONCLUSION: One-third of the patients with esophageal achalasia treated by PD will experience symptomatic recurrence during a 4-yr period. Long-term remission can be achieved in virtually all the patients treated by repeated PD according to an "on-demand" strategy based on symptom recurrence.

Pathogen evolution in vivo: genome dynamics of two isolates obtained 9 years apart from a duodenal ulcer patient infected with a single Helicobacter pylori strain.

The survival and microevolution of Helicobacter pylori strains in the niches of the stomach after eradication therapy have largely been unexplored. We analyzed genomic signatures for two successive isolates obtained 9 years apart from a duodenal ulcer patient who underwent eradication therapy for H. pylori. These isolates were genotyped based on 50 different parameters involving three different fingerprinting approaches and several evolutionarily significant and virulence-associated landmarks in the genome, including nine informative gene loci, the cag pathogenicity island and its right junction, members of the plasticity region cluster, and vacA and iceA alleles. Our observations reveal that the two isolates were derived from the same strain that colonized the patient for almost a decade and were almost identical. Microevolution, however, was observed in the cagA gene and its right junction, the vacA m1 allele, and a member of the plasticity region cluster (JHP926). These results suggest that H. pylori has a great ability to survive and reemerge as a microevolved strain posteradication, thereby hinting at the requirement for follow-up of patients after therapy.

Real-time PCR assay for rapid and accurate detection of point mutations conferring resistance to clarithromycin in Helicobacter pylori.

The main cause of failure of Helicobacter pylori eradication therapy is resistance to clarithromycin. The resistance is due to three point mutations in two positions on the 23S rRNA (A2142C, A2142G, and A2143G). Our aim was to develop a rapid and accurate method to detect these mutations directly on biopsy specimens. We developed a real-time PCR that included a simultaneous detection of the amplicons by hybridization of two probes labeled with LC-Red and fluorescein by using the fluorescence resonance energy transfer (FRET) technology and melting curve analysis with the LightCycler thermocycler. The assay was first applied successfully on reference strains, reference plasmids, and H. pylori-negative biopsies. Biopsies from 200 patients having failed a first eradication attempt and for whom the H. pylori strain was available were then tested with the new assay. A result was obtained in 199 cases; a single genotype was detected in 157 cases, two genotypes were detected in 41 cases, and three genotypes were detected in one case. There were, in total, seven discrepancies between the real-time PCR and the phenotypic method of determination of clarithromycin susceptibility, and in an additional four cases the two phenotypic methods were in disagreement. PCR-restriction fragment length polymorphism was applied to a sampling of biopsies, including all of the cases with multiple genotypes and all the cases with discrepant results. Finally, in four cases with discrepant results, the real-time PCR detected the resistant population at a concentration so low that it could not be detected by the phenotypic method, while in three cases other mutations could be involved. This assay had an accuracy at least as satisfactory as that of the phenotypic tests and could be performed within 2 h, allowing it to be used before the administration of therapy in the case of a first H. pylori eradication.

Effects of bronchial obstruction on lower esophageal sphincter motility and gastroesophageal reflux in patients with asthma.

The relationship between gastroesophageal reflux and asthma remains unclear. The aim of this study was to analyze the effect of bronchial obstruction on lower esophageal sphincter (LES) motility and reflux in patients with asthma. LES motility and esophageal pH were assessed in eight subjects with intermittent asthma and eight healthy volunteers during three consecutive 30-minute periods: baseline, methacholine-induced bronchospasm, and after inhalation of the beta2-agonist salbutamol. Healthy subjects inhaled 2 mg of methacholine, whereas subjects with asthma inhaled the dose of methacholine causing a 15% fall in FEV(1), as determined by a previous methacholine challenge. LES motility, esophageal pH, and FEV(1) were not significantly different between the three periods in healthy subjects. In patients with asthma, methacholine induced a 21.9 +/- 2.6% decrease in FEV(1) and a concomitant increase in the rate of transient LES relaxation (TLESR) and reflux episodes. Inhalation of salbutamol decreased the rate of TLESRs but not the number of reflux episodes. We conclude that in patients with asthma, methacholine-induced bronchospasm increases the rate of TLESR and the number of reflux episodes. These results support the belief that, in asthma, bronchial obstruction may be responsible for reflux or may aggravate reflux through a mechanism that remains to be further clarified.