Search

In 2015, capsule endoscopy was introduced as the main investigation method for small bowel mucosal diseases, and its role in colonic diseases has been gradually revealed. Future challenges for capsule endoscopy, besides improvements of image quality and visualization of each part of the small bowel and colonic mucosa, include the development of gastric capsules, the capacity to perform histological examination of the mucosa, and maybe in the future, some capsule endoscopy-driven therapeutics. The aim of this review was to evaluate the clinical demands and feasibility of achieving the aforementioned objectives.

Capsule endoscopy (CE) has become a first-line noninvasive tool for visualisation of the small bowel (SB) and is being increasingly used for investigation of the colon. The European Society of Gastrointestinal Endoscopy (ESGE) guidelines have specified requirements for the clinical applications of CE. However, there are no standardized recommendations yet for CE training courses in Europe. The following suggestions in this curriculum are based on the experience of European CE training courses directors. It is suggested that 12 hours be dedicated for either a small bowel capsule endoscopy (SBCE) or a colon capsule endoscopy (CCE) course with 4 hours for an introductory CCE course delivered in conjunction with SBCE courses. SBCE courses should include state-of-the-art lectures on indications, contraindications, complications, patient management and hardware and software use. Procedural issues require approximately 2 hours. For CCE courses 2.5 hours for theoretical lessons and 3.5 hours for procedural issued are considered appropriate. Hands-on training on reading and interpretation of CE cases using a personal computer (PC) for 1 or 2 delegates is recommended for both SBCE and CCE courses. A total of 6 hours hands-on session- time should be allocated. Cases in a SBCE course should cover SB bleeding, inflammatory bowel diseases (IBD), tumors and variants of normal and cases with various types of polyps covered in CCE courses. Standardization of the description of findings and generation of high-quality reports should be essential parts of the training. Courses should be followed by an assessment of traineesʼ skills in order to certify readers’ competency.

Background: A nationwide colorectal cancer (CRC) screening program was set up in France from 2009 for average-risk, asymptomatic people aged 50–74 years based on an immunochemical fecal occult blood test [faecal immunochemical test (FIT)] every 2 years, followed by colonoscopy if positive. The European standard recommends a participation rate of 45% for the program to be cost-effective, yet the latest published rate in France was 34%. The objective of this study was to compare the cost effectiveness of screening alternatives taking real-world participation rates into account. Methods: Eight screening strategies were compared, based either on a screening test (Guaiac or FIT testing, blood-based, stool DNA, computed tomography colonography, colon capsules, and sigmoidoscopy) followed by full colonoscopy if positive or direct colonoscopy. A microsimulation model was used to estimate the cost effectiveness associated with each strategy. Results: Compared with no screening, FIT was associated with a 14.0 quality-adjusted life year (QALY) increase of €50,520 per 1000 individuals, giving an incremental cost-effectiveness ratio (ICER) of €3600/QALY. Only stool DNA and blood-based testing were associated with a QALY increase compared with FIT, with stool DNA weakly dominated by blood-based testing, and the latter associated with an ICER of €154,600/QALY compared with FIT. All other strategies were dominated by FIT. Conclusion: FIT every 2 years appears to be the most cost-effective CRC screening strategy when taking into account a real-world participation rate of 34%.

Background Oesophago-gastroduodenoscopy is the standard method for the diagnosis of recurrent oesophago-gastric varices after endoscopic treatment and eradication. The aim of this study was to evaluate the PillCam®Eso capsule endoscopy in this setting. Methods Prospective, multicentre study in which patients with history of oesophageal varices treated by band ligation underwent PillCam®Eso capsule and oesophago-gastroduodenoscopy. Capsule recordings were blindly read by two endoscopists. Indication for a new prophylactic treatment and patient satisfaction were determined for both procedures. Results 80 patients (80% males, mean age: 57 ± 12 years) were included, after a median delay of 16 months from last endoscopic treatment. Recurrent oesophageal varices requiring a new prophylactic treatment were detected in 26 patients (32.5%). The mean oesophageal transit time of the capsule was 153 s (range 2–930 s). Capsule sensitivity, specificity, negative and positive predictive values for indication of new prophylactic treatments were 65%, 83%, 83%, and 65%, respectively. Capsule adequately classified 77.5% of the patients for prophylaxis indication. Inter-observer concordance for capsule readings was 88% for the prophylaxis indication. Conclusion This study demonstrates that accuracy of PillCam®Eso capsule for the diagnosis of recurrent oesophageal varices after endoscopic eradication is suboptimal. PillCam®Eso capsule might therefore be proposed in patients unable or unwilling to undergo oesophago-gastroduodenoscopy.

SummaryRibosomes are specialized entities that participate in regulation of gene expression through their rRNAs carrying ribozyme activity. Ribosome biogenesis is overactivated in p53-inactivated cancer cells, although involvement of p53 on ribosome quality is unknown. Here, we show that p53 represses expression of the rRNA methyl-transferase fibrillarin (FBL) by binding directly to FBL. High levels of FBL are accompanied by modifications of the rRNA methylation pattern, impairment of translational fidelity, and an increase of internal ribosome entry site (IRES)-dependent translation initiation of key cancer genes. FBL overexpression contributes to tumorigenesis and is associated with poor survival in patients with breast cancer. Thus, p53 acts as a safeguard of protein synthesis by regulating FBL and the subsequent quality and intrinsic activity of ribosomes.

// Zeina Bash-Imam 1 * , Gabriel Therizols 1 * , Anne Vincent 1 , Florian Laforets 1 , Micaela Polay Espinoza 1 , Nathalie Pion 1 , Francoise Macari 4 , Julie Pannequin 4 , Alexandre David 4 , Jean-Christophe Saurin 1 , Hichem C. Mertani 1 , Julien Textoris 3 , Didier Auboeuf 1 , Frederic Catez 1 , Nicole Dalla Venezia 1 , Martin Dutertre 2 ** , Virginie Marcel 1 ** and Jean-Jacques Diaz 1 ** 1 Univ Lyon, Universite Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Leon Berard, Centre de recherche en cancerologie de Lyon, F-69373 Lyon, France 2 Institut Curie, CNRS UMR 3348, Centre Universitaire, F-91405 Orsay, France 3 EA7426, Universite Lyon 1, Hospices Civils de Lyon, bioMerieux S.A. Pathophysiology of injury-induced immunosuppression (PI3), F69003 Lyon, France 4 IGF, CNRS, INSERM, Universite Montpellier, F-34094 Montpellier, France * These authors have equally contributed to this work ** Senior authors have equally contributed to this work Correspondence to: Jean-Jacques Diaz, email: jean-jacques.diaz@lyon.unicancer.fr Keywords: 5-fluorouracil, translation, translatome profiling, miRNA, colorectal cancer Received: February 24, 2017 Accepted: April 06, 2017 Published: May 03, 2017 ABSTRACT 5-Fluorouracil (5-FU) is a widely used chemotherapeutic drug in colorectal cancer. Previous studies showed that 5-FU modulates RNA metabolism and mRNA expression. In addition, it has been reported that 5-FU incorporates into the RNAs constituting the translational machinery and that 5-FU affects the amount of some mRNAs associated with ribosomes. However, the impact of 5-FU on translational regulation remains unclear. Using translatome profiling, we report that a clinically relevant dose of 5-FU induces a translational reprogramming in colorectal cancer cell lines. Comparison of mRNA distribution between polysomal and non-polysomal fractions in response to 5-FU treatment using microarray quantification identified 313 genes whose translation was selectively regulated. These regulations were mostly stimulatory (91%). Among these genes, we showed that 5-FU increases the mRNA translation of HIVEP2 , which encodes a transcription factor whose translation in normal condition is known to be inhibited by mir-155. In response to 5-FU, the expression of mir-155 decreases thus stimulating the translation of HIVEP2 mRNA. Interestingly, the 5-FU-induced increase in specific mRNA translation was associated with reduction of global protein synthesis. Altogether, these findings indicate that 5-FU promotes a translational reprogramming leading to the increased translation of a subset of mRNAs that involves at least for some of them, miRNA-dependent mechanisms. This study supports a still poorly evaluated role of translational control in drug response.

Background and study aim: As duodenal neuroendocrine tumors (NETs) are rare, their optimal management has not been clearly established. The aim of this study was to evaluate the feasibility and outcome of endoscopic treatment of duodenal NETs. Patients and methods: We reviewed the files of all patients who underwent endoscopic resection of a sporadic duodenal or ampullary NET between 1996 and 2014 at two centers. Results: A total of 29 patients with 32 uT1N0M0 NETs Conclusions: Endoscopic treatment of small duodenal NETs was associated with significant morbidity, a difficulty in obtaining an R0 specimen, and the risk of lymph node metastasis. Nevertheless, it represents an interesting alternative in small grade 1 duodenal lesions and in patients at high surgical risk.

Background: Endoscopic resections have low morbidity and mortality. Delayed bleeding has been reported in approximately 1 – 15 % of cases, increasing with antiplatelet/anticoagulant therapy or portal hypertension. A self-assembling peptide (SAP) forming a gel could protect the mucosal defect during early healing. This retrospective trial aimed to assess the safety and efficacy of SAP in preventing delayed bleeding after endoscopic resections. Methods: Consecutive patients with endoscopic resections were enrolled in two tertiary referral centers. Patients with a high risk of bleeding (antiplatelet agents, anticoagulation drugs with heparin bridge therapy, and cirrhosis with portal hypertension) were also included. The SAP gel was applied immediately after resection to cover the whole ulcer bed. Results: In total, 56 patients were included with 65 lesions (esophagus [n = 8], stomach [n = 22], duodenum [n = 10], ampullary [n = 3], colon [n = 7], and rectum [n = 15]) in two centers. Among those 65 lesions, 29 were resected in high risk situations (9 uninterrupted aspirin therapy, 6 heparin bridge therapies, 5 cirrhosis and portal hypertension, 1 both cirrhosis and heparin bridge, 3 both cirrhosis and uninterrupted aspirin, 3 large duodenal lesions > 2 cm, and 2 early introduction of clopidogrel at day 1). The resection technique was endoscopic submucosal dissection (ESD) in 40 cases, en bloc endoscopic mucosal resection (EMR) in 16, piecemeal EMR in 6, and ampullectomy in 3. The mean lesion size was 37.9 mm (SD: 2.2 mm) with a mean area of 6.3 cm2 (SD: 3.5 cm2). No difficulty was noted during application. Four delayed overt bleedings occurred (6.2 %) (3 hematochezia, 1 hematemesis) requiring endoscopic hemostasis. The mean hemoglobin drop off was 0.6 g/dL (– 0.6 to 3.1 g/dL). No adverse events occurred. Conclusion: The use of this novel extracellular matrix scaffold may help to reduce post-endoscopic resection bleedings including in high risk situations. Its use is easy and safe but further comparative studies are warranted to completely evaluate its effectiveness.

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.

Aliment Pharmacol Ther 2010; 32: 1145–1153 Summary Background Colon capsule endoscopy (CCE) is a new, non-invasive technology. Aim To conduct a prospective, multicentre trial to compare CCE and colonoscopy in asymptomatic subjects enrolled in screening or surveillance programmes for the detection of colorectal neoplasia. Methods Patients underwent CCE on day one and colonoscopy (gold standard) on day two. CCE and colonoscopy were performed by independent endoscopists. Results A total of 545 patients were recruited. CCE was safe and well-tolerated. Colon cleanliness was excellent or good in 52% of cases at CCE. Five patients with cancer were detected by colonoscopy, of whom two were missed by CCE. CCE accuracy for the detection of polyps ≥6 mm was 39% (95% CI 30–48) for sensitivity, 88% (95% CI 85–91) for specificity, 47% (95% CI 37–57) for positive predictive value and 85% (95% CI 82–88) for negative predictive value. CCE accuracy was better for the detection of advanced adenoma, in patients with good or excellent cleanliness and after re-interpretation of the CCE videos by an independent expert panel. Conclusions Although well-tolerated, CCE cannot replace colonoscopy as a first line investigation for screening and surveillance of patients at risk of cancer. Further studies should pay attention to colonic preparation (Clinicaltrial.gov number NCT00436514).

Only one third of anemias diagnosed in patients older than 65 years are iron-deficiency anemias. In these iron-deficiency anemias after 65 years, bidirectional endoscopy diagnoses a cause in up to 90% of cases. In case of negative bidirectional endoscopy, capsule endoscopy is clearly the best approach. After a negative capsule, a new bidirectional endoscopy for the detection of previously missed lesions is the recommended option. In young women with anemia is much more often an iron-deficiency anemia. The causes of this anemia can be multiple: low iron-intake, gynaecologic, and finally digestive. A step-by-step approach is thus of utmost importance to avoid unjustified examinations. In case of digestive symptoms, an upper (or in rare cases lower) endoscopy can be justified, major diagnoses being Helicobacter Pylor gastritis and celiac disease. The clinical relevance of capsule endoscopy is poorly evaluated in this group of patients, and seems of minimal impact.

Capsule endoscopy (CE) has become a standard non-invasive tool for small bowel (SB) examination. However, with an average number of 50,000 SB still frames per CE video, lesions can be missed and CE reading remains a timeconsuming activity. Therefore, the development of computer-aided algorithms for lesions’ detection has become an active research area in CE. Gastro-intestinal angiodysplasias (AGD) are the most common SB vascular lesions with an inherent risk of bleeding. This study aimed to develop a computer-assisted diagnosis (CAD) tool for SB-AGD detection in CE.

Hepatic involvement occurs in up to 74% of patients with hereditary hemorrhagic telangiectasia (HHT) and is characterized by a spectrum of arteriovenous malformations. Three different types of intrahepatic shunting may be present: hepatic artery to hepatic veins, hepatic artery to portal vein, and portal vein to hepatic vein. Hepatic involvement in HHT may lead to biliary ischemia, portal hypertension, or high-output cardiac failure (HOCF). Orthotopic liver transplantation (OLT) has been proposed as the only definitive curative treatment. The aim of this study was to evaluate the long-term outcome of patients with hepatic involvement due to HHT after OLT with respect to mortality, cardiac and hepatic status, epistaxis, and quality of life. Patients with HHT and severe hepatic vascular malformations who underwent OLT in the Lyon Liver Transplant Unit (LLTU) from 1993 to 2007 were followed at the LLTU and the French Reference Center for HHT. Quality of life was evaluated with the Short Form 36 questionnaire. There were 13 patients who fulfilled the entry criteria of the study (12 women and 1 man). The mean age at the time of OLT was 51.8 years (range = 33-65 years). Indications for OLT were cardiac failure (n = 9), biliary necrosis (n = 2), both cardiac failure and biliary necrosis (n = 1), and hemobilia (n = 1). The mean duration of follow-up was 109 months (range = 1-200 months). Twelve patients (92.3%) are still alive. For the 9 patients with HOCF, the mean cardiac index decreased from 5.4 L/minute/m(2) before OLT to 3.0 L/minute/m(2) after OLT. No severe hepatic complications were observed after OLT. Nine of the surviving patients (75%) experienced dramatic improvements in epistaxis and quality of life, including an ability to undertake more physical activity. In conclusion, OLT is an important therapeutic option for patients with HHT who have severe hepatic involvement. In the reported cohort, the mortality after OLT for this indication was low.

Organised since 1990 in France, cancer genetics has been strengthened since 2003 by the programme "Plan Cancer" which resulted in an improvement of the organisation of activities. The aim of this review is to present an update of the estimation of the needs of the population in this field for the next ten years, provided by a group of experts mandated by the French National Cancer Institute. Identification and management of major hereditary predispositions to cancer have a major impact on decrease in mortality and incidence. Sensitivity of criteria for the detection of BRCA1/2 mutations could be substantially improved by enlarging the indication for genetic testing to isolated cases of ovarian cancer occurring before 70 years and to familial cases occurring after this age limit. In the Lynch syndrome, the present criteria would have an excellent sensitivity for the detection of mutations in the mismatch repair (MMR) genes if the pre-screening of tumours on microsatellite instability (MSI) phenotype was effective, but these criteria are actually poorly applied. However, genetic testing should not be proposed to all the patients affected by tumours belonging to the spectrum of major predispositions and a fortiori to unaffected persons unless an affected relative has been identified as a carrier. The prescription of tests should continue to be strictly controlled and organised, in patients as well as in at-risk relatives. The enlargement of criteria and the improvement in the spreading of recommendations should result in an increase of genetic counselling activity and of the prescriptions of tests by a factor 2 to 4, and to a lesser extent in the clinical management of at risk persons. In a near future, it appears important to mandate experts on specific issues such as the determinants of the lack of effective application of tumour screening for MSI phenotype, the recommendations for the identification and the management of MYH-associated polyposis, or the predictive value of tumour characteristics for the identification of BRCA1/2 mutations. The expected increase in cancer genetics activity will need an optimal organisation to increase the throughput. Such measures will help in facing up to new predispositions that will probably be identified in common cancers.

Esophagogastroduodenoscopy (EGD) is the standard method for the diagnosis of esophago-gastric varices. The aim of this prospective multicenter study was to evaluate the PillCam esophageal capsule endoscopy (ECE) for this indication.Patients presenting with cirrhotic or noncirrhotic portal hypertension underwent ECEfollowed by EGD at the time of diagnosis. Capsule recordings were blindly read by two endoscopists.A total of 120 patients (72 males, mean age: 58 years; mean Child-Pugh score: 7.2) were included. Esophageal varices were detected in 74 patients. No adverse event was observed after either EGD or ECE. Seven (6%) patients were unable to swallow the capsule. The mean recording time was 204 s (range 1-876). Sensitivity, specificity, negative predictive value, and positive predictive value of ECE for the detection of esophageal varices were 77%, 86%, 69%, and 90%, respectively. Sensitivity, specificity, negative and positive predictive values of ECE for the indication of primary prophylaxis (esophageal varicesor = grade 2 and/or red signs) were 77, 88, 90, and 75%, respectively, and 85% of the patients were adequately classified for the indication (or not) of prophylaxis. Interobserver concordance for ECE readings was 79.4% for the diagnosis of varices, 66.4% for the grading of varices, and 89.7% for the indication of prophylaxis.This large multicenter study confirms the safety and acceptable accuracy of ECE for the evaluation of esophageal varices. ECE might be proposed as an alternative to EGD for the screening of portal hypertension, especially in patients unable or unwilling to undergo EGD.

Introduction Data on endoscopic resection of sporadic duodenal adenoma (SDA) are sparse; we present our results concerning safety and efficacy in a retrospective analysis of saline-assisted endoscopic resection of SDA. Patients and methods The cases of all patients who underwent endoscopic resection for SDA between May 1998 and May 2006 were analyzed. Endoscopic resection was carried out using standard injection and cut methods. In some patients hemoclips and argon plasma coagulation were used, either for prophylaxis or for the treatment of procedure-related bleeding. Results Thirty-six patients with a total of 37 lesions (mean size 19 mm, range 4 - 50 mm) were analyzed. Lesions larger than 20 mm were more frequently resected piecemeal ( P = 0.022). Intraprocedural bleeding occurred in 14 % of cases, without any significant association with lesion size or the resection technique. One fatal perforation occurred. Macroscopically complete resection was achieved in 97 % of cases, as confirmed by at least one negative control endoscopy with biopsies after a mean follow-up of 15 months. Although clipping and argon plasma coagulation were not applied in any systematic way, it was noticeable that in the 20 cases in which they were used for hemostasis or prevention, no delayed bleeding was observed after the procedures. In contrast, bleeding occurred in 22 % of the 23 procedures performed without these additional techniques. Conclusion Endoscopic resection is an efficient and acceptably safe technique for treating SDA. Further studies need to assess whether systematic bleeding prophylaxis will reduce the incidence of delayed hemorrhage after endoscopic resection.

Small bowel capsule endoscopy (CE) is a method of endoluminal examination of the small bowel using a wireless disposable capsule-shaped tool which is swallowed and then propelled by gut motility through the gastrointestinal tract. Since its first use more than 10 years ago, CE has been a first-line diagnostic method for the evaluation of the small bowel. The most common indications for CE include obscure gastrointestinal bleeding (OGIB), suspected Crohn's disease, small bowel tumor, and polyposis syndrome. Up until now, the application of CE has been widened based on the results of many clinical studies. In the current special issue, issues other than OGIB, such as Crohn's disease, ileitis, and portal-hypertensive enteropathy (PHE), have been focused on. However, CE has some limitations, such as inadequate bowel preparation and incompletion. To increase diagnosis yield, adequate bowel preparation and complete examination of the entire small bowel are important. And another important limitation of CE is the risk of retention. As one of the efforts to solve this problem, the real clinical experience with the PillCam patency capsule prior to CE was introduced. D.-H. Yang et al. have extensively reviewed the diagnostic accuracy and the therapeutic impact of CE in Crohn's disease. However, clinical experience with CE for the diagnosis and management of Crohn's disease is still limited despite the advantages of CE over other modalities. The risk of capsule retention, lack of evidence on the clinical benefit, and lack of established indications for CE in Crohn's disease may limit the widespread use of CE in clinical practice for suspected or established Crohn's disease. Ileitis is defined as inflammation of the ileum, and various etiologies are associated with ileitis. However, the differential diagnosis of terminal ileitis can be difficult in many cases. H. S. Lee and Y. J. Lim have described each of the various conditions associated with ileitis and the diagnostic value of CE for ileitis, which may help identify and evaluate these conditions in clinical practice. S. R. Jeon and J.-O. Kim have reviewed that CE has enabled the identification of PHE as a potentially significant complication of portal hypertension. In patients with liver cirrhosis and OGIB, PHE might be a possible cause for GI blood loss. CE can be a useful method for identifying treatable lesions in patients with PHE and can help optimize treatment on a case-by-case basis. Bowel preparation before CE is as essential as bowel preparation before colonoscopy. To date, there have been many comparative studies, consensus, and guidelines regarding different kinds of bowel cleansing agents in bowel preparation for small bowel CE. H. J. Song et al. have reviewed previous studies regarding bowel preparation for small bowel CE and suggested optimal bowel preparation of VCE. C. Rommele et al. have performed a retrospective analysis of 38 patients with risk factors for capsule retention and have indicated that CE could safely be performed even if the patency capsule excretion time is longer than 30 hours and the excreted patency capsule was not screened for damage.

International audience; To determine if the at-risk single-nucleotide polymorphism (SNP) alleles for colorectal cancer (CRC) could contribute to clinical situations suggestive of an increased genetic risk for CRC, we performed a prospective national case-control study based on highly selected patients (CRC in two first-degree relatives, one before 61 years of age; or CRC diagnosed before 51 years of age; or multiple primary CRCs, the first before 61 years of age; exclusion of Lynch syndrome and polyposes) and controls without personal or familial history of CRC. SNPs were genotyped using SNaPshot, and statistical analyses were performed using Pearson's chi(2) test, Cochran-Armitage test of trend and logistic regression. We included 1029 patients and 350 controls. We confirmed the association of CRC risk with four SNPs, with odds ratio (OR) higher than previously reported: rs16892766 on 8q23.3 (OR: 1.88, 95% confidence interval (CI): 1.30-2.72; P=0.0007); rs4779584 on 15q13.3 (OR: 1.42, CI: 1.11-1.83; P=0.0061) and rs4939827 and rs58920878/Novel 1 on 18q21.1 (OR: 1.49, CI: 1.13-1.98; P=0.007 and OR: 1.49, CI: 1.14-1.95; P=0.0035). We found a significant (P

BACKGROUND AND STUDY AIMS: The high cumulative risk of colorectal cancer in patients with familial adenomatous polyposis (FAP) justifies prophylactic colectomy with either ileorectal (IRA) or ileal-pouch-anal anastomosis (IPAA). Our aim was to evaluate retrospectively the frequency of and time interval to adenoma development in the ileal mucosa of patients with both types of surgery. PATIENTS AND METHODS: Retrospective study of 44 FAP patients with IRA (n = 21) and IPAA (n = 23). All patients were followed with a standardized procedure including chromoscopy and biopsies of visible polyps. In patients with IRA, specific attention was paid to the ileal mucosa above the anastomosis. RESULTS: In the IPAA group, 18/23 patients (78 %) presented with visible polyps [histology: 16 (70 %) had adenoma with low-grade dysplasia; 1 (4 %) had adenoma with high-grade dysplasia; 1 had normal mucosa]. The mean interval between colectomy and the diagnosis of adenoma was 4.7 +/- 3.3 years. In the IRA group, 16/21 patients (77 %) presented visible polyps in the ileal mucosa [adenoma with low-grade dysplasia in 8 patients (38 %), with high-grade dysplasia in 2 (10 %), and lymphoid nodular hyperplasia in 6]. The mean interval between colectomy and adenoma diagnosis was significantly shorter in the IPAA than in the IRA group (4.76 +/- 3.3 vs. 16.4 +/- 8.5 years, P< 0.0001). CONCLUSION: Our results show a high frequency of adenomas in the ileal mucosa of patients with IPAA and IRA (74 % and 48 % respectively), with evolution into high-grade dysplasia in 6.7 % of cases.

Resume A la suite de la 4e Conference internationale sur l’endoscopie par videocapsule endoscopique (ICCE, Miami, 2005), les principales indications de la videocapsule endoscopique (VCE) ont ete revues et le resultat de ce consensus a ete publie dans la revue Endoscopy en 2005. Les propositions de ces consensus sur la VCE etaient basees sur l’analyse des travaux de la litterature et des communications publies jusqu’en 2005. La methodologie comprenait pour chaque theme choisi un rapport par les specialistes de la question concernee, une discussion de ce rapport en petits groupes d’experts avant une presentation en seance pleniere aux medecins utilisateurs de la VCE et enfin, apres discussion par cette assemblee pleniere, redaction des conclusions et publication. La reunion de l’ICCE, qui s’est tenue en juin 2006 a Paris, a permis d’ameliorer et de completer la premiere version de ce consensus.

International audience; Actin depolymerizing factor (ADF)/cofilin family proteins are key regulators of actin filament turnover and cytoskeleton reorganization. The role of cofilin-1 in cell motility has been demonstrated in several cell types but remained poorly documented in the case of colon cancer. In addition, the putative function of destrin (also known as ADF) had not been explored in this context despite the fact that it is expressed in all colon cancer cell lines examined. We were therefore prompted to evaluate the respective contributions of these proteins to the invasive properties of the human colon cancer Isreco1 cell line, which expresses a comparatively high destrin/cofilin ratio. Reduction of cofilin-1 or destrin expression in Isreco1 cells using RNA interference led to an increase of the number of multinucleated cells and altered polarized lamellipodium protrusion and distribution of paxillin-containing adhesions. Both cofilin-1 and destrin silencing enhanced cell adhesion to extracellular matrix components. However, only destrin appeared to be required for cell migration on collagen I and for cell invasion through Matrigel in response to the proinvasive neuroendocrine peptide bombesin. This differential functional involvement was supported by a destrin-dependent, cofilin-independent phosphorylation of p130Crk-associated substrate (p130Cas) upon cell adhesion to collagen I or Matrigel. Taken together, our results suggest that destrin is a significant regulator of various processes important for invasive phenotype of human colon cancer Isreco1 cells whereas cofilin-1 may be involved in only a subset of them.

Among 353 patients with hereditary hemorrhagic telangiectasia retrospectively analyzed during the period 1985-2005, we identified 67 cases of severe infection that affected 48 patients (13.6%). Extracerebral infections accounted for 67% of all infections, and most involved Staphylococcus aureus and were associated with prolonged epistaxis. Cerebral infections accounted for 33% of all infections, were mainly due to multiple and anaerobic bacteria, and were associated with the presence of pulmonary arteriovenous malformations and a short duration of epistaxis.

The Enki-2 water jet system (Nestis SASA prospective study including 18 patients with esophageal, gastric and rectal superficial neoplasms treated by ESD using Enki-2 was designed.Eighteen lesions (6 esophageal, 3 gastric, 9 rectal, mean diameter 43.5 mm) in 17 patients (10 men, mean age 65.9) were included. The mean procedure time was 65.6 min. One patient needed clipping for an incomplete muscle tear during procedure; there were neither delayed bleedings nor perforation. The "en bloc" resection rate was 100 %, the R0 resection rate was 88.9 % (16/18 lesions), and the curative resection rate was 77.8 %. The 3-month disease-free rate was 92.3 % (12/13 patients, 13/14 lesions, 1 patient lost to follow-up). The 12-month disease-free rate was 69.2 % (9/13 patients, 10/14 lesions, 4 patients lost to follow-up).ESD with Enki-2 water jet system is effective and safe for superficial neoplastic digestive lesions.

Resume: Introduction: L'ESD a connu deux optimisations majeures depuis les premiers cas avec les solutions visqueuses macromoleculaires qui ameliorent le soulevement et les catheters bi-fonction couples a des systemes d'injection haute pression qui permettent de travailler avec un seul outil. Il n'etait jusqu'alors pas possible techniquement de les associer. Le systeme Nestis Enki II autorise ceci et a montre ses benefices par rapport a la methode classique dans deux precedentes etudes animales.Nous rapportons les 45 premiers cas d'ESD realisees sur ce principe a Lyon, Marseille et Louvain dans 4 centres experts. Patients et Methodes: Il s'agit d'une etude retrospective multicentrique regroupant tous les 45 cas consecutifs realises entre janvier 2013 et 2014 dans 4 centres par 6 endoscopistes. La nature histologique des lesions, les caracteristiques de la procedure (temps, complications), la qualite de resection, le suivi et les problemes techniques etaient collectes a partir d'une fiche de bloc remplie prospectivement. Le suivi etait ensuite collecte retrospectivement. Resultats: Les 45 procedures se sont revelees en bloc avec 91.1% de resections completes R0 et 88.9% de resections curatives. Les lesions etaient 22 LST rectales, 11 lesions gastriques, 10 lesions oesophagiennes (3 epidermoides, 7 Barrett), 1 lesion du colon droit et 1 lesion duodenale. Les solutions injectees par le water jet haute pression etaient l'hydroxyethylstarch (Voluven) dans 25 cas, le melange de glycerol dans 14 cas, le carboxymethylcellulose dans 5 cas et le lactate de sodium dans 1 cas (Geloplasma). L'injection etait de bonne qualite y compris en retroflexion maximale. 6 obstructions sont survenues (3 voluven, 3 glycerol) en cours d'intervention apres 58 minutes en moyenne, toujours dans un contexte de saignement. 2 patients ont presente une bulle autour du rectum sans symptomes associes et traites conservativement et 2 hemorragies retardees sont survenues dont une necessitant un traitement endoscopique. Le suivi est pour l'instant disponible chez 32 malades sans aucune recidive pour un suivi moyen de 3.8 mois avec 2 patients operes secondairement. 1 malade traite par ESD ciromferentielle a presente une stenose traitee par 2 seances de dilatation. Conclusion: Le systeme Nestis permet de coupler l'injection haute pression pulsee aux solutions macromoleculaires de maniere efficace et sure. Deux cas realises dans le colon droit et le duodenum ont mis en lumiere la securite et le confort de l'injection haute pression dans les situations difficiles. Quelques obstructions du catheter sont survenues en contexte hemorragique mettant en lumiere la necessite d'injecter frequemment pour rendre la procedure plus sure mais aussi pour nettoyer l'orifice du canal d'injection. Un essai multicentrique prospectif va demarrer prochainement pour confirmer ces donnees dans le colon a grande echelle. Structure: Endoscopie - imagerie

Resume Des etudes recentes ont montre la forte incidence de survenue de GIST, souvent multiples et localisees habituellement a l’intestin grele, au cours de la maladie de Von Recklinghausen. Nous en rapportons une nouvelle observation, particuliere par son mode de revelation et par le role joue par l’imagerie radiologique dans le diagnostic pre-operatoire. Un malade de 56 ans, atteint d’une maladie de Von Recklinghausen connue, etait hospitalise pour le bilan d’hemorragies digestives basses sous antiagregants. L’exploration endoscopique etait negative. L’enteroscanner mettait en evidence quatre localisations tumorales, trois de siege jejunal et une de siege ileal. Les lesions etaient traitees par resections chirurgicales segmentaires. L’etude histologique concluait a la presence de 2 GIST jejunales de faible risque de malignite, presentant un phenotype caracteristique, CD117+, CD34+, associees a 2 tumeurs fibroides de siege jejuno-ileal. La recherche de mutations du gene c-kit et du gene codant pour PDGF-Rα etait negative. L’evolution post-operatoire etait favorable, sans recidive hemorragique. Notre observation souligne les bonnes performances de l’enteroscanner dans la prise en charge des malades atteints de maladie de von Recklinghausen suspects de complications digestives. Elle souligne egalement l’importance d’une identification correcte des tumeurs digestives associees a la maladie de Von Recklinghausen : les GIST sont frequentes dans ce contexte et ne doivent pas etre confondues avec des neurofibromes.

Background The "Suspected Blood Indicator" (SBI), a feature included in the software for interpretation of capsule endoscopy (CE), is designed to facilitate detection of bleeding lesions in the small bowel. This study evaluated the sensitivity and the specificity of the SBI in patients who underwent CE for obscure GI bleeding (OGIB). Methods CE recordings from patients with OGIB recruited in 7 centers were read by experts blinded to the red SBI tags. They classified lesions of interest as bleeding or as having a potential for bleeding that was high (P2), low (P1), or absent (P0). The SBI tags then were marked by a another investigator. Concordance was acknowledged when frames selected by the expert reader, and those tagged by the SBI had the same time code. Results A total of 156 recordings were evaluated. In 83, there was either no lesion (n=71) or a P0 lesion (n=12); these CE recordings were regarded as normal. Among the 73 abnormal recordings, 114 P2 and 92 P1 lesions were identified. A total of 154 red tags were analyzed. Sensitivity, specificity, and positive and negative predictive values of SBI were 37%, 59%, 50%, and 46%, respectively, for detection of the presence of a P2 or P1 lesion in front of a red tag. Conclusions SBI-based detection of intestinal lesions with the potential for bleeding is of limited clinical value in practice and does not reduce the time required for interpretation of CE.

Numerous observations suggest that chromosome instability is caused by mitotic abnormalities such as errors in the partitioning of chromosomes. Chfr was recently defined as a central component of a new mitotic checkpoint that delays chromosome condensation in response to mitotic stress. Chfr was shown to be frequently inactivated in several human neoplasms, including colon, lung and esophageal cancers. To test whether Chfr inactivation may lead or participate to chromosomal instability (CIN), we analysed the genetic and epigenetic status of the gene in a large panel of primary colon and breast cancers, as well as in colon and breast cancer cell lines displaying either a microsatellite instability or a CIN. Our results confirm that Chfr is frequently inactivated in colon cancers, through a mechanism of hypermethylation of the promoter sequences. In contrast, the loss of Chfr expression appears to be a rare event in breast cancers. Furthermore, our data demonstrate that Chfr inactivation is not associated with CIN in these frequent types of human cancers.

The three mammalian receptors UNC5H1, UNC5H2, and UNC5H3 (also named UNC5A, UNC5B, and UNC5C in human) that belong to the family of the netrin-1 receptors, UNC5H, were initially proposed as mediators of the chemorepulsive effect of netrin-1 on specific axons. However, they were also recently shown to act as dependence receptors. Such receptors induce apoptosis when unbound to their ligand. We show here that the expression of the human UNC5A, UNC5B, or UNC5C is down-regulated in multiple cancers including colorectal, breast, ovary, uterus, stomach, lung, or kidney cancers. In colorectal tumors, this down-regulation is associated with loss of heterozygosity occurring within UNC5A , UNC5B , and UNC5C genes but may also be partially related to epigenetic processes because histone deacetylase inhibitor increased UNC5C expression in various cancer cell lines. Moreover, sequencing of UNC5C gene in patients with colorectal tumors revealed the presence of missense mutations. The loss/reduction of expression may be a crucial mechanism for tumorigenicity because the expression of UNC5H1, UNC5H2, or UNC5H3 inhibits tumor cell anchorage-independent growth and invasion. Moreover, these hallmarks of malignant transformation can be restored by netrin-1 addition or apoptosis inhibition. Hence, UNC5H1, UNC5H2, and UNC5H3 receptors may represent tumor suppressors that inhibit tumor extension outside the region of netrin-1 availability by inducing apoptosis.

Background: Gastrointestinal angiodysplasias (GIADs) could be responsible for recurrent bleeding and severe anemia. Somatostatin analogs could reduce transfusion requirements in these patients but no randomized controlled study is available. The main objective of the ANGIOPAS phase II double-blinded randomized, noncomparative study was to assess the effectiveness of pasireotide-LAR in reducing transfusion requirements in patients with refractory GIADs bleeding. Methods: A total of 22 patients with transfusion requirements ⩾6 units of packed red blood cells (pRBCs) during the 6 months prior to inclusion were randomized to receive pasireotide-LAR 60 mg ( n = 10) or placebo ( n = 12) every 28 days for 6 months. Patients were then followed for an additional 6 months after stopping treatment. Results: The pasireotide-LAR and placebo groups were equivalent for age, sex, comorbidities and transfusion requirement during the reference period (median 13 and 9.5 pRBCs). A 50 and 83% success rate (success defined as a decrease of at least 30% of transfused pRBCs) was observed in the pasireotide-LAR arm in the Intent to Treat (ITT) and per protocol (PP) analysis respectively. The need for transfusion during the intervention period was 3 pRBC units in the pasireotide-LAR group (range 0–26) and 11.5 pRBC units in the placebo group (range 0–23). Overall, three cases with glycemic control impairment were observed in the pasireotide-LAR group including one de novo diabetes. Conclusion: This double-blinded noncomparative randomized phase II study suggests, for the first time, the effectiveness of pasireotide-LAR 60 mg every 28 days to decrease the transfusion requirement in patients with recurrent bleeding due to GIADs.