Cell cycle arrest and p53 prevent ON-target megabase-scale rearrangements induced by CRISPR-Cas9.

The CRISPR-Cas9 system has revolutionized our ability to precisely modify the genome and has led to gene editing in clinical applications. Comprehensive analysis of gene editing products at the targeted cut-site has revealed a complex spectrum of outcomes. ON-target genotoxicity is underestimated with standard PCR-based methods and necessitates appropriate and more sensitive detection methods. Here, we present two complementary Fluorescence-Assisted Megabase-scale Rearrangements Detection (FAMReD) systems that enable the detection, quantification, and cell sorting of edited cells with megabase-scale loss of heterozygosity (LOH). These tools reveal rare complex chromosomal rearrangements caused by Cas9-nuclease and show that LOH frequency depends on cell division rate during editing and p53 status. Cell cycle arrest during editing suppresses the occurrence of LOH without compromising editing. These data are confirmed in human stem/progenitor cells, suggesting that clinical trials should consider p53 status and cell proliferation rate during editing to limit this risk by designing safer protocols.

CRISPR-Cas9 globin editing can induce megabase-scale copy-neutral losses of heterozygosity in hematopoietic cells.

CRISPR-Cas9 is a promising technology for gene therapy. However, the ON-target genotoxicity of CRISPR-Cas9 nuclease due to DNA double-strand breaks has received little attention and is probably underestimated. Here we report that genome editing targeting globin genes induces megabase-scale losses of heterozygosity (LOH) from the globin CRISPR-Cas9 cut-site to the telomere (5.2 Mb). In established lines, CRISPR-Cas9 nuclease induces frequent terminal chromosome 11p truncations and rare copy-neutral LOH. In primary hematopoietic progenitor/stem cells, we detect 1.1% of clones (7/648) with acquired megabase LOH induced by CRISPR-Cas9. In-depth analysis by SNP-array reveals the presence of copy-neutral LOH. This leads to 11p15.5 partial uniparental disomy, comprising two Chr11p15.5 imprinting centers (H19/IGF2:IG-DMR/IC1 and KCNQ1OT1:TSS-DMR/IC2) and impacting H19 and IGF2 expression. While this genotoxicity is a safety concern for CRISPR clinical trials, it is also an opportunity to model copy-neutral-LOH for genetic diseases and cancers.

Ultrasound-induced Cavitation enhances the efficacy of Chemotherapy in a 3D Model of Pancreatic Ductal Adenocarcinoma with its microenvironment.

Pancreatic ductal adenocarcinoma (PDAC) is supported by a complex microenvironment whose physical contribution to chemoresistance could be overcome by ultrasound (US) therapy. This study aims to investigate the ability of US-induced inertial cavitation in association with chemotherapy to alter tumor cell viability via microenvironment disruption. For this purpose, we used a 3D-coculture PDAC model partially mimicking the tumor and its microenvironment. Coculture spheroids combining DT66066 cells isolated from KPC-transgenic mice and murine embryonic fibroblasts (iMEF) were obtained by using a magnetic nanoshuttle method. Spheroids were exposed to US with incremental inertial cavitation indexes. Conditions studied included control, gemcitabine, US-cavitation and US-cavitation + gemcitabine. Spheroid viability was assessed by the reduction of resazurin and flow cytometry. The 3D-coculture spheroid model incorporated activated fibroblasts and produced type 1-collagen, thus providing a partial miniature representation of tumors with their microenvironment. Main findings were: (a) Gemcitabine (5 µM) was significantly less cytotoxic in the presence of KPC/iMEFs spheroids compared with KPC (fibroblast-free) spheroids; (b) US-induced inertial cavitation combined with Gemcitabine significantly decreased spheroid viability compared to Gemcitabine alone; (c) both cavitation and chemotherapy affected KPC cell viability but not that of fibroblasts, confirming the protective role of the latter vis-à-vis tumor cells. Gemcitabine toxicity is enhanced when cocultured spheroids of KPC and iMEF are exposed to US-cavitation. Although the model used is only a partial representation of PDAC, this experience supports the hypothesis that US-inertial cavitation can enhance drug penetration and cytotoxicity by disrupting PDAC microenvironment.

Outcomes of endoscopic ultrasound-guided biliary drainage: A systematic review and meta-analysis.

Background: Success and event rates of endoscopic ultrasound (EUS)-guided biliary drainage vary with techniques, and results from different studies remain inconsistent. Objective: We conducted a proportion meta-analysis to evaluate the efficacy and safety of EUS-guided biliary drainage and compare the outcomes of current procedures. Methods: We searched MEDLINE, Embase, Cochrane and Web of knowledge to identify studies reporting technical success, clinical success and complication rates of EUS-guided biliary drainage techniques to estimate their clinical and technical efficacy and safety. Results: We identified 17 studies including a total of 686 patients. The overall clinical success and technical success rates were respectively 84% confidence interval (CI) 95% (80-88) and 96% CI 95% (93-98) for hepaticogastrostomy, and respectively 87% CI 95% (82-91) and 95% CI 95 (91-97) for choledochoduodenostomy. Reported adverse event rates were significantly higher (p = 0.01) for hepaticogastrostomy (29% CI 95% (24-34)) compared to choledochoduodenostomy (20% CI 95% (16-25)). Compared with hepaticogastrostomy, the pooled odds ratio for the complication rate of choledochoduodenostomy was 2.01 (1.25; 3.24) (p = 0.0042), suggesting that choledochoduodenostomy might be safer than hepaticogastrostomy. Conclusion: The available literature suggests choledochoduodenostomy may be a safer approach compared to hepaticogastrostomy. Randomized controlled trials with sufficiently large cohorts are needed to compare techniques and confirm these findings.

Self-assembling peptide matrix for the prevention of esophageal stricture after endoscopic resection: a randomized controlled trial in a porcine model.

Esophageal stricture formation after extensive endoscopic resection remains a major limitation of endoscopic therapy for early esophageal neoplasia. This study assessed a recently developed self-assembling peptide (SAP) matrix as a wound dressing after endoscopic resection for the prevention of esophageal stricture. Ten pigs were randomly assigned to the SAP or the control group after undergoing a 5-cm-long circumferential endoscopic submucosal dissection of the lower esophagus. Esophageal diameter on endoscopy and esophagogram, weight variation, and histological measurements of fibrosis, granulation tissue, and neoepithelium were assessed in each animal. The rate of esophageal stricture at day 14 was 40% in the SAP-treated group versus 100% in the control group (P = 0.2). Median interquartile range (IQR) esophageal diameter at day 14 was 8 mm (2.5-9) in the SAP-treated group versus 4 mm (3-4) in the control group (P = 0.13). The median (IQR) stricture indexes on esophagograms at day 14 were 0.32 (0.14-0.48) and 0.26 (0.14-0.33) in the SAP-treated and control groups, respectively (P = 0.42). Median (IQR) weight variation during the study was +0.2 (-7.4; +1.8) and -3.8 (-5.4; +0.6) in the SAP-treated and control groups, respectively (P = 0.9). Fibrosis, granulation tissue, and neoepithelium were not significantly different between the groups. The application of SAP matrix on esophageal wounds after a circumferential endoscopic submucosal dissection delayed the onset of esophageal stricture in a porcine model.

Antireflux versus conventional self-expanding metallic Stents (SEMS) for distal esophageal cancer: results of a multicenter randomized trial.

INTRODUCTION: Self-expanding metal stents (SEMS) are commonly used in the palliation of dysphagia in patients with inoperable esophageal carcinoma. However, they predispose to gastroesophageal reflux when deployed across the gastroesophageal junction. The aims of this study were to: 1) assess the influence of the antireflux valve on trans-prosthetic reflux (primary outcome); and 2) compare the results of SEMS with and without antireflux valve in terms of reflux symptoms, quality of life (QOL), improvement of dysphagia and adverse events (secondary outcomes). PATIENTS AND METHODS: Thirty-eight patients were enrolled in nine centers. Carcinomas were locally advanced (47 %) or metastatic. After randomization, patients received either a covered SEMS with antireflux valve (n = 20) or a similar type of SEMS with no antireflux device but assigned to standard proton pump inhibitor therapy and postural advice (n = 18). Trans-prosthetic reflux was assessed at day 2 using a radiological score based on barium esophagography performed after Trendelenburg maneuver and graded from 0 (no reflux) to 12 (maximum). Monthly telephone interviews were conducted for Organisation Mondiale de la Santé (OMS) scoring from 0 (excellent) to 5 (poor), QOL assessment (based on the Reflux-Qual Simplifié scoring system) from 0 (poor) to 100 (excellent), dysphagia scoring from 0 (no dysphagia) to 5 (complete dysphagia) and regurgitation scoring from 0 (no regurgitation) to 16 (maximum). RESULTS: No difference was noted in terms of age, sex, size of lesion, prosthesis length or need for dilation prior to SEMS placement. No difficulty in placing SEMS nor complications were noted. Radiological scores of reflux were found to be significantly lower in patients with an antireflux stent compared to the conventional stent and associated measures. The regurgitation scores were significantly decreased in patients with antireflux stents during the first 2 months after stent placement and thereafter, they were similar in the two groups. QOL and dysphagia were improved in both groups. Survival rates were comparable in the two groups. CONCLUSIONS: No difference was observed between the two types of SEMS regarding the palliation of dysphagia and improvement of QOL. However, SEMS with an antireflux valve were more effective in preventing trans-prosthetic gastroesophageal reflux but at the cost of an increased likehood of minor adverse events (migrations and/or obstruction of the SEMS).

Safety and feasibility of endoscopic biliary radiofrequency ablation treatment of extrahepatic cholangiocarcinoma.

BACKGROUND: Biliary bipolar radiofrequency ablation (RFA) is a new treatment for extrahepatic cholangiocarcinoma (CCA) currently under evaluation. The purpose of this study was to evaluate the safety, particularly biliary fistula occurrence, and the feasibility of biliary RFA in a homogeneous group of patients treated using the same RFA protocol. METHODS: Twelve patients with inoperable or unresectable CCA were included in a bicentric case series study. After removal of biliary plastic stents, a radiofrequency treatment with a new bipolar probe (Habib™ EndoHBP) was applied. The energy was delivered by a RFA generator (VIO 200 D), supplying electrical energy at 350 kHz and 10 W for 90 s. At the end of the procedure, one or more biliary stents were left in place. Adverse events were assessed per-procedure and during follow-up visits. RESULTS: CCA was confirmed in all patients by histology (66%), locoregional evolution or metastatic evolution. The types of CCA were Bismuth I stage (N = 4), Bismuth II stage (N = 3), Bismuth III stage (N = 2) and Bismuth IV stage (N = 3). No serious adverse events occurred within 30 days following endoscopic treatment: One patient had a sepsis due to bacterial translocation on day 1 and another had an acute cholangitis on day 12 due to early stent migration. No immediate or delayed biliary fistula was reported. The ergonomics of the probe made treatment easy in 100 % of cases. Mean survival was 12.3 months. CONCLUSION: Endoscopic radiofrequency treatment of inoperable CCA appears without major risks and is feasible. No major adverse events or biliary fistula were identified.

Topical hemostatic powder promotes reepithelialization and reduces scar formation after extensive esophageal mucosal resection.

The development of techniques for endoscopic resection has provided new strategies for radical conservative treatment of superficial esophageal neoplasms, even those that are circumferential, such as Barrett's neoplasia. However, it is necessary to prevent the formation of scar tissue that can be responsible for esophageal strictures following circumferential resection. Preliminary data have suggested the possible efficacy of a hemostatic powder in the promotion of wound healing. The study aims to assess the effectiveness of Hemospray (Cook Medical) in a swine model of post-endoscopic esophageal stricture. Our prospective controlled study included 21 pigs. A 6-cm circumferential submucosal dissection of the esophagus (CESD) was performed in each pig. Group 1 (n = 11) only underwent CESD and Group 2 (n = 10) had repeated Hemospray applications after CESD. Clinical, endoscopic, and radiological monitoring were performed, blood levels of four inflammatory or pro-fibrotic cytokines were assessed, and histological analysis was performed. Median esophageal diameter was greater in the group treated with Hemospray (2 mm [1-3] vs. 3 mm [2-4], P = 0.01), and the rate of symptomatic esophageal stricture was 100% and 60% in Groups 1 and 2, respectively (P = 0.09). The thicknesses of esophageal fibrosis and inflammatory cell infiltrate were significantly lower in Group 2 than in Group 1 (P = 0.002 and 0.0003, respectively). The length of the neoepithelium was greater in Group 2 than in Group 1 (P = 0.0004). Transforming growth factor-ß levels were significantly lower in Group 2 than in Group 1 (P = 0.01). The application of Hemospray after esophageal CESD reduces scar tissue formation and promotes reepithelialization, and therefore is a promising therapeutic approach in the prevention of post-endoscopic esophageal stricture.

Systematic review: the prevention of oesophageal stricture after endoscopic resection.

BACKGROUND: Extensive endoscopic resections for the treatment of early oesophageal neoplasia can result in fibro-inflammatory strictures that require repeated interventions, which significantly alter the patients' quality of life. AIMS: To review current evidence about the prevention of oesophageal strictures following endoscopic resections. METHODS: Systematic search of PubMed and Embase from inception to March 2015 using appropriate keywords. All original publications in English were included, and articles on the treatment of oesophageal stricture were excluded. RESULTS: Of the 461 hits, 62 studies were included in the analysis. Among the wound-protective strategies, polyglycolic acid sheets showed the most convincing evidence with a 37.5% stricture rate and excellent safety. Regenerative medicine, using cell sheets of autologous keratinocytes, resulted in a 25% stricture rate, although with cost and availability concerns. Among anti-proliferative treatment modalities, steroid treatment, either endoscopically injected triamcinolone in the resection wound or orally administered prednisolone, proved effective with an overall stricture rate of 13.5%, with safety concerns regarding late oesophageal perforations and infectious morbidity. Among mechanical treatment options, poorly effective and high-risk preventive balloon dilation tend to be replaced by prophylactic covered stent, with 18-28% stricture rates. CONCLUSIONS: Although oral or locally injected steroids are promising options, no currently available technique is sufficiently efficient and devoid of significant safety concerns to recommend its routine use for the prevention of strictures after extensive endoscopic resection. Improving our knowledge in the mechanisms of oesophageal wound healing will guide the development of novel methods for stricture prevention.

An observational study of driving distractions on urban roads in Spain.

The present research investigated the prevalence of driver engagement in secondary tasks and whether there were any differences by age and gender, as well as day of the week and time of the day. Two independent researchers observed 6578 drivers at nine randomly selected urban locations in Girona, Spain. Nearly 20% of the drivers observed were engaged in some type of secondary task, with the most common being: conversing with a passenger (11.1%), smoking (3.7%) and talking on a handheld mobile phone (1.3%). Surprisingly there were no differences by gender, but there were age-related differences with younger drivers being more frequently observed engaged in a number of different types of secondary tasks while driving (i.e. drinking, talking on a handheld mobile phone, and texting or keying numbers). Logistic regression showed that younger drivers, and to a lesser extent middle-age drivers, were significantly more likely to be observed engaged in a technological distraction than older drivers. Conversely, non-technological distractions were significantly predicted by day of the week, time of the day and location. A substantial number of the drivers observed in this study were putting themselves at an increased risk of becoming involved in a crash by engaging in non-driving related tasks at the same time as driving. Furthermore, the higher crash rate among young drivers may be partially accounted for by their more frequent engagement in some types of secondary tasks while driving.

Self-expanding plastic stent removed after radiochemotherapy for advanced esophageal cancer.

Endoscopic evaluation after chemoradiotherapy (CR) is impossible with an esophageal stent in place. The main study objective was to evaluate self-expanding plastic stent (SEPS) removal post-CR. Secondary end-points were the improvement of dysphagia and patients' quality of life. From October 2008 to March 2011, 20 dysphagic patients who suffered from advanced esophageal cancer were enrolled in a multicenter, prospective study. SEPS was inserted prior to CR and then removed endoscopically. SEPS efficiency (dysphagia score) and tolerance, as well as the patients' quality of life (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire validated for the esophagus), were monitored. Continuous variables were compared using a paired t-test analysis for matched data. A P-value of less than 0.05 was considered statistically significant. Twenty patients (15 men and 5 women), aged 61.5 years (±9.88) (range 43-82 years), with adenocarcinoma (n = 12) and squamous cell carcinoma (n = 8), were enrolled. SEPS were successfully inserted in all patients (100%). There was one perforation and three episodes of migration. All of these complications were medically treated. The mean dysphagia score at the time of stent placement was 2.79 (0.6). Mean dysphagia scores obtained on day 1 and day 30 post-SEPS placement were 0.7 (0.9) (P < 0.0001) and 0.45 (0.8) (P < 0.0001), respectively. Quality of Life Questionnaire validated for the esophagus score showed an improvement in dysphagia (P = 0.01) and quality of oral feeding (P = 0.003). All SEPS were removed endoscopically without complications. In two patients, the stent was left in place due to metastatic disease. SEPS are extractable after CR of esophageal cancer. Early stenting by SEPS prior to and during CR may reduce dysphagia and improve quality of oral alimentation.

Endoscopic submucosal dissection in a European setting. A multi-institutional report of a technique in development.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is a technique for "en bloc" resection of superficial tumors of the gastrointestinal tract. In France, experience with this technique is still limited. We wanted to assess the development of ESD in France, with special attention to short term outcomes. PATIENTS AND METHODS: Members of the Société Française d'Endoscopie Digestive (SFED) who declared performing ESD reported their cases prospectively on a voluntary basis. Demographic, clinical, and technical data, and the results of immediate complications were collected. Case reports were completed prospectively by each investigator before pooled analysis. RESULTS: A total of 188 consecutive case reports were collected from 16 centers. The median case mix per center was 6 patients (range 1-43). The lesion sites treated by ESD were the stomach (n = 75), esophagus (n = 27), duodenum (n = 1), cecum (n = 2), right colon (n = 3), transverse colon (n = 5), sigmoid (n = 3), and rectum (n = 72). The median size of the lesions was 26 mm (range 2-150 mm). En bloc resection was achieved in 77.1% of cases, with complete R0 resection in 72.9%. Histopathology results showed high grade dysplasia or superficial cancer in 71.2%. The median duration of ESD was 105 minutes (range 20-450 minutes). The short term morbidity was 29.2% including 34 cases of perforation (18.1%), and 21 hemorrhages (11.2%) during the 24 hours following ESD, 89% of which were managed conservatively or endoscopically. CONCLUSION: In this early experience, the feasibility of ESD appeared to be good but R0 resection and complication rates did not match those reported by Japanese authors and must be improved by an extended practice.

Long-term follow-up after biliary stent placement for postcholecystectomy bile duct strictures: a multicenter study.

BACKGROUND AND STUDY AIMS: Endoscopic stenting is a recognized treatment of postcholecystectomy biliary strictures. Large multicenter reports of its long-term efficacy are lacking. Our aim was to analyze the long-term outcomes after stenting in this patient population, based on a large experience from several centers in France. METHODS: Members of the French Society of Digestive Endoscopy were asked to identify patients treated for a common bile duct postcholecystectomy stricture. Patients with successful stenting and follow-up after removal of stent(s) were subsequently included and analyzed. Main outcome measures were long-term success of endoscopic stenting and related predictors for recurrence (after one stenting period) or failure (at the end of follow-up). RESULTS: A total of 96 patients were eligible for inclusion. The mean number of stents inserted at the same time was 1.9±0.89 (range 1-4). Stent-related morbidity was 22.9% (n=22). The median duration of stenting was 12 months (range 2-96 months). After a mean follow-up of 6.4±3.8 years (range 0-20.3 years) the overall success rate was 66.7% (n=64) after one period of stenting and 82.3% (n=79) after additional treatments. The mean time to recurrence was 19.7±36.6 months. The most significant independent predictor of both recurrence and failure was a pathological cholangiography at the time of stent removal. CONCLUSION: Endoscopic stenting helps to avoid surgery in more than 80% of patients bearing postcholecystectomy common bile duct strictures. However, a persistent anomaly on cholangiography at the time of stent removal is a strong predictor of recurrence and may lead to consideration of surgery.

Application of ANAES guidelines for colonoscopy in France: a practical survey.

OBJECTIVES: In 2004, the French health authorities published guidelines on the indications for colonoscopy. However, no study has evaluated the awareness of healthcare practitioners of these guidelines. The aim of this study was to determine the level of awareness of the ANAES guidelines among French gastroenterologists. PATIENTS AND METHODS: A questionnaire comprising 20 multiple choice questions (MCQ) was presented to a group of 79 gastroenterologists between February and June in 2008. The questions covered screening tests for colon cancer (one question), endoscopic mucosal resection (two questions) and the ANAES guidelines (17 questions). According to the number of colonoscopies performed per year (less than 100, 100-500, more than 500), the answers to these questions were analyzed separately. RESULTS: Among the practitioners carrying out less than 100, 100-500 and more than 500 colonoscopies per year, the guidelines for colon cancer screening were known by 33, 50 and 56%, respectively, the quality criteria for endoscopic mucosal resection by 0, 0 and 3.7%, respectively, and the ANAES guideline indications for colonoscopy by 34.3, 51.2 and 48.9%, respectively (P<0.001). The ANAES guidelines were significantly better known by practitioners who were performing more than 100 colonoscopies per year, while the indications for control colonoscopy were less often correctly anticipated. No differences were found concerning postponed indications. CONCLUSION: The ANAES guidelines consists of the following elements: (1) awareness of the ANAES guidelines is poor, with control colonoscopy being correctly anticipated in just over a third of the gastroenterologists; (2) performing more than 100 colonoscopies per year improves knowledge of the ANAES guidelines; and (3) the ANAES guidelines need to be simplified and should be covered by continuing medical education.

Contribution of endoscopic ultrasound-guided fine-needle aspiration in the workup of mediastinal lymph nodes.

BACKGROUND AND AIM: The aim of this retrospective study was to assess endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), a minimally invasive technique, to determine its diagnostic accuracy and morbidity in the etiological diagnoses of mediastinal lymph nodes. METHODS: A total of 84 patients underwent EUS-FNA biopsy of the mediastinal lymph nodes, and were classified as either malignant disease, inflammatory disease or incidental diagnosis, according to the suspected clinical condition. To evaluate the diagnostic accuracy of EUS-FNA in each group, a comparison of the cytological results obtained with 19- and 22-gauge needles was performed. RESULTS: All 84 procedures were carried out between January 2004 and June 2008. Six patients were excluded because of non-contributory results. On analyzing the results of EUS-FNA in the malignant group (n=41), the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 93, 100, 100 and 85%, respectively. In the inflammatory (n=20) and incidental diagnosis (n=17) groups, the sensitivity, specificity, PPV and NPV were 85, 100, 100 and 75%, and 80, 100, 100 and 77%, respectively. There was no significant difference between the FNA results with the 19-gauge (20/78 patients) versus 22-gauge (58/78 patients) needles (P=0.55). Also, no complications were reported either during the procedure or after the 6-month follow-up. CONCLUSION: EUS-FNA is a safe and accurate diagnostic procedure for the study of mediastinal lymph nodes not only for malignancy, but also for inflammatory diseases and incidental diagnoses. In addition, there is no difference in diagnostic accuracy whether FNA is carried out with a 19-gauge or 22-gauge needle.

Quality control of colonoscopy procedures: a prospective validated method for the evaluation of professional practices applicable to all endoscopic units.

OBJECTIVES: To produce valid information, an evaluation of professional practices has to assess the quality of all practices before, during and after the procedure under study. Several auditing techniques have been proposed for colonoscopy. The purpose of this work is to describe a straightforward original validated method for the prospective evaluation of professional practices in the field of colonoscopy applicable in all endoscopy units without increasing the staff work load. METHODS: Pertinent quality-control criteria (14 items) were identified by the endoscopists at the Cochin Hospital and were compatible with: findings in the available literature; guidelines proposed by the Superior Health Authority; and application in any endoscopy unit. Prospective routine data were collected and the methodology validated by evaluating 50 colonoscopies every quarter for one year. RESULTS: The relevance of the criteria was assessed using data collected during four separate periods. The standard checklist was complete for 57% of the colonoscopy procedures. The colonoscopy procedure was appropriate according to national guidelines in 94% of cases. These observations were particularly noteworthy: the quality of the colonic preparation was insufficient for 9% of the procedures; complete colonoscopy was achieved for 93% of patients; and 0.38 adenomas and 0.045 carcinomas were identified per colonoscopy. CONCLUSION: This simple and reproducible method can be used for valid quality-control audits in all endoscopy units. In France, unit-wide application of this method enables endoscopists to validate 100 of the 250 points required for continuous medical training. This is a quality-control tool that can be applied annually, using a random month to evaluate any changes in routine practices.

Esophageal lichen planus: a series of eight cases including a patient with esophageal verrucous carcinoma. A case series.

Esophageal lichen planus is a rare condition. Its risk of malignant transformation is unknown. We report a series of eight patients with esophageal lichen planus referred to our unit between 1990 and 2005. Clinical, endoscopic, radiological and histological data of these patients were retrospectively reviewed. Seven patients were women. All patients had oral lichen planus. Endoscopic lesions were located in the upper third of the esophagus in seven patients and in the mid third in two patients. Five patients had esophageal stricture. Seven patients had peeling, friable esophageal mucosa. Histological examination of esophageal biopsies found characteristic features of lichen planus in two patients and nonspecific changes in five patients. All patients received corticosteroids. Patients with stricture underwent esophageal dilation. Esophageal perforation after dilation occurred in one patient. Corticosteroids improved dysphagia in all patients; steroid dependence occurred in two patients with stricture. One patient had an esophageal verrucous carcinoma, which was treated with radiotherapy and chemotherapy. Upper endoscopy should be performed in patients with mucosal lichen planus presenting with dysphagia to assess esophageal involvement. Esophageal strictures are frequent and require dilation. Corticosteroids are the first-line treatment, but steroid dependence may occur. Cancer can arise on esophageal lichen planus and justifies endoscopic follow-up.

Computed virtual chromoendoscopy system (FICE): a new tool for upper endoscopy?

OBJECTIVES: A newly developed computed virtual chromoendoscopy system, Fuji Intelligent Color Enhancement (FICE) technology, decomposes images by wavelength, then directly produces reconstructed images with enhanced mucosal surface contrast. The aims of the present study were to determine the quality of information provided by computed virtual chromoendoscopy for detecting gastrointestinal polyps and to identify the best channel setting for imaging. PATIENTS AND METHODS: Thirty-one upper endoscopy procedures were performed in 31 patients using Fujinon 1.3-million-pixel endoscopes with zoom. A polyp was diagnosed in 45% of the patients. Six experienced endoscopists, who had never used the computed virtual chromoendoscopy system before, analysed the 31 endoscopy reports. Each endoscopy report included 11 images (one conventional image and one image for each FICE channel). The endoscopists used a 10-cm analog visual scale to determine the three best FICE channels, and to evaluate the quality and pit pattern of the chromoendoscopy images. RESULTS: Channel 4 (red: 520; green: 500; blue: 405) was considered the best channel in 39.7% of the reports (p<0.0001) and was among the best three in 77%. For 94.1% of the reports, the best FICE channel image was considered superior to the conventional image (p<0.0001). Median pit pattern score was 9.43 for computed virtual chromoendoscopy and 7.08 for conventional endoscopy (p<0.001). CONCLUSION: Fuji Intelligent Color Enhancement (FICE) channel 4 images were significantly better than conventional images. Computed virtual chromoendoscopy enabled better analysis of the pit pattern and the normal-pathological mucosal junction. Computed virtual chromoendoscopy can be used to identify gastroduodenal polyps and to assist in complete polypectomy.