A guide for assessing the clinical relevance of findings in small bowel capsule endoscopy: analysis of 8064 answers of international experts to an illustrated script questionnaire.

BACKGROUND AND AIM: Although recommended, the P-score used for assessing the pertinence / relevance of findings seen in small bowel (SB) capsule endoscopy (CE) is based on a low level of knowledge. The aim of this study was to evaluate the clinical relevance of the most frequent SBCE findings through an illustrated script questionnaire. MATERIALS AND METHODS: Sixteen types of SBCE findings were illustrated four times each in three different settings (occult and overt obscure gastrointestinal bleeding and suspected Crohn's disease), and with a variable number (n = 1/n = 2-5/n ≥ 6), thus providing a questionnaire with 192 scenarios and 576 illustrated questions. Fifteen international experts were asked to rate the finding's relevance for each question as very unlikely (-2) / unlikely (-1) / doubtful (0) / likely (+1) / very likely (+2). The median score (≤-0.75, between -0.75 and 0.75, or ≥0.75) obtained for each scenario determined a low (P0), intermediate (P1) or high (P2) relevance, respectively. RESULTS: 8064 answers were analyzed. Participation and completion rates were 93% and 100%, respectively. In overt or occult OGIB, resultant P2 findings were 'typical angiectasia', 'deep ulceration', 'stenosis', and'blood', whatever their numbers, and 'superficial ulcerations' when multiple. While in suspected CD, consensus P2 lesions were 'deep ulceration' and 'stenosis' whatever their numbers, and 'aphthoid erosions' and 'superficial ulcerations' when multiple. CONCLUSION: This study establishes a guide for the evaluation of relevance of SBCE findings. It represents a step forward for SB-CE interpretation and is intended to be used as a tool for teaching and academic research.

Efficacy, Tolerability, and Safety of Low-Volume Bowel Preparations for Patients with Inflammatory Bowel Diseases: The French Multicentre CLEAN Study.

BACKGROUND: Standard high-volume polyethylene glycol [PEG] bowel preparations [PEG-4L] are recommended for patients with inflammatory bowel disease [IBD] undergoing colonoscopy. However, low-volume preparations [≤2 L of active volume] are often used in clinical practice. The aim of this study was to evaluate the efficacy, tolerability, and safety of the various bowel preparations for patients with IBD, including low-volume preparations. METHODS: We conducted a French prospective multicentre observational study over a period of 1 month. Patients aged 18-75 years with IBD with an indication of colonoscopy independent of the study were enrolled. The choice of the preparation was left to the investigators, as per their usual protocol. The patients' characteristics, disease, and colonoscopy characteristics were recorded, and they were given self-reported questionnaires. RESULTS: Twenty-five public and private hospitals enrolled 278 patients. Among them, 46 had a disease flare and 41 had bowel stenoses. Bowel preparations for colonoscopy were as follows: 42% received PEG-2L, 29% received sodium picosulfate [Pico], 15% received PEG-4L, and 14% had other preparations. The preparation did not reach the Boston's score efficacy outcome in the PEG-4L group in 51.2% of the patients [p = 0.0011]. The preparation intake was complete for 59.5% in the PEG-4L group, compared with 82.9% in the PEG-2L group and 93.8% in the Pico group [p < 0.0001]. Tolerability, as assessed by the patients' VAS, was significantly better for both Pico and PEG-2L compared with PEG-4L, and better for Pico compared with PEG-2L [p = 0.008; p = 0.0003]. In multivariate analyses, low-volume preparations were independent factors of efficacy and tolerability. Adverse events occurred in 4.3% of the patients. CONCLUSIONS: Preparations with PEG-2L and Pico were equally safe, with better efficacy and tolerability outcomes compared with PEG-4L preparations. The best efficacy/tolerance/safety profile was achieved with the Pico preparation.

What Is the most Important for Elite Control: Genetic Background of Patient, Genetic Background of Partner, both or neither? Description of Complete Natural History within a Couple of MSM.

BACKGROUND: We describe a homosexual man who strongly controlled HIV-1 for ten years despite lack of protective genetic background. METHODS: HIV-1 DNA was measured in blood and other tissues. Cell susceptibility was evaluated with various strains. HIV-1-specific (CD4 and CD8 activation markers and immune check points) and NK cells responses were assessed; KIRs haplotypes and HLA alleles were determined. FINDINGS: Two HIV-1 RNA copies/mL of plasma were detected in 2009, using an ultra-sensitive assay. HIV-DNA was detected at 1.1 and 2 copies/106 PBMCs in 2009 and 2015 respectively, at 1.2 copies/106 cells in rectal cells in 2011. WBs showed weak reactivity with antibodies to gp160, p55 and p25 from 2007 to 2014, remaining incomplete in 2017. CD4 T cells were susceptible to various strains including HIVKON, a primary isolate of his own CRF02_AG variant. CD8 T cells showed a strong poly-functional response against HIV-Gag, producing mainly IFN-γ; a robust capacity of antibody-dependant cell cytotoxicity (ADCC) was observed in NK cells. Case patient was group B KIR haplotype. Neutralizing antibodies were not detected. CD4 and CD8 blood T cells showed normal proportions without increased activation markers. Phylogenetic analyses identified the same CRF02_AG variant in his partner. The patient and his partner were heterozygous for the CCR5ΔD32 deletion and shared HLA-B*07, C*07 non-protective alleles. INTERPRETATION: This thorough description of the natural history of an individual controlling HIV-1 in various compartments for ten years despite lack of protective alleles, and of his partner, may have implications for strategies to cure HIV-1 infection.

Extra-intestinal malignancies in inflammatory bowel diseases: An update with emphasis on MDCT and MR imaging features.

Inflammatory bowel diseases (IBD) are associated with an increased risk of gastrointestinal cancers and more specifically in sites affected by chronic inflammation. However, patients with IBD have also an increased risk for developing a variety of extra-intestinal cancers. In this regard, hepatobiliary cancers, such as cholangiocarcinoma, are more frequently observed in IBD patients because of a high prevalence of primary sclerosing cholangitis, which is considered as a favoring condition. Extra-intestinal lymphomas, mostly non-Hodgkin lymphomas, and skin cancers are also observed with an increased incidence in IBD patients by comparison with that in patients without IBD. This review provides an update on demographics, risk factors and clinical features of extra-intestinal malignancies, including cholangiocarcinoma, hepatocellular carcinoma and lymphoma, that occur in patients with IBD along with a special emphasis on the multidetector row computed tomography and magnetic resonance imaging features of these uncommon conditions.

Computer-assisted segmentation of videocapsule images using alpha-divergence-based active contour in the framework of intestinal pathologies detection.

Visualization of the entire length of the gastrointestinal tract through natural orifices is a challenge for endoscopists. Videoendoscopy is currently the "gold standard" technique for diagnosis of different pathologies of the intestinal tract. Wireless capsule endoscopy (WCE) has been developed in the 1990s as an alternative to videoendoscopy to allow direct examination of the gastrointestinal tract without any need for sedation. Nevertheless, the systematic postexamination by the specialist of the 50,000 (for the small bowel) to 150,000 images (for the colon) of a complete acquisition using WCE remains time-consuming and challenging due to the poor quality of WCE images. In this paper, a semiautomatic segmentation for analysis of WCE images is proposed. Based on active contour segmentation, the proposed method introduces alpha-divergences, a flexible statistical similarity measure that gives a real flexibility to different types of gastrointestinal pathologies. Results of segmentation using the proposed approach are shown on different types of real-case examinations, from (multi)polyp(s) segmentation, to radiation enteritis delineation.

Towards real-time in situ polyp detection in WCE images using a boosting-based approach.

This paper presents a new embeddable method for polyp detections in Wireless Capsule Endoscopic - WCE images. this approach consists first of extracting candidate polyps within the image using geometric considerations about related shape, and second, in classifying (polyp/non-polyp) obtained candidates by a boosting-based method using texture features. The proposed approach has been designed in accordance with the hardware constraints related to FPGA implementation for integration within WCE imaging device. The classification performance of the method have been evaluated on a large dataset of 300 polyps, and 1200 non-polyps images. Experiments show interesting and promising performance: the boosting-based classification is characterized by a sensitivity of 91%, a specificity of 95% and a false detection rate of 4.8%, the detection rate of the overall processing chain being of 68%. The performance of the boosting-based classification are in accordance with the most recent reference on this particular topic using the same dataset. Building of a dedicated WCE image database should permit the improvement of the global detection rate.

Validation of a live animal model for training in endoscopic hemostasis of upper gastrointestinal bleeding ulcers.

BACKGROUND AND STUDY AIMS: The management of upper gastrointestinal bleeding requires training of the endoscopist. We aimed to validate a live animal model of bleeding ulcers for training in endoscopic hemostasis. MATERIALS AND METHODS: Bleeding ulcers were created by repeated grasp-and-snare gastric mucosectomies in pigs rendered "bleeders" by preadministration of clopidogrel, aspirin, and unfractionated heparin. The feasibility and reproducibility of the model (proportion of bleeding ulcers, number of ulcers per animal, and time needed to produce a bleeding ulcer) were prospectively evaluated in six animals. Ten endoscopic experts assessed the similarity of this pig model to human bleeding ulcers (four-point Likert scale). The training capabilities of the model for hemostatic techniques (needle injection, bipolar electrocoagulation, and hemoclipping) were evaluated in 46 fellows (four-point Likert scale). RESULTS: A total of 53 gastric ulcers were created in 6 animals (8.8 ± 1.5 ulcers/animal). Successful active ulcer bleeding (Forrest Ib) was achieved in 96.2 % of cases. Bleeding was moderate to abundant in 79 % of cases. Ulcerations consistently reached the submucosal layer. The mean (± SD) time taken to create a bleeding ulcer was 3.8 ± 0.6 minutes. Endoscopic experts assessed the realism of the ulcers and bleeding at 3.2 ± 0.7 and 3.6 ± 0.7 respectively on a four-point Likert scale. The training significantly improved the endoscopic skills of the 46 fellows (P < 0.0001) in all hemostatic techniques. CONCLUSIONS: The live porcine model of bleeding ulcers was demonstrated to be realistic, reproducible, feasible, time efficient, and easy to perform. It was favorably assessed as an excellent model for training in endoscopic treatment of bleeding ulcers.

Endoscopic management of complications in digestive surgery.

Endoscopy has an ever-increasing role in the treatment of complications in digestive surgery. Endoscopic treatment is essentially used for (i) fistula or intra-abdominal collection secondary to anastomotic dehiscence and (ii) anastomotic stricture, especially esophagogastric, but also sometimes after colorectal surgery. First intention treatment of fistula following esophagogastric surgery is the insertion of an extractable self-expandable metallic stent (partially or entirely covered); this is supported by a low level of scientific evidence, but clinical experience has been satisfactory. Other techniques for treatment of anastomotic leak have also been reported anecdotally (clip placement, sealing with glue). There are few data available in the literature on endoscopic management (stents essentially) of postoperative colonic fistula. Whatever the approach chosen to treat a postoperative digestive tract fistula, management is medico-surgical and cannot be limited to simple closure of the digestive tube wall defect. Drainage of any collections by endoscopic, radiologic or surgical approach, systemic treatment of infection and nutritional support are essential adjuvant treatment modalities. Treatment of postoperative esophageal or colonic strictures is essentially endoscopic and is based on initial dilatation (endoscopic with hydrostatic balloon or bougie), and placement of extractable metallic stents (partially or entirely covered) in case of refractory outcome.

Flexible versus rigid single-port peritoneoscopy: a randomized controlled trial in a live porcine model followed by initial experience in human cadavers.

INTRODUCTION: We compared single incision laparoscopic surgery with flexible endoscope ("flexible SILS") and with rigid optic ("rigid SILS") for access to 11 elective sites of peritoneal carcinomatosis. MATERIALS AND METHODS: Back-to-back flexible and rigid SILS peritoneoscopy were performed in ten live pigs. SILS peritoneoscopy was performed using a flexible endoscope or a rigid optic, in random order, together with two rigid 5-mm laparoscopic forceps. Primary endpoint was access success rate to 11 elective sites of peritoneal carcinomatosis. Findings for the most favorable option were then assessed in four human cadavers. RESULTS: In the porcine model, the overall rate of access to targets was 98% with flexible SILS and 87% with rigid SILS (p < 0.001). Both flexible and rigid SILS allowed a 100% access rate to diaphragmatic domes, paracolic gutters, splenic and hepatic hilum, pelvic floor, and trigonal bladder. The rates of access to other sites by flexible versus rigid SILS, respectively, were: root of the mesentery (90 vs. 50%), origin of the inferior mesenteric vein (90 vs. 50%), inferior vena cava (100 vs. 90%), and cul-de-sac of Douglas (100 vs. 50%). No complications were observed. Procedures were performed in mean time of 26 and 24 min, respectively. These findings were confirmed for flexible SILS in four human cadavers. CONCLUSIONS: Flexible SILS is superior to rigid SILS to evaluate the peritoneal cavity in a timely manner. This suggests a need for flexible instrumentation or other technical solutions to perform thorough minimally invasive surgical evaluation of peritoneal carcinomatosis.

Long-term randomized controlled trial of a novel nanopowder hemostatic agent (TC-325) for control of severe arterial upper gastrointestinal bleeding in a porcine model.

BACKGROUND AND STUDY AIM: Endoscopic therapy of brisk upper gastrointestinal bleeding remains challenging. A proprietary nanopowder (TC-325) has been proven to be effective in high pressure bleeding from external wounds. The efficacy and safety of TC-325 were assessed in a survival gastrointestinal bleeding animal model. METHOD: 10 animals were randomized to treatment or sham. All animals received intravenous antibiotics, H2-blockers and heparin (activated clotting time 2 × normal). In a sterile laparotomy the gastroepiploic vessels were dissected, inserted through a 1-cm gastrotomy, and freely exposed in the gastric lumen, and the exposed vessel lacerated by needle knife. The treatment group received TC-325 by a modified delivery catheter while the sham group received no endoscopic treatment. Time to hemostasis, and mortality at 60 minutes, 24 hours, 48 hours, and 7 days were noted. Necropsy was performed in all animals. RESULTS: Spurting arterial bleeding was achieved in all animals. No control animal showed hemostasis within the first hour compared with 100 % (5 / 5) in the treatment arm (mean 13.8 minutes, P < 0.0079). Durable hemostasis was achieved with no evidence of rebleeding after 1 and 24 hours in 80 % (4 / 5) of the treated animals compared with none in the control group ( P < 0.0098). None of the control animals survived more than 6 hours. Necropsy at 1 week in treated animals revealed healed gastrotomy without foreign body granuloma or embolization to the lung or brain. CONCLUSION: TC-325 is safe and highly effective in achieving hemostasis in an anticoagulated severe arterial gastrointestinal bleeding animal model.

Esophageal perforations.

The incidence of esophageal perforation (EP) has risen with the increasing use of endoscopic procedures, which are currently the most frequent causes of EP. Despite decades of clinical experience, innovations in surgical technique and advances in intensive care management, EP still represents a diagnostic and therapeutic challenge. EP is a devastating event and mortality hovers close to 20%. Ambiguous presentations leading to misdiagnosis and delayed treatment and the difficulties in management are responsible for the high morbidity and mortality rates. A high variety of treatment options are available ranging from observational medical therapy to radical esophagectomy. The potential role of interventional endoscopy and the use of stents for the treatment of EP seem interesting but remain to be evaluated. Surgical primary repair, with or without reinforcement, is the preferred approach in patients with EP. Prognosis is mainly determined by the cause, the location of the injury and the delay between perforation and initiation of therapy.

Adhesion formation after peritoneoscopy with liver biopsy in a survival porcine model: comparison of laparotomy, laparoscopy, and transgastric natural orifice transluminal endoscopic surgery (NOTES).

BACKGROUND AND STUDY AIMS: Minimizing the invasiveness of operations by using natural orifice transluminal endoscopic surgery (NOTES) may reduce adhesion formation. The aim of the study was to compare rates of adhesion formation after peritoneoscopy with liver biopsy by laparotomy, laparoscopy, and transgastric NOTES. MATERIALS AND METHODS: Experimental comparative survival study, at a university hospital. using 18 female pigs weighing 35 - 40 kg. Peritoneoscopy with liver biopsy was randomized to one of three groups: laparotomy, laparoscopy, and transgastric NOTES. Preoperative, operative, and postoperative care was standardized. Main outcome measures were: (i) survival and complication rates; (ii) assessment of adhesion formation using the Hopkins Adhesion Formation Score at necropsy (day 14). RESULTS: 100 % of pigs with laparotomy and 33.3 % with laparoscopy had adhesions compared with 16.7 % who underwent transgastric NOTES. Documented adhesion bands totals for each group were: transgastric NOTES 1; laparoscopy 4; laparotomy 17. Median adhesion formation scores were: laparotomy 2.5 (range 2 - 4), compared with laparoscopy 0.0 (0 - 2), and transgastric NOTES 0.0 (0 - 1) ( P < 0.001). Spearman coefficient analysis revealed that correlation between adhesion scores assigned by two investigators was excellent (r = 0.99, P < 0.001, 95 % confidence interval [CI] 0.9978 - 0.9996). CONCLUSIONS: Although this was a short-term study, with a low number of animals, it showed that transgastric NOTES and laparoscopy are associated with statistically significantly lower rates of adhesion formation than open surgery when peritoneoscopy with liver biopsy is performed. Incidence and severity of adhesions were lowest with transgastric NOTES.

[The future of gastrointestinal therapeutic endoscopy: NOTES]. / Nouvelles perspectives en endoscopie thérapeutique: NOTES.

Natural orifice translumenal endoscopic surgery (NOTES) allows access into the peritoneal cavity with a flexible endoscope, through the wall of the digestive or urogenital tracts. NOTES can be combined to laparoscopic surgery in so-called << hybrid >> techniques. In the absence of any incision of the abdominal wall, NOTES procedures provide perfect cosmetic results, with virtually no risk of parietal complications, and with decreased postoperative pain. NOTES could particularly benefit to overweight patients and to patients receiving intensive or palliative care. Most NOTES studies have been performed on animal models, with great interest for both transgastric and transpelvic approaches. Successful NOTES peritoneoscopy, hysterectomy, oophorectomy, tubal ligation, gastrojejunal anastomosis, cholecystectomy, splenectomy, nephrectomy, and abdominal-wall hernia repair have been described. In human studies, the transvaginal route is preferred. NOTES clinical research focuses on low-morbidity procedures, such as cholecystectomy, appendectomy, and peritoneoscopy. Indirect benefits are expected from this research, with possible technological innovations in the field of endoscopic instrumentation (including sutures, anastomosis, traction and triangulation). Overall, NOTES is believed to make evolve both interventional endoscopy and minimally invasive surgery.

Plexitis as a predictive factor of early postoperative clinical recurrence in Crohn's disease.

BACKGROUND AND AIMS: A previous study suggested that the presence of myenteric plexitis in the proximal resection margins could be predictive of early endoscopic recurrence after ileocolonic or ileal resection for Crohn's disease (CD). The aim of the present study was to assess the predictive value of plexitis for early clinical CD recurrence. METHODS: All consecutive patients with ileocolonic or ileal resection for active CD in Lariboisière Hospital (Paris) between 1995 and 2006 were included. Clinical, surgical, histological and follow-up data were extracted from medical charts. Early clinical recurrence was defined as the reappearance of CD clinical manifestations requiring a specific treatment within 2 years postsurgery. The proximal resection margin was analysed using haematein eosin saffron (HES) staining and immunochemistry targeting mastocytes (anti-CD117 antibody) and lymphocytes (anti-CD3 antibody). Eosinophils were detected by HES staining. Ten cases of ileocolonic resections for caecal carcinoma served as controls. RESULTS: Data were available from 171 postoperative follow-up periods in 164 patients with CD. Early clinical recurrence of CD occurred in 28.1%. In multivariate analysis, factors associated with postoperative recurrence were active smoking (hazard ratio (HR) = 1.94; 95% CI 1.06 to 3.60; p = 0.033), submucosal plexitis with >or=3 mastocytes (HR = 1.87; 95% CI 1.00 to 3.46; p = 0.048) and a disease-free resection margin <5 cm (HR = 0.52; 95% CI 0.27 to 1.02; p = 0.059). CONCLUSIONS: Submucosal plexitis is associated with early clinical recurrence and could be taken into account in studies searching for new treatment strategies in the immediate postoperative period.

[Imaging of gastrointestinal stromal tumors]. / Imagerie des tumeurs stromales digestives.

Gastrointestinal stromal tumors (GIST) arising from interstitial cells of Cajal, represent the first type of solid tumor, which is very sensitive to a specific molecularly targeted tyrosine kinase receptor blocker (i. e., imatinib). On CT, which is considered as the reference technique, GISTs typically present as large, well-delineated, heterogeneous and sometimes exophytic masses. In contrast with the absence of lymph node involvement, hepatic metastasis as well as mesenteric involvement can be observed. MR-enteroclysis is indicated to investigate the local extent of the disease in specific cases whereas MR imaging is used to detect hepatic metastasis. Because of a specific treatment, contrast-enhanced imaging is needed for the follow-up of treated tumors. Evaluation of tumor response to treatment is best assessed with CT which still remains the reference imaging technique whereas FDG-PET imaging is used in specific cases.

Bacteriotherapy for inflammatory bowel disease: therapeutic tool and/or pharmacological vectors?

Inflammatory bowel diseases are the result of an abnormal immune response to environmental factors including the intestinal microbiota. Epithelial and immune cells of the intestinal mucosa recognise specific bacterial molecules via Toll like and NOD like receptors and this interaction modulates the inflammatory response (activation of the NF-kappaB pathway). It is thus rational to try treatments which could modify the intestinal microbiota i.e. antibiotics, new substrates (prebiotics) or new micro-organisms (probiotics). We review the literature on existing evidence for the efficacy of probiotic strains or combinations in patients with pouchitis (good evidence), ulcerative colitis (fair evidence), and Crohn's disease (no evidence at the present time). We also discuss the mechanisms of action, the use of microbial agents as pharmacological vectors, the development of genetically modified probiotics (including a clinical pilot trial in patients with Crohn's disease), and safety issues.