Marlys Anderson

Contribution of intraoperative enteroscopy in the management of obscure gastrointestinal bleeding

Obscure gastrointestinal bleeding remains a significant diagnostic challenge. Our aims were (1) to determine the efficacy of intraoperative enteroscopy (IOE) in identifying lesions responsible for obscure gastrointestinal bleeding and (2) to determine the outcome of patients after treatment of these lesions. We retrospectively reviewed all patients who underwent IOE for obscure gastrointestinal bleeding from 1992 to 1998. Patients were divided into those with overt and those with occult gastrointestinal bleeding. Follow-up was complete in 67 patients (96%), with a median of 32 months (range 1 to 91 months). Seventy patients (52 overt and 18 occult) underwent IOE after extensive preoperative evaluation. Median duration of bleeding was 12 months, requiring a median of 14 blood transfusions. Risk factors for bleeding were identified in 46 patients (61 %). A lesion was identified and treated in 52 patients (74%)—39 in the overt group and 13 in the occult group. Lesions identified were vascular (54%), ulcerations (31%), tumors (11%), and small bowel diverticula (4%). Overall, 35 patients (52%) were found to have one or more lesions at IOE that were treated surgically and had no further bleeding. IOE, through a mid-small bowel enterotomy, has low morbidity and is effective in that it identified a treatable lesion in 74% of patients, which led to cure of bleeding in 52%.

Comparative diagnostic performance of volumetric laser endomicroscopy and confocal laser endomicroscopy in the detection of dysplasia associated with Barrett’s esophagus

BACKGROUND AND AIMS Probe-based confocal laser endomicroscopy (pCLE) and volumetric laser endomicroscopy (VLE) (also known as frequency domain optical coherence tomography) are advanced endoscopic imaging modalities that may be useful in the diagnosis of dysplasia associated with Barretts esophagus (BE). We performed pCLE examination in ex-vivo EMR specimens and compared the diagnostic performance of using the current VLE scoring index (previously established as OCT-SI) and a novel VLE diagnostic algorithm (VLE-DA) for the detection of dysplasia. METHODS A total of 27 patients with BE enrolled in a surveillance program at a tertiary-care center underwent 50 clinically indicated EMRs that were imaged with VLE and pCLE and classified into neoplastic (N = 34; high-grade dysplasia, intramucosal adenocarcinoma) and nonneoplastic (N = 16; low-grade dysplasia, nondysplastic BE), based on histology. Image datasets (VLE, N = 50; pCLE, N = 50) were rated by 3 gastroenterologists trained in the established diagnostic criteria for each imaging modality as well as a new diagnostic algorithm for VLE derived from a training set that demonstrated association of specific VLE features with neoplasia. Sensitivity, specificity, and diagnostic accuracy were assessed for each imaging modality and diagnostic criteria. RESULTS The sensitivity, specificity, and diagnostic accuracy of pCLE for detection of BE dysplasia was 76% (95% confidence interval [CI], 59-88), 79% (95% CI, 53-92), and 77% (95% CI, 72-82), respectively. The optimal diagnostic performance of OCT-SI showed a sensitivity of 70% (95% CI, 52-84), specificity of 60% (95% CI, 36-79), and diagnostic accuracy of 67%; (95% CI, 58-78). The use of the novel VLE-DA showed a sensitivity of 86% (95% CI, 69-96), specificity of 88% (95% CI, 60-99), and diagnostic accuracy of 87% (95% CI, 86-88). The diagnostic accuracy of using the new VLE-DA criteria was significantly superior to the current OCT-SI (P < .01). CONCLUSION The use of a new VLE-DA showed enhanced diagnostic performance for detecting BE dysplasia ex vivo compared with the current OCT-SI. Further validation of this algorithm in vivo is warranted.

Diagnostic performance of two confocal endomicroscopy systems in detecting Barrett's dysplasia: a pilot study using a novel bioprobe in ex vivo tissue

BACKGROUND There are currently 2 existing confocal laser endomicroscopy (CLE) platforms: probe-based CLE (pCLE) and endoscope-based CLE (eCLE) systems, each with its own criteria for identifying dysplasia in Barretts esophagus (BE). The diagnostic performance of these 2 systems has not been directly compared. DESIGN Preclinical, feasibility study. OBJECTIVES We compared the interrater agreement and diagnostic performance of the pCLE and eCLE systems. In addition, we evaluated a new BE endomicroscopy criteria based on fluorescent glucose intensity uptake. PATIENTS Thirteen patients with Barretts esophagus and high-grade dysplasia or early cancer undergoing 16 EMR. INTERVENTION CLE imaging was performed using two different probes with 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl)amino]-2-deoxyglucose, a fluorescent glucose analog with preferential uptake in dysplastic mucosa to supply contrast. Four quadrants were imaged per specimen with a total of 64 imaged mucosal sites presented to three gastroenterologists. MAIN OUTCOME MEASUREMENTS Interobserver agreement and accuracy for dysplasia was assessed of images classified according to Miami criteria, stacked eCLE images classified using the Mainz criteria and a novel fluorescence intensity criteria. RESULTS The interrater agreements were 0.17, 0.68, and 0.87 for the Miami, Mainz, and the fluorescence intensity criteria, respectively. Overall accuracy in detecting dysplasia was 37% (95% CI, 30.3-43.9), 44.3% (95% CI, 37.3-50.9), and 78.6% (95% CI, 72.2-83.3) for the Miami, Mainz, and the fluorescence intensity criteria, respectively. LIMITATIONS This imaging technique and proposed fluorescence intensity criteria using 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl)amino]-2-deoxyglucose in EMR tissue will require in vivo validation and cannot be directly used with the current eCLE and pCLE clinical applications. CONCLUSIONS In this preclinical feasibility study, the use of an eCLE system with a topical fluorescent contrast in ex vivo EMR tissue demonstrated higher interrater agreement and accuracy.

Breath Testing for Barrett’s Esophagus Using Exhaled Volatile Organic Compound Profiling With an Electronic Nose Device

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Jacques Bergman and Patrick Yachimski, Section Editors 61 62 63 64 65 Breath Testing for Barrett’s Esophagus Using Exhaled Volatile Organic Compound Profiling With an Electronic Nose Device 66 67 68 69 70 71 Daniel K. Chan, Liam Zakko, Kavel H. Visrodia, Cadman L. Leggett, Lori S. Lutzke, Magdalen A. Clemens, James D. Allen, Marlys A. Anderson, and Kenneth K. Wang

Volumetric laser endomicroscopy detects subsquamous Barrett's adenocarcinoma.

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A new era: endoscopic tissue transplantation.

Purpose of review To describe basic principles of tissue engineering with emphasis on the potential role of gastrointestinal endoscopy in regenerative medicine. Recent findings Stricturing associated with endoscopic submucosal resection and circumferential endoscopic mucosal resection can be prevented through transplantation of autologous epidermal cell sheets or seeded decellularized biological scaffolds. Lower esophageal sphincter augmentation through injection of muscle-derived cells is a novel potential treatment for gastroesophageal reflux disease. Stem cell derived tissue has been used to repair injured colon in a mouse model of colitis. A bioengineered internal anal sphincter has been successfully implanted in mice and showed preserved functionality. Summary The immediate foreseeable application of tissue engineering in gastrointestinal endoscopy is in the field of mucosal repair after acute injury. Tissue regeneration can be achieved through expansion of autologous somatic cells or by induction of multipotent or pluripotent stem cells. Advances in cellular scaffolding have made bioengineering of complex tissues a reality. Tissue engineering in endoscopy is also being pioneered by studies looking at enteral sphincter augmentation and regeneration. The availability of engineered tissue for endoscopic application will increase with advances in cell-culturing techniques.

Synergistic effects of photodynamic therapy with HPPH and gemcitabine in pancreatic cancer cell lines

Photodynamic therapy (PDT) is a potential treatment for pancreatic cancer. A second‐generation photosensitizer, 2‐[1‐hexyloxyethyl]‐2‐devinyl pyropheophorbide (HPPH) has a long wavelength absorption, high‐tumor selectivity, and shorter duration of skin photosensitivity. We investigated the efficacy of PDT with HPPH and gemcitabine in inducing cell death in multiple pancreatic cancer cell lines.

The Role of Cellular Senescence in the Gastrointestinal Mucosa

Cellular senescence is a biologically irreversible state of cell-growth arrest that occurs following either a replicative or an oncogenic stimulus. This phenomenon occurs as a response to the presence of premalignant cells and appears to be an important anticancer mechanism that keeps these transformed cells at bay. Many exogenous and endogenous triggers for senescence have been recognized to act via genomic or epigenomic pathways. The most common stimulus for senescence is progressive loss of telomeric DNA, which results in the loss of chromosomal stability and eventual unregulated growth and malignancy. Senescence is activated through an interaction between the p16 and p53 tumor-suppressor genes. Senescent cells can be identified in vitro because they express senescence-associated β-galactosidase, a marker of increased lysosomal activity. Cellular senescence plays an integral role in the prevention and development of both benign and malignant gastrointestinal diseases. The senescence cascade and the cell-cycle checkpoints that dictate the progression and maintenance of senescence are important in all types of gastrointestinal cancers, including pancreatic, liver, gastric, colon, and esophageal cancers. Understanding the pathogenic mechanisms involved in cellular senescence is important for the development of agents targeted toward the treatment of gastrointestinal tumors.

Su1352 Detection of Clostridium difficile-Infected Stool by Electronic-Nose Analysis of Fecal Headspace Volatile Organic Compounds

Introduction Electronic-noses (e-noses) have the ability of converting smells to digital signatures. By interacting with volatile organic compounds (VOCs) emitted by metabolic end-products of disease, e-noses create distinct patterns of aggregate VOCs to generate unique signatures that can be used to identify disease. The detection of Clostridium difficile (C. diff) by VOCs is prototypic as it has been successfully identified by scent using canines. We seek to pilot a novel portable e-nose device to profile fecal headspace to diagnose C. diff infection. Methods We are prospectively enrolling patients undergoing stool testing by C. diff PCR for infectious diarrhea for fecal headspace analysis using the Aetholab e-nose (eNose Company, Zutphen, NL). Stool specimens were obtained from the clinical microbiology lab of our institution within 7 days of ambient collection and aliquots of 10-ml of homogenized stool were transferred to disposable analysis bottles. The e-nose circulates fecal headspace gas within each analysis bottle to allow interaction with its respective sensor array. Each sensor array comprises of three metal-oxide sensors that undergo reversible redox reactions with VOCs at an electrochemical interface. Electrical resistance changes are measured by applying a 32-point thermal cycle to the sensor array generating a digital signature (Figure 1). This process has been shown to interact with a wide range of VOCs. Combined data from the 3 sensors in 7 combinations (A, B, C, AB, AC, AC, ABC) is permuted across 3 scaling factors generating a total of 21 data sets per analysis. These are then compressed through a multi-way analysis to reduce the large amount of data to avoid spurious associations. Finally each samples compressed dataset is introduced into an artificial neural network (ANN) using a supervised approach. The 5 best models generated using a leave-one-out approach are used to obtain the reported results. Results Separation was observed using all 20 C. diff-PCR positive and 53 C. diff-PCR negative stools. The ROC curve for this model is shown in Figure 2 with an AUC = 0.85. This demonstrated 80% sensitivity, 85% specificity with 84% accuracy. The positive predictive value was 0.67 and the negative predictive value 0.92. Matthews correlation coefficient was 0.64. Conclusion Through the use of a pattern-recognition e-nose device it is possible to distinguish C. diffinfected stools. This is the first time that this type of device has been used for this diagnosis, and also the first time this e-nose has been applied for fecal headspace analysis of infectious disease. This indicates that C. diff testing can translate into a point-of-care evaluation.

A Potential New Marker of Dysplasia: 2-Nbdg in Barrett's Esophagus Cell Lines

100.0%) and 85.7% (67.4-100.0%) respectively. Seven patients had gastro-duodenal lesions classified as probable or suspected source of bleeding. None had a positive FIT. Conclusion: the specificity of FIT for SB lesions classified as probable or suspected source of bleeding is quite high. Further studies are still needed to evaluate whether asymptomatic patients with positive FIT and non-explanatory colonoscopy should undergo further study of the small bowel