1104 First Assessment of Needle-Based Confocal Laser Endomicroscopy (nCLE) During EUS-FNA Procedures of the Pancreas

1104 First Assessment of Needle-Based Confocal Laser Endomicroscopy (nCLE) During EUS-FNA Procedures of the Pancreas

Abstracts fashion. Results: Among new users, sensitivity for diagnosing BE-related neoplasia (interpreted as HGD or cancer vs. benign epithelium) was...

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Abstracts

fashion. Results: Among new users, sensitivity for diagnosing BE-related neoplasia (interpreted as HGD or cancer vs. benign epithelium) was 90% (95% CI: 85-95%) with a specificity of 82% (95% CI: 76-88%), and an overall accuracy of 84% (95% CI: 79-89%). Among experienced microendoscopists, sensitivity and specificity were both 100%, yielding an accuracy of 100%. Positive predictive value was 72% (95% CI: 65-79%), and negative predictive value was 94% (95% CI: 91-97%) in new users, with both increasing to 100% in experienced endomicroscopists. The interobserver reliability for distinguishing BE-related neoplasia among new users corresponded to a kappa statistic of 0.56 (1.00 in experts). Conclusions: Overall, gastroenterologists with no prior microendoscopic experience were very accurate in diagnosing BE-associated neoplasia, with significantly higher accuracy noted in those with ⬎ 50 cases with HRME. While prospective evaluation is still needed, the high negative predictive value suggests the device has the potential to increase diagnostic yield and reduce biopsy number. Moreoever, the low cost of the device and minimal training required to achieve reasonable accuracy rates suggest that the device may be a cost-effective option to consider for community-based settings.

1103 First Clinical Trial on Gastric Examination With a Magnetically Guided Capsule Endoscope Keiichi Ikeda1, Jean-Francois Rey3, Ileana Pangtay-Chio3, Haruhiko Ogata4, Naoki Hosoe4, Kazuo Ohtsuka5, Noriyuki Ogata5, Hiroyuki Aihara1, Toshifumi Hibi4, Shin-Ei Kudo5, Hisao Tajiri1,2 1 Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan; 2Department of Gastroenterology and Hepatology, The Jikei University School of Medicine, Tokyo, Japan; 3Department of Gastroenterology, Institut Arnault Tzanck, St Laurent du Var, France; 4 Department of Gastroenterology, Keio University School of Medicine, Tokyo, Japan; 5Digestive disease center, Showa University Northern Yokohama Hospital, Yokohama, Japan Background and Aims: Passive video capsule endoscopy had been considered as a gold standard for small bowel and under clinical investigations for esophagus and colon. It was impossible to elaborate any clinical trial for gastric exploration due to the technical limitations. We report the first clinical trial on comparative study between high definition gastroscopy and a Magnetically Guided Capsule Endoscope (MGCE). Materials and Methods: This trial was achieved in 85 patients with clinical indication for gastric examination using high definition endoscope and a MGCE. The guidance system with low magnetic force was designed by Siemens Healthcare and pictures obtained with a 2 sensors video capsule built by Olympus Medical Systems Corporation. The guidance system produces a very low magnetic field in order to avoid side-effects but is very effective allowing the capsule maneuverability. In order to conduct stomach examination, we have developed a protocol to get rid of gastric mucus but also to obtain an air water stomach interface: 500 ml of drinking water; repeated one hour later with 400 ml, followed 15 minutes later with 400 ml of 35° drinking water, the capsule being guided at water surface or diving near the gastric wall. Patients were included in 2 steps. 24 first patients in order to overcome our learning curve on capsule examination, then 61 patients where comparative examinations were carried on blindly by 2 physicians for gastroscopy, then capsule examination. Results: 97 patients have been included and 85 patients completed the trial. 1 minor abdominal pain was reported and resolved spontaneously. After a learning curve in Step 1 including 24 patients, the comparative study in Step 2 was carried on 61 patients. Visualization of gastric pylorus, antrum, body, fundus and cardia was felt to be completed in 88.5%, 86.9%, 93.4%, 85.2% and 88.5% respectively. There were 12 cases of incomplete visualization. 4 cases were incomplete due to early pyloric passage of the capsule and the rest 8 cases had mixture of multiple reasons for incomplete. This was achieved in a mean total examination time of 17.4 min (range 9-26). In total, 108 gastric findings (gastritis, angioma, polyp . . .) were identified. 63 jointly by gastroscopy and capsule but 31 lesions detected with capsule were missed by conventional endoscopy and 14 lesions detected by gastroscopy were missed by capsule. Conclusion: This first trial shows the feasibility of gastric exploration with a MGCE opens a new field for further studies on gastric cancer screening. Although more data needs to be collected, MGCE is a new break-through in capsule technology for non invasive examination of the stomach. At present, there remains some technical challenges on MGCE. However, it is expected that such a current technical challenge as maneuverability will be improved.

1104 First Assessment of Needle-Based Confocal Laser Endomicroscopy (nCLE) During EUS-FNA Procedures of the Pancreas Irving Waxman1, Harry R. Aslanian2, Vani J. Konda1, Uzma D. Siddiqui2, Michael B. Wallace3 1 Medicine, The University of Chicago, Chicago, IL; 2Medicine, Yale University, New Haven, CT; 3Gastroenterology & Hepatology, Mayo Clinic, Jacksonville, Jacksonville, FL

Figure 1. Representative HRME images of benign squamous mucosa, gastric mucosa, Barrett’s esophagus, and adenocarcinoma (Left) with corresponding H⫹E histopathologic images (Right). (A) Benign squamous mucosa. Note the bright, evenly spaced, evenly sized nuclei surrounded by dark cytoplasm with a hexagonal border. (B) Benign gastric mucosa. Note the thin, single cell epithelial layer, with large elongated lumens, giving the stomach a web-like, or honeycomb appearance. (C) Barrett’s esophagus. Note the elongated glands with a wide epithelial layer. (D) Esophageal adenocarcinoma. Note the loss of cellular architecture with no glands visible, and dense overlapping of nuclei.

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Background: The true clinical impact of EUS has been achieved with fine needle aspiration (FNA), which has been able to provide tissue confirmation of malignancy in extraluminal solid organs and lymph nodes. However, FNA is still fraught with significant challenges due to insufficient cells on cytological analysis, sampling error, need for multiple passes, and limited on-site cytological evaluation. Advances in optical technology now allow sub-millimeter imaging probes that can be passed through needles into cystic lesions and tumors. A prototype needle-based Confocal Laser Endomicroscopy probe (nCLE, Mauna Kea Technologies, Paris) provides real time imaging of the gastrointestinal superficial layers at the microscopic level. The aim of the study was to evaluate the feasibility of nCLE during EUS-FNA in patients with pancreatic lesions. Methods: An investigational prototype of a confocal laser endomicroscopic probe has been developed that is compatible with a 19-gauge FNA needle apparatus for microscopic imaging of solid organs. It has a diameter of 0.85 mm, a resolution of 3.5 microns, and a field of view of 320 microns. Subjects presenting for EUS with fine needle aspiration of the pancreas were consented at three tertiary care centers. Following an injection of 2.5 cc of 10% fluorescein, nCLE

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imaging was performed in the pancreas via the 19g needle with subsequent tissue acquisition. Final diagnosis was obtained either through surgical pathology or cytology. Results: 18 patients undergoing EUS-FNA were enrolled in the study. Cases included 16 pancreatic cysts and 2 pancreatic solid masses. Technical feasibility to perform confocal endomicroscopic imaging during an EUS-FNA procedure was achieved in 17 out of 18 cases. There were no device malfunctions. 13 of 17 cases had good to very good image quality of the cyst wall. Two adverse events of mild pancreatitis occurred with unknown relation to the study protocol. In 3 cases, villous structures were identified on endomicroscopy and diagnosed as IPMN by surgical pathology. Other vascular and epithelial structures were identified. Conclusions: Needle-based CLE of the pancreas is technically feasible under endosonographic guidance. This device and its ability to provide real time microscopic information may increase yield of FNA sampling and have the potential to provide diagnostic information where tissue samples are limited such as in pancreatic cysts. Two cases of pancreatitis were encountered. Future studies will address identification of structures, accuracy of image interpretation, complication profiles, and whether this device facilitates real time histopathology during EUS FNA procedures and improves diagnostic yield.

Figure 1. Images obtained via nCLE demonstrating papillary projections in a pancreatic cystic lesion, which was an IPMN by histology.

Figure 2. nCLE miniprobe shown in position in a 19 gauge needle.

1105 In Vivo Confocal Laser Endomicroscopic Observation of the Muscularis Propria and the Myenteric Plexus Using Submucosal Endoscopy With Mucosal Safety Flap Valve (SEMF) Technique Tomohiko R. Ohya1, Kazuki Sumiyama1, Junko Takahashi-Fujigasaki2, Akira Dobashi1, Hisao Tajiri3,2 1 Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan; 2Division of Neuropathology, The Jikei University School of Medicine, Tokyo, Japan; 3Department of Internal Medicine, Division of Gastroenterology and Hepatology, The Jikei University School of Medicine, Tokyo, Japan Backgrounds: Histological evaluation of the GI functional disorders is challenging due to the difficulty of tissue sampling of the culprit of the diseases, the dysfunctional muscularis propria (MP) underlying the mucosa. We have been exploring a way to endoscopically evaluate histology of the MP, and succeeded it by inserting an optical endomircoscope into a purposefully created submucosal tunnel in preceding experiments 1). Also, ex vivo evaluations with a bench confocal microscope revealed that MP including neural components could be selectively stained with fluorescent molecular probes by topically applying them on the exposed muscularis propria within the submucosal tunnel. Study aim: In this study, we evaluated the technical feasibility of real-time confocal imaging of MP with a miniature probe type confocal laser endomicroscopy (CLE), and explored appropriate staining conditions to selectively distinguish myenteric neurons in vivo. Methods: Four gastric sites of a porcine stomach sample were studied to define suitable staining conditions to be evaluated in vivo. Five gastric and 4 esophageal sites in 4 in vivo porcine models were then examined. First, submucosal tunnels were created with the previously reported submucosal endoscopy with mucosal safety flap valve (SEMF) technique. A neuronal

fluorescent molecular probe (NeuroTrace500/525, Invitrogen) was endoscopically sprayed onto the top of the exposed muscularis propria within the SEMF submucosal space. A miniature probe type CLE (Cellvizio, Mauna Kea Technologies, France) was inserted into the submucosal space via an accessory channel of a gastroscope. Obtained CLE images of MP were compared with corresponding histology. Results: In the ex vivo experiment, both smooth muscle layer and clusters (3⭌cells) of neuron-like cells (NLC) (spheroidal somata with processes, ⭌20␮m in diameter, located in intermuscular connective tissues) were visualized at 3 of 4 gastric sites with CLE. The tissue selectivity of fluorescent staining corresponded well to the stain concentrations. In the in vivo models, the smooth muscle layer was visualized at 4 of 5 gastric sites and 4 of 4 esophageal sites, and clusters of NLCs were visualized at 3 of 5 gastric sites and 4 of 4 esophageal sites. The histological evaluation of studied sites confirmed the myenteric neurons morphologically similar to NLCs in CLE. Conclusions: MP and myenteric neurons could be selectively visualized with CLE in vivo. This technology may provide a great opportunity to endoscopically and histologically analyze a series of GI motility disorders caused by neuroenteric dysfunctions. References: Sumiyama K, Tajiri H, Kato F et al. Pilot Study for in vivo cellular imaging of the muscularis propria and ex vivo molecular imaging of myenteric neurons. Gastrointest Endosc 2009; 69: 1129-34.

1172 Long-Term Outcomes of Early Gastric Cancers Treated by Endoscopic Submucosal Dissection: A Large Consecutive Series At a Single Center Haruhisa Suzuki, Ichiro Oda, Shigetaka Yoshinaga, Satoru Nonaka, Yutaka Saito Division of Endoscopy, National Cancer Center Hospital, Tokyo, Japan Background: Endoscopic submucosal dissection (ESD) has been utilized to treat early gastric cancers (EGCs) including larger than 2cm and ulcerated lesions for the past decade, but there is still a lack of published data on long-term outcomes of such gastric ESD. Aim: Assess the long-term outcomes of EGCs treated by ESD. Method: We retrospectively reviewed 1,926 consecutive lesions of intestinal-type EGCs that fulfilled the criteria for node-negative EGCs prior to treatment in 1,709 patients who had undergone ESDs from January 1999 to December 2005. Results: 1) All lesions were divided into two groups according to applicable criteria for endoscopic treatment of EGCs based on clinical diagnosis with 1,187 (62%) meeting guideline criteria (cG) and 739 (38%) satisfying expanded criteria (cE). 2) En-bloc resection rate was 98% (cG) and 97% (cE); complete resection rate was 96% (cG) and 90% (cE); and curative resection (CR) rate was 89% (cG) and 71% (cE). 3) In analyzing long-term outcomes, all patients were divided into two groups according to curability of EGCs by ESD with 1,368 (80%) undergoing CRs and 341 (20%) receiving nonCRs. Of 1,368 CR patients, 711 (52%) were pathologically diagnosed as having CRs based on guideline criteria (pG) and 657 (48%) were pathologically diagnosed as having CRs based on expanded criteria (pE). Of 341 patients with non-CRs, 188 (55%) underwent radical surgical resections with lymph-node (LN) dissection while 153 patients (45%), who did not undergo surgery because of high surgical risk, concomitant cancer and/or patient choice, were monitored carefully. Of 711 CR/pG patients, there were no cases of local recurrence, LN or distant metastasis with a median follow-up period of 43 months (range, 14-101) and only one case (0.1%) of gastric cancer-related death in a patient with LN metastasis due to metachronous advanced gastric cancer. Of 657 CR/pE patients, LN metastasis occurred in one patient (0.2%) who subsequently underwent distal gastrectomy with LN dissection, but there were no cases of local recurrence or gastric cancer-related deaths with a median follow-up period of 45 months (range, 12-101). In contrast, there were four (2%) gastric cancer-related deaths with LN or distant metastasis among 188 non-CR surgical patients with a median follow-up period of 45 months (range, 12-97). In addition, local recurrences developed in 11 patients (7%), LN or distant metastasis occurred in five patients (3%) and there were four (3%) gastric cancer-related deaths among 153 non-CR patients who did not undergo surgical resections with a median follow-up period of 46 months (range, 12-103). Conclusion: ESD was an effective curative treatment not only for EGCs of pG, but also for EGCs of pE based on the excellent long-term outcome results of this study.

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