Yutaka Tomizawa

The Risk of Endoscopic Mucosal Resection in the Setting of Clopidogrel Use

Objective. Guidelines on antiplatelet medication use during endoscopy are based on limited evidence. We investigate the risk of bleeding and ischemic events in patients undergoing endoscopic mucosal resection (EMR) of esophageal lesions in the setting of scheduled cessation and prompt resumption of clopidogrel. Design. Single centre retrospective review. Patients. Patients undergoing EMR of esophageal lesions. Interventions. Use of clopidogrel before EMR and resumption after EMR. Patients cease antiplatelets and anticoagulants 7 days before EMR and resume clopidogrel 2 days after EMR in average risk patients. Main Outcomes. Gastrointestinal bleeding (GIB) and ischemic events (IE) within 30 days of EMR. Results. 798 patients underwent 1716 EMR. 776 EMR were performed on patients on at least 1 antiplatelet/anticoagulant (APAC). 17 EMR were performed following clopidogrel cessation. There were 14 GIB and 2 IE. GIB risk in the setting of recent clopidogrel alone (0%) was comparable to those not on APAC (1.1%) (P = 1.0). IE risk on clopidogrel (6.3%) was higher than those not on APAC (0.1%) (P = 0.03). Limitations. Retrospective study. Conclusions. Temporary cessation of clopidogrel before EMR and prompt resumption is not associated with an increased risk of gastrointestinal bleeding but may be associated with increased ischemic events.

Efficacy, Durability, and Safety of Complete Endoscopic Mucosal Resection of Barrett Esophagus: A Systematic Review and Meta-Analysis.

Goals: To report the rate of eradication and recurrence of both neoplasia and intestinal mucosa and the rate of adverse events for complete endoscopic resection (CER) of Barrett esophagus (BE). Background: There is limited composite data on the clinical efficacy of CER of BE with high-grade dysplasia or neoplasia. Study: We performed a systematic review and meta-analysis of cohort studies that reported the clinical outcome of patients with BE who underwent CER and had at least 15-month follow-up after the time of elimination of BE. Main outcome of interests were pooled estimated rates of complete eradication of intestinal metaplasia and neoplasia, recurrence of intestinal metaplasia and neoplasia, and incidence of esophageal stricture, bleeding, and perforation. Results: We identified 8 studies reporting on 676 patients (high-grade dysplasia 54%) that met our criteria. Pooled estimated rates of complete eradication of intestinal metaplasia and complete eradication of intestinal neoplasia were 85.0% [95% confidence interval (CI), 79.4%-89.2%] and 96.6% (95% CI, 94.0%-98.1%), respectively, and rates of recurrence of intestinal metaplasia and recurrence of intestinal neoplasia were 15.7% (95% CI, 8.0%-28.4%) and 5.8% (95% CI, 3.9%-8.6%), respectively. Estimated incidences of adverse events were stricture 37.4 (95% CI, 24.4%-52.6%), bleeding 7.9% (95% CI, 4.4%-13.8%) and perforation 2.3% (95% CI, 1.3%-4.1%). Conclusions: CER achieves an 85% complete eradication rate of BE with recurrent rate of neoplasia of 6%. Estimated rate of postprocedural stricture was 37.4%. On the basis of this high rate of adverse events and significant heterogeneity in the studies included, the present meta-analysis cannot endorse CER as sole therapy for BE.

Altered Bowel Movements: A Rare Rectal Lesion

DIS 5.4.0 DTD YGAST60275 proof 24 March 2016 5:18 am ce Gas 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 Question: A 45-yearold man with a remote history of testicular cancer status post chemoradiation therapy, which was completed 20 years before this presentation and currently in clinical remission, was referred to our institution for intermittent rectal bleeding and diarrhea. He denied weight loss and never 86 87 88 89 90 91 92 93 94 underwent colonoscopy. No palpable lymphadenopathy or abdominal masses were appreciated on physical examination. Colonoscopy showed a 3-cm mass lesion at 10 cm from the anal verge. The lesion had a central umbilication with raised edges, and no obvious ulceration was seen (Figure A). Endoscopic ultrasonography revealed a hypoechoic mass with central depression and the endosonographic borders were smooth. There was sonographic evidence suggesting that the mass remained confined to the mucosa (layers 1 and 2) without extension into the submucosa despite the centrally depressed region (Figure B, arrows). No lymph nodes were seen in the perirectal region. Correlating his clinical and endoscopic findings, what is the diagnosis? Look on page 000 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. 95 96 97 98 99 100 101 Conflicts of interest The authors disclose no conflicts.

Diagnostic and Interventional Endoscopy

In endoscopic management of patients with esophageal malignancy, the most common aim is to diagnose and treat mucosal-based neoplasia. Esophagectomy is a curative therapy, but despite technical advances in surgical procedures, it is still associated with considerable perioperative risks, especially for the elderly. The increased perioperative risk can be partially explained by the existence of comorbidities in an aging population, notably obesity and ongoing tobacco and alcohol consumption. Most endoscopic therapy has been focused on high-grade dysplasia (HGD), primarily because of the risk of progression to cancer. HGD represents a threshold for intervention, whereas low-grade dysplasia (LGD) often just requires frequent endoscopic surveillance following society guidelines [1–4]. Endoscopic therapy has been applied to early-stage cancer since the publication of more favorable outcome data on mucosal resection and ablation therapy for mucosal esophageal cancer [5–7].

A Rare Cause of Diarrhea and Weight Loss

Question: A 70-year-old man with a history of gastric bypass surgery was transferred to our institution for evaluation regarding severe diarrhea, malnutrition and weight loss of 45 lbs in 6 weeks. He denied recent travel, antibiotics use, or significant alcohol consumption. Physical examination was notable for temporal wasting and bilateral pitting edema. He did not have any palpable lymphadenopathy or abdominal masses. Laboratory tests were pertinent for WBC 5,100/mL (normal differential), hemoglobin of 15.1 g/dL, potassium of 2.9 mEq/L, albumin of 2.2 g/dL, prealbumin of 6 mg/dL, and normal liver function tests, thyroid function, total immunoglobulin (Ig)A level, and tissue-transglutaminase IgA level. Additional tests for endomysial IgA antibody and HLA-DQ2/DQ8 were both negative. Stool studies for culture, parasite, and Clostridium difficile were all negative. CT of the abdomen and pelvis showed normal appearance of pancreas, but diffuse mild bowel dilation with wall thickening and enhancement (Figure A). Esophagogastroduodenoscopy showed an intact gastrojejunostomy anastomosis and normal appearing jejunum with intact villi within the examined portion (Figure B). Colonoscopy was unremarkable with normal biopsies of the terminal ileum and throughout the colon. Pathologic examination of the small intestinal biopsies showed patchy villous blunting with extensive infiltration of the lamina propria and epithelium by monomorphic intermediate-sized atypical lymphocytes (Figure C). Despite the marked intraepithelial infiltrate, the overlying epithelium remained intact, indicating there was no lymphoepithelial lesion. Correlating his clinical, radiologic, and histologic findings, what is the diagnosis? Look on page 1289 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.

Nausea, Vomiting, and Weight Loss: Common Symptoms of an Uncommon Disease

Gastroe Question: A 36-year-old black woman with no significant past medical history presented with progressive nausea, vomiting, and weight loss for several months. She had no lymphadenopathy or hepatomegaly on physical examination. Laboratory tests showed hemoglobin of 11 g/dL and normal liver functions tests. An esophagogastroduodenoscopy revealed diffuse erythematous, nodular, friable mucosa in the stomach and the antrum was not easily distended on insufflations (Figure A). The pylorus was narrowed but was easily traversed by the endoscope (Figure B). Computed tomography of the abdomen and pelvis showed thickening of the antral wall of the stomach but was otherwise unremarkable (Figure C, arrow). An upper gastrointestinal series confirmed a conical configuration and lack of distension throughout the gastric antrum with patulous pyloric channel (FigureD). Small bowel follow-throughshowednoevidenceof activeor chronic inflammatorydisease in the small intestine. What is your diagnosis? Look on page 574 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.

Confocal Laser Endomicroscopy: The Potential Role of In Vivo Characterization of Neoplasia in the Gastrointestinal Tract

Confocal laser endomicroscopy (CLE) is a novel microscope which enables real-time imaging with detailed mucosal and sub mucosal architectures throughout the gastrointestinal tract. New optical technology using the principle of light reflection, scattering and refocusing dramatically increases image resolution thus has the potential of real time optical biopsy. Two types of CLE system are commercially available; endoscope-based type (eCLE) which integrated CLE in the tip of scope and probe-based type (pCLE) which uses a probe through the accessory channel of a traditional endoscope. Clinical data applying CLE for the detection of neoplastic lesions in the gastrointestinal tract have been increasingly reported including esophagus, stomach and colon. The probe based system has a probe that can be used in the bile ducts to evaluate biliary strictures. More recently, a needle based CLE which passes through a fine-needle aspiration needle has been introduced into pancreatic cystic lesions. CLE has demonstrated promising in vivo data in various clinical arenas. Further validation regarding reproducible image classification, inter and intra observer variability, learning curve, and cost effectiveness remain to be demonstrated.

Enhanced Mucosal Imaging and the Esophagus—Ready for Prime Time?

Innovation of endoscopic technology has recently been introduced to improve real-time visualization of mucosal architecture and subepithelial vascular structures. Since the esophagus is easily accessible using endoscopy and the length of required observation is limited, many different types of new imaging modalities have been reported and showing promising data. Early detection of neoplastic changes in the esophagus is devoted to the treatment in early stage cancer and theoretically leads to better prognosis. This review will focus on the emerging endoscopic technologies for the management of esophageal cancer.

Parastomal Variceal Bleeding Attributed to Obstructive Pathology Successfully Treated by Percutaneous Variceal Embolization

Parastomal variceal bleeding is a rare cause of gastrointestinal bleeding, but it should be considered as a potential etiology in patients with portal hypertension and surgical stomas. Though standard endovascular management has not yet been established, transjugular intrahepatic portosystemic shunt (TIPS) is a recommended treatment option leading to decompression of underlying portal hypertension. We present a case of parastomal bleeding treated with percutaneous parastomal variceal embolization, which is an emerging alternative therapy when TIPS cannot be performed.

S1064 Evaluation of Epithelial Mesenchymal Transition (EMT) and Cancer Stem Cell (CSC) in Esophageal Adenocarcinoma in Barrett's Esophagus

Background:Epithelial mesenchymal transition(EMT) is a crucial event in the metastatisis of carcinoma. EMT enables epithelial tumors to invade into the mesenchymal submucosa. The key feature of EMT is E-cadherin down-regulation. Snail, Slug and Twist are well recognized transcriptional factors as repressors of E-cadherin expression. Recently, a direct link has been shown between the EMT and cancer stem cell(CSC). CSC has the ability to self-renew and continually sustain tumorigenesis. Cells undergoing an EMT could be the precursors to metastatic carcinoma, perhaps as CSCs. CD133 is recognized marker for gastrointestinal CSCs. Aim:To characterize expressions of Snail, Slug, Twist and CD133 in the metastatic esophageal adenocarcinoma(EAC) in Barretts esophagus(BE). Method:Formalin-fixed, paraffin embedded specimens of surgically treated early EAC were used. All slides were first reviewed by a well experienced GI pathologist, then were immunohistochemically stained for primary antibodies to Snail, Slug, Twist and CD133. We assessed if invading edges of tumor in the submucosa were stained for each antibody, and if there were differences of intensity of staining between in intramucosal cancer cells and in submucosal metastatic cells. The slides were scored by (1) intensity of staining (0=negative, 1=weak, 2=moderate, 3= intense);(2) percentage of epithelial cells staining (0=0-5%, 1=6-25%, 2=26-50%, 3=5175%, 4=76-100%);(3) percentage of invading cancer cells staining (same as epithelial cells). Cellular localization (nuclear, cytoplasm, cell surface) and uniformity (focal, general) were also assessed. Result:10 patients were analyzed. All four proteins were expressed in the cancers with uniform staining in both the mucosa and submucosa with Snail being more localized in the nucleus while Slug, Twist and CD133 were exclusively in the cytoplasm. Intensity of staining of metastatic cancer cells in submucosa was similar to those in the mucosa. Semi-quantitative scored analyses of Snail, Slug, Twist and CD133 for overall intensity were 2.5, 2.8, 1.9, and 2.4, respectively. For epithelial tumor cells, the scores were 4.0, 3.8, 3.3, and 3.2, respectively, whereas for invading metastatic cells, 4.0, 3.6, 3.1, and 3.6. Conclusion:This is the first report assessing the expression of known E-cadherin repressors, Snail, Slug, Twist and CSC marker, CD133 in the development of EAC in BE. All invading edges of tumor were found to abundantly express Snail, Slug, Twist and CD133 suggesting that unlike late staged cancers, early staged cancers are predominantly made of cells with metastatic potential which emphasizes the need to completely remove these early cancers.