Sunguk Jang

Safety and efficacy of endoscopic spray cryotherapy for Barrett's dysplasia: results of the National Cryospray Registry

Retrospective series have shown the efficacy of endoscopic spray cryotherapy in eradicating high-grade dysplasia (HGD) in Barretts esophagus (BE); however, prospective data are lacking, and efficacy for low-grade dysplasia (LGD) is unclear. The aim of this study was to assess the efficacy and safety of spray cryotherapy in patients with LGD or HGD. A multicenter, prospective open-label registry enrolled patients with dysplastic BE. Spray cryotherapy was performed every 2-3 months until there was no endoscopic evidence of BE and no histological evidence of dysplasia, followed by surveillance endoscopies up to 2 years. Primary outcome measures were complete eradication of dysplasia (CE-D) and complete eradication of all intestinal metaplasia (CE-IM). Ninety-six subjects with Barretts dysplasia (67% HGD; 65% long-segment BE; mean length 4.5 cm) underwent 321 treatments (mean 3.3 per subject). Mean age was 67 years, 83% were male. Eighty patients (83%) completed treatment with follow-up endoscopy (mean duration 21 months). In patients with LGD, rate of CE-D was 91% (21/23) and rate of CE-IM was 61% (14/23). In HGD, CE-D rate was 81% (46/57) and CE-IM was 65% (37/57). In patients with short-segment BE (SSBE) with any dysplasia, CE-D was achieved in 97% (30/31) and CE-IM in 77% (24/31). There were no esophageal perforations or related deaths. One subject developed a stricture, which did not require dilation. One patient was hospitalized for bleeding in the setting of non-steroidal anti-inflammatory drug use. In the largest prospective cohort to date, data suggest endoscopic spray cryotherapy is a safe and effective modality for eradication of BE with LGD or HGD, particularly with SSBE.

Lipidomic profiling of bile in distinguishing benign from malignant biliary strictures: a single-blinded pilot study.

OBJECTIVES:Ascertaining the benign or malignant nature of biliary strictures may be challenging. Oxidized phospholipids (oxPLs) play an important role in tumor apoptosis and may be elevated in malignant biliary strictures. The objective of the study was to investigate whether oxPLs are enriched in the bile of malignant biliary strictures.METHODS:In this prospective single-blinded study, bile was obtained from 46 patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis and management of biliary strictures, including 17 with pancreatic cancer, 6 with primary sclerosing cholangitis (PSC), 8 with cholangiocarcinoma (CCA), and 15 with benign biliary conditions (sphincter of Oddi dysfunction (SOD) or choledocholithiasis or chronic pancreatitis). Bile samples were stored under conditions to minimize artificial oxidation. Levels of 10 different oxPLs were measured blindly by one investigator using liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS).RESULTS:Of the 10 different phospholipids measured, the levels of two phosphatidylcholines (PCs; i.e., ON-PC and S-PC) were elevated in CCA as compared with other biliary strictures. Among these, ON-PC was most useful and a cutoff value of 6,020.1 nm distinguished CCA from other biliary strictures with a sensitivity and specificity of 85.7% and 80.3%, respectively (area under curve (AUC) 0.86). A combination of ON-PC and S-PC at a cutoff value of 6,032.2 nm distinguished CCA from other biliary strictures with a sensitivity and specificity of (100% and 83.3%, respectively (AUC 0.91).CONCLUSIONS:The measurement of specific oxPL products may help to distinguish CCA from other biliary strictures. Measurement of these products in bile may enhance the endoscopic diagnosis of indeterminate biliary strictures.

Volatile organic compounds in bile can diagnose malignant biliary strictures in the setting of pancreatic cancer: a preliminary observation

BACKGROUND Ascertaining the nature of biliary strictures is challenging. The role of volatile organic compounds (VOCs) in bile in determining the cause of biliary strictures is not known. OBJECTIVE To identify potential VOCs in the headspaces (gas above the sample) of bile in patients with malignant biliary strictures from pancreatic cancer. DESIGN Prospective cross-sectional study. SETTING Referral center. PATIENTS Prospective study in which bile was aspirated in 96 patients undergoing ERCP for benign and malignant conditions. MAIN OUTCOME MEASUREMENTS Selected ion flow tube mass spectrometry (VOICE200R SIFT-MS instrument; Syft Technologies Ltd, Christchurch, New Zealand) was used to analyze the headspace and to build a predictive model for pancreatic cancer. RESULTS The headspaces from 96 bile samples were analyzed, including 24 from patients with pancreatic cancer and 72 from patients with benign biliary conditions. The concentrations of 6 compounds (acetaldehyde, acetone, benzene, carbon disulfide, pentane, and trimethylamine [TMA]) were increased in patients with pancreatic cancer compared with controls (P < .05). By using receiver-operating characteristic curve analysis, we developed a model for the diagnosis of pancreatic cancer based on the levels of TMA, acetone, isoprene, dimethyl sulfide, and acetaldehyde. The model [10.94 + 1.8229* log (acetaldehyde) + 0.7600* log (acetone) - 1.1746* log (dimethyl sulfide) + 1.0901* log (isoprene) - 2.1401 * log (trimethylamine) ≥ 10] identified the patients with pancreatic cancer (area under the curve = 0.85), with 83.3% sensitivity and 81.9% specificity. LIMITATIONS Sample size. CONCLUSIONS The measurement of biliary fluid VOCs may help to distinguish malignant from benign biliary strictures. Further studies are warranted to validate these observations. (Clinical Trial Registration Number NCT01565460.).

Video-based supervision for training of endoscopic submucosal dissection

BACKGROUND AND STUDY AIM Adoption of endoscopic submucosal dissection (ESD) in Western countries has been limited by the difficulty in learning the procedure. Although a porcine model is commonly used for ESD training, without expert guidance the procedure is difficult to master. The availability of Western ESD experts is limited, and expert supervision through a remote video-based system may be a practical method for Western endoscopists to learn ESD. The aim of this study was to assess the value of video-based remote evaluation in supervising ESD training. METHODS Two Western endoscopists performed ESD training procedures in an ex vivo porcine model at least every 2 weeks until competency was achieved. Competency was defined as consistent en bloc resection of a 3-cm area within 30 minutes, and without perforation, using the proper ESD technique. A Japanese ESD expert at the National Cancer Center in Tokyo, Japan, analyzed the training videos, scored them, and provided written feedback for improvement after each training session and before the trainees next training session. RESULTS Endoscopist 1 reached competency at 23 procedures and endoscopist 2 reached competency at 25 procedures. No difference in skill improvement between the two endoscopists was noted. One trainee subsequently completed eight ESD procedures in patients, with curative en bloc resection and no complications. CONCLUSION A standardized ESD training program including educational presentations/videos and preclinical animal training with expert guidance through a remote video-based system is an effective tool for learning ESD techniques in preparation for performing the procedure in humans.

Digital, Catheter-Based Single-Operator Cholangiopancreatoscopes: Can Pancreatoscopy and Cholangioscopy Become Routine Procedures?

Working length 214cm Accessory channel diameter 1.2mm (3.6 French) outine visualization of the pancreatobiliary ductal Rsystem is probably the last endoscopic frontier in the alimentary tract. Although miniature endoscopes for insertion into the biliary or pancreatic ducts have been around for many years, cholangioscopy and pancreatoscopy are yet to become routine procedures. Performance of these procedures has remained mostly confined to large academic medical centers because of a variety of factors including lack of access to appropriate equipment, lack of expertise, and lack of user-friendliness of currently available endoscopes. The birth of catheter-based cholangiopancreatoscopes in the last decade by introduction of the Spyglass Direct Visualization System (DVS) (Boston Scientific, Natick, MA) led to more widespread use of cholangiopancreatoscopy. However, due to less that optimal image quality, the initial enthusiasm for routine use of this device soon faded. A new version of this catheter-based system with improved digital image has now been released. This article and the accompanying video present the use of this new technology in the pancreatobiliary ductal system and illustrate how it may lead to more widespread use of cholangiopancreatoscopy.

Utility of urgent colonoscopy in acute lower gastro-intestinal bleeding: a single-center experience

Background. The role of urgent colonoscopy in lower gastro-intestinal bleeding (LGIB) remains controversial. Over the last two decades, a number of studies have indicated that urgent colonoscopy may facilitate the identification and treatment of bleeding lesions; however, studies comparing this approach to elective colonoscopy for LGIB are limited. Aims. To determine the utility and assess the outcome of urgent colonoscopy as the initial test for patients admitted to the intensive care unit (ICU) with acute LGIB. Methods. Consecutive patients who underwent colonoscopy at our institution for the initial evaluation of acute LGIB between January 2011 and January 2012 were analysed retrospectively. Patients were grouped into urgent vs. elective colonoscopy, depending on the timing of colonoscopy after admission to the ICU. Urgent colonoscopy was defined as being performed within 24 hours of admission and those performed later than 24 hours were considered elective. Outcomes included length of hospital stay, early re-bleeding rates, and the need for additional diagnostic or therapeutic interventions. Multivariable logistic regression analysis was performed to identify factors associated with increased transfusion requirements. Results. Fifty-seven patients underwent colonoscopy for the evaluation of suspected LGIB, 24 of which were urgent. There was no significant difference in patient demographics, co-morbidities, or medications between the two groups. Patients who underwent urgent colonoscopy were more likely to present with hemodynamic instability (P = 0.019) and require blood transfusions (P = 0.003). No significant differences in length of hospital stay, re-bleeding rates, or the need for additional diagnostic or therapeutic interventions were found. Patients requiring blood transfusions (n = 27) were more likely to be female (P = 0.016) and diabetics (P = 0.015). Fourteen patients re-bled at a median of 2 days after index colonoscopy. Those with hemodynamic instability were more likely to re-bleed [HR 3.8 (CI 1.06–13.7)], undergo angiography [HR 9.8 (CI 1.8–54.1)], require surgery [HR 13.5 (CI 3.2–56.5)], and had an increased length of hospital stay [HR 1.1 (1.05–1.2)]. Conclusion: The use of urgent colonoscopy, as an initial approach to investigate acute LGIB, did not result in significant differences in length of ICU stay, re-bleeding rates, the need for additional diagnostic or therapeutic interventions, or 30-day mortality compared with elective colonoscopy. In a pre-specified subgroup analysis, patients with hemodynamic instability were more likely to re-bleed after index colonoscopy, to require additional interventions (angiography or surgery) and had increased length of hospital stay.

Safety and efficacy of endoscopic spray cryotherapy for esophageal cancer

Although surgery is traditionally the standard of care for esophageal cancer, esophagectomy carries significant morbidity. Alternative endoscopic therapies are needed for patients who are not candidates for conventional treatment. The objective of this study is to assess the safety, efficacy, and tolerability of spray cryotherapy of esophageal adenocarcinoma. This study includes patients with esophageal adenocarcinoma who had failed or were not candidates for conventional therapy enrolled retrospectively and prospectively in an open-label registry and patients in a retrospective cohort from 11 academic and community practices. Endoscopic spray cryotherapy was performed until biopsy proven local tumor eradication or until treatment was halted due to progression of disease, patient withdrawal or comorbidities. Eighty-eight patients with esophageal adenocarcinoma (median age 76, 80.7% male, mean length 5.1 cm) underwent 359 treatments (mean 4.4 per patient). Tumor stages included 39 with T1a, 25 with T1b, 9 with unspecified T1, and 15 with T2. Eighty-six patients completed treatment with complete response of intraluminal disease in 55.8%, including complete response in 76.3% for T1a, 45.8% for T1b, 66.2% for all T1, and 6.7% for T2. Mean follow-up was 18.4 months. There were no deaths or perforations related to spray cryotherapy. Strictures developed in 12 of 88 patients (13.6%) but were present before spray cryotherapy in 3 of 12. This study suggests that endoscopic spray cryotherapy is a safe, well-tolerated, and effective treatment option for early esophageal adenocarcinoma.

Novel Therapeutic Strategies in the Management of Non-Variceal Upper Gastrointestinal Bleeding

Non-variceal upper gastrointestinal bleeding, the most common etiology of which is peptic ulcer disease, remains a persistent challenge despite a reduction in both its incidence and mortality. Both pharmacologic and endoscopic techniques have been developed to achieve hemostasis, with varying degrees of success. Among the pharmacologic therapies, proton pump inhibitors remain the mainstay of treatment, as they reduce the risk of rebleeding and requirement for recurrent endoscopic evaluation. Tranexamic acid, a derivative of the amino acid lysine, is an antifibrinolytic agent whose role requires further investigation before application. Endoscopically delivered pharmacotherapy, including Hemospray (Cook Medical), EndoClot (EndoClot Plus Inc.), and Ankaferd Blood Stopper (Ankaferd Health Products), in addition to standard epinephrine, show promise in this regard, although their mechanisms of action require further investigation. Non-pharmacologic endoscopic techniques use one of the following two methods to achieve hemostasis: ablation or mechanical tamponade, which may involve using endoscopic clips, cautery, argon plasma coagulation, over-the-scope clipping devices, radiofrequency ablation, and cryotherapy. This review aimed to highlight these novel and fundamental hemostatic strategies and the research supporting their efficacy.

Cryotherapy and Radiofrequency Ablation for Eradication of Barrett’s Esophagus with Dysplasia or Intramucosal Cancer

Background and AimsEndoscopic ablation therapy has become the mainstay of treatment of Barrett’s associated dysplasia and intramucosal cancer (IMC). The widely available techniques for ablation are radiofrequency ablation (RFA) and cryotherapy. Our aim was to compare eradication rates of metaplasia and dysplasia with both these modalities.Patients and MethodsRetrospective review of prospectively collected database of patients who underwent endoscopic therapy for Barrett’s dysplasia or IMC from 2006 to 2011 was performed. Demographic features, comorbidities, and endoscopic data including length of Barrett’s segment, hiatal hernia size, interventions during the endoscopy and histological results were reviewed.ResultsAmong 154 patients included, 73 patients were in the RFA and 81 patients were in the cryotherapy group. There was complete eradication of intestinal metaplasia (CE-IM) in 81 (52.6%), complete eradication of dysplasia (CE-D) in 133 (86.4%), and persistent dysplasia or cancer in 19 patients (12.3%). Compared to RFA, cryotherapy patients were found to be older and less likely to have undergone endoscopic mucosal resection. On multivariate analysis, patients who underwent RFA had a threefold higher odds of having CE-IM than those who underwent cryotherapy (odds ratio [OR] 2.9, 95% confidence interval [CI] 1.4–6.0, p = 0.004), but CE-D were similar between the two groups (OR 1.7, 95% CI 0.66–4.3, p = 0.28).ConclusionsEndoscopic therapy is highly effective in eradication of Barrett’s associated neoplasia. Patients who underwent cryotherapy were equally likely to achieve CE-D but not CE-IM than patients who underwent RFA. Patient characteristics and preferences may effect choice of treatment selection and outcomes.

Aspirin Use Is Associated With Reduced Risk of Occlusion of Metallic Biliary Stents.

BACKGROUND & AIMS Biliary self‐expandable metallic stents (SEMSs) are widely used to treat malignant and benign conditions of bile duct. Despite their lower rate of occlusion and longer patency than plastic stents, SEMSs still have significant rates of occlusion. We aimed to identify factors associated with occlusion of biliary SEMS. METHODS We performed a retrospective study of consecutive patients who underwent endoscopic retrograde cholangiopancreatography with biliary SEMS placement at the Cleveland Clinic Foundation from March 2011 to April 2016. We collected clinical, endoscopic, radiographic, and surgical data from medical records and performed multivariable analysis to identify factors associated with SEMS patency. Subjects that received minimal daily dose of 81 mg at the time of stent placement until the end of follow‐up were assigned to the aspirin exposure group (n = 157) and compared with subjects with no aspirin exposure (n = 436). Patients were followed for a median 81 days. The primary outcome was hazard ratio for SEMS occlusion requiring an interventional maneuver for biliary drainage. RESULTS We analyzed data from patients receiving a total of 593 biliary SEMS for treatment of malignant and benign conditions of bile duct. Stent occlusion was observed in 126 cases. Multivariable analysis showed that daily use of aspirin (81 mg or more) was associated with 51% lower risk of stent occlusion than in patients without daily use of aspirin (hazard ratio, 0.49; 95% confidence interval, 0.32–0.75). Furthermore, SEMSs had a longer duration of stent patency in patients in the aspirin exposure group (434.4 days) versus the no aspirin exposure group (339.9 days) (P < .001). Stricture location limited to distal bile duct (in comparison with strictures involving proximal extrahepatic duct) was associated with lower risk of stent occlusion (hazard ratio, 0.39; 95% CI, 0.22–0.71). CONCLUSIONS In an analysis of a large cohort of subjects with metallic biliary stent placement for malignant and benign conditions of bile duct, we associated daily use of aspirin (81 mg or more) with lower risk of SEMS occlusion and longer stent patency duration.