Jennifer M. Kolb

Gastrointestinal bleeding with the new oral anticoagulants--defining the issues and the management strategies.

Gastrointestinal bleeding with the new oral anticoagulants – defining the issues and the management strategies -

Initial experience with a novel EUS-guided core biopsy needle (SharkCore): results of a large North American multicenter study.

Background and aims: The ability to safely and effectively obtain sufficient tissue for pathologic evaluation by using endoscopic ultrasound (EUS) guidance remains a challenge. Novel designs in EUS needles may provide for improved ability to obtain such core biopsies. The aim of this study was to evaluate the diagnostic yield of core biopsy specimens obtained using a novel EUS needle specifically designed to obtain core biopsies. Patients and methods: Multicenter retrospective review of all EUS-guided fine-needle biopsies obtained using a novel biopsy needle (SharkCore FNB needle, Medtronic, Dublin, Ireland). Data regarding patient demographics, lesion type/location, technical parameters, and diagnostic yield was obtained. Results: A total of 250 lesions were biopsied in 226 patients (Median age 66 years; 113 (50 %) male). Median size of all lesions (mm): 26 (2 – 150). Overall, a cytologic diagnosis was rendered in 81 % specimens with a median number of 3 passes. When rapid onsite cytologic evaluation (ROSE) was used, cytologic diagnostic yield was 126/149 (85 %) with a median number of 3 passes; without ROSE, cytologic diagnostic yield was 31/45 (69 %, P = 0.03) with a median number of 3 passes. Overall, a pathologic diagnosis was rendered in 130/147 (88 %) specimens with a median number of 2 passes. Pathologic diagnostic yield for specific lesion types: pancreas 70/81 (86 %), subepithelial lesion 13/15 (87 %), lymph node 26/28 (93 %). Ten patients (10/226, 4 %) experienced adverse events: 4 acute pancreatitis, 5 pain, 1 fever/cholangitis. Conclusions: Initial experience with a novel EUS core biopsy needle demonstrates excellent pathologic diagnostic yield with a minimum number of passes.

Major Gastrointestinal Bleeding Often Is Caused by Occult Malignancy in Patients Receiving Warfarin or Dabigatran to Prevent Stroke and Systemic Embolism From Atrial Fibrillation

Background & Aims Gastrointestinal (GI) bleeding in patients receiving anticoagulation agents can be caused by occult malignancies. We investigated the proportions and features of major GI bleeding (MGIB) events related to occult GI cancers in patients receiving anticoagulation therapy. Methods We analyzed data from the Randomized Evaluation of Long Term Anticoagulant Therapy study (conducted between December 2005 and March 2009 in 951 clinical centers in 44 countries worldwide), which compared the abilities of dabigatran vs warfarin to prevent stroke and systemic embolism in 18,113 patients with atrial fibrillation. Two blinded gastroenterologists independently reviewed source documents of MGIB events (n = 595) that occurred during the study period. We collected data on MGIB events caused by previously unidentified GI malignancies, and compared characteristics of MGIB events in patients who received dabigatran vs warfarin (primary end point), and in patients with bleeding from cancer, vs patients bleeding from a nonmalignant or unidentified source. Results Of 546 unique MGIB events, 44 (8.1%) were found to be from GI cancers (34 of 398 MGIB events in dabigatran users and 10 of 148 MGIB events in warfarin users; P = .60). Colorectal cancer accounted for 35 of 44 of all cancers identified. There were more colorectal cancer–associated MGIB events in the dabigatran group (30 of 34) than in the warfarin group (5 of 10) (P = .02), but more gastric cancer–associated MGIB events in the warfarin group (5 of 10) than in the dabigatran group (1 of 34) (P = .001). There were no differences in the short‐term outcomes of cancer‐related MGIB events in the dabigatran vs the warfarin group, but 75% of all cancer‐related MGIB events required at least 1 blood transfusion and the mean hospital stay was 10.1 days. Compared with MGIB events from a nonmalignant or unidentified source, MGIB from cancer occurred sooner (343.0 vs 223.1 d; P = .003), but the bleeding was more likely to be chronic (for >7 d) (27.3% vs 63.6%; P < .001). Conclusions In evaluating data from a study of the effects of anticoagulation therapy, we found approximately 1 of every 12 MGIB events to be related to an occult cancer. Approximately two thirds of cancer‐related MGIB presents with chronic bleeding, and morbidity, and resource utilization is high.

Does Better Specimen Orientation and a Simplified Grading System Promote More Reliable Histologic Interpretation of Serrated Colon Polyps in the Community Practice Setting? Results of a Nationwide Study.

Introduction: Colonoscopic surveillance guidelines for serrated polyps (SPs) are predicated upon the histologic characteristics of the index polyp. However, discrimination between SP subtypes [hyperplastic polyps vs. sessile serrated adenoma/polyps (SSA/P)] is often unreliable. Materials and Methods: We studied the impact of (1) a novel tissue orientation method, performed in the endoscopy laboratory, whereby polyps are flattened in a small paper envelope immediately after resection (modified protocol); and (2) 2012 consensus-modified criteria (CM-2012). These interventions were compared with conventional tissue-handling protocol (CP) and traditional 2008 World Health Organization criteria (WHO). Twenty blinded community pathologists from around the United States scored 100, independent, 0.5 to 2.0 cm, proximal colonic SPs randomly selected from a 2-site tissue section archive. We compared interobserver agreement and diagnostic grading. Results: Interobserver agreement was higher using CM-2012 than WHO criteria (absolute agreement: 13% vs. 4%, P<0.01; 75% agreement: 54% vs. 38%, P<0.01). Interobserver agreement was higher with the modified protocol than with CP (WHO absolute agreement: 6% vs. 2%, P>0.05; WHO 75% agreement: 46% vs. 30%, P>0.05, and CM-2012 absolute agreement: 20% vs. 6%, P=0.07; CM-2012 75% agreement: 66% vs. 42%, P=0.03). Compared with WHO, use of CM-2012 criteria resulted in fewer diagnoses of “indeterminate”; more diagnoses of SSA/P (P<0.01); and “upgraded” the diagnosis from hyperplastic polyps to SSA/P in approximately 7% of cases. These observations were independent of polyp size, patient gender, and study site. Conclusions: Simple enhancements to postresection SP handling and diagnostic criteria markedly improve interobserver agreement of SP diagnosis among nongastrointestinal community pathologists. This finding, if confirmed, has important implications for SP colonoscopy surveillance guidelines.

Implementation of New Knowledge, Technique, and Technology to Survey Barrett's Is Urgently Needed

Dear Sir: Corley et al are to be commended for studying the outcomes of endoscopic surveillance of Barrett’s esophagus (BE) in a large, community setting. They showed that surveillance does not decrease the risk of death from esophageal adenocarcinoma. The report is of significant concern because endoscopy is needed to visualize precancerous lesions and early cancers, which are curable. The description of the nonpolypoid colorectal neoplasms and their association with early cancers, however, made us wonder about the conclusions of Corley et al’s study. Is it possible that a similar nonpolypoid story exists in Barrett’s? Is it also possible that random biopsy is inadequate to detect Barrett’s with early cancers? Finally, is it possible that recognition of nonpolypoid Barrett’s high-grade dysplasia (HGD) and early cancers requires specialized training, technique, and newer technology? Indeed, it is now recognized that the harder-to-detect nonpolypoid lesion is the most frequent shape of Barrett’s early neoplasms. Pech et al prospectively studied 380 early Barrett’s neoplastic lesions detected by highresolution video endoscopy with 4-quadrant biopsies and/or chromoendoscopy using methylene blue or acetic acid. They showed 85% of the lesions appeared macroscopically as nonpolypoid lesions. Furthermore, of the high-grade intraepithelial lesions, 70% appeared completely flat. It is now also known that random four quadrant biopsies every 2 cm—the technique used by the physicians studied by Corley et al—is inadequate to detect Barrett’s with early neoplasms. The blind biopsy technique has significant sampling error and is fraught with misses, even when used by experienced endoscopists. Sharma et al compared the outcomes of high-definition white light endoscopy with Seattle biopsy protocol to narrow-band imaging with targeted biopsies for BE surveillance. Using high-definition white light endoscopy, they missed 2 (out of 3) cases of early cancers as HGD and 1 case of HGD as no intestinal metaplasia. Gastroenterologists require specialized training to be able to detect nonpolypoid colorectal neoplasms. The detection of Barrett’s HGD nonpolypoid early cancers may also require similar training. If insufficient training led to missed nonpolypoid BE early cancers during surveillance, then the potential mortality benefit would not be appreciated. Corley et al did not describe the endoscopist skill level at recognizing mucosal abnormalities in Barrett’s or whether they received additional training. Surveillance, defined in their study as 1 endoscopy within 3 years before cancer diagnosis, occurred in over half of fatal cases (55.3%). Lastly, image-enhanced endoscopy (IEE) seems to be necessary to detect BE with early neoplasia. Corley et al did not describe the use of IEE to increase the sensitivity to detect BE with early cancers. Qumseya et al provide an excellent comprehensive review of 14 studies (843 patients) comparing dye-based and equipment-based IEE with standard white light endoscopy with random biopsies. They showed that image enhancement increases the diagnostic yield of dysplasia or cancer by 34%, with similar benefit seen in dye-based and equipment-based IEE. Corley et al showed the inadequacy of current knowledge and endoscopy practice to survey BE; fortunately, there is room for improvement. We call for improved training for recognition of Barrett’s containing flat neoplasia and integration of new techniques and technology.

The Role of Endoscopic Hemostasis Therapy in Acute Lower Gastrointestinal Hemorrhage

Acute severe lower gastrointestinal bleeding (LGIB) can be treated by endoscopy safely and effectively. At present, the data on the efficacy of endoscopy in the treatment of patients with LGIB are still being collected. Thus, guidelines to manage patients with LGIB are still in development. Herein, based on the recent literature and their twenty year experience in their units in the US and in Japan, the authors summarize the role of endoscopic hemostasis therapy in acute severe LGIB with a focus on how to perform the hemostasis techniques.

Eltrombopag Use in Thrombocytopenia for Endoscopic Submucosal Dissection of a Gastric Carcinoid

Severe thrombocytopenia is a contraindication for therapeutic endoscopy due to the risk of bleeding. Platelet transfusions can temporarily increase platelet count, but are difficult to administer in the 2 weeks following endoscopic resection, during which the patient is at high risk for delayed bleeding. We present the use of a novel thrombopoietin receptor agonist, eltrombopag, to sustain platelet levels for the safe and complete endoscopic submucosal dissection of a gastric carcinoid in a patient with severe thrombocytopenia due to cirrhosis and idiopathic thrombocytopenic purpura. We performed complete and safe endoscopic removal of a gastric carcinoid after correcting the thrombocytopenia.