Paul J. Belletrutti

Endoscopic Management of Gastric Varices: Efficacy and Outcomes of Gluing with N-Butyl-2-Cyanoacrylate in a North American Patient Population

BACKGROUND: Gastric variceal bleeding is associated with significant morbidity and mortality in patients with portal hypertension. Outside of North America, gastric variceal injection of N-butyl-2-cyanoacrylate has been shown to be safe and effective. The majority of studies on this mode of therapy are in Asian populations in which the etiology of portal hypertension differs from North America.

Incremental benefit of preoperative EUS for the detection of pancreatic neuroendocrine tumors: a meta-analysis

BACKGROUND Current guidelines recommend CT scan or magnetic resonance imaging as the initial imaging modalities for the work-up of suspected pancreatic neuroendocrine tumors (PNETs). OBJECTIVE To determine the incremental benefit of preoperative EUS (IBEUS) for the detection of suspected PNETs after other investigative modalities have been attempted. DESIGN This systematic review searched MEDLINE, EMBASE, bibliographies of included articles, and conference proceedings for studies reporting original data regarding the preoperative detection of PNETs. Pooled IBEUS was calculated by using random effects models. Heterogeneity was explored by using stratified meta-analysis and meta-regression. Evidence of small-study effects was assessed by using funnel plots and the Begg test. PATIENTS Patients with suspected PNETs. INTERVENTIONS EUS evaluation. MAIN OUTCOME MEASUREMENTS The pooled IBEUS for the detection of PNETs after CT scan, with or without additional investigative modalities. RESULTS Among 4505 citations identified, we included 17 cohort studies (612 patients). EUS identified PNETs in 97% of cases. Improved PNET identification with EUS was observed in all of the studies. After adjusting for small-study effects, meta-analysis showed that EUS alone could identify PNETs in approximately 1 in 4 patients (adjusted IBEUS 26%; 95% confidence interval, 17%-37%). The pooled IBEUS varied based on the study design, study size, type of CT scan used, and the number of modalities used prior to EUS. LIMITATIONS The majority of included studies were retrospective. Small-study effects were observed. CONCLUSION Preoperative EUS is associated with an increase in PNET detection after other modalities are attempted.

Management of anticoagulants and antiplatelet agents in elective endoscopy: Weighing the risks and benefits

As the indications for endoscopic diagnosis and therapy continue to expand, an increasing number of patients receiving anticoagulants and antiplatelet agents will be encountered in gastroenterology practice. The management of these patients at the time of elective endoscopy can be challenging. Furthermore, this population has not been well studied, and thus, current guidelines are largely based on expert opinion. Ultimately, the risk of bleeding must be weighed against the risk of thromboembolic events when deciding whether to reverse anticoagulation or discontinue antiplatelet therapy before endoscopy. The present paper discusses three scenarios to highlight the authors’ own clinical practice, and reviews the current published guidelines on this topic.

The incremental benefit of EUS for identifying unresectable disease among adults with pancreatic adenocarcinoma: A meta-analysis

Background and study aims It is unclear to what extent EUS influences the surgical management of patients with pancreatic adenocarcinoma. This systematic review sought to determine if EUS evaluation improves the identification of unresectable disease among adults with pancreatic adenocarcinoma. Patients and methods We searched MEDLINE, EMBASE, bibliographies of included articles and conference proceedings for studies reporting original data regarding surgical management and/or survival among patients with pancreatic adenocarcinoma, from inception to January 7th 2017. Our main outcome was the incremental benefit of EUS for the identification of unresectable disease (IBEUS). The pooled IBEUS were calculated using random effects models. Heterogeneity was explored using stratified meta-analysis and meta-regression. Results Among 4,903 citations identified, we included 8 cohort studies (study periods from 1992 to 2007) that examined the identification of unresectable disease (n = 795). Random effects meta-analysis suggested that EUS alone identified unresectable disease in 19% of patients (95% confidence interval [CI], 10–33%). Among those studies that considered portal or mesenteric vein invasion as potentially resectable, EUS alone was able to identify unresectable disease in 14% of patients (95% CI 8–24%) after a CT scan was performed. Limitations The majority of the included studies were retrospective. Conclusions EUS evaluation is associated with increased identification of unresectable disease among adults with pancreatic adenocarcinoma.

Duodenal ulcers are a major cause of gastrointestinal bleeding after cardiac surgery

Objective: To determine the incidence of gastrointestinal (GI) bleeding in patients after cardiac surgery, assess the perioperative risk factors, and determine the type of GI tract pathology associated with bleeding events. Methods: At a tertiary referral hospital, all cardiac surgery patients having a postoperative GI bleed from April 2002 to March 2012 were identified. To determine bleeding etiology, only patients requiring endoscopy were included in the analysis. By retrospective review of 3 prospectively maintained databases, the incidence and independent predictors of GI bleeding, as well as endoscopic findings, were determined. Results: Ninety‐one GI bleeding events that required endoscopy were identified in 9017 patients. Those that bled were aged 71 ± 12 years, and 76% were men. Sixty‐three percent of these patients had valve surgery and 37% had an isolated coronary artery bypass grafting. The overall incidence of GI bleeding was 1.01%, with an upper GI source accounting for 78%. Endoscopy data found a duodenal ulcer as the bleeding source in 71%, whereas stress gastritis accounted for 8%. Preoperative risk factors for bleeding included age ≥70 years, ejection fraction <35%, congestive heart failure, cerebrovascular disease, chronic kidney disease, and gastrointestinal disease. A preoperative history of atrial fibrillation and anticoagulation with Coumadin also was associated with bleeding. Patients that bled had a 30‐day mortality rate of 8.8%, which was significantly greater than patients who did not bleed (4.3%; P = .03). Conclusions: Clinical variables can be used to identify patients at high risk for GI bleeding after cardiac surgery. When GI bleeding occurs, the most common cause is duodenal ulceration, which has an association with Helicobacter pylori infection. These findings may provide an opportunity to initiate preoperative preventative strategies.

Diagnostic yield of small histological cores obtained with a new EUS-guided fine needle biopsy system

BackgroundAs endoscopic ultrasound-guided tissue acquisition techniques evolve, there is increasing interest in obtaining optimal histological samples to improve diagnostic accuracy. In this study, we aimed to assess the tissue acquisition success rate and test performance characteristics of a novel endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) system.MethodsWe performed a retrospective review of consecutive patients undergoing EUS-guided tissue sampling of solid lesions using the SharkCore fine needle system in a tertiary referral facility. At least two passes were submitted for histology and diagnostic accuracy was evaluated. Comparison standard was based on final surgical pathology or minimum six-month clinical follow-up.ResultsSeventy-nine patients underwent 85 EUS-FNB procedures. Of the 85 histology specimens, 78 (91.7%) were adequate for diagnostic examination (includes six atypical/suspicious for adenocarcinoma). The sensitivity, specificity, and accuracy for diagnosis of malignancy with FNB were 87.1, 100, and 90.6%, respectively. Cytology was simultaneously sent in 43 cases with the same needle in addition to histology. Out of the 14 cases that were atypical/suspicious for adenocarcinoma or non-diagnostic on cytology, 11 cases (78.6%) achieved definite diagnoses on histology. The overall sensitivity, specificity, and accuracy for diagnosis of malignancy combining histology and cytology were 90.3, 100, and 92.9%, respectively. No complications were reported after the procedures.ConclusionIn this initial experience with a new EUS-guided FNB system, obtaining small cores to submit for histological analysis was safe, technically feasible, and highly accurate. Most of the histological cores obtained via FNB yielded a definite diagnosis including in cases with equivocal cytomorphology. Further study is required to confirm these findings.

An Unusual Case of Pancreatic Metastasis from Squamous Cell Carcinoma of the Lung Diagnosed by EUS-Guided Fine Needle Biopsy

We report a case of a 70-year-old man who presented with abdominal pain and weight loss, with initial imaging showing simultaneous mass lesions in the pancreas and lungs along with extensive lymphadenopathy in the thorax up to the left supraclavicular region. Core biopsies of the left supraclavicular lymph node showed squamous cell carcinoma, which required differentiation between secondary and primary pancreatic neoplasms. Endoscopic ultrasound-guided sampling using a novel fine needle biopsy system was key to making a definite histological diagnosis and determining the best treatment plan.

Incremental Benefit of Preoperative Endoscopic Ultrasound for the Detection of Pancreatic Neuroendocrine Tumors : A Meta-Analysis

Multidisciplinary Team (MDT) in Neuroendocrine Tumor (NET) Management : Results from the First Global NET Patient (pt) Survey - A Collaboration between the International Neuroendocrine Cancer Alliance (INCA) and Novartis PharmaceuticalsRadioembolization with 90Y-Labelled Resin Microspheres in Patients with Liver Metastases from Neuroendocrine TumorsIncremental Benefit of Preoperative Endoscopic Ultrasound for the Detection of Pancreatic Neuroendocrine Tumors : A Meta-AnalysisSmall intestinal neuroendocrine tumors (SI-NETs) originate from serotonin-producing enterochromaffin (EC) cells in the intestinal mucosa. Somatostatin analogs (SSAs) are mainly used to control hormonal secretion and tumor growth. However, the molecular mechanisms leading to the control of SI-NETs are unknown. Although microRNAs (miRNAs) are post transcriptional regulators deeply studied in many cancers, are not well-defined in SI-NETs. We adopted a two-pronged strategy to investigate SSAs and miRNAs: first, to provide novel insights into how SSAs control NET cells, and second, to identify an exclusive SI-NET miRNA expression, and investigate the biological functions of miRNA targets.To accomplish the first aim, we treated CNDT2.5 cells with octreotide for 16 months. Affymetrix microarray was performed to study gene variation of CNDT2.5 cells in the presence or absence of octreotide. The study revealed that octreotide induces six genes, ANXA1, ARHGAP18, EMP1, GDF15, TGFBR2 and TNFSF15.To accomplish the second aim, SI-NET tissue specimens were used to run genome-wide Affymetrix miRNA arrays. The expression of five miRNAs (miR-96, -182, -183, -196a and -200a) was significantly upregulated in laser capture microdissected (LCM) tumor cells versus LCM normal EC cells, whereas the expression of four miRNAs (miR-31, -129-5p, -133a and -215) was significantly downregulated in LCM tumor cells. We also detected nine tissue miRNAs in serum samples, showing that the expression of five miRNAs is significantly increased in SSA treated patients versus untreated patients. Conversely, SSAs do not change miRNA expression of four low expressed miRNAs. Silencing miR-196a expression was used to investigate functional activities in NET cells. This experimental approach showed that four miR-196a target genes, HOXA9, HOXB7, LRP4 and RSPO2, are significantly upregulated in silenced miR-196a NET cells.In conclusion, ANXA1, ARHGAP18, EMP1, GDF15, TGFBR2 and TNFSF15 genes might regulate cell growth and differentiation in NET cells, and play a role in an innovative octreotide signaling pathway. The global SI-NET miRNA profiling revealed that nine selected miRNAs might be involved in tumorigenesis, and play a potential role as novel markers for follow-up. Indeed, silencing miR-196a demonstrated that HOXA9, HOXB7, LRP4 and RSPO2 genes are upregulated at both transcriptional and translational levels.

Endoscopic Management of Gastric Varices; Efficacy and Outcomes of Gluing with N-Butyl-2-Cyanoacrylate

BACKGROUND Gastric variceal bleeding is associated with significant morbidity and mortality in patients with portal hypertension. Outside of North America, gastric variceal injection of N-butyl-2-cyanoacrylate has been shown to be safe and effective. The majority of studies on this mode of therapy are in Asian populations in which the etiology of portal hypertension differs from North America. AIM To assess the safety and efficacy of gastric variceal glue injection in a North American population. METHODS Consecutive patients that underwent glue injection of gastric varices in the Calgary Health Region from 2001 to 2006 were assessed. RESULTS Thirty-four patients (19 men, 15 women) underwent a total of 47 separate gluing procedures. Of those presenting with active bleeding at endoscopy, immediate hemostasis was achieved in 93.8% of patients. Rebleeding within 48 h of gluing was observed after four procedures. Gastric varices were eradicated in 84.0% of cases. Complications included superior mesenteric vein thrombosis in one patient. Twenty-eight (82.4%) patients were alive at the end of follow-up. The treatment failure-related mortality rate was 2.1%. CONCLUSIONS The present study is one of the few to assess the role of gastric variceal gluing in a North American population. Glue injection with cyanoacrylate is safe and effective in the treatment of bleeding gastric varices.