Mouen A. Khashab

The management of antithrombotic agents for patients undergoing GI endoscopy.

Ruben D. Acosta, MD, Neena S. Abraham, MD, MSCE, FASGE (invited content expert, ad-hoc member), Vinay Chandrasekhara, MD, Krishnavel V. Chathadi, MD, Dayna S. Early, MD, FASGE, Mohamad A. Eloubeidi, MD, MHS, FASGE, John A. Evans, MD, Ashley L. Faulx, MD, FASGE, Deborah A. Fisher, MD, MHS, FASGE, Lisa Fonkalsrud, BSN, RN, CGRN, Joo Ha Hwang, MD, PhD, FASGE, Mouen A. Khashab, MD, Jenifer R. Lightdale, MD, MPH, FASGE, V. Raman Muthusamy, MD, FASGE, Shabana F. Pasha, MD, John R. Saltzman, MD, FASGE, Aasma Shaukat, MD, MPH, FASGE, Amandeep K. Shergill, MD, Amy Wang, MD, Brooks D. Cash, MD, FASGE, previous Committee Chair, John M. DeWitt, MD, FASGE, Chair

EUS is still superior to multidetector computerized tomography for detection of pancreatic neuroendocrine tumors

BACKGROUND The role of EUS for detection of pancreatic neuroendocrine tumors (PNETs) is not clearly defined in institutions that use multidetector CT for pancreatic imaging. OBJECTIVE The aims of this study were to (1) compare the detection rates of EUS and CT by type and size of PNET and calculate the incremental benefit of EUS over CT, (2) evaluate the CT detection rate for PNETs adjusted for improved CT technology over time, and (3) determine the factors associated with CT-negative PNETs. DESIGN Retrospective single-center cohort study. SETTING Johns Hopkins Hospital. PATIENTS Patients with pathologically proven PNETs with preoperative CT. Incidentally found PNETs (resection specimens) and those without Johns Hopkins Hospital CT imaging were excluded. MAIN OUTCOME MEASUREMENT Detection rates of CT and EUS were compared by using pathology as the reference standard. RESULTS In 217 patients (with 231 PNETs) studied, CT detected 84% of tumors (54.3% of insulinomas). The sensitivity of CT for the detection of PNETs significantly increased with improvement in CT technology (P = .02; χ(2) for trend). CT was more likely to miss lesions <2 cm (P = .005) and insulinomas (P < .0001). In 56 patients who had both CT and EUS, the sensitivity of EUS was greater than CT (91.7% vs 63.3%; P = .0002), particularly for insulinomas (84.2% vs 31.6%; P = .001). EUS detected 20 of 22 CT-negative tumors (91%). LIMITATIONS Retrospective nonrandomized design and referral bias. CONCLUSIONS The detection rate of CT has significantly improved over time. CT-negative tumors are small and more likely to be insulinomas. A sequential approach of CT followed by EUS can detect most PNETs. EUS is a more sensitive initial test for the detection of suspected insulinomas.

Bowel preparation before colonoscopy

This is one of a series of documents discussing the use of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy prepared this document that updates a previously issued consensus statement and a technology status evaluation report on this topic. In preparing this guideline, a search of the medical literature was performed by using PubMed between January 1975 and March 2014 by using the search terms “colonoscopy,” “bowel preparation,” “intestines,” and “preparation.” Additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants. When limited or no data exist from well-designed prospective trials, emphasis is given to results from large series and reports from recognized experts. Recommendations for appropriate use of endoscopy are based on a critical review of the available data and expert consensus at the time that the documents are drafted. Further controlled clinical studies may be needed to clarify aspects of recommendations contained in this document. This document may be revised as necessary to account for changes in technology, new data, or other aspects of clinical practice. The recommendations were based on reviewed studies and were graded on the strength of the supporting evidence (Table 1). The strength of individual recommendations is based both on the aggregate evidence quality and an assessment of the anticipated benefits and harms. Weaker recommendations are indicated by phrases such as “we suggest,” whereas stronger recommendations are typically stated as “we recommend.” This guideline is intended to be an educational device to provide information that may assist endoscopists in providing care to patients. It is not a rule and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment. Clinical decisions in any particular case involve a complex analysis of the patient’s condition and available courses of action. Therefore, clinical considerations may lead an endoscopist to take a course of action that varies from these recommendations and suggestions.

A comparative evaluation of single-balloon enteroscopy and spiral enteroscopy for patients with mid-gut disorders.

BACKGROUND Single-balloon enteroscopy (SBE) and spiral enteroscopy (SE) are recently described device-assisted techniques in endoluminal evaluation of the small bowel. No studies comparing SBE and SE in patients with suspected small-bowel disorders have previously been reported. OBJECTIVE The aims of this study were to compare SBE and SE in terms of diagnostic yield, procedure time, depth of maximal insertion, and complications. DESIGN Retrospective cohort study. SETTING Tertiary-care referral center. PATIENTS A retrospective analysis was performed on all patients at our institution undergoing anterograde SBE or SE between 2007 and 2009. Patients with altered anatomy or prior small-bowel surgery were excluded. INTERVENTION Deep enteroscopy. MAIN OUTCOME MEASUREMENT Diagnostic yield. RESULTS During the study period, 92 patients underwent 105 procedures (52 SBE, 53 SE). The most common indication for small-bowel endoscopy was obscure GI bleeding (n = 42). The diagnostic yield was not statistically different between SBE and SE (59.6% and 43.4%, respectively, P = .12). The overall diagnostic yield in patients with obscure GI bleeding was 67%. There was no significant difference between mean SBE and SE procedure times (53 minutes [range 15-99 minutes] vs 47 minutes [range 20-125 minutes], respectively; P = .2). The mean depth of maximal insertion beyond the ligament of Treitz for SE was significantly higher than that for SBE (301 cm [range 175-400 cm] vs 222 cm [range 110-400 cm], respectively; P < .001). Perforation occurred in one SBE procedure. LIMITATIONS Retrospective design and nonstandardized gas insufflation. CONCLUSION This is the first report comparing SE and SBE. Although SE yielded greater depth of maximal insertion than SBE, both techniques had similar diagnostic yields and procedure times. In addition, both techniques were safe and were particularly useful in patients with obscure GI bleeding.

A Systematic Review of Solid-Pseudopapillary Neoplasms: Are these rare lesions?

Objective The aim of the study was to determine if there had been any change in the number of solid-pseudopapillary neoplasm (SPN) cases detected and their evaluation or management over time. Methods A systematic review of SPN was performed of all articles published in English in PubMed and Scopus. Results A total of 2744 patients with SPN were identified in 484 studies published between 1961 and 2012; 87.8% of the cases were reported between 2000 and 2012. A total of 2408 (87.8%) were females, and the mean age was 28.5 (SD, 13.7) years. The most common symptom was abdominal pain in 63.6% of the cases and incidentally detected in 38.1% of the cases. There were 2285 patients who underwent pancreatic resection. The mean tumor size was 8.6 (SD, 4.3) cm. Follow-up was reported for 1952 (90.5%) patients, with a mean follow-up of 36.1 (SD, 32.8) months. Disease-free survival was documented in 1866 (95.6%) patients with recurrence in 86 (4.4%) patients; the median time to recurrence was 50.5 months. Conclusions The number of SPNs reported in the literature has seen a 7-fold increase in the number of cases reported since 2000 compared with before. Solid-pseudopapillary neoplasms continue to be primarily found in young women and present with nonspecific symptoms. Surgery remains the mainstay of treatment with an excellent long-term prognosis.

Long non-coding RNA HNF1A-AS1 regulates proliferation and migration in oesophageal adenocarcinoma cells

Objectives Long non-coding RNAs (lncRNA) have been shown to play important roles in the development and progression of cancer. However, functional lncRNAs and their downstream mechanisms are largely unknown in the molecular pathogenesis of oesophageal adenocarcinoma (EAC) and its progression. Design lncRNAs that are abnormally upregulated in EACs were identified by RNA-sequencing analysis, followed by quantitative RT-PCR (qRTPCR) validation using tissues from 25 EAC patients. Cell biological assays in combination with small interfering RNA-mediated knockdown were performed in order to probe the functional relevance of these lncRNAs. Results We discovered that a lncRNA, HNF1A-AS1, is markedly upregulated in human primary EACs relative to their corresponding normal oesophageal tissues (mean fold change 10.6, p<0.01). We further discovered that HNF1A-AS1 knockdown significantly inhibited cell proliferation and anchorage-independent growth, suppressed S-phase entry, and inhibited cell migration and invasion in multiple in vitro EAC models (p<0.05). A gene ontological analysis revealed that HNF1A-AS1 knockdown preferentially affected genes that are linked to assembly of chromatin and the nucleosome, a mechanism essential to cell cycle progression. The well known cancer-related lncRNA, H19, was the gene most markedly inhibited by HNF1A-AS1 knockdown. Consistent to this finding, there was a significant positive correlation between HNF1A-AS1 and H19 expression in primary EACs (p<0.01). Conclusions We have discovered abnormal upregulation of a lncRNA, HNF1A-AS1, in human EAC. Our findings suggest that dysregulation of HNF1A-AS1 participates in oesophageal tumorigenesis, and that this participation may be mediated, at least in part, by modulation of chromatin and nucleosome assembly as well as by H19 induction.

Should we do EUS/FNA on patients with pancreatic cysts? The incremental diagnostic yield of EUS over CT/MRI for prediction of cystic neoplasms.

Objectives To evaluate the performance characteristics of endoscopic ultrasonography (EUS) compared with computed tomography (CT) and magnetic resonance imaging (MRI) and determine the incremental diagnostic yield and accuracy of EUS with or without fine needle aspiration (FNA) over CT and MRI for prediction of neoplastic pancreatic cysts. Methods The EUS database was queried for procedures performed for pancreatic cysts between March 2006 and January 2010. Cystic pancreatic ductal adenocarcinoma, cystic pancreatic neuroendocrine tumor, mucinous cystic neoplasm, intraductal papillary neoplasm, and solid pseudopapillary neoplasm were categorized as neoplastic; pseudocysts and serous cysts were designated as nonneoplastic/low risk. Results Final diagnoses were established by surgery in 154 patients (mucinous cystic neoplasm/intraductal papillary neoplasm [69.4%], pancreatic neuroendocrine tumor [10%], pancreatic ductal adenocarcinoma [6.4%], solid pseudopapillary neoplasm [0.6%], nonneoplastic/low risk [13.6%]). Endoscopic ultrasonography with or without FNA was superior to CT and MRI in accurately classifying a cyst as neoplastic (P < 0.0001). After CT and MRI, EUS increased the rate of correctly predicting neoplastic cysts in 43 (36%) and 27 (54%) additional cases, respectively. Conclusions The incremental increase in diagnostic yield of EUS and fluid analysis over CT and MRI for prediction of a neoplastic cyst is 36% and 54%, respectively. The addition of EUS-FNA to abdominal imaging significantly increases overall accuracy for diagnosis of neoplastic pancreatic cysts.

International multicenter experience with peroral endoscopic myotomy for the treatment of spastic esophageal disorders refractory to medical therapy (with video)

BACKGROUND Limited data exist on the use of peroral endoscopic myotomy (POEM) for therapy of spastic esophageal disorders (SEDs). OBJECTIVE To study the efficacy and safety of POEM for the treatment of patients with diffuse esophageal spasm, jackhammer esophagus, or type III (spastic) achalasia. DESIGN Retrospective study. SETTING International, multicenter, academic institutions. PATIENTS All patients who underwent POEM for treatment of SEDs refractory to medical therapy at 11 centers were included. INTERVENTIONS POEM. MAIN OUTCOME MEASUREMENTS Eckardt score and adverse events. RESULTS A total of 73 patients underwent POEM for treatment of SEDs (diffuse esophageal spasm 9, jackhammer esophagus 10, spastic achalasia 54). POEM was successfully completed in all patients, with a mean procedural time of 118 minutes. The mean length of the submucosal tunnel was 19 cm, and the mean myotomy length was 16 cm. A total of 8 adverse events (11%) occurred, with 5 rated as mild, 3 moderate, and 0 severe. The mean length of hospital stay was 3.4 days. There was a significant decrease in Eckardt scores after POEM (6.71 vs 1.13; P = .0001). Overall, clinical response was observed in 93% of patients during a mean follow-up of 234 days. Chest pain significantly improved in 87% of patients who reported chest pain before POEM. Repeat manometry after POEM was available in 44 patients and showed resolution of initial manometric abnormalities in all cases. LIMITATIONS Retrospective design and selection bias. CONCLUSION POEM offers a logical therapeutic modality for patients with SEDs refractory to medical therapy. Results from this international study suggest POEM as an effective and safe platform for these patients.

EUS-guided biliary drainage by using a standardized approach for malignant biliary obstruction: rendezvous versus direct transluminal techniques (with videos).

BACKGROUND EUS-guided biliary drainage (EGBD) can be performed via direct transluminal or rendezvous techniques. It is unknown how both techniques compare in terms of efficacy and adverse events. OBJECTIVE To describe outcomes of EGBD performed by using a standardized approach and compare outcomes of rendezvous and transluminal techniques. DESIGN Retrospective analysis of prospectively collected data. SETTING Two tertiary-care centers. PATIENTS Consecutive jaundiced patients with distal malignant biliary obstruction who underwent EGBD after failed ERCP between July 2006 and December 2012 were included. INTERVENTION EGBD by using a standardized algorithm. MAIN OUTCOME MEASUREMENTS Technical success, clinical success, and adverse events. RESULTS During the study period, 35 patients underwent EGBD (rendezvous n = 13, transluminal n = 20). Technical success was achieved in 33 patients (94%), and clinical success was attained in 32 of 33 patients (97.0%). The mean postprocedure bilirubin level was 1.38 mg/dL in the rendezvous group and 1.33 mg/dL in the transluminal group (P = .88). Similarly, length of hospital stay was not different between groups (P = .23). There was no significant difference in adverse event rate between rendezvous and transluminal groups (15.4% vs 10%; P = .64). Long-term outcomes were comparable between groups, with 1 stent migration in the rendezvous group at 62 days and 1 stent occlusion in the transluminal group at 42 days after EGBD. LIMITATIONS Retrospective analysis, small number of patients, and selection bias. CONCLUSION EGBD is safe and effective when the described standardized approach is used. Stent occlusion is not common during long-term follow-up. Both rendezvous and direct transluminal techniques seem to be equally effective and safe. The latter approach is a reasonable alternative to rendezvous EGBD.

Human bile contains MicroRNA‐laden extracellular vesicles that can be used for cholangiocarcinoma diagnosis

Cholangiocarcinoma (CCA) presents significant diagnostic challenges, resulting in late patient diagnosis and poor survival rates. Primary sclerosing cholangitis (PSC) patients pose a particularly difficult clinical dilemma because they harbor chronic biliary strictures that are difficult to distinguish from CCA. MicroRNAs (miRs) have recently emerged as a valuable class of diagnostic markers; however, thus far, neither extracellular vesicles (EVs) nor miRs within EVs have been investigated in human bile. We aimed to comprehensively characterize human biliary EVs, including their miR content. We have established the presence of extracellular vesicles in human bile. In addition, we have demonstrated that human biliary EVs contain abundant miR species, which are stable and therefore amenable to the development of disease marker panels. Furthermore, we have characterized the protein content, size, numbers, and size distribution of human biliary EVs. Utilizing multivariate organization of combinatorial alterations (MOCA), we defined a novel biliary vesicle miR‐based panel for CCA diagnosis that demonstrated a sensitivity of 67% and specificity of 96%. Importantly, our control group contained 13 PSC patients, 16 with biliary obstruction of varying etiologies (including benign biliary stricture, papillary stenosis, choledocholithiasis, extrinsic compression from pancreatic cysts, and cholangitis), and 3 with bile leak syndromes. Clinically, these types of patients present with a biliary obstructive clinical picture that could be confused with CCA. Conclusion: These findings establish the importance of using extracellular vesicles, rather than whole bile, for developing miR‐based disease markers in bile. Finally, we report on the development of a novel bile‐based CCA diagnostic panel that is stable, reproducible, and has potential clinical utility. (Hepatology 2014;60:896–907)