Michelle A. Anderson

Management of antithrombotic agents for endoscopic procedures

This is one of a series of statements discussing the use of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy (ASGE) prepared this text. This guideline combines and updates 2 previously issued guidelines, ‘‘Guideline on the management of antithrombotic and antiplatelet therapy for endoscopic procedures’’ and ‘‘ASGE guideline: the management of lowmolecular-weight heparin and nonaspirin antiplatelet agents for endoscopic procedures.’’ To prepare this guideline, a search of the medical literature was performed using PubMed. Studies or reports that described fewer than 10 patients were excluded from analysis if multiple series with more than 10 patients addressing the same issue were available. Additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants. Guidelines for appropriate use of endoscopy are based on a critical review of the available data and expert consensus at the time the guidelines are drafted. Further controlled clinical studies may be needed to clarify aspects of this guideline. This guideline may be revised as necessary to account for changes in technology, new data, or other aspects of clinical practice. The recommendations are based on reviewed studies and were graded on the strength of the supporting evidence (Table 1). The strength of individual recommendations is based on both 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. This guideline 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 this guideline.

Complications of ERCP

d ( t s f t c s n d i a s a This is one of a series of position statements discussing the use of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy prepared this text. This document is an update of a previous ASGE publication.1 In preparing this document, a search of the medical iterature was performed using PubMed. Additional refernces were obtained from the bibliographies of the identied articles and from recommendations of expert consulants. When limited or no data exist from well-designed rospective trials, emphasis is given to results from large eries and reports from recognized experts. Position stateents are based on a critical review of the available data nd expert consensus at the time that the document was rafted. Further controlled clinical studies may be needed o clarify aspects of this document, which may be revised s necessary to account for changes in technology, new ata, or other aspects of clinical practice. This document is intended to be an educational device o provide information that may assist endoscopists in roviding care to patients. This position statement is not a ule and should not be construed as establishing a legal tandard of care or as encouraging, advocating, requirng, or discouraging any particular treatment. Clinical ecisions in any particular case involve a complex analsis of the patient’s condition and available courses of ction. Therefore, clinical considerations may lead an ndoscopist to take a course of action that varies from this osition statement. Since its introduction in 1968, ERCP has become a comonly performed endoscopic procedure.2 The diagnostic nd therapeutic utility of ERCP has been well demonstrated or a variety of disorders, including the management of choedocholithiasis, the diagnosis and management of biliary nd pancreatic neoplasms, and the postoperative manageent of biliary perioperative complications.3-5 The evolution of the role of ERCP has occurred simultaneously with that of other diagnostic and therapeutic modalities, most notably magnetic resonance imaging/MRCP, laparoscopic cholecystectomy (with or without intraoperative cholangiography), and EUS. For endoscopists to accurately assess the clinical appropriateness of ERCP, it is important to have a thorough

Endoscopic ultrasound is highly accurate and directs management in patients with neuroendocrine tumors of the pancreas

OBJECTIVE:Preoperative localization of pancreatic neuroendocrine tumors with traditional imaging fails in 40–60% of patients. Endoscopic ultrasound (EUS) is highly sensitive in the detection of these tumors. Previous reports included relatively few patients or required the collaboration of multiple centers. We report the results of EUS evaluation of 82 patients with pancreatic neuroendocrine tumors.METHODS:We prospectively used EUS early in the diagnostic evaluation of patients with biochemical or clinical evidence of neuroendocrine tumors. Patients had surgical confirmation of tumor localization or clinical follow-up of >1 yr.RESULTS:Eighty-two patients underwent 91 examinations (cases). Thirty patients had multiple endocrine neoplasia syndrome type I. One hundred pancreatic tumors were visualized by EUS in 54 different patients. The remaining 28 patients had no pancreatic tumor or an extrapancreatic tumor. Surgical/pathological confirmation was obtained in 75 patients. The mean tumor diameter was 1.51 cm and 71% of the tumors were ≤2.0 cm in diameter. Of the 54 explorations with surgical confirmation of a pancreatic tumor, EUS correctly localized the tumor in 50 patients (93%). Twenty-nine insulinomas, 18 gastrinomas, as well as one glucagonoma, one carcinoid tumor, and one somatostatinoma were localized. The most common site for tumor localization was the pancreatic head (46 patients). Most tumors were hypoechoic, homogenous, and had distinct margins. EUS of the pancreas was correctly negative in 20 of 21 patients (specificity, 95%). EUS was more accurate than angiography with or without stimulation testing (secretin for gastrinoma, calcium for insulinoma), transcutaneous ultrasound, and CT in those patients undergoing further imaging procedures. EUS was not reliable in localizing extrapancreatic tumors.CONCLUSIONS:In this series, the largest single center experience reported to date, EUS had an overall sensitivity and accuracy of 93% for pancreatic neuroendocrine tumors. Our results support the use of EUS as a primary diagnostic modality in the evaluation and management of patients with neuroendocrine tumors of the pancreas.

The role of endoscopy in the evaluation of suspected choledocholithiasis

This is one of a series of statements discussing the use of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy prepared this text. In preparing this guideline, a search of the medical literature was performed by using PubMed. Additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants. When few or no data exist from well-designed prospective trials, emphasis is given to results of large series and reports from recognized experts. Guidelines for appropriate use of endoscopy are based on a critical review of the available data and expert consensus at the time that the guidelines are drafted. Further controlled clinical studies may be needed to clarify aspects of this guideline. This guideline 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). This guideline is intended to be an educational device to provide information that may assist endoscopists in providing care to patients. This guideline 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 guidelines. Gallstone disease affects more than 20 million American adults at an annual cost of

Management of ingested foreign bodies and food impactions

6.2 billion. A subset of these patients will also have choledocholithiasis, including 5% to 10% of those undergoing laparoscopic cholecystectomy for symptomatic cholelithiasis and 18% to 33% of patients with acute biliary pancreatitis. The approach to patients with suspected choledocholithiasis requires careful consideration because missed common bile duct (CBD) stones pose a risk of recurrent symptoms, pancreatitis, and cholangitis. However, the morbidity and cost

A Mouse to Human Search for Plasma Proteome Changes Associated with Pancreatic Tumor Development

i d t i i t i t f o This is one of a series of statements discussing the use of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy (ASGE) prepared this text. In preparing this guideline, a search of the medical literature was performed by using PubMed. Studies or reports that described fewer than 10 patients were excluded from analysis if multiple series with more than 10 patients addressing the same issue were available. Additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants. Guidelines for appropriate use of endoscopy are based on a critical review of the available data and expert consensus at the time that the guidelines are drafted. Further controlled clinical studies may be needed to clarify aspects of this guideline. This guideline may be revised as necessary to account for changes in technology, new data, or other aspects of clinical practice. The original guideline was published in 1995 and last updated in 2002. The recommendations are based on reviewed studies and are graded on the strength of the supporting evidence (Table 1).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. This guideline 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 guidelines.

Alcohol and Smoking as Risk Factors in an Epidemiology Study of Patients With Chronic Pancreatitis

Background The complexity and heterogeneity of the human plasma proteome have presented significant challenges in the identification of protein changes associated with tumor development. Refined genetically engineered mouse (GEM) models of human cancer have been shown to faithfully recapitulate the molecular, biological, and clinical features of human disease. Here, we sought to exploit the merits of a well-characterized GEM model of pancreatic cancer to determine whether proteomics technologies allow identification of protein changes associated with tumor development and whether such changes are relevant to human pancreatic cancer. Methods and Findings Plasma was sampled from mice at early and advanced stages of tumor development and from matched controls. Using a proteomic approach based on extensive protein fractionation, we confidently identified 1,442 proteins that were distributed across seven orders of magnitude of abundance in plasma. Analysis of proteins chosen on the basis of increased levels in plasma from tumor-bearing mice and corroborating protein or RNA expression in tissue documented concordance in the blood from 30 newly diagnosed patients with pancreatic cancer relative to 30 control specimens. A panel of five proteins selected on the basis of their increased level at an early stage of tumor development in the mouse was tested in a blinded study in 26 humans from the CARET (Carotene and Retinol Efficacy Trial) cohort. The panel discriminated pancreatic cancer cases from matched controls in blood specimens obtained between 7 and 13 mo prior to the development of symptoms and clinical diagnosis of pancreatic cancer. Conclusions Our findings indicate that GEM models of cancer, in combination with in-depth proteomic analysis, provide a useful strategy to identify candidate markers applicable to human cancer with potential utility for early detection.

Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study

BACKGROUND & AIMS Alcohol has been implicated in the development of chronic pancreatitis (CP) in 60%-90% of patients, although percentages in the United States are unknown. We investigated the epidemiology of alcohol-related CP at tertiary US referral centers. METHODS We studied data from CP patients (n = 539) and controls (n = 695) enrolled in the North American Pancreatitis Study-2 from 2000 to 2006 at 20 US referral centers. CP was defined by definitive evidence from imaging or histologic analyses. Subjects and physicians each completed a study questionnaire. Using physician-assigned diagnoses, patients were assigned to an etiology group: alcohol (with/without other diagnoses), nonalcohol (any etiology of CP from other than alcohol), or idiopathic (no etiology identified). RESULTS The distribution of patients among etiology groups was: alcohol (44.5%), nonalcohol (26.9%), and idiopathic (28.6%). Physicians identified alcohol as the etiology more frequently in men (59.4% men vs 28.1% women), but nonalcohol (18% men vs 36.7% women) and idiopathic etiologies (22.6% men vs 35.2% women) more often in women (P < .01 for all comparisons). Nonalcohol etiologies were equally divided among obstructive, genetic, and other causes. Compared with controls, patients with idiopathic CP were more likely to have ever smoked (58.6% vs 49.7%, P < .05) or have a history of chronic renal disease or failure (5.2% vs 1.2%, P < .01). In multivariate analyses, smoking (ever, current, and amount) was independently associated with idiopathic CP. CONCLUSIONS The frequency of alcohol-related CP at tertiary US referral centers is lower than expected. Idiopathic CP and nonalcohol etiologies represent a large subgroup, particularly among women. Smoking is an independent risk factor for idiopathic CP.

CEACAM1, a novel serum biomarker for pancreatic cancer

Objective To compare patients with chronic pancreatitis (CP) with constant pain patterns to patients with CP with intermittent pain patterns. Methods This was a prospective cohort study conducted at 20 tertiary medical centers in the USA comprising 540 subjects with CP. Patients with CP were asked to identify their pain from five pain patterns (A–E) defined by the temporal nature (intermittent or constant) and the severity of the pain (mild, moderate or severe). Pain pattern types were compared with respect to a variety of demographic, quality of life (QOL) and clinical parameters. Rates of disability were the primary outcome. Secondary outcomes included: use of pain medications, days lost from school or work, hospitalisations (preceding year and lifetime) and QOL as measured using the Short Form-12 (SF-12) questionnaire. Results Of the 540 CP patients, 414 patients (77%) self-identified with a particular pain pattern and were analysed. Patients with constant pain, regardless of severity, had higher rates of disability, hospitalisation and pain medication use than patients with intermittent pain. Patients with constant pain had lower QOL (by SF-12) compared with patients who had intermittent pain. Additionally, patients with constant pain were more likely to have alcohol as the aetiology for their pancreatitis. There was no association between the duration of the disease and the quality or severity of the pain. Conclusions This is the largest study ever conducted of pain in CP. These findings suggest that the temporal nature of pain is a more important determinant of health-related QOL and healthcare utilisation than pain severity. In contrast to previous studies, the pain associated with CP was not found to change in quality over time. These results have important implications for improving our understanding of the mechanisms underlying pain in CP and for the goals of future treatments and interventions.

Pancreatic Cancer Serum Detection Using A Lectin/Glyco-Antibody Array Method

Objectives: Serum biomarkers for early diagnosis of pancreatic adenocarcinoma are not currently available. We recently observed elevated expression of CEACAM1 in pancreatic adenocarcinomas and sought to determine whether serum CEACAM1 levels were elevated in pancreatic cancer patients. Methods: CEACAM1 messenger RNA levels were measured in pancreatic tissue samples using quantitative reverse transcription-polymerase chain reaction. CEACAM1 was localized by immunohistochemistry in adenocarcinomas and in pancreatic intraductal neoplasia lesions. CEACAM1 serum levels were assessed by a double determinant enzyme-linked immunosorbent assay and compared with serum levels of CA19-9. Results: CEACAM1 had higher expression levels in pancreatic adenocarcinomas compared with noncancerous pancreas (P < 0.0001) and was localized to neoplastic cells (95% (45/47) of adenocarcinomas and 85% (17/20) of pancreatic intraductal neoplasia 3 lesions. CEACAM1 was expressed in the sera of 91% (74/81) of pancreatic cancer patients, 24% (15/61) of normal patients, and 66% (35/53) of patients with chronic pancreatitis, with a sensitivity and specificity superior to CA19-9. The combination of CEACAM1 and CA19-9 had significantly higher diagnostic accuracy than CA19-9. Conclusions: CEACAM1 is expressed in pancreatic adenocarcinoma, and serum levels of CEACAM1 serve as a useful indicator for the presence of pancreatic cancer. Additional validation studies on the use of serum CEACAM1 as a diagnostic marker in pancreatic cancer are warranted.Abbreviations: AUC - area under the curve, ROC - receiver operator characteristics