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CCR Translation for This Article from Serum Biomarker Panels for the Detection of Pancreatic Cancer

Purpose: Serum–biomarker based screening for pancreatic cancer could greatly improve survival in appropriately targeted high-risk populations.Experimental Design: Eighty-three circulating proteins were analyzed in sera of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC, n = 333), benign pancreatic conditions (n = 144), and healthy control individuals (n = 227). Samples from each group were split randomly into training and blinded validation sets prior to analysis. A Metropolis algorithm with Monte Carlo simulation (MMC) was used to identify discriminatory biomarker panels in the training set. Identified panels were evaluated in the validation set and in patients diagnosed with colon (n = 33), lung (n = 62), and breast (n = 108) cancers.Results: Several robust profiles of protein alterations were present in sera of PDAC patients compared to the Healthy and Benign groups. In the training set (n = 160 PDAC, 74 Benign, 107 Healthy), the panel of CA 19–9, ICAM-1, and OPG discriminated PDAC patients from Healthy controls with a sensitivity/specificity (SN/SP) of 88/90%, while the panel of CA 19–9, CEA, and TIMP-1 discriminated PDAC patients from Benign subjects with an SN/SP of 76/90%. In an independent validation set (n = 173 PDAC, 70 Benign, 120 Healthy), the panel of CA 19–9, ICAM-1 and OPG demonstrated an SN/SP of 78/94% while the panel of CA19–9, CEA, and TIMP-1 demonstrated an SN/SP of 71/89%. The CA19–9, ICAM-1, OPG panel is selective for PDAC and does not recognize breast (SP = 100%), lung (SP = 97%), or colon (SP = 97%) cancer.Conclusions: The PDAC-specific biomarker panels identified in this investigation warrant additional clinical validation to determine their role in screening targeted high-risk populations. Clin Cancer Res; 17(4); 805–16. ©2010 AACR.

Supplementary Figures S1-S2; Supplementary Tables S1-S2.

Background Acute pancreatitis is a serious complication of endoscopic retrograde cholangiopancreatography (ERCP). The aim of this noninferiority study was to evaluate the effectiveness of pancreatic duct (PD) stenting plus pharmacological prophylaxis vs. pharmacological prophylaxis alone in the prevention of post-ERCP pancreatitis (PEP) in high risk patients. Methods In this randomized, controlled, double-blind, noninferiority trial, patients at high risk of developing PEP were randomly allocated to pharmacological prophylaxis (rectal indomethacin, sublingual isosorbide dinitrate, and intravenous hydration with Ringer’s lactate) plus PD stenting (group A) or pharmacological prophylaxis alone (group B). The rate and severity of PEP, serum amylase levels, and length of hospital stay after ERCP were assessed. Results During 21 months, a total of 414 patients (mean age 55.5 ± 17.0 years; 60.2 % female) were enrolled (207 in each group). PEP occurred in 59 patients (14.3 %, 95 % confidence interval [CI] 11.1 % – 17.9 %: 26 patients [12.6 %, 95 %CI 8.6 % – 17.6 %] in group A and 33 [15.9 %, 95 %CI 11.4 % – 21.4 %] in group B). There was no significant difference between the two groups in PEP severity (P = 0.59), amylase levels after 2 hours (P = 0.31) or 24 hours (P = 0.08), and length of hospital stay (P = 0.07). Conclusions The study failed to demonstrate noninferiority or inferiority of pharmacological prophylaxis alone compared with PD stenting plus pharmacological prophylaxis in the prevention of PEP in high risk patients.

Background: Referral for endosonographic evaluation of subepithelial lesions seen in the gastrointestinal (GI) tract is fairly common. Although rarely studied separately in details, esophageal lesions have some unique differences from other GI sites and might deserve some special considerations regarding follow-up and management. Materials and Methods: All cases referred for endoscopic ultrasound (EUS) evaluation of subepithelial esophageal lesions at Bezmialem University Hospital, a tertiary center in Istanbul, Turkey were retrospectively reviewed. Data were collected for patient and lesion characteristics as well as for pathology results and follow-up if available. Lesions were subcategorized according to their size, location, and final diagnosis. Results: A total of 164 EUS examinations were identified. In 22.5% of cases, the lesion could not be identified by EUS. Of the remaining cases, 57.6% had a lesion larger than 1 cm in size. Extramural compression was the diagnosis in 12% and leiomyoma in around 60%. Thirteen patients had follow-up examinations with only two showing an increase in size after 12 months. Sixty-five EUS-guided fine needle aspirations (EUS-guided FNAs) were performed, with around 50% having nondiagnostic samples and 94% of the remaining samples confirming the presumptive diagnosis. Conclusions: The majority of subepithelial lesions in the esophagus are benign with extremely low malignancy potential. EUS examinations performed for lesions smaller than 2 cm as well as FNAs taken from lesions smaller than 3 cm might have minimal impact on their ultimate management and outcome. More than one FNA pass should be attempted in order to improve the yield.

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

OBJECTIVES: The objective of guideline was to provide clear and relevant consensus statements to form a practical guideline for clinicians on the indications, optimal technique, safety and efficacy of endoscopic ultrasound guided celiac plexus neurolysis (EUS-CPN).METHODS: Six important clinical questions were determined regarding EUS-CPN. Following a detailed literature review, 6 statements were proposed attempting to answer those questions. A group of expert endosonographers convened in Chicago, United States (May 2016), where the statements were presented and feedback provided. Subsequently a consensus group of 35 expert endosonographers voted based on their individual level of agreement. A strong recommendation required 80% voter agreement. The modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria were used to rate the strength of recommendations and the quality of evidence.RESULTS: Eighty percent agreement was reached on 5 of 6 consensus statements, 79.4% agreement was reached on the remaining one.CONCLUSIONS: EUS-CPN is efficacious, should be integrated into the management of pancreas cancer pain, and can be considered early at the time of diagnosis of inoperable disease. Techniques may still vary based on operator experience. Serious complications exist, but are rare.

Background and Objectives: Currently, pancreatic cystic lesions (PCLs) are recognized with increasing frequency and have become a more common finding in clinical practice. EUS is challenging in the diagnosis of PCLs and evidence-based decisions are lacking in its application. This study aimed to develop strong recommendations for the use of EUS in the diagnosis of PCLs, based on the experience of experts in the field. Methods: A survey regarding the practice of EUS in the evaluation of PCLs was drafted by the committee member of the International Society of EUS Task Force (ISEUS-TF). It was disseminated to experts of EUS who were also members of the ISEUS-TF. In some cases, percentage agreement with some statements was calculated; in others, the options with the greatest numbers of responses were summarized. Results: Fifteen questions were extracted and disseminated among 60 experts for the survey. Fifty-three experts completed the survey within the specified time frame. The average volume of EUS cases at the experts' institutions is 988.5 cases per year. Conclusion: Despite the limitations of EUS alone in the morphologic diagnosis of PCLs, the results of the survey indicate that EUS-guided fine-needle aspiration is widely expected to become a more valuable method.

Treatment of choledocholithiasis and cholelithiasis in patients with cirrhosis often requires diagnostic and therapeutic endoscopy such as endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP). Patients with underlying cirrhosis may have coagulopathy, hepatic encephalopathy, ascites and other comorbidities associated with cirrhosis that can make endoscopic therapy challenging and can be associated with a higher risk of adverse events. Given the unique derangements of physiologic parameters associated with cirrhosis this population requires a truly multifaceted and multidisciplinary understanding between therapeutic endoscopists, hepatologists and anesthesiologists. For therapeutic endoscopists, it is critical to be aware of the specific issues unique to this population of patients to optimize outcomes and avoid adverse events. The epidemiology of gallstone disease, the diagnostic and therapeutic approach to patients with varying degree of hepatic dysfunction, and a review of the available literature in this area are presented.

Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) has transformed the evaluation of solid pancreas masses. This approach is more likely to yield answers, is less likely to result in peritoneal seeding, and is safer than competing methods. Challenges include sampling error, false negatives in the setting of inflammation, and assessment of nonepithelial lesions. Ongoing work, including special tissue processing methods, elastography, and contrast-enhanced harmonic EUS, are being used to overcome these limitations. Optimizing the use of techniques including the use of stylet, suction, and needle types are the subject of ongoing work.

OAE is commonly used. The majority of patients referred for OAE are considered appropriate for endoscopy according to ASGE guidelines. Most patients undergoing OAE procedures are knowledgeable about the study and are satisfied with the experience. Several potential problems have been identified, including inappropriate referrals, communication errors, and inadequately prepared or informed patients. OAE can be safely used if preprocedure assessment, informed consent, information transfer, patient safety, and satisfaction are addressed in all cases.

We recommend that uncomplicated GERD be diagnosed on the basis of typical symptoms without the use of diagnostic testing, including EGD. We recommend EGD for patients who have symptoms suggesting complicated GERD or alarm symptoms. We recommend that EGD not be routinely performed solely for the assessment of extraesophageal GERD symptoms. We recommend that endoscopic findings of reflux esophagitis be classified according to an accepted grading scale or described in detail. We suggest that repeat EGD be performed in patients with severe erosive esophagitis after at least an 8-week course of PPI therapy to exclude underlying BE or dysplasia. 44BB We recommend against obtaining tissue samples from endoscopically normal tissue to diagnose GERD or exclude BE in adults. We suggest that endoscopy be considered in patients with multiple risk factors for Barrett’s esophagus. We recommend that tissue samples be obtained to confirm endoscopically suspected Barrett’s esophagus. We suggest that endoscopic antireflux therapy be considered for selected patients with uncomplicated GERD after careful discussion with the patient regarding potential adverse effects, benefits, and other available therapeutic options.

Endoscopic ultrasound (EUS) has evolved into a first line modality for diagnostic and therapeutic procedures in managing gastrointestinal conditions. Currently, two types of echoendoscopes are available: radial array and curved linear array. The radial scope allows for a 360° cross-sectional view. The linear array scope has a scanning range of 120–180° and allows performance of fine-needle aspiration (FNA). The role of EUS is not only for diagnostic and staging purposes of gastrointestinal lesions, but also to obtain tissue diagnosis by FNA. There are currently a multitude of EUS-guided needles and brushes available to obtain cytological diagnosis of solid and cystic lesions. This chapter will provide a brief synopsis of the equipment available for performing endosonography and the current tools to obtain cytological diagnosis from gastrointestinal lesions.

Background and Aims EUS-guided FNA (EUS-FNA) is increasingly being used for tissue diagnosis of extrahepatic biliary strictures. The aim of this study was to determine the diagnostic yield of EUS-FNA in malignant biliary strictures. Methods A comprehensive literature review was carried out by 2 reviewers for studies evaluating the accuracy of EUS-FNA in biliary stricture. A meta-analysis was performed to determine the pooled estimates of sensitivity, specificity, likelihood ratios, and diagnostic odds ratio for EUS-FNA of extrahepatic biliary stricture. A Quality Assessment of Diagnostic Accuracy Studies questionnaire was used to assess the quality of the selected studies. Several sensitivity analyses were performed to assess the effect of the quality of the studies on the accuracy of the final results of the meta-analysis. Results Twenty studies involving 957 patients met inclusion criteria and were included in the meta-analysis. The pooled sensitivity and specificity of EUS-FNA for diagnosis of malignant biliary stricture were 80% (95% confidence interval [CI], 74%-86%), and 97% (95% CI, 94%-99%), respectively. The pooled positive likelihood ratio was 12.35 (95% CI, 7.37-20.72), and the negative likelihood ratio was 0.26 (95% CI, 0.18-0.38). The pooled diagnostic odds ratio for diagnosing a malignant biliary stricture was 70.53 (95% CI, 38.62-128.82). The area under the receiver-operating characteristic curve was 0.97. Sensitivity analyses showed that the quality of the included studies did not affect the accuracy of the final results of the meta-analysis. Conclusion This meta-analysis demonstrates that EUS-FNA is sensitive and highly specific for diagnosing malignancy in biliary strictures. Further studies are needed to compare EUS--FNA with emerging methods including cholangioscopy-guided biopsy and laser endomicroscopy.

Background and Objectives: Data on the risk of acute pancreatitis following endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic cystic lesions are limited. The aim of our study was to evaluate the frequency of acute pancreatitis after EUS-FNA of pancreatic cysts and solid lesions, and determine whether there was a difference in pancreatitis risk in patients with side branch intraductal papillary mucinous neoplasms (SB-IPMN). Patients and Methods: A retrospective review of patients who underwent EUS-FNA of pancreatic cysts and solid lesions was performed. The primary outcome measure was development of acute pancreatitis after EUS-FNA. Factors associated with acute pancreatitis were examined by statistical analysis to determine independent predictors of acute pancreatitis. Statistical significance was determined at a P ≤ 0.05. Results: We identified 186 patients with pancreatic cystic lesions and 557 with solid lesions in which EUS-FNA was performed. The median size of the cysts was 19 mm (range: 10-66 mm). There were 37 IPMNs, 33 mucinous cystic neoplasms, 58 serous cysts and 46 pseudocysts and 12 solid-cystic ductal carcinomas. The majority of patients (75%) with solid lesions were diagnosed with adenocarcinoma. Patients with pancreatic cysts had a statistically greater frequency of developing pancreatitis after EUS-FNA when compared to those with solid lesions (2.6% vs. 0.36% respectively; P = 0.13). In patients with cysts, there were no statistically significant differences between the two groups (with and without pancreatitis) with regard to a cyst location, size of the cyst, and number of needle passes or trainee involvement. Patients with SB-IPMN had a statistically higher frequency of pancreatitis after EUS-FNA compared to those with other cyst types (8% vs. 1.3% respectively; odds ratio = 6.4, 95% confidence intervals = 1.0-40.3, P = 0.05). Discussion: Patients with SB-IPMN are at a higher risk of developing acute pancreatitis after a EUS-FNA. Alternative means of diagnosis such as magnetic resonance cholangiopancreatogram might be necessary to avoid risk of EUS-FNA.