OBJECTIVE:Autoimmune pancreatitis (AIP) responds dramatically to corticosteroids treatment. We reviewed our experience to determine the safety and effectiveness of treating obstructive jaundice in definitive AIP with corticosteroids alone without biliary stenting. METHODS:From our AIP database, we retrospectively identified type 1 AIP subjects whose jaundice was treated with corticosteroids alone without biliary stenting. Their medical records were reviewed and clinical data were evaluated to determine the outcomes. RESULTS:Fifteen AIP subjects (87% male, mean age 68.4 years) were treated with corticosteroids at initial presentation (n = 8), first (n = 5) or subsequent (n = 2) relapse. Mean values (upper limit of normal, ULN) of liver tests prior to corticosteroids were aspartate aminotransferase (AST) 203.5u/l (4 × ULN), alanine aminotransferase (ALT) 325.8u/l (6 × ULN), alkaline phosphatase (ALP) 567.4u/l (5 × ULN), and total bilirubin (TB) 5.9 mg/dl (5.9 × ULN). At first follow-up (mean 4 days) the decrease was 54.9% for AST, 51.6% for ALT, 33% for ALP and 47.2% for TB (all p < 0.05). After 15-45 days, all patients had normal AST, 3/15 had ALT > 1.5 × ULN, 1/15 had ALP > 1.5 × ULN, 1/15 had TB > 1.5 × ULN. No patient required biliary stent placement, or developed cholangitis or other infectious complications during steroid treatment. CONCLUSION:Under the supervision of an experienced pancreatologist and with close monitoring of patients, obstructive jaundice secondary to definitive AIP can be safely and effectively managed with corticosteroids alone, without the need for biliary stenting.

Pancreatic cancer (PC) often produces pain that is difficult to control.Celiac neurolysis (CN) is performed with the goal of improving pain control and quality of life while reducing opioid-related side effects.The authors aimed to evaluate whether CN provides a survival advantage for PC patients.This was a retrospective case control study set in a single tertiary-care referral center.A review of a prospectively maintained database identified patients with unresectable PC who underwent CN over a 12-year period.Each patient was matched to 2 control patients with unresectable PC.A total of 417 patients underwent CN and were compared with 840 controls with PC.Baseline characteristics were similar except the CN group had greater weight loss and pain requiring opioids.A mean of 16.6 AE 5.8 mL of alcohol was administered.For patients who underwent CN, the median survival from the time of presentation was shorter compared with controls (193 vs 246 days; hazard ratio 1.32; 95% CI, 1.13-1.54).There was no difference in survival with unilateral or bilateral injection.However, EUS-guided CN was associated with longer survival compared with non-EUS approaches, and those who received CPN had longer survival compared with celiac ganglia neurolysis (CGN).Dr Fujii-Lau and colleagues suggest that CN is an independent predictor of shortened survival in PC patients.A prospective study is needed to verify the findings and to determine whether shortened survival results from CN or from other features, such as performance status and tumor-related characteristics.It is also imperative to verify the authors' finding that EUS-guided CN provides a survival advantage over other approaches, and verify whether CPN prolongs survival compared with CGN.

BACKGROUND AND STUDY AIMS:Pancreas cyst fluid analysis does not provide optimal discrimination between mucinous and nonmucinous cysts. The aim of this study was to assess the performance characteristics of the "string sign" - a test performed at the time of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), for the diagnosis of mucinous pancreatic cysts (branch duct intraductal papillary mucinous neoplasms [bIPMN] and mucinous cystic neoplasms). PATIENTS AND METHODS:Patients undergoing EUS-FNA of pancreatic cystic lesions at one referral center between 2003 and 2012 were included. The string sign was performed prospectively, and was considered positive if ≥ 1 cm string formed in cyst fluid and lasted for ≥ 1 second. Performance characteristics of the string sign and a sequential cyst fluid test interpretation model were assessed. RESULTS:For 98 histologically proven cases, the sensitivity, specificity, positive predictive value, and negative predictive value of the string sign for diagnosis of mucinous cysts were 58 % (95 % confidence interval [CI] 44 % - 70 %), 95 % (83 % - 99 %), 94 % (81 % - 99 %), and 60 % (46 % - 72 %), respectively. When string sign results and carcinoembryonic antigen (CEA) concentration (≥ 200 ng/mL) were combined, diagnostic accuracy improved from 74 % and 83 %, respectively, to 89 % (P ≤ 0.03). Among bIPMN, a positive string sign was associated with gastric and intestinal epithelial subtypes. The sequential cyst fluid test interpretation model (including cytology, mucin stain, CEA, and string sign) yielded an overall sensitivity for mucinous lesions of 96 %, with a specificity of 90 %. CONCLUSIONS:The string sign is highly specific for diagnosis of mucinous pancreatic cysts, and improves overall diagnostic accuracy of pancreatic cyst fluid analysis. Sequential cyst fluid test interpretation yields high diagnostic sensitivity and specificity for mucinous cysts.

Objective Idiopathic duct-centric chronic pancreatitis (IDCP), also known as type 2 autoimmune pancreatitis (AIP), is an uncommon subtype of AIP. International Consensus Diagnostic Criteria for IDCP propose that the diagnosis requires pancreatic histology and/or concurrent IBD. We examined our experience with IDCP (type 2 AIP) to assess the appropriateness of these criteria, and identify unique characteristics in patients presenting with acute pancreatitis. Design We reviewed the Mayo Clinic AIP database through May 2014 to identify subjects with either definitive (n=31) or probable (n=12) IDCP. We compared demographic and clinical factors based on strength of diagnostic confidence (definitive versus probable), presence of IBD, and acute pancreatitis as the presenting manifestation. Relapse-free survival was determined using the Kaplan-Meier method. Results The clinical profiles were similar irrespective of the diagnostic criteria fulfilled. Common clinical presentations included acute pancreatitis (n=25, 58.1%, 12 of whom (27.9%) had recurrent pancreatitis) and pancreatic mass/obstructive jaundice (n=15, 34.9%). The cumulative relapse rate was 10.6% at 3 years (median follow-up 2.9 years). Relapse-free survival was similar for the different diagnostic categories, but was decreased in those initially presenting with acute pancreatitis (p=0.047) or treated with steroids (vs surgery, p=0.049). Conclusions The current diagnostic classification of probable IDCP and the inclusion of IBD as a supportive criterion appear valid, because patients have similar clinical profiles and disease-related outcomes to those with definitive IDCP. Concurrent IBD, especially in young patients, may suggest when IDCP is the underlying cause of recurrent acute pancreatitis, but additional studies are needed for validation.

Background: Detection of hepatic metastases during EUS is an important component of tumor staging.Objective: To describe our experience with EUS-guided FNA (EUS-FNA) of solid hepatic masses and derive and validate criteria to help distinguish between benign and malignant hepatic masses.Design: Retrospective study, survey.Setting: Single, tertiary-care referral center.Patients: Medical records were reviewed for all patients undergoing EUS-FNA of solid hepatic masses over a 12-year period.Interventions: EUS-FNA of solid hepatic masses.Main Outcome Measurements: Masses were deemed benign or malignant according to predetermined criteria. EUS images from 200 patients were used to create derivation and validation cohorts of 100 cases each, matched by cytopathologic diagnosis. Ten expert endosonographers blindly rated 15 initial endosonographic features of each of the 100 images in the derivation cohort. These data were used to derive an EUS scoring system that was then validated by using the validation cohort by the expert endosonographer with the highest diagnostic accuracy.Results: A total of 332 patients underwent EUS-FNA of a hepatic mass. Interobserver agreement regarding the initial endosonographic features among the expert endosonographers was fair to moderate, with a mean diagnostic accuracy of 73% (standard deviation 5.6). A scoring system incorporating 7 EUS features was developed to distinguish benign from malignant hepatic masses by using the derivation cohort with an area under the receiver operating curve (AUC) of 0.92; when applied to the validation cohort, performance was similar (AUC 0.86). The combined positive predictive value of both cohorts was 88%.Limitations: Single center, retrospective, only one expert endosonographer deriving and validating the EUS criteria.Conclusion: An EUS scoring system was developed that helps distinguish benign from malignant hepatic masses. Further study is required to determine the impact of these EUS criteria among endosonographers of all experience.

Pre-surgical imaging is key for selecting stage appropriate therapy for rectal cancer patients. A recent overview (2014) of international guidelines failed to reach a consensus on staging guidelines. Aims: To prospectively evaluate MRI and EUS staging concordance and performance characteristics. Over a 24 month period, 42 patients with primary rectal adenocarcinoma were enrolled, 39 of whom [59.3 ± 13.1 years, male (n=24; 61.5%), CEA (median (IQR): 2 (1.2-3.9)] completed MRI and subsequent EUS ± FNA staging, by an endosonographer who was blinded to the MRI findings. The Kappa statistic for T and N staging by MRI and EUS was 0.474 (95% CI 0.183-0.765) and 0.541 (95% CI 0.287-0.796), respectively. Patients with MRI and EUS TNM staging indicating a need for neoadjuvant therapy (≥ T3 and/or ≥ N1) were identified in 30 (76.9%) and 26 (66.7%), respectively, reflecting a clinically relevant discordance rate of 10%. EUS upstaged MRI T and N findings in 3 (7.7%) and 6 (15.4%) and downstaged MRI T and N findings in 8 (20.5%) and 5 (12.8%) patients. The Kappa statistic and agreement for T and N staging by MRI or EUS to gold standard surgical pathology in the absence of neoadjuvant therapy is highlighted in Table 1. Only 18% of patients had identical MRI, EUS and surgical pathology TNM staging. For T Stage (≥ T3), MRI and EUS had similar sensitivity (80% each) and EUS had greater specificity (100% vs. 83%; P=0.0001). For T Stage (≤ T2), EUS had greater sensitivity (100% vs. 75%; p=0.0001) with similar specificity to MRI (80% each). For N Stage, MRI had greater sensitivity (50% vs. 25%; p=0.0004) but EUS was more specific (100% vs. 80%; p=0.0001). Rectal EUS has superior sensitivity (≤ T2) and specificity (≥ T3) when compared to pelvic MRI. However, both imaging modalities had only fair kappa values when evaluating malignant nodal status. MRI and EUS are complementary rather than competitive to each other. A combined staging algorithm with enhanced features to include lymph node contrast enhancement patterns and elastography may enhance nodal staging accuracy.Table 1MRI - TEUS - TMRI - NEUS - NKappa0.63395% CI 0.174-1.00.81495% CI 0.471-1.00.308-0.307-0.9220.298-0.185-0.78AgreementGoodVery goodFairFair Open table in a new tab

BACKGROUND:The true efficacy of EUS-guided ethanol lavage (EEL) of pancreatic cystic neoplasms is unclear. This study aimed to assess long-term outcomes and adverse events of EEL by using a standardized protocol. METHODS:Single-center, prospective, pilot study in which participants with suspected mucinous cyst neoplasms or branch duct intraductal papillary mucinous neoplasms ≥1 cm in maximum diameter underwent EEL with 80% ethanol. Follow-up cross-sectional imaging was obtained to assess for changes in cyst volume. RESULTS:Twenty-three patients underwent EEL (57% male, mean age 70 years). Mean duration of follow-up was 40 months (range 9-82 months). Mean calculated final concentration of ethanol achieved in treated cysts was 50% (range 0%-79%). Complete resolution of pancreatic cystic neoplasms occurred in 2 participants (9%). When stratified into those participants who achieved ≥80% versus <80% reduction in cyst volume, no statistically significant differences were seen with regard to patient demographics, cyst characteristics, or final concentration of ethanol achieved in the treated cyst. Greater decreases in cyst volume were seen in presumed nonmucinous cysts compared with presumed mucinous cysts (P = .006). Two early adverse events occurred. Five participants died during the study follow-up period (4 from nonpancreatic causes), including 1 participant who was diagnosed with pancreatic adenocarcinoma thought to have arisen from the treated branch duct intraductal papillary mucinous neoplasm 41 months after undergoing EEL. CONCLUSIONS:As performed in this study, EEL therapy does not appear to be a promising method for prevention of malignancy in pancreatic cysts. Endoscopic methods that effectively and completely ablate pancreatic cystic neoplasms are needed. ( CLINICAL TRIAL REGISTRATION NUMBER:NCT02158039.).

OBJECTIVES:Chronic pancreatitis (CP) may be difficult to diagnose in early stages. We aimed to measure pancreatic juice (PJ) prostaglandin E2 (PGE2) concentrations to determine whether they are elevated in CP and improve diagnosis of early disease. METHODS:We measured PJ PGE2 in 10 patients with established CP, 25 patients who met criteria for "minimal change" chronic pancreatitis (MCCP), and 10 normal control participants. RESULTS:Median PJ PGE2 was elevated in CP (307 pg/ml, IQR (249-362)) and MCCP (568 pg/ml, (418-854)) compared with normal controls (104 pg/ml, (68-206)) (P≤ 0.001). Area under receiving operator curve (AUROC) for diagnosis of CP and MCCP was 0.9 and 0.62, respectively, for PJ bicarbonate concentration alone; AUROC was 1.0 and 0.94 for the combination of PJ bicarbonate and PGE2 concentrations. CONCLUSIONS:PJ PGE2 appears to be a biomarker for CP and is elevated in both established and "minimal change" chronic pancreatitis.

BACKGROUND:Peritoneal carcinomatosis (PC) greatly affects cancer staging and resectability.OBJECTIVE:To compare the PC detection rate by using EUS and noninvasive imaging and to determine the impact on staging and resectability.DESIGN:Retrospective study.SETTING:Single tertiary-care referral center.PATIENTS:A prospectively maintained EUS database was reviewed to identify patients who underwent EUS-guided FNA (EUS-FNA) of a peritoneal anomaly. Findings were compared with a strict criterion standard that incorporated cytohistologic, radiologic, and clinical data.INTERVENTION:EUS-FNA of a peritoneal anomaly.MAIN OUTCOME MEASUREMENTS:Safety and diagnostic yield.RESULTS:Of 106 patients, a criterion standard was available in 98 (39 female patients; median age, 65 years). The sensitivity, specificity, and accuracy of EUS-FNA versus CT/magnetic resonance imaging (MRI) was 91% versus 28%, 100% versus 85%, and 94% versus 47%, respectively. In newly diagnosed cancer patients, peritoneal FNA upstaged 17 patients (23.6%). Of 32 patients deemed resectable by pre-EUS CT/MRI, 15 (46.9%) were deemed unresectable based solely on peritoneal FNA. The odds of FNA changing the resectability status remained highly significant after adjustment for cancer type, time between CT/MRI and EUS-FNA, and the quality of CT/MRI. The malignant appearance of the peritoneal anomaly but not the presence of ascites on EUS predicted a positive FNA finding (odds ratio 2.56; 95% confidence interval, 1.23-5.4 and odds ratio 0.83; 95% confidence interval, 0.4-1.8, respectively). There were 3 adverse events among 4 patients. Two of the patients developed abdominal pain and one each hypertensive urgency and pancreatitis.LIMITATIONS:Retrospective design, single-center, bias toward EUS as a diagnostic test.CONCLUSION:Peritoneal EUS-FNA appears to safely detect radiographically occult PC and improve cancer staging and patient care.

BACKGROUND:Pancreatic cancer (PC) often produces pain that is difficult to control. Celiac neurolysis (CN) is performed with the goal of improving pain control and quality of life while reducing opioid-related side effects. OBJECTIVE:We aimed to evaluate whether CN provides a survival advantage for PC patients. DESIGN:Retrospective case-control study. SETTING:Single tertiary-care referral center. PATIENTS:Review of a prospectively maintained database identified patients with unresectable PC who underwent CN over a 12-year period. Each patient was matched to 2 control patients with unresectable PC. INTERVENTION:CN, which included both celiac plexus neurolysis (CPN) and celiac ganglia neurolysis (CGN). MAIN OUTCOME MEASUREMENTS:Median survival in Kaplan-Meier curves and hazard ratios. RESULTS:A total of 417 patients underwent CN and were compared with 840 controls with PC. Baseline characteristics were similar except the CN group had greater weight loss and pain requiring opioids. A mean of 16.6 ± 5.8 mL of alcohol was administered. For patients who underwent CN, the median survival from the time of presentation was shorter compared with controls (193 vs 246 days; hazard ratio 1.32; 95% confidence interval, 1.13-1.54). There was no difference in survival with unilateral or bilateral injection. However, EUS-guided CN was associated with longer survival compared with non-EUS approaches, and those who received CPN had longer survival compared with CGN. LIMITATIONS:Single center, retrospective. CONCLUSION:Our study suggests that CN is an independent predictor of shortened survival in PC patients. A prospective study is needed to verify the findings and determine whether shortened survival results from CN or from other features such as performance status and tumor-related characteristics. It is also imperative to verify our finding that EUS-guided CN provides a survival advantage over other approaches and whether CPN prolongs survival compared with CGN.

Pancreatic cystic neoplasms (PCN) may require surgical resection. A safe and non-operative treatment of these lesions is desirable. Endoscopic ultrasound (EUS) guided ethanol injection of PCNs has shown to be partially effective but studies are limited.

OBJECTIVES:There are virtually no data concerning the risk of adverse events (AEs) following lower gastrointestinal (LGI) endoscopic ultrasound (EUS). Our aim was to determine the incidence and factors associated with AEs following LGI EUS fine needle aspiration (FNA). METHODS:We conducted a prospective cohort study at a tertiary referral center. Five hundred and sixty-three patients underwent LGI EUS FNA between 1 January 2004 and 1 January 2012. We analyzed the 502 patients who had complete follow-up. AE severity was graded (1-5) utilizing Common Terminology Criteria or Visual Analog Scale. AEs were assessed during the procedures, in clinical follow-up, during phone interviews conducted at 7-14 days, and final clinical and/or phone interviews at 2-4 months. RESULTS:AEs developed in 103 (20.5%) patients and were classified as grade 1, 2, 3, or 4 in 34 (6.8%), 41 (8.2%), 23 (4.6%), and 5 (1.0%) patients, respectively. Bleeding and pain were the commonest AEs. No deaths occurred. On multivariate analysis, AEs were associated with prior pain (odds ratio (OR): 3.83, 95% confidence interval (CI): 2.35-6.25), FNA from a site other than a lymph node (LN) or gut wall (OR: 2.26, 95% CI: 1.10-4.70), and malignant FNA cytology (OR: 1.80, 95% CI: 1.10-2.97); serious (grade 3-4) AEs were associated with prior pain (OR: 15.21, 95% CI: 5.04-45.85) and FNA from a site other than a LN or gut wall (OR: 3.25, 95% CI: 1.15-9.20). CONCLUSIONS:LGI EUS FNA is associated with a high rate of serious grades 3-4 AEs. This may reflect the total number of associated interventions and the frequency of underlying pathology and symptoms.

Pancreatic cancer (PC) often produces pain that is difficult to control. Although opioids effectively relieve pain, they are associated with many side effects. Celiac neurolysis (CN) is performed with the goal of improving pain control and quality of life while reducing the risk of opioid-related side effects. Limited data suggest CN may also prolong survival. We aimed to determine whether CN provides a survival advantage for patients with PC.

Detection of omental metastases significantly affects cancer staging and resectability, but may be difficult to detect with current imaging. EUS and FNA may allow for increased detection rates.

EUS is routinely used to diagnose and stage gastrointestinal cancers. The detection of hepatic metastases enhances staging accuracy and helps direct patient care. We previously derived and validated EUS criteria that help distinguish benign from malignant hepatic masses. We now aim to determine whether educational material based on these EUS criteria improve the accuracy of identifying benign and malignant hepatic masses.

Introduction: To evaluate experience with endoscopic ultrasound (EUS)-guided treatment of pancreaticocutaneous fistulas (PCFs) at a tertiary referral center. Methods: Retrospective review of patients who underwent EUS-guided management of PCFs. Demographic, clinical, imaging, procedural, and outcome variables were abstracted. Results: Four patients (3 female, age range 30-71 years) presented with PCFs. In all cases the fistula was due to an obstructed and leaking pancreatic duct in tail: 3 developed PCFs after Whipple procedure for malignancy (n=2) or an inflammatory mass (n=1), and the fourth developed a PCF following percutaneous drainage of a pancreatic fluid collection in the setting of severe acute pancreatitis with disconnected pancreatic duct syndrome. Mean duration of the fistula was 189 days (range: 80-233). PCFs persisted despite trials of nil by mouth with TPN (n=1), octreotide therapy (n=2), and failed attempts at ERCP (n=4). The mean output was 350 cc/day (range: 200-500 cc), and mean amylase concentration was 15,866 U/L. Patients underwent EUS-guided transmural puncture of the pancreatic duct (n=2), fistula track (n=1), or both (n=1), with placement of 1 or 2 plastic transmural stents providing internal drainage to the stomach (n=3) or duodenum (n=1). Patients underwent a mean of 1.75 endoscopic procedures (range: 1-2), with placement of additional stents in the transmural track during the second procedure, as well as transmural drainage of an additional site of pancreatic duct leakage in 1 patient. Drainage from PCFs ceased after the first endoscopic intervention in 3 patients and after the second procedure in the fourth patient, and all percutaneous drains were removed. Stents were left in place indefinitely. One patient was lost to follow-up; mean follow-up for the remainder was 226 days (range: 170-410). In all 3 cases there has been no recurrence of PCFs, and no patient developed symptoms of pancreatitis, pancreatic fluid collections, or hyperglycemia requiring medical therapy. Weight stabilized or increased in all, and PCF-related pain resolved. Follow-up CT or MR performed in all patients after PCF drain removal showed no pancreatitis or fluid collections. Conclusion: EUS-guided pancreatic duct intervention may successfully treat pancreaticocutaneous fistulas, allowing removal of percutaneous drains. EUS-guided therapy is an attractive alternative for patients who might otherwise require pancreatic tail resection or completion pancreatectomy to achieve resolution of a PCF.

for HMGA2.Results: A total of 32 patients were identified.IPMN types were as noted: branch duct (n = 20), main duct (n = 4), mixed type (n = 8).LGD was present in 5 patients, MD in 17 patients, HGD in 9 patients, and invasive cancer in 1 patient.HMGA2 protein was detected in the cyst fluid of 30/32 (94%) specimens.Mean HMGA2 concentration (ng/ ml): LGD 0.52 ± 0.40, MD 2.56 ± 2.52, HGD 10.5 ±15.22 (p , 0.05).No HMGA2 was detected in the one sample from IPMN with invasive cancer.The mean HMGA2 concentration was significantly higher in the HGD group (10.5 ± 15.22 ng/ml) compared to the concentration in the low-risk IPMN group (2.1 ± 2.38 ng/ml, p = 0.03).The ROC for HMGA2 had an area under the curve of 0.74.Conclusions: HMGA2 protein is present in the cyst fluid of IPMN.Significantly higher concentrations of cyst fluid HMGA2 proteins are found in IPMN with HGD as compared to lesions with LGD or MD.Cyst fluid concentration of HMGA2 may thus serve as a biomarker to differentiate patients with high-risk IPMN lesions from patients with low-risk IPMN lesions.Such a biomarker could help guide clinical decision making regarding which patients may benefit from surgical resection of their IPMN.Further investigation of this cyst fluid biomarker on prospectively obtained samples from EUS-FNA is warranted.