Antonella Giussani

Risk factors for post-ERCP pancreatitis in high- and low-volume centers and among expert and non-expert operators: a prospective multicenter study.

OBJECTIVES:Prospective studies have identified a number of patient- and procedure-related independent risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, with different conclusions, so various questions are still open. The endoscopists expertise, case volume, and case mix can all significantly influence the outcome of ERCP procedures, but have been investigated little to date.METHODS:We identified patient- and procedure-related risk factors for post-ERCP pancreatitis and the impact of the endoscopists experience and the centers case volume, using univariate and multivariate analysis, in a multicenter, prospective study involving low- and high-volume centers, over a 6-month period.RESULTS:A total of 3,635 ERCP procedures were included; 2,838 (78%) ERCPs were performed in the 11 high-volume centers (median 257 each) and 797 in the 10 low-volume centers (median 45 each). Overall, 3,331 ERCPs were carried out by expert operators and 304 by less-skilled operators. There were significantly more grade 3 difficulty procedures in high-volume centers than in low-volume ones (P<0.0001). Post-ERCP pancreatitis occurred in 137 patients (3.8%); the rates did not differ between high- and low-volume centers (3.9% vs. 3.1%) and expert and non-expert operators (3.8% vs. 5.5%). However, in high-volume centers, there were 25% more patients with patient- and procedure-related risk factors, and the pancreatitis rate was one-third higher among non-expert operators. Univariate analysis found a significant association with pancreatitis for history of acute pancreatitis, either non-ERCP- or ERCP-related and recurrent, young age, absence of bile duct stones, and biliary pain among patient-related risk factors, and >10 attempts to cannulate the Vaters papilla, pancreatic duct cannulation, contrast injection of the pancreatic ductal system, pre-cut technique, and pancreatic sphincterotomy, among procedure-related risk factors. Multivariate analysis also showed that a history of post-ERCP pancreatitis, biliary pain, >10 attempts to cannulate the Vaters papilla, main pancreatic duct cannulation, and pre-cut technique were significantly associated with the complication.CONCLUSIONS:A history of pancreatitis among patient-related factors, and multiple attempts at cannulation among procedure-related factors, were associated with the highest rates of post-ERCP pancreatitis. Pre-cut sphincterotomy, although identified as another significant risk factor, appeared safer when done early (fewer than 10 attempts at cannulating), compared with repeated multiple cannulation. The risk of post-ERCP pancreatitis was not associated with the case volume of either the single endoscopist or the center; however, high-volume centers treated a larger proportion of patients at high risk of pancreatitis and did a significantly greater number of difficult procedures.

Guidewire biliary cannulation does not reduce post-ERCP pancreatitis compared with the contrast injection technique in low-risk and high-risk patients

BACKGROUND Guidewire (GW) cannulation can reduce the risk of post-ERCP pancreatitis (PEP) by avoiding the opacification of the main pancreatic duct. OBJECTIVE To compare the effects of conventional contrast ERCP and GW cannulation of the common bile duct on the rate of PEP in low- and high-risk patients. DESIGN Prospective, comparative-intervention single-center study. SETTING Tertiary referral center. PATIENTS Patients with biliary disease with an intact papilla were prospectively examined by ERCP. INTERVENTIONS Biliary cannulation using a sphincterotome with contrast injection (ConI) or a hydrophilic GW without contrast injection. MAIN OUTCOME MEASUREMENTS Pancreatitis rate in the GW group and the contrast injection (ConI) group. RESULTS PEP occurred in 60 of 1249 patients (4.8%), 35 of 678 (5.2%) in the GW group and 25 of 571 (4.4%) in the ConI group (not significant). The overall rate of PEP was significantly higher in high-risk patients (12.2%) than in low-risk patients (3.5%) (P < .001), but was similar for the 2 techniques within each of these 2 groups. In patients with unintended main pancreatic duct (MPD) cannulation or opacification, the rate of PEP was not significantly different with the GW (15.2%) and ConI (8.4%) techniques but was associated with a significantly higher rate of pancreatitis (11.9%) than in patients in whom the contrast medium or GW did not enter the MPD (3.5%) (P < .001). Multivariate analysis indicated that more than 10 papillary cannulation attempts, MPD cannulation or opacification, suspected sphincter of Oddi dysfunction, and precut methods were significant risk factors independently associated with PEP. LIMITATIONS Lack of randomization. CONCLUSIONS For selective cannulation of the CBD, the risk of inducing PEP is similar with the ConI and GW techniques in high-risk and low-risk patients. Any manipulation of the MPD must be considered a high-risk factor for PEP, such as multiple attempts on the papilla or use of the precut method.

Diagnostic yield of ERCP and secretin-enhanced MRCP and EUS in patients with acute recurrent pancreatitis of unknown aetiology

BACKGROUND Magnetic resonance cholangio-pancreatography (MRCP), endoscopic ultrasonography (EUS), and endoscopic cholangio-pancreatography (ERCP) are the most frequently employed second-step procedures to detect biliary and pancreatic abnormalities in patients with acute recurrent pancreatitis (ARP) of unknown aetiology. MRCP and EUS both give a better view of the bilio-pancreatic ductal system after secretin stimulation (MRCP-S, EUS-S). EUS also serves to identify changes in the pancreatic parenchyma consistent with chronic pancreatitis, at an early stage. However, no studies have compared MRCP-S, EUS-S, and ERCP in the diagnosis of recurrent pancreatitis. AIM To prospectively compare the diagnostic yield of MRCP-S, EUS-S, and ERCP in the evaluation of patients with acute recurrent pancreatitis with non-dilated ducts, of unknown aetiology. METHODS Forty-four consecutive patients with ARP were prospectively scheduled to undergo MRCP-S, EUS-S and ERCP, in accordance with a standard protocol approved by the institutional review board. Diagnoses such as biliary microlithiasis, congenital variants of the pancreatic ducts, chronic pancreatitis and sphincter of Oddi dysfunction were compared between the three procedures. The diagnosis of chronic pancreatitis was established according to ductal morphology by MRCP-S and ERCP, ductal and parenchymal morphology by EUS-S. RESULTS The three procedures combined achieved a diagnosis that could have explained the recurrence of pancreatitis in 28/44 patients (63.6%). EUS-S recognized ductal and/or parenchymal abnormalities with the highest frequency (35/44 patients, 79.5%). Both MRCP-S and EUS-S were superior to ERCP for detecting pancreatic ductal abnormalities. EUS-S showed up pancreatic parenchymal changes in more than half the cases. Both EUS and MRCP secretin kinetics were concordant in identifying two cases with sphincter of Oddi dysfunction. CONCLUSIONS The diagnostic yield of EUS-S in recurrent pancreatitis with non-dilated ducts and unknown aetiology was 13.6% and 16.7% higher than MRCP-S and ERCP respectively (although not significant), which both gave substantially similar diagnostic yields. In no case did ERCP alone find a diagnosis missed by the other two procedures. MRCP-S and EUS-S should both be used in the diagnostic work-up of idiopathic recurrent pancreatitis as complementary, first-line, techniques, instead of ERCP.

Pancreatic Ductal Abnormalities Documented by Secretin-Enhanced MRCP in Asymptomatic Subjects With Chronic Pancreatic Hyperenzymemia

OBJECTIVES:Persistently high serum pancreatic enzymes in asymptomatic subjects are considered a benign idiopathic condition called “non-pathological chronic pancreatic hyperenzymemia” (CPH). However, recent studies with advanced imaging techniques have brought to light abnormal pancreatic findings in a significant proportion of these subjects. The objective of this study was to evaluate pancreatic ductal morphology by secretin-enhanced magnetic resonance cholangiopancreatography (MRCP-S) in subjects with CPH and compare MRCP imaging before and after secretin injection.METHODS:In total, 25 consecutive patients with CPH were investigated by MRCP and MRCP-S and compared with 28 consecutive age-matched controls with recurrent upper abdominal pain and normal pancreatic enzymemia.RESULTS:MRCP-S showed abnormal pancreatic morphological findings in 13 of the 25 CPH cases (52%) and 1/28 controls (3.6%) (P<0.001). MRCP findings consistent with a diagnosis of chronic pancreatitis, according to the Cambridge classification, were detected in eight CPH cases (32%) after secretin injection but none of the controls. Secretin stimulation boosted the diagnostic yield of MRCP for the diagnosis of chronic pancreatitis fourfold. Pancreas divisum was identified in two CPH cases and one control. A 15-min persisting dilation of the main pancreatic duct was noted in three cases in each group. Compared with MRCP, MRCP-S showed significantly fewer CPH patients with normal findings (P<0.02).CONCLUSIONS:MRCP-S detected ductal findings consistent with chronic pancreatitis in one-third of CPH cases. Pancreas divisum and some dysfunction at the level of Vaters papilla were reported in 8 and 12% of the patients, respectively. MRCP-S is to be recommended, instead of MRCP, in the diagnostic work-up of CPH subjects.

Difficult biliary cannulation during ERCP: How to facilitate biliary access and minimize the risk of post-ERCP pancreatitis

Endoscopic retrograde cholangio-pancreatography (ERCP) is one of the most technically challenging procedures in therapeutic endoscopy; difficulties in biliary cannulation and post-ERCP pancreatitis are still significant problems. Deep cannulation of Vaters papilla may fail in up to 5% of cases; selective biliary cannulation reportedly fails in 15-35% of cases, even in experienced hands; repeated and prolonged attempts at cannulation increase the risk of post-procedure pancreatitis. Therefore, cannulation technique plays a pivotal role in successful cannulation and occurrence of post-procedure pancreatitis. This review presents and discusses the techniques that can be used for achieving biliary cannulation after an initial failure and for minimizing the risk of pancreatitis, including guide wire assisted technique, needle knife precutting, trans-pancreatic sphincterotomy, and pancreatic stenting.

Early precut sphincterotomy for difficult biliary access to reduce post-ERCP pancreatitis: a randomized trial

BACKGROUND AND STUDY AIM Precut sphincterotomy is a technique usually employed for difficult biliary cannulation during endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of bile duct disease. It is a validated risk factor for post-ERCP pancreatitis (PEP), but it is not clear whether the risk is related to the technique itself or to the repeated biliary cannulation attempts preceding it. The primary aim of the study was to assess the incidence of PEP in early precut compared with the standard technique in patients with difficult biliary cannulation. Secondary aims were to compare complications and cannulation success. PATIENTS AND METHODS In this prospective, multicenter, randomized, clinical trial, patients who were referred for therapeutic biliary ERCP and difficult biliary cannulation were randomized to early precut (Group A) or repeated papillary cannulation attempts followed, in cases of failure, by late precut (Group B). PEP was defined as the onset of upper abdominal pain associated with an elevation in serum pancreatic enzymes of at least three times the normal level at more than 24 hours after the procedure. No rectal indomethacin or diclofenac was used for prevention of PEP. RESULTS A total of 375 patients were enrolled. PEP developed in 10 of the 185 patients (5.4 %) in Group A and 23 of the 190 (12.1 %) in Group B (odds ratio [OR] 0.35; 95 % confidence interval [CI] 0.16 - 0.78). The incidence of PEP was significantly lower in the early precut group (10/185, 5.4 %) than in the delayed precut subgroup (19/135 [14.1 %]; OR 0.42, 95 %CI 0.17 - 1.07). There were no differences in biliary cannulation success rates, bleeding, perforation, and cholangitis. CONCLUSIONS In patients with difficult biliary cannulation, early precut is an effective technique and can significantly reduce the incidence of PEP. Repeated biliary cannulation attempts are a real risk factor for this complication.

Outcome of endotherapy for pancreas divisum in patients with acute recurrent pancreatitis

AIM To assess the rate of relapses of acute pancreatitis (AP), recurrent AP (RAP) and the evolution of endosonographic signs of chronic pancreatitis (CP) in patients with pancreas divisum (PDiv) and RAP. METHODS Over a five-year period, patients with PDiv and RAP prospectively enrolled were divided into two groups: (1) those with relapses of AP in the year before enrollment were assigned to have endoscopic therapy (recent RAP group); and (2) those free of recurrences were conservatively managed, unless they relapsed during follow-up (previous RAP group). All patients in both groups entered a follow-up protocol that included clinical and biochemical evaluation, pancreatic endoscopic ultrasonography (EUS) every year and after every recurrence of AP, at the same time as endoscopic retrograde cholangiopancreatography (ERCP). RESULTS Twenty-two were treated by ERCP and 14 were conservatively managed during a mean follow-up of 4.5 ± 1.2 years. In the recent RAP group in whom dorsal duct drainage was achieved, AP still recurred in 11 (57.9%) after the first ERCP, in 6 after the second ERCP (31.6%) and in 5 after the third ERCP (26.3%). Overall, endotherapy was successful 73.7%. There were no cases of recurrences in the previous RAP group. EUS signs of CP developed in 57.9% of treated and 64.3% of untreated patients. EUS signs of CP occurred in 42.8% of patients whose ERCPs were successful and in all those in whom it was unsuccessful (P = 0.04). There were no significant differences in the rate of AP recurrences after endotherapy and in the prevalence of EUS signs suggesting CP when comparing patients with dilated and non-dilated dorsal pancreatic ducts within each group. CONCLUSION Patients with PDiv and recent episodes of AP can benefit from endoscopic therapy. Effective endotherapy may reduce the risk of developing EUS signs of CP at a rate similar to that seen in patients of previous RAP group, managed conservatively. However, in a subset of patients, endotherapy, although successful, did not prevent the evolution of endosonographic signs of CP.

ERCP-induced and non-ERCP-induced acute pancreatitis: Two distinct clinical entities with different outcomes in mild and severe form?

BACKGROUND Acute pancreatitis is a complication of endoscopic retrograde cholangio-pancreatography. Aim of the study was to compare endoscopic retrograde cholangio-pancreatography-related acute pancreatitis with attacks caused by other factors. METHODS A series of consecutive patients with non-endoscopic retrograde cholangio-pancreatography-related acute pancreatitis referred to our hospital in 2007-2008 were examined retrospectively, and compared with the same number of patients with post-endoscopic retrograde cholangio-pancreatography acute pancreatitis done in the same institution. Both groups comprised 116 patients and were comparable for mean age, sex, and body mass index. Duration of abdominal pain, pancreatic enzyme elevation, hospital stay, and type of analgesia administered were retrieved. RESULTS There were no differences between the groups as regards the severity of pancreatitis, mortality rate and hospitalisation, although mortality was double in severe post-endoscopic retrograde cholangio-pancreatography acute pancreatitis. In the mild acute pancreatitis cases, serum amylase fell 50% from the peak in a mean of 46.4h (range 24-72) in group 1 and 38.9h (range 24-72) in group 2 (p<0.001). The peak amylase serum level halved within 48h in 73.6% of cases with non-endoscopic retrograde cholangio-pancreatography-related acute pancreatitis, and in 92% of patients with endoscopic retrograde cholangio-pancreatography-related acute pancreatitis (p<0.001). CONCLUSIONS Non-endoscopic retrograde cholangio-pancreatography- and endoscopic retrograde cholangio-pancreatography-induced pancreatitis did not differ as regards severity, hospital stay or mortality; in mild pancreatitis, serum amylase halved significantly sooner in post-endoscopic retrograde cholangio-pancreatography cases.

Acute hemorrhage with retroperitoneal hematoma after endoscopic ultrasound-guided fine-needle aspiration of an intraductal papillary mucinous neoplasm of the pancreas.

Acute Hemorrhage With Retroperitoneal Hematoma After Endoscopic Ultrasound-Guided Fine-Needle Aspiration of an Intraductal Papillary Mucinous Neoplasm of the Pancreas

S1302 Synchronous Intraductal Papillary Mucinous Neoplasm and Autoimmune Pancreatitis: An Original Association

tertiary care referral centers experience with EUS-FNA of pancreatic cysts. Medical records of patients who had more than one EUS-FNA from 2003 to 2007 were reviewed. Cyst size, location, CEA level, cytopathology and interval between EUS-FNA examinations were recorded. For each patient, cyst diagnosis was determined by surgical pathology (when available) or via established criteria for diagnosis of mucinous cystic neoplasms by cyst fluid chemistry (CEA >192 ng/mL) and/or cytopathologic analysis. Results: 197 patients underwent EUS-FNA for the evaluation of a pancreatic cyst, of which 31 (16%) had more than one examination. A total of 71 exams were performed in these patients. Repeat EUS-FNA led to a new diagnosis in 9 patients (29%). Two were found to have a malignancy, 4 patients had a pseudocyst, 2 patients had a mucinous cystic neoplasm and 1 patient had a serous cystadenoma. The average interval between exams among patients in which a repeat EUSFNA made a diagnostic difference was 20.6 vs. 13.0 months in those in which it did not (p=0.15). Pancreatic cysts increased in size by, on average, 0.53cm/yr +/0.82 cm among patients in which repeat EUS-FNA made a definitive diagnosis. In patients where the initial EUS-FNA was non-diagnostic, insufficient cyst fluid aspiration was noted in comparison to those in whom a definitive diagnosis was made (33% vs.72%p=0.056). Conclusion: This is the first study, to our knowledge, to evaluate the role of repeat EUS-FNA for the definitive diagnosis of indeterminant pancreatic cysts. In our small sample, repeat EUS-FNA led to a clear diagnosis in 29% of patients. Although the statistical power of this study is limited, it appears that repeat EUS-FNA should be considered in patients who have a cyst increasing in size or if insufficient cyst fluid was aspirated initially to quantify a CEA level.