Impact of needle-based confocal laser endomicroscopy on the therapeutic management of single pancreatic cystic lesions.

BACKGROUND AND AIM: The diagnosis and therapeutic management of large single pancreatic cystic lesions (PCLs) represent major issues for clinicians and essentially rely on endoscopic ultrasound fine-needle aspiration (EUS-FNA) findings. Needle-based confocal laser endomicroscopy (nCLE) has high diagnostic performance for PCLs. This study aimed to evaluate the impact of nCLE on the therapeutic management of patients with single PCLs. METHODS: Retrospective and comparative study. Five independent pancreatic disease experts from tertiary hospitals independently reviewed data from a prospective database of 206 patients with single PCL, larger than 2 cm and who underwent EUS-FNA and nCLE. Two evaluations were performed. The first one included the sequential review of clinical information, EUS report and FNA results. The second one included the same data + nCLE report. Participants had to propose a therapeutic management for each case. RESULTS: The addition of nCLE to EUS-FNA led to significant changes in therapeutic management for 28% of the patients (p < 0.001). nCLE significantly increased the interobserver agreement of 0.28 (p < 0.0001), from 0.36 (CI 95% 0.33-0.49) to 0.64 (CI 95% 0.61-0.67). nCLE improved the rates of full agreement among the five experts of 24% (p < 0.0001), from 30 to 54%. With nCLE, the surveillance rate of benign SCAs fell by 35%, from 40 (28/70) to 5% (4/76). CONCLUSION: The addition of nCLE to EUS-FNA significantly improves reliability of PCL diagnosis and could impact the therapeutic management of patients with single PCLs. ClinicalTrials.gov number, NCT01563133.

19 G nitinol needle versus 22 G needle for transduodenal endoscopic ultrasound-guided sampling of pancreatic solid masses: a randomized study.

BACKGROUND: The aim of this prospective multicenter study was to compare a flexible 19 G needle with nitinol shaft (19 G Flex) with a standard 22 G needle for transduodenal endoscopic ultrasound (EUS)-guided sampling of pancreatic head tumors. METHODS: Patients with pancreatic head tumors requiring tissue diagnosis were randomized into two arms: puncture with either a 19 G Flex needle or a 22 G needle. The primary end point was diagnostic accuracy for malignancy. The secondary end points were ergonomic scores, sample cytohistological quality, and complications. A 6-month follow-up was performed. RESULTS: 125 patients were randomized and 122 were analyzed: 59 patients in the 19 G Flex arm and 63 patients in the 22 G arm. The final diagnosis was malignancy in 111 patients and benign condition in 11. In intention-to-treat analysis, the diagnostic accuracy for malignancy of the 19 G Flex and 22 G needles was 69.5 % (95 % confidence interval [CI] 56.1 % - 80.8 %) vs. 87.3 % (95 %CI 76.5 % - 94.4 %), respectively (P = 0.02). In per-protocol analysis excluding eight technical failures in the 19 G Flex group, the diagnostic accuracy of the 19 G Flex and 22 G needles was not statistically different: 80.4 % (95 %CI 66.9 % - 90.2 %) vs. 87.3 % (95 %CI 76.5 % - 94.4 %; P = 0.12). Technical success was higher in the 22 G arm than in the 19 G Flex arm: 100 % (95 %CI 94.3 % - 100 %) vs. 86.4 % (95 %CI 75.0 % - 94.0 %), respectively (P = 0.003). Transduodenal EUS-guided sampling was more difficult with the 19 G Flex (odds ratio 0.68, 95 %CI 0.47 - 0.97). CONCLUSION : The 19 G Flex needle was inferior to a standard 22 G needle in diagnosing pancreatic head cancer and more difficult to use in the transduodenal approach.

Needle-based confocal laser endomicroscopy of pancreatic cystic lesions: a prospective multicenter validation study in patients with definite diagnosis.

BACKGROUND: Needle-based confocal laser endomicroscopy (nCLE) enables observation of the inner wall of pancreatic cystic lesions (PCLs) during an endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). This study prospectively evaluated the diagnostic performance of nCLE for large, single, noncommunicating PCLs using surgical histopathology or EUS-FNA cytohistopathology as a reference diagnosis. METHODS: From April 2013 to March 2016, consecutive patients referred for EUS-FNA of indeterminate PCLs without evidence of malignancy or chronic pancreatitis were prospectively enrolled at five centers. EUS-FNA and nCLE were performed and cystic fluid was aspirated for cytohistopathological and carcinoembryonic antigen (CEA) analysis. The diagnostic performance of nCLE was assessed against the reference standard and compared with that of EUS and CEA. This study was registered on ClinicalTrials.gov (NCT01563133). RESULTS: 206 patients underwent nCLE and 78 PCLs (mean size 40 mm, range 20 - 110 mm) had reference diagnoses (53 premalignant and 25 benign PCLs). Post-procedure pancreatitis occurred in 1.3 % of the patients. nCLE was conclusive in 71 of the 78 cases (91 %). The sensitivies and specifities of nCLE for the diagnosis of serous cystadenoma, mucinous PCL, and premalignant PCL were all ≥ 0.95 (with 95 % confidence interval from 0.85 to 1.0). The AUROC was significantly larger for nCLE than for CEA or EUS. CONCLUSIONS: nCLE had excellent diagnostic performance that surpassed that of CEA and EUS for the diagnosis of large, single, noncommunicating PCLs. The nCLE procedure should be considered in patients with indeterminate PCLs to ensure a more specific diagnosis.

The long term risk of malignancy in patients with branch duct intraductal papillary mucinous neoplasms of the pancreas.

UNLABELLED: In patients (pts) with branch duct intraductal papillary mucinous neoplasms of the pancreas (BD-IPMN), the risk of malignant progression is well described at short- and mid-term. Few data beyond 5 years are available. PATIENTS AND METHODS: Prospective study in consecutive patients (pts) with BD-IPMN and follow-up (F/U) ≥60 months to assess long term risk of malignant progression. All computed tomographies and magnetic resonance cholangiopancreatographies performed every 1 or 2 years (depending on the maximum size of cyst) were read by the same radiologist. EUS was performed in case of occurrence of main pancreatic duct (MPD) dilation or mural nodule >5 mm. Size increase was considered significant if >5 mm. Size variation, criteria suggestive of malignancy, operative therapy and pathology were recorded. RESULTS: 53 pts were included (median age at diagnosis: 61 years, median F/U: 84 months (range: 60-132) including 5 F/U >120 months). Lesions were stable in 38 pts (72%). Size increased in 8 pts (15%) (median increase : 11 (5-33) mm) without mural nodule (MN). One of those was operated on (low-grade dysplasia). A MN appeared in 5 pts (9%). ≥5 mm in 2 pts (5 and 15 mm) who were operated on (intermediate-grade dysplasia in both). The 3 remaining pts (MN < 5 mm) were carefully followed-up. Invasive advanced carcinoma occurred in 2 pts, both after 84 months F/U. In one of these, no imaging changes were noted 12 months before diagnosis of malignancy. CONCLUSION: In BD-IPMN, the risk of malignant evolution persists after 60 months F/U including invasive carcinomas. F/U imaging surveillance is still necessary beyond this delay in patients fit for potential surgery.

Single-operator cholangioscopy monitoring of a remaining bile duct after congenital choledochal cyst surgery: a case report with an innovative approach.

Video 1Single-operator cholangioscopy monitoring of a remaining bile duct after congenital choledochal cyst surgery: a case report with an innovative approach. After removing remaining pancreatic stones in the remnant bile duct, we inserted a Spyglass choledochoscope. Mucosa was regular and monochromatic. We performed biopsies with a Spybite miniforceps in the remnant cyst and its junction.

Mucinous cystic neoplasms of the pancreas: definition of preoperative imaging criteria for high-risk lesions.

BACKGROUND/AIM: Pancreatic mucinous cystic neoplasms (MCN) are premalignant lesions whose natural history is poorly known. Whether the dysplasia grade might be determined with precision by preoperative clinical and imaging criteria is not known. We aimed to determine if CT scan data might be useful to predict the grade of dysplasia in a series of 60 histologically proven MCN. METHODS: All consecutive patients who were operated on with pathological confirmation of MCN were included. Careful CT scan evaluation was reviewed without knowledge of pathological results. Imaging and pathological results were correlated. RESULTS: Sixty patients (59 females) were included. Low- and intermediate-grade dysplasias were identified in 47 and 3 patients (benign MCN), respectively, and high-grade dysplasia and invasive carcinoma in 7 and 3 patients (malignant MCN), respectively. Patients with benign lesions were significantly younger. None of the studied clinical data were statistically different to distinguish benign and malignant MCN, except age (42 vs. 48 years, p < 0.05). Only maximal diameter and mural nodules on CT scan were significantly more frequent in the malignant group. No malignant MCN had a maximal diameter <40 mm. At a 40-mm threshold, the sensitivity and specificity of the maximal diameter to diagnose malignant MCN were 100 and 54%, respectively. Mural nodules seen on CT scan were confirmed in all cases but one upon pathological examination of the surgical specimen. The sensitivity and specificity of the presence of a mural nodule seen on CT scan for the diagnosis of a malignant lesion were 100 and 98%, respectively. CONCLUSION: Preoperative CT scan detection of a mural nodule within a cystic pancreatic neoplasm suggestive of MCN strongly suggests malignancy. A diameter <40 mm is associated with no risk of malignancy.

Safety of different electrocautery modes for endoscopic sphincterotomy: a Bayesian network meta-analysis.

BACKGROUND AND AIMS: Post-endoscopic retrograde cholangiopancreatography acute pancreatitis (PAP) and post-sphincterotomy hemorrhage are known adverse events of post-endoscopic retrograde cholangiopancreatography. Various electrosurgical currents can be used for endoscopic sphincterotomy. The extent to which this influences adverse events remains unclear. We assessed the comparative safety of different electrosurgical currents, through a Bayesian network meta-analysis of published studies merging direct and indirect comparison of trials. METHODS: We performed a Bayesian random-effects network meta-analysis of randomized controlled trials that compared the safety of different electrocautery modes for endoscopic sphincterotomy. RESULTS: Nine studies comparing four electrocautery modes (blended cut, pure cut, endocut, and pure cut followed by blended cut) with a combined enrollment of 1615 patients were included. The pooled results of the network meta-analysis did not show a significant difference in preventing post-sphincterotomy pancreatitis when comparing electrocautery modes. However, pure cut was associated with a statistically significant increased risk of bleeding compared with endocut [relative risk = 4.30; 95% confidence interval (1.53-12.87)]. On the other hand, the pooled results of the network meta-analysis showed no significant difference in prevention of bleeding when comparing blended cut versus endocut, pure cut followed by blended cut versus endocut, pure cut followed by blended cut versus blended cut, pure cut versus blended cut, and pure cut versus pure cut followed by blended cut. The results of rank probability found that endocut was most likely to be ranked the best. CONCLUSION: No electrocautery mode was superior to another with regard to preventing PAP. Endocut was superior with respect to preventing bleeding. Therefore, we suggest performing endoscopic sphincterotomy with endocut.

Role of endoscopic ultrasound in the screening and follow-up of high-risk individuals for familial pancreatic cancer.

Managing familial pancreatic cancer (FPC) is challenging for gastroenterologists, surgeons and oncologists. High-risk individuals (HRI) for pancreatic cancer (PC) (FPC or with germline mutations) are a heterogeneous group of subjects with a theoretical lifetime cumulative risk of PC over 5%. Screening is mainly based on annual magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS). The goal of screening is to identify early-stage operable cancers or high-risk precancerous lesions (pancreatic intraepithelial neoplasia or intraductal papillary mucinous neoplasms with high-grade dysplasia). In the literature, target lesions are identified in 2%-5% of HRI who undergo screening. EUS appears to provide better identification of small solid lesions (0%-46% of HRI) and chronic-pancreatitis-like parenchymal changes (14%-77% of HRI), while MRI is probably the best modality to identify small cystic lesions (13%-49% of HRI). There are no specific studies in HRI on the use of contrast-enhanced harmonic EUS. EUS can also be used to obtain tissue samples. Nevertheless, there is still limited evidence on the accuracy of imaging procedures used for screening or agreement on which patients to treat. The cost-effectiveness of screening is also unclear. Certain new EUS-related techniques, such as searching for DNA abnormalities or protein markers in pancreatic fluid, appear to be promising.

Morphologic changes in branch duct intraductal papillary mucinous neoplasms of the pancreas: a midterm follow-up study.

BACKGROUND & AIMS: Because there is a low risk of malignancy for intraductal papillary and mucinous neoplasms of the pancreas (IPMNs) confined to branch ducts (BD), patient follow-up evaluation without surgery is possible. The aim of this study was to assess time-related morphologic changes and risk of progress to malignancy in patients with BD IPMN. A prospective design was used in an academic tertiary referral center. METHODS: All consecutive patients seen from 1999 to 2005 with highly suspected IPMNs confined to BD without criteria suggesting a malignant development (mural nodule, cyst wall thickness >2 mm, BD diameter >30 mm, or main pancreatic duct involvement) were followed up prospectively using computerized tomography, magnetic resonance cholangiopancreatography, and endoscopic ultrasonography. RESULTS: A total of 121 patients (median age, 63 y) were included. After a median follow-up period of 33 months, no morphologic changes had occurred in 88 patients. The size of the cyst increased in 30 of the 33 remaining patients, and 12 developed criteria suggesting a malignant development. Surgery, performed in 8 of 12 patients, found 4 IPMN-adenomas, 1 borderline-IPMN, and 4 IPMN carcinoma in situ. The 4 remaining patients did not undergo surgery because of severe comorbid conditions in 2, change in reference hospital in 1, and a mural nodule considered being sequelae of previous fine-needle aspiration in 1 patient. The only factor associated with signs suggesting malignant development was an increase in cyst size to more than 5 mm during the follow-up evaluation. CONCLUSIONS: In patients with IPMNs confined to BD, morphologic changes are rare events, justifying a nonsurgical approach. Careful follow-up evaluation remains necessary, particularly in patients with an increase in BD size.

Intraductal papillary mucinous neoplasms of the pancreas: performance of pancreatic fluid analysis for positive diagnosis and the prediction of malignancy.

INTRODUCTION: The preoperative diagnosis of intraductal papillary mucinous neoplasms (IPMN) of the pancreas must be as reliable as possible because large or even total pancreatectomy may be necessary. Early diagnosis of malignant forms is important to improve prognosis. The diagnostic accuracy of fluid analysis using endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has been confirmed in cystic lesions of the pancreas. It is not known if these results can be applied to IPMN. AIMS: To determine the levels of biochemical and tumor markers in fluid from EUS-FNA in patients with IPMN and to assess the impact on the diagnosis of IPMN. PATIENTS AND METHODS: In total, 41 patients (14 men, median age 64 yr) underwent EUS-FNA before surgical resection of IPMN in our center. Levels of amylase, lipase, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19.9, and CA 72.4 were measured in the cyst fluid. The performance of the markers was retrospectively evaluated for: (a) a positive diagnosis of IPMN, using cutoffs validated in the literature for mucinous pancreatic lesions and (b) an assessment of malignancy (i.e., high-grade dysplasia or invasive carcinoma) compared with the final pathological examination of the surgical specimen. RESULTS: EUS-FNA was performed in dilated branch ducts (BD) in 39 cases and in the main pancreatic duct in 2 cases. No serious complications occurred. The median fluid levels of amylase, lipase, CEA, CA 19.9, and CA 72.4 were 20,155 U/mL, 59,500 U/mL, 173 ng/mL, 6,400 U/mL, and 11.5 U/mL, respectively. A CEA level >200 ng/mL and a CA 72.4 >40 U/mL had a 44% and a 39% sensitivity, respectively, for the diagnosis of IPMN. The levels of CEA, CA 19.9, and CA 72.4 were significantly different between benign and malignant IPMN. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of a CEA level >200 ng/mL for the diagnosis of malignant IPMN were 90%, 71%, 50%, and 96%, respectively. The sensitivity, specificity, PPV, and NPV of a CA 72.4 level >40 U/mL for this purpose were 87.5%, 73%, 47%, and 96%, respectively. CONCLUSION: CEA and CA 72.4 in pancreatic cyst fluid have excellent NPVs in the preoperative differential diagnosis of benign versus malignant IPMN, and might reinforce the decision of not to operate on patients with BD-type without predictive factors of malignancy.

[Suspected malignant cancer of the pancreas associated with pseudo-invasive duodenal hamartomas in a patient with Peutz-Jeghers syndrome]. / Suspicion de tumeur pancréatique maligne liée à des hamartomes duodénaux pseudo-invasifs au cours d'un syndrome de Peutz-Jeghers.

A 29-year-old man with a previously known Peutz-Jeghers syndrome (PJS) was admitted for epigastric pain, emesis and weight loss due to both intestinal intussusception causing bowel obstruction and obstructive pancreatitis. The patient had cholestasis with an enlarged common bile duct on imaging. Because duodenal and/or pancreatic cancer was suspected due to weight loss, the pancreatic and bile duct obstruction, and the increased risk of small intestine and pancreatic adenocarcinoma in patients with PSJ, a pancreatoduodenectomy was performed. Pathological examination revealed a duodenal polyp with epithelial misplacement invading the ampulla and compressing the main bile duct. Twenty months after surgery, there was no relapse of symptoms or cholestasis. This is the first case showing a direct role of pseudo-invasive duodenal harmatomas in the development of biliary obstruction and chronic obstructive pancreatitis.

[Diffuse primary fat replacement of the pancreas: an unusual cause of steatorrhea]. / Infiltration graisseuse diffuse et primitive du pancréas: une cause rare de stéatorrhée.

Diffuse and primitive fat replacement of the exocrine pancreas is a rare cause of exocrine pancreatic insufficiency in adults. We report two adult patients with chronic diarrhoea and steatorrhea whose morphologic abnormalities revealed diffuse fat replacement of the pancreas. Tomodensitometry detected diffuse characteristic abnormalities with fat intermixed with normal pancreatic lobules or a "vanishing pancreas". In one patient, magnetic resonance imaging and echo-endoscopy suggested abnormalities. Administration of pancreatic extracts improved symptoms.

Accuracy of 2012 International Consensus Guidelines for the prediction of malignancy of branch-duct intraductal papillary mucinous neoplasms of the pancreas.

OBJECTIVE: To determine accuracy of 2012 International Consensus Guidelines (ICG) predicting malignancy in a surgical cohort of branch-duct intraductal papillary mucinous neoplasms (BD-IPMN). METHODS: This study included all consecutive patients with final pathological diagnosis of pure BD-IPMN resected between 2006 and 2014 at Beaujon Hospital. Neoplasms were classified as malignant in presence of high-grade dysplasia (HGD) or invasive carcinoma. Medical, pathological, and radiological data were retrospectively recorded. RESULTS: One hundred and twenty patients (65 males, mean age: 57.9 ± 10.8 years) were included. Malignant BD-IPMN accounted for 30% (HGD: 18%, invasive: 12%). Thickened cyst walls (odds ratio (OR): 3.058, 95% confidence interval (CI 95%): 1.102-8.484, p = 0.032), main duct diameter 5-9 mm (OR: 3.395, CI 95%: 1.349-8.543, p = 0.007), and mural nodule (OR: 3.802, CI 95%: 1.156-12.511, p = 0.028) were independently associated with malignancy in multivariate analysis. Among the 89 patients (74%) who underwent surgical resection with ICG criteria, the malignancy rate was 38%, compared with 6% in the 31 ICG-negative group. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for malignancy of having at least one ICG criteria were 94%, 34%, 38%, 94%, and 53%, respectively. Patients with malignant tumors had more ICG criteria than those with benign lesions (2.06 ± 0.98 vs. 0.99 ± 0.95, p < 0.001). CONCLUSIONS: 2012 ICG criteria are useful to manage BD-IPMN permitting not to miss a malignant form (NPV of 94%), but frequently point out unnecessary surgery (PPV of 38%). Malignancy rate increases with the number of ICG criteria. In patients with only one criterion, additional criteria would be necessary.

Irregular narrowing of the main pancreatic duct in association with a wall thickening is a key sign at endoscopic ultrasonography for the diagnosis of autoimmune pancreatitis.

OBJECTIVES: The aim of this study was to assess the accuracy of key signs identified at endoscopic ultrasonography in diagnosing an autoimmune pancreatitis (AIP). METHODS: Between January 2007 and December 2011, a retrospective case-control study was conducted in 177 patients with AIP (n = 30), pancreatic adenocarcinoma (n = 42), pancreatic neuroendocrine tumor (n = 21), alcoholic chronic pancreatitis (n = 32), and symptomatic common bile duct stones (n = 52). RESULTS: An irregular narrowing of the main pancreatic duct in association with a wall thickening was seen in 28 of 30 AIP, 1 of 42 pancreatic adenocarcinoma, 0 of 21 pancreatic neuroendocrine tumor, 0 of 32 alcoholic chronic pancreatitis, and 0 of 52 common bile duct stones (P < 0.05). Sensitivity, specificity, positive and negative predictive values, and overall diagnostic accuracy of this sign for the diagnosis of AIP were 93%, 99.3%, 96.3%, 98.6%, and 98.3%, respectively. In type 1 AIP, hyperechoic parietal thickening was more frequent (92.3% vs 33.3%, P < 0.05). In type 2 AIP, hypoechoic parietal thickening was more frequent (83.3% vs 23.1%, P < 0.05). CONCLUSIONS: An irregular narrowing of the main pancreatic duct in association with a wall thickening seen at endoscopic ultrasonography is accurate in diagnosing AIP. The type of echogenicity of the thickening is well correlated with the type of AIP.

Can pancreatic neuroendocrine tumour biopsy accurately determine pathological characteristics?

BACKGROUND: Assessment of the pathological characteristics of pancreatic neuroendocrine tumours is crucial for appropriate management. We compared preoperative pathological data with surgical specimens for accuracy. METHODS: Surgical patients with pancreatic neuroendocrine tumours who underwent preoperative endoscopic ultrasound-guided fine needle aspiration of the primary tumour or biopsy of liver metastasis were retrospectively included. Tumour differentiation and the Ki67 proliferation index on biopsies were compared with pancreatic specimens. RESULTS: Fifty-seven patients were included. A preoperative biopsy of the primary tumour or of a liver metastasis was obtained in 48 and 9 patients respectively. Tumour differentiation was high in 98%, and poor in 2% on biopsy and high in 100% of surgical specimens. Ki67 index values were 0 (0-19) and 2 (0-15) on biopsy and surgical specimens (p=0.01). Correlation between preoperative and surgical findings was stronger for liver (r=0.62, p=0.001) than for pancreas (r=0.23, p=0.11). Correlation for pancreas varied according to the tumour pattern: solid (r=0.24, p=0.16), mixed (r=0.91, p=0.0036) or cystic (r=0.04, p=0.89). Tumour grade was different between pancreatic biopsies and surgical specimens, for grade 1 (63% vs 37%) and grade 2 (28% vs 72%), p=0.0007. CONCLUSIONS: Tumour grade assessment is accurate in biopsies of liver metastases of pancreatic neuroendocrine tumours, while pancreatic fine-needle aspiration biopsies are less accurate.

Pancreatic intraepithelial neoplasia in patients with intraductal papillary mucinous neoplasms: the interest of endoscopic ultrasonography.

OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasia (PanIN) are both precancerous lesions. Papillary mucinous neoplasms have been described in patients with IPMN, but their relationship is still poorly understood. The aims of this study were to look for PanIN lesions in patients operated on for IPMN and to search for correlations between endoscopic ultrasonography(EUS) features and pathologic findings. METHODS: Endoscopic ultrasonography was preoperatively performed in all patients with IPMN consecutively operated on in our center. Endoscopic ultrasonography features were prospectively compared with pathologic data from surgical specimen. RESULTS: Forty patients underwent resection for benign (52.5%) or malignant (47.5%) IPMN. Pancreatic intraepithelial neoplasia lesions were observed in 78% of cases (PanIN-3 in 19% of patients). PanIN-3 lesions were observed in 11% and 26% of patients with benign and malignant IPMN, respectively. Endoscopic ultrasonography changes(microcysts and/or hyperechoic foci) corresponded to PanIN lesions in 83% of cases. Endoscopic ultrasonography detected 69% of patients with PanIN lesions and 57% of those with panIN-3 lesions. CONCLUSIONS: Pancreatic intraepithelial neoplasia lesions are very frequently associated with IPMN, and 19% of patients with IPMN had PanIN-3 lesions. In two thirds of patients, EUS can detect minimal changes in the pancreas corresponding to PanIN lesions.