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Background & Aims: Duodenoscope-associated transmission of infections has raised questions about efficacy of endoscope reprocessing using high-level disinfection (HLD). Although ethylene oxide (ETO) gas sterilization is effective in eradicating microbes, the impact of ETO on endoscopic ultrasound (EUS) imaging equipment remains unknown. In this study, we aimed to compare the changes in EUS image quality associated with HLD vs HLD followed by ETO sterilization. Methods: Four new EUS instruments were assigned to 2 groups: Group 1 (HLD) and Group 2 (HLD + ETO). The echoendoscopes were assessed at baseline, monthly for 6 months, and once every 3 to 4 months thereafter, for a total of 12 time points. At each time point, review of EUS video and still image quality was performed by an expert panel of reviewers along with phantom-based objective testing. Linear mixed effects models were used to assess whether the modality of reprocessing impacted image and video quality. Results: For clinical testing, mixed linear models showed minimal quantitative differences in linear analog score (P =. 04; estimated change, 3.12; scale, 0–100) and overall image quality value (P =. 007; estimated change, −0.12; scale, 1–5) favoring ETO but not for rank value (P =. 06). On phantom testing, maximum depth of penetration was lower for ETO endoscopes (P

Background Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has been suggested for obtaining high quality tissue samples from pancreatic tumors. We performed a multicenter randomized crossover trial comparing EUS-FNB with a 20G Procore needle vs. a 22G Acquire needle. The aims were to compare the quantity of targeted tissue (pancreas) and diagnostic accuracy for the two needles.Methods 60 patients admitted for EUS-FNB in three endoscopy units were included. One pass was performed consecutively with each needle, in a randomized order. Histologic material was studied in a blinded manner with respect to the needle. The primary end point was mean cumulative length of tissue core biopsies per needle pass.Results Final diagnosis was adenocarcinoma (n = 46; 77 %), neuroendocrine neoplasm (n = 11; 18 %), autoimmune pancreatitis (n = 2), and mass-forming chronic pancreatitis (n = 1). The mean cumulative length of tissue core biopsies per needle pass was significantly higher with the 22G Acquire needle at 11.4 mm (95 % confidence interval [CI] 9.0 – 13.8] vs. 5.4 mm (95 %CI 3.8 – 7.0) for the 20G Procore needle (P Conclusions EUS-guided biopsy of pancreatic masses with the 22G Acquire needle provided more tissue for histologic evaluation and better diagnostic accuracy than the 20G Procore needle.

Background and study aims Feasibility of EUS-guided choledochoduodenostomy (EUS-CDS) using available lumen-apposing stents (LAMS) is limited by the size of the common bile duct (CBD) (≤ 12 mm, cut-off for experts; 15 mm, cut-off for non-experts). We aimed to assess the prevalence and predictive factors associated with CBD size ≥ 12 and 15 mm in naïve patients with malignant distal biliary obstruction (MDBO). Patients and methods This was a prospective cohort study involving 22 centers with assessment of CBD diameter and subjective feasibility of the EUS-CDS performance in naïve jaundiced patients undergoing EUS evaluation for MDBO. Results A total of 491 patients (mean age 69 ± 12 years) with mean serum bilirubin of 12.7 ± 6.6 mg/dL entered the final analysis. Dilation of the CBD ≥ 12 and 15 mm was detected in 78.8 % and 51.9 % of cases, respectively. Subjective feasibility of EUS-CDS was expressed by endosonographers in 91.2 % for a CBD ≥ 12 mm and in 96.5 % for a CBD ≥ 15 mm. On multivariate analysis, age (P Conclusions Our study showed that at presentation in a large cohort of patients with MDBO, EUS-CDS can be potentially performed in three quarters to half of cases by expert and less experienced endosonographers, respectively. Dedicated stents or devices with different designs able to overcome the limitations of existing electrocautery-enhanced LAMS for EUS-CDS are needed.

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 p p 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.

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.

Background standard B-mode EUS assessment and EUS-guided tissue acquisition present sub-optimal diagnostic yield in the differential diagnosis of gastric submucosal tumors (SMTs). Aims to evaluate the performances of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) to differentiate gastric SMTs and predict malignancy risk of gastrointestinal stromal tumors (GIST). Methods a retrospective analysis was performed retrieving consecutive patients with gastric SMTs who underwent EUS between 2009 and 2014. Patients with available EUS video recordings and histological diagnosis were included. De-identified videos were presented to experts who made a diagnosis on B-mode EUS and CH-EUS. Results fifty-four patients (29 female, 64-year-old) were included. Final diagnoses were 40 GISTs (8 high-grade), 9 leiomyomas, 5 rare SMTs. The sensitivity, specificity, and accuracy of B-mode and CH-EUS for the differential diagnosis of GIST were 95.0% vs. 85.0%, 57.1% for both techniques, and 85.2% vs. 77.8%, respectively. The sensitivity, specificity, and accuracy of B-mode and CH-EUS for the estimation of the malignancy GISTs risk were 62.5% vs. 100%, 83.3% vs. 82.1%, and 78.9% vs. 86.1%, respectively. Conclusions CH-EUS showed better diagnostic performance than B-mode EUS in differentiating leiomyomas and risk stratification of GIST. When considering high-grade GISTs, the addition of CH-EUS allowed an improvement in diagnostic accuracy.

Background and Aims Contrast harmonic EUS (CH-EUS) has the ability to depict tumor microvasculature. Decreased microvascular density has been identified as a factor associated with tumor aggressiveness. We aimed to study the accuracy of CH-EUS for the prediction of pancreatic neuroendocrine tumor (PNET) aggressiveness. Methods Between June 2009 and March 2015, all consecutive patients with histology-proven PNETs and CH-EUS examination were included. Nine endosonographers blindly analyzed all videos. CH-EUS tumor aggressiveness was defined as a heterogeneous enhancement at the early arterial phase. The final diagnosis of tumor aggressiveness was defined as follows: G3 tumors, morphologic and/or histologic findings of metastatic disease in G1/G2 tumors. Diagnostic values were calculated. Intratumoral microvascular density and fibrosis were assessed on pathologic specimens. Results Eighty-one tumors were included, of which 26 were aggressive (32.1%). In CH-EUS 35 tumors (43.2%) had a heterogeneous enhancement. The overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of CH-EUS for the diagnosis of tumor aggressiveness were 86%, 96%, 82%, 71%, and 98%, respectively. The interobserver agreement among the 9 endosonographers was good (k = .66). The intraobserver agreement was excellent for the junior (κ = .83) and senior (κ = .82) endosonographers. Heterogeneous tumors at CH-EUS corresponded to fewer vascular and more fibrotic tumors ( P Conclusions CH-EUS is accurate in the prediction of PNET aggressiveness and could be a decision-making element in their management.

Objectives Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening disease characterized by multiple small-vessel occlusions of rapid onset. Ischemic pancreatic duct lesions secondary to CAPS have never been reported. Methods We describe 4 patients who presented lesions suspected to be intraductal papillary mucinous neoplasm (IPMN) of the pancreas following a CAPS. Results All patients had a history of CAPS months or years before the IPMN diagnosis. They had abdominal pain or abnormal liver test results and had undergone radiography. In a 36-year-old man, endoscopic ultrasonography and magnetic resonance cholangiopancreatography demonstrated parietal thickening, stenoses and dilatations of the main pancreatic duct, which suggested IPMN. A pancreatic resection was performed because of presumed risk of malignancy. Histology revealed pancreatitis and thrombosis of small pancreatic vessels but no IPMN. The 3 other cases had lesions consistent with IPMN disclosed on MRI. From the first case experience, regular radiography surveillance was decided for the 3 other patients. After more than 4 years of follow-up, lesions remained unchanged. Conclusion Physicians must be aware that these lesions may be encountered in CAPS and may closely mimic IPMN, with subsequent risk of performing unnecessary pancreatectomy.

Background and study aims The low sensitivity of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), especially for the diagnosis of serous cystadenomas (SCAs), can be associated with diagnostic uncertainty that can regularly lead to unnecessary surgical procedures. Needle-based confocal laser endomicroscopy (nCLE) used with EUS-FNA improves diagnostic accuracy, helping to reduce unnecessary surgery and patient follow-up. This study was conducted to evaluate the economic benefit of EUS-FNA + nCLE. Patients and methods Probabilities used were derived from two studies representative of the two diagnostic strategies: a retrospective analysis of patients diagnosed by EUS-FNA alone and a prospective study of patients diagnosed by EUS-FNA + nCLE. Costs were based on French healthcare system rates; both private and public sector rates were included. A decision tree structure model used these probabilities and costs for two hypothetical cohorts of 1000 patients. Results EUS-FNA + nCLE resulted in a reduction of 23 % in the total rate of surgical intervention, which translated to a reduction in clinical costs of 13 % (public sector) and 14 % (private sector). Additionally, the reduced rate of surgery would save the lives of 4 in 1000 patients. A stochastic sensitivity analysis using 100 simulations showed that in all cases the number of interventions was less for EUS-FNA + nCLE than for EUS-FNA. There was also a reduction in the incidence of false negatives using EUS-FNA + nCLE. Conclusions EUS-FNA + nCLE results in significant economic benefits by reducing the incidence of misdiagnosis through improved diagnostic accuracy.

International audience; Background & aims: Pancreatic ductal adenocarcinoma (PDAC) is associated with the highest incidence of venous thromboembolism (VTE) of any cancer type. However, little is known about risk factors for VTE or its outcomes in patients with PDAC.Methods: We collected data from a prospective, observational study performed at multiple centers in France from May 2014 through November 2018 (the Base Clinico-Biologique de l'Adénocarcinome Pancréatique [BACAP] study) linked to a database of patients with a new diagnosis of PDAC of any stage. Data were collected from 731 patients at baseline and during clinical follow-up or in the event of symptoms. The primary endpoint was the onset of VTE during follow-up. The secondary endpoints were progression-free survival (PFS) and overall survival (OS) times.Results: During a median follow-up of 19.3 months, 152 patients (20.79%) developed a VTE. The median time from PDAC diagnosis to the onset of VTE was 4.49 months. Cumulative incidence values of VTE were 8.07% (95% confidence interval [CI], 6.31-10.29) at 3 months and 19.21% (95% CI, 16.27-22.62) at 12 months. In multivariate analysis, PDAC primary tumor location (isthmus vs head: hazard ratio [HR], 2.06; 95% CI, 1.09-3.91; P = .027) and stage (locally advanced vs resectable or borderline: HR, 1.66; 95% CI, 1.10-2.51, P = .016; metastatic vs resectable or borderline: HR, 2.50; 95% CI, 1.64-3.79; P < .001) were independent risk factors for the onset of VTE. Patients who developed VTE during follow-up had shorter times of PFS (HR, 1.74; 95% CI, 1.19-2.54; P = .004) and OS (HR, 2.02; 95% CI, 1.57-2.60; P < .001).Conclusion: In an analysis of data from the BACAP study, we found that frequent and early onsets of VTE after diagnoses of PDAC are associated with significant decreases in times of PFS and OS. Studies are needed to determine whether primary prophylaxis of VTE in patients with PDAC will improve morbidity and mortality related to VTE. (ClinicalTrials.gov, Number: clinicaltrials.gov as number NCT02818829).

Background and study aims: The differential diagnosis of solid pancreatic masses by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is currently suboptimal in centers that are not equipped with rapid on-site evaluation. Needle-based confocal laser endomicroscopy (nCLE) enables real-time in vivo microscopic imaging during endoscopy. This study aimed to describe nCLE interpretation criteria for the characterization of pancreatic masses, with histopathological correlation, and to perform the first validation of these criteria. Patients and methods: A total of 40 patients were evaluated by EUS-FNA combined with nCLE for the diagnosis of pancreatic masses. Final diagnosis was based on EUS-FNA histology and follow-up at 1 year. Five unblinded examiners defined nCLE criteria for adenocarcinoma, chronic pancreatitis, and neuroendocrine tumor (NET) using a set of video sequences from 14 patients with confirmed pathology (Step 1). These criteria were retrospectively validated by four independent, blinded examiners using sequences from 32 patients (Step 2). Results: nCLE criteria were described for adenocarcinoma (dark cell aggregates, irregular vessels with leakages of fluorescein), chronic pancreatitis (residual regular glandular pancreatic structures), and NET (black cell aggregates surrounded by vessels and fibrotic areas). These criteria correlated with the histological features of the corresponding lesions. In the validation review, a conclusive nCLE result was obtained in 75 % of cases (96 % correct). Statistical evaluation provided promising results, with high specificity, and negative and positive predictive values for all types of pancreatic masses. Conclusion: Considering the low negative predictive value of EUS-FNA, nCLE could help to rule out malignancy after a previous inconclusive EUS-FNA. Larger studies are required to confirm these findings and to establish the role of nCLE in the diagnosis of pancreatic masses. Trial registration: ClinicalTrials.gov (NCT01563133).

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.

Background Rapid on-site evaluation of cytologic specimens is a way of determining the adequacy of fine-needle aspiration (FNA). However, alternatives may be useful when the presence of a cytotechnologist and/or pathologist is not possible. Objective To evaluate the feasibility of using full-field optical coherence tomography (FFOCT) for FNA specimen quality assessment. Design FFOCT images were acquired on gastric, pancreatic, pelvic, and lymph-node formalin-fixed FNA specimens and were compared with histology of the same samples. Setting Pathology suite in a hospital. Patients Fourteen patients undergoing gastric, pancreatic, pelvic, or lymph-node EUS-guided FNA biopsy. Interventions FFOCT imaging on formalin-fixed samples before histologic procedures. Main Outcome Measurements FFOCT imaging feasibility and visibility of normal and abnormal features on images. Results FFOCT imaging was possible. Blood, mucus, muscle, collagen, and digestive mucosa could be identified as well as abnormal architectural features including infiltrative pancreatic ductal carcinoma and a neuroendocrine neoplasm. Lesions at the individual cell level could not be detected. Limitations The study was performed on a limited number of cases. Conclusion FFOCT offers rapid, noninvasive, nondestructive imaging of FNA biopsy specimens. In the future, it could be performed in the endoscopy suite to improve detection of satisfactory specimens and obviate the need for rapid on-site evaluation.

Study Objective To compare the accuracies of magnetic resonance imaging (MRI) and rectal endoscopic sonography (RES) in the prediction of the infiltration depth of colorectal endometriosis. Design A retrospective cohort study (Canadian Task Force classification II-2). Setting A university teaching hospital. Patients Forty patients with symptomatic deep infiltrating endometriosis (DIE) of the rectum who underwent colorectal resection were included. Interventions All patients underwent abdominopelvic MRI and RES preoperatively to assess the infiltration depth of colorectal endometriosis, and segmental resection of the rectosigmoid by laparoscopy was performed if RES showed bowel invasion. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive and negative likelihood ratios (LRs), and intermethod agreement were calculated for DIE muscularis and submucosal/mucosal infiltration confirmed by histopathological analysis. Measurements and Main Results For MRI detection of DIE muscularis infiltration, the sensitivity, specificity, PPV, NPV, and negative LR were 68%, 100%, 100%, 20%, and 0.32, respectively. For the MRI detection of DIE submucosal/mucosal involvement, the sensitivity, specificity, PPV, NPV, and positive and negative LRs were 47%, 81%, 69%, 63%, 2.49, and 0.65, respectively. The PPV of RES detection of DIE muscularis infiltration was 93%. For the RES detection of DIE submucosal/mucosal layers, the sensitivity, specificity, PPV, NPV, and positive and negative LRs were 79%, 48%, 58%, 71%, 1.51, and 0.44, respectively. Conclusion In the current study, MRI is valuable for detecting endometriosis of the rectum but is less accurate in detecting submucosal/mucosal involvement than RES. Magnetic resonance imaging was not successful for preoperative determination of segmental resection versus a more conservative approach. When bowel involvement is detected by MRI, RES is not essential. When symptoms suggest DIE in patients without intestinal lesions detected by MRI, RES is necessary to exclude bowel invasion.

Technologic advances in endoscopic imaging have improved the visualization of mucosal layer, allowing to distinguish neoplastic vs nonneoplastic tissue; however, the imaging is far from a perfect tool. Although histology is a highly accurate technique, it has few limitations: false-negative results in case of ulcers or inflammation, delayed final diagnosis and treatment, and increased costs in pathology procedures with consequently repeated procedures. Moreover in some GI districts, the accuracy of cytopathology results is low like pancreatic cyst and bile duct due to the difficulties in acquiring tissue. Nevertheless histology is a postmortem analysis without informations about in vivo processes (blood flow, mucosal junction exchanges).

Pancreatic serous cystadenomas are uncommon benign tumours that are often found incidentally on routine imaging examinations. Radiological imaging techniques alone have proven to be suboptimal to fully characterize cystic pancreatic lesions. Endoscopic ultrasound, with the addition of fine-needle aspiration in difficult cases, has showed greater diagnostic accuracy than conventional imaging techniques. The best management strategy of these neoplasms is still debated. Surgery should be limited only to symptomatic and highly selected cases and most of the patients should only be strictly monitored. In the current paper, we provide an updated overview on pancreatic serous cystadenomas, focusing our attention on epidemiology, clinical characteristics and diagnostic evaluation; finally, we also discuss different management strategies and areas for future research.

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.

Synchronous gastric and pancreatic cancers represent a very rare association. The role of tomodensitometry, endoscopic ultrasound and histology is primordial to differentiate between double tumors, local extension or metastasis. We report in our paper two cases of synchronous gastric and pancreatic cancers treated with Folforinox. Then, we discuss the risk factors, the diagnostic methods, the treatment modalities and the prognosis of these rare double cancers.

Background and Objectives: EUS-guided biliary drainage (EUS-BD) was shown to be useful for malignant biliary obstruction (MBO). However, there is lack of consensus on how EUS-BD should be performed. Methods: This was a worldwide multi-institutional survey among members of the International Society of EUS conducted in February 2018. The survey consisted of 10 questions related to the practice of EUS-BD. Results: Forty-six endoscopists of them completed the survey. The majority of endoscopists felt that EUS-BD could replace percutaneous transhepatic biliary drainage after failure of ERCP. Among all EUS-BD methods, the rendezvous stenting technique should be the First choice. Self-expandable metal stents (SEMSs) were recommended by most endoscopists. For EUS-guided hepaticogastrostomy (HGS), superiority of partially-covered SEMS over fully-covered SEMS was not in agreement. 6-Fr cystotomes were recommended for fistula creation. During the HGS approach, longer SEMS (8 or 10 cm) was recommended. During the choledochoduodenostomy approach, 6-cm SEMS was recommended. During the intrahepatic (IH) approach, the IH segment 3 was recommended. Conclusion: This is the first worldwide survey on the practice of EUS-BD for MBO. There were wide variations in practice, and randomized studies are urgently needed to establish the best approach for the management of this condition.

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.

Submucosal tumours (SMTs) are relatively common findings in patients undergoing endoscopy, especially in upper gastrointestinal (GI) tract. This term includes various non-neoplastic and neoplastic conditions. Endoscopic ultrasonography (EUS) is the best imaging procedure to characterise SMT and to determine the need for further explorations. In this review, the following issues will be addressed: the endosonographic features of SMT; the diagnostic accuracy of EUS; the ability of EUS to distinguish benign and malignant SMTs; the value of EUS-guided fine-needle aspiration (FNA); and the influence of EUS on clinical management.

Drainage of a biliary obstruction can be accomplished in several ways: (1) placement of an internal biliary stent at ERCP, (2) placement of percutaneous transhepatic biliary drainage catheter (PTBD), and (3) surgical anastomosis (ie, hepaticogastrostomy or choledochojejunostomy). Recently, the role of EUS was evaluated in several studies as an alternative treatment modality for the management of patients with obstructive jaundice. This section of the EUS 2008 Working Group Proceedings evaluates the current evidence and potential role of EUS-guided hepaticogastrostomy in the management of patients with obstructive jaundice.

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.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.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.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 level200 ng/mL and a CA 72.440 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 level200 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 level40 U/mL for this purpose were 87.5%, 73%, 47%, and 96%, respectively.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.

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.

Despite advances in radiological and metabolic imaging, standard axial endoscopy and endoscopic ultrasonography (EUS) still play a pivotal role in a number of neuroendocrine neoplasms (NENs) of the gastrointestinal and duodenopancreatic region. Upper gastrointestinal endoscopy is essential for the detection and characterization of NEN up to the angle of Treitz (esophageal, gastric and duodenal). Ileocolonoscopy allows the assessing and diagnosing of rectal, colonic and very occasionally distal ileal lesions. Endoscopic assessment is the mainstay for diagnosing gastric NENs associated with hypergastrinemia, but is also useful in detecting and diagnosing duodenal NENs (both functional and nonfunctional) and ampullary NENs. As rectal NENs are on the increase, standard colonoscopy (often combined with endorectal EUS) is also useful in detecting and treating small rectal NENs. EUS is the modality of choice for diagnosing pancreatic NENs and for locoregional staging of esophageal, gastric, duodenal, pancreatic and rectal NENs. This chapter will expand on the diagnostic and therapeutic role of endoscopy and EUS in the field of gastrointestinal and pancreatic NENs.

The differential diagnosis of solitary pancreatic cystic lesions is sometimes difficult. Needle-based confocal laser endomicroscopy (nCLE) performed during endoscopic ultrasound–fine-needle aspiration (EUS-FNA) enables real-time imaging of the internal structure of such cysts. Criteria have already been described for serous cystadenoma and intraductal papillary mucinous neoplasm (IPMN). The aims of the study were to determine new nCLE criteria for the diagnosis of pancreatic cystic lesions, to propose a comprehensive nCLE classification for the characterization of those lesions, and to carry out a first external retrospective validation . Thirty-three patients with a lone pancreatic cystic lesion were included (CONTACT 1 study). EUS-FNA was combined with nCLE. Diagnosis was based on either pathology result (Group 1, n = 20) or an adjudication committee consensus (Group 2, n = 13). Six investigators, unblinded, studied cases from Group 1 and identified nCLE criteria for mucinous cystic neoplasm (MCN), pseudocyst (PC), and cystic neuroendocrine neoplasm (NEN). Four external reviewers assessed, blinded, the yield and interobserver agreement for the newly identified (MCN, PC) and previously described (IPMN, SC) criteria in a subset of 31 cases. New nCLE criteria were described for MCN (thick gray line), PC (field of bright particles), and cystic NEN (black neoplastic cells clusters with white fibrous areas). These criteria correlated with the histological features of the corresponding lesions. In the retrospective validation, a conclusive nCLE result was obtained for 74 % of the cases (87 % “true” and 13 % “false” with respect to the final diagnosis). On this limited case series, the nCLE criteria showed a trend for high diagnostic specificity (>90 % for mucinous cysts, 100 % for non-mucinous cysts). Based on this newly completed atlas of interpretation criteria, nCLE could facilitate the diagnosis of pancreatic cystic lesion types.

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.

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.

Despite advances in radiological and metabolic imaging, standard axial endoscopy and endoscopic ultrasonography (EUS) still play a pivotal role in a number of neuroendocrine neoplasms (NENs) of the gastrointestinal and duodenopancreatic region. Upper gastrointestinal endoscopy is essential for the detection and characterization of NEN up to the angle of Treitz (esophageal, gastric and duodenal). Ileocolonoscopy allows the assessing and diagnosing of rectal, colonic and very occasionally distal ileal lesions. Endoscopic assessment is the mainstay for diagnosing gastric NENs associated with hypergastrinemia, but is also useful in detecting and diagnosing duodenal NENs (both functional and nonfunctional) and ampullary NENs. As rectal NENs are on the increase, standard colonoscopy (often combined with endorectal EUS) is also useful in detecting and treating small rectal NENs. EUS is the modality of choice for diagnosing pancreatic NENs and for locoregional staging of esophageal, gastric, duodenal, pancreatic and rectal NENs. This chapter will expand on the diagnostic and therapeutic role of endoscopy and EUS in the field of gastrointestinal and pancreatic NENs.

Cette mise au point a pour objectif de donner quelques recommandations mettant l’accent sur l’importance de l’equipe formee par l’endoscopiste et le pathologiste pour permettre aux centres qui debutent les ponctions sous echoendoscopie ou qui sont peu satisfaits des resultats de gagner en efficacite. L’endoscopiste est le garant de la selection des patients, de la qualite du recueil et des informations transmises au pathologiste. Le pathologiste privilegie une etude combinee d’etalements directs sur lames, de cytologie en milieu liquide et de coupes histologiques de micro fragments inclus en cytobloc. Cette collaboration permet de fournir au clinicien un diagnostic plus precis et plus fiable pour la prise en charge du traitement du patient. The objective of this update is to put forth recommendations that underline the importance of the team formed by the endoscopist and the pathologist in order to help centres that are starting to perform endoscopic ultrasound-guided fine needle aspiration (EUS guided FNAB), or that are unsatisfied with their results, to become more efficient. The endoscopist assures the selection of patients, and the quality of collection and information transmitted to the pathologist. The pathologist privileges a combined study of direct smear slides, liquid-based cytology and histological sections of small fragments in cytoblock. This collaboration gives the clinician a more specific and reliable diagnosis for management of the patient’s treatment.

Natural history of intraductal papillary mucinous tumors of the pancreas (IPMTs) is unknown. Cross-sectional studies suggest that exclusive branch duct (BD) involvement is associated with a lower risk of carcinoma than main pancreatic duct (MPD) involvement. The aim of our study was to calculate longitudinal risk of malignant transformation of IPMT since the first sign.All the patients with a diagnosis of highly probable or histologically proven IPMT were included. Actuarial risks of occurrence of at least low-grade dysplasia (or=LGD), high-grade dysplasia (or=HGD), or invasive carcinoma (IC) were calculated by Kaplan-Meier method from the first sign attributable to IPMT. The risks according to sex, acute pancreatitis, tumor size, and involvement of MPD were compared by log-rank test.One hundred six patients were included with a proven (n = 76) or probable (n = 30) IPMT. The tumor was confined to BD in 53 cases. Median duration since the onset of the first sign to the end of follow-up was 21 months (range, 0-241). Ten-year actuarial risk that IPMT grade wasor=LGD,or=HGD, or IC was 67%, 49%, and 29%, respectively. The only morphologic risk factor of malignant transformation was involvement of MPD, with a 5-year actuarial risk ofor=HGD of 63% in the MPD group compared with 15% in the BD group (P.001).Longitudinal risk of at least HGD or IC is time-dependent. Patients with BD IPMT present a much lower risk, justifying a nonoperative surveillance.

Background and study aims: The differential diagnosis of solitary pancreatic cystic lesions is frequently difficult. Needle-based confocal laser endomicroscopy (nCLE) performed during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a new technology enabling real-time imaging of the internal structure of such cysts. The aim of this pilot study was to identify and validate new diagnostic criteria on nCLE for pancreatic cystic lesions. Patients and methods: A total of 31 patients with a solitary pancreatic cystic lesion of unknown diagnosis were prospectively included at three centers. EUS-FNA was combined with nCLE. The final diagnosis was based on either a stringent gold standard (surgical specimen and/or positive cytopathology) or a committee consensus. Six nonblinded investigators reviewed nCLE sequences from patients with the most stringent final diagnosis, and identified a single feature that was only present in serous cystadenoma (SCA). The findings were correlated with the pathology of archived specimens. After a training session, four blinded independent observers reviewed a separate independent video set, and the yield and interobserver agreement for the criterion were assessed. Results: A superficial vascular network pattern visualized on nCLE was identified as the criterion. It corresponded on pathological specimen to a dense and subepithelial capillary vascularization only seen in SCA. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of this sign for the diagnosis of SCA were 87 %, 69 %, 100 %, 100 %, and 82 %, respectively. Interobserver agreement was substantial (κ = 0.77). Conclusion: This new nCLE criterion seems highly specific for the diagnosis of SCA. The visualization of this criterion could have a direct impact on the management of patients by avoiding unnecessary surgery or follow-up. Clinicaltrials.gov NCT01563133.

The widespread availability of endoscopic ultrasound has facilitated the evaluation of the pancreas and extrahepatic biliary system. Endosonography has been shown to be highly sensitive in the detection of choledocholithiasis (especially in patients with small stones and nondilated bile ducts) and gallbladder microlithiasis; however, the use of this technique in relation to endoscopic retrograde cholangiography and laparoscopic surgery in gallstone disease remains confusing. This article highlights the clinical performance and results of endoscopic ultrasound in this context and proposes strategies in relation to its use in association with endoscopic retrograde cholangiopancreatography and surgery in common clinical practice. Endosonography allows the correct identification of patients with acute biliary pancreatitis and proves an important adjunct in eliminating other causes of undetermined pancreatitis.