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Early detection of high-risk pancreatic cystic lesions enables potentially curative surgical resection, and early detection of lesions without worrisome features may lead to appropriate surveillance. Regrettably, differentiating premalignant and malignant cysts from nonmalignant ones remains challenging. However, emerging additional diagnostic tools, including the needle biopsy with microforceps and needle-based confocal laser endomicroscopy, are of exciting potential along with cyst fluid analysis".

Objective Prospective evaluation of 2 clinical-molecular models in patients with unknown pathology who underwent endoscopic ultrasound with fine-needle aspiration (EUS-FNA) for a cystic lesion of the pancreas. Summary of background data Preoperative prediction of histologic subtype (mucinous vs nonmucinous) and grade of dysplasia in patients with pancreatic cystic neoplasms is challenging. Our group has previously published 2 clinical-molecular nomograms for intraductal papillary mucinous neoplasms (IPMN) that incorporated both clinical/radiographic features and cyst fluid protein markers (sFASL, CA72-4, MMP9, IL-4). Methods This multiinstitutional study enrolled patients who underwent EUS-FNA for a cystic lesion of the pancreas. Treatment recommendations regarding resection were based on standard clinical, radiographic, and endoscopic features. Predicted probabilities of high-risk IPMN (high-grade dysplasia/invasive cancer) were calculated using the previously developed clinical-molecular nomograms. Results Cyst fluid was obtained from 100 patients who underwent diagnostic EUS-FNA. Within this group there were 35 patients who underwent resection, and 65 were monitored radiographically. Within the group that underwent resection, 26 had low-risk IPMN or benign non-IPMN lesions, and 9 had high-risk IPMN. Within the surveillance group, no patient progressed to resection or developed cancer after a median follow-up of 12 months (range: 0.5-38). Using the clinical/radiographic nomogram alone, 2 out of 9 patients with high-risk IPMN had a predicted probability >0.5. In the clinical-molecular models, 6 of 9 patients in model 1, and 6 of 9 in model 2, had scores >0.5. Conclusions This prospective study of patients with unknown cyst pathology further demonstrates the importance of cyst fluid protein analysis in the preoperative identification of patients with high-risk IPMN. Longer follow-up is necessary to determine if this model will be useful in clinical practice.

Colonoscopy for colorectal cancer screening is endoscopist dependent, and colonoscopy quality improvement programs aim to improve efficacy. This study evaluated the clinical benefit and safety of using a computer-aided detection (CADe) device in colonoscopy procedures.This randomized study prospectively evaluated the use of a CADe device at 5 academic and community centers by US board-certified gastroenterologists (n = 22). Participants aged ≥40 scheduled for screening or surveillance (≥3 years) colonoscopy were included; exclusion criteria included incomplete procedure, diagnostic indication, inflammatory bowel disease, and familial adenomatous polyposis. Patients were randomized by endoscopist to the standard or CADe colonoscopy arm using computer-generated, random-block method. The 2 primary endpoints were adenomas per colonoscopy (APC), the total number of adenomas resected divided by the total number of colonoscopies; and true histology rate (THR), the proportion of resections with clinically significant histology divided by the total number of polyp resections. The primary analysis used a modified intention-to-treat approach.Between January and September 2021, 1440 participants were enrolled to be randomized. After exclusion of participants who did not meet the eligibility criteria, 677 in the standard arm and 682 in the CADe arm were included in a modified intention-to-treat analysis. APC increased significantly with use of the CADe device (standard vs CADe: 0.83 vs 1.05, P = .002; total number of adenomas, 562 vs 719). There was no decrease in THR with use of the CADe device (standard vs CADe: 71.7% vs 67.4%, P for noninferiority.001; total number of non-neoplastic lesions, 284 vs 375). Adenoma detection rate was 43.9% and 47.8% in the standard and CADe arms, respectively (P = .065).For experienced endoscopists performing screening and surveillance colonoscopies in the United States, the CADe device statistically improved overall adenoma detection (APC) without a concomitant increase in resection of non-neoplastic lesions (THR).gov registration: NCT04754347.

Introduction Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the standard diagnostic procedure for many intrathoracic and intra-abdominal lesions. Next-generation fine-needle biopsies (FNBs) can increase diagnostic yield by procuring tissue suitable for histological processing. We evaluate the diagnostic yield and operating characteristics of the SharkCore (SC; Medtronic Corp., Minneapolis, MN) FNB in a tertiary referral facility. Materials and methods We performed a single-center retrospective review of SC-FNB–acquired tissue between January 2014 and March 2018. Patient demographic data, endoscopic features, and pathology data were obtained from the electronic medical record. Diagnostic yield was assessed by the ability to obtain a definitive diagnosis, defined as malignant or benign interpretations. Operating characteristics were also calculated. Results A total of 179 lesions were sampled with the SC-FNB in 157 patients (mean age: 63 years, 57% male). Of these, 31 lesions were concomitantly sampled with a conventional FNA needle. Most lesions were pancreatic (49%). Diagnostic yield was 86%, which was independent of lesion location, lesion size and needle gauge. Diagnostic accuracy was highest when both histology and cytology specimens were analyzed concurrently (96.5%). In patients with a history of chronic pancreatitis, accuracy, sensitivity, and negative predictive value were reduced (71.4%, 20.0%, and 69.2%, respectively). Rapid onsite evaluation (ROSE) occurred in 64.8% of cases and was more likely to be diagnostic at the time of rapid evaluation if SC-acquired tissue was utilized versus FNA-acquired tissue (P = 0.03); however, final diagnostic yield did not differ between needles (P = 0.13). Conclusions SC-FNB shows high diagnostic yield and accuracy and provides diagnostic tissue for ROSE. SC-FNB is an effective alternative to conventional FNA.

Background Making a specific diagnosis of pancreatic cysts preoperatively is difficult. The new disposable Moray micro forceps biopsy (MFB) device allows tissue sampling from the pancreatic cyst wall/septum and aims to improve diagnosis. This study compares the diagnostic performance of the MFB with the current conventional analysis of pancreatic cyst fluid (PCF). Methods A total of 48 patients sampled with MFB were identified. Cysts were classified as mucinous on PCF based on extracellular mucin/mucinous epithelium, carcinoembryonic antigen (CEA) levels ≥192 ng/mL, or KRAS/GNAS mutation. A diagnosis of intraductal papillary mucinous neoplasm was supported by GNAS mutation; a diagnosis of serous cystadenoma was supported by Von Hippel-Lindau tumor suppressor (VHL) mutation. A diagnosis of mucinous cystic neoplasm required the presence of subepithelial ovarian-type stroma. A high-risk cyst was defined as a mucinous cyst with high-grade dysplasia or an adenocarcinoma. Comparisons in diagnostic performance between PCF and MFB were made. Results The mean age of the patients was 69.6 years (range, 27-90 years); 25 of 48 patients (52.1%) were female. Cysts were in the pancreatic head (13 patients), neck (2 patients), body (20 patients), and tail (13 patients), averaging 3.1 cm (range, 1.2-6.0 cm). There was concordance with mucinous versus nonmucinous classification (60.4% for PCF vs 58.3% for MFB; P = .949). Three high-risk cysts were detected by PCF and 2 were detected by MFB (P = .670). However, MFB diagnosed significantly more specific cysts compared with PCF (50.0% for MFB vs 18.8% for PCF; P Conclusions PCF analysis and MFB have comparable performance in distinguishing between mucinous and nonmucinous cysts and for detecting high-risk cysts. However, MFB was found to be superior for diagnosing specific cyst subtypes, thus adding significant value to preoperative patient management. Cancer Cytopathol 2018;126:414-20. © 2018 American Cancer Society.

Objective To describe our institutional experience with resected cystic tumors of the pancreas with emphasis on changes in clinical presentation and accuracy of preoperative diagnosis. Summary background data Incidental-discovery of pancreatic cystic lesions has increased and has led to a rise in pancreatic resections. It is important to analyze surgical outcomes from these procedures, and the prevalence of malignancy, pre-malignancy and resections for purely benign lesions, some of which may be unintended. Methods Retrospective review of a prospective database spanning 3 decades. Presence of symptoms, incidental discovery, diagnostic studies, type of surgery, postoperative outcomes, and concordance between presumptive diagnosis and final histopathology were recorded. Results 1290 patients were identified, 62% female with mean age of 60 y. 57% of tumors were incidentally-discovered. 90-day operative mortality was 0.9% and major morbidity 14.4%. There were 23 different diagnosis, but IPMN, MCN and serous cystadenoma comprised 80% of cases. Concordance between preoperative and final histopathological diagnosis increased by decade from 45%, to 68%, and is currently 80%, rising in parallel with the use of EUS, cytology and molecular analysis. The addition of molecular analysis improved accuracy to 91%. Of mis-diagnosed cases, half were purely benign and taken to surgery with the presumption of malignancy or premalignancy. The majority of these were serous cystadenomas. Conclusions Indications and diagnostic work-up of cystic tumors of the pancreas have changed over time. Surgical resection can be performed with very low mortality and acceptable morbidity and diagnostic accuracy is currently 80%. About 10% of patients are still undergoing surgery for purely benign lesions that were presumed to be malignant or premalignant. Further refinements in diagnostic tests are required to improve accuracy.

A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to address the research gaps and opportunities in pancreatic endoscopic ultrasound (EUS). The event occurred on July 26, 2017 in 4 sessions: (1) benign pancreatic diseases, (2) high-risk pancreatic diseases, (3) diagnostic and therapeutics, and (4) new technologies. The current state of knowledge was reviewed, with identification of numerous gaps in knowledge and research needs. Common themes included the need for large multicenter consortia of various pancreatic diseases to facilitate meaningful research of these entities; to standardize EUS features of different pancreatic disorders, the technique of sampling pancreatic lesions, and the performance of various therapeutic EUS procedures; and to identify high-risk disease early at the cellular level before macroscopic disease develops. The need for specialized tools and accessories to enable the safe and effective performance of therapeutic EUS procedures also was discussed.

Endoscopic ultrasonography (EUS) has become an interventional procedure for the diagnosis and treatment of various gastrointestinal and pancreatic tumors. Because of the unique anatomical location of the pancreas, EUS-guided therapies offer substantial promise for the delivery of targeted treatments. This article reviews the recent EUS-guided various therapeutic methods for pancreatic cyst and tumor ablation, especially focusing on cystic neoplasms.

Endoscopic ultrasound (EUS) plays an important role as a diagnostic and therapeutic modality in gastroenterology. New developments have emerged, especially in the last decade, and are being introduced to endoscopists. The ability to readily visualize and access organs in the gastrointestinal tract has allowed endoscopists to perform new interventional procedures. EUS procedures have taken the place of conventional approaches for the treatment of various gastrointestinal diseases, including pancreatic cystic lesions. This article focuses on the advances and future of diagnostic and therapeutic EUS.

The ACR Incidental Findings Committee (IFC) presents recommendations for managing pancreatic cysts that are incidentally detected on CT or MRI. These recommendations represent an update from the pancreatic component of the JACR 2010 white paper on managing incidental findings in the adrenal glands, kidneys, liver, and pancreas. The Pancreas Subcommittee—which included abdominal radiologists, a gastroenterologist, and a pancreatic surgeon—developed this algorithm. The recommendations draw from published evidence and expert opinion, and were finalized by informal iterative consensus. Algorithm branches successively categorize pancreatic cysts based on patient characteristics and imaging features. They terminate with an ascertainment of benignity and/or indolence (sufficient to discontinue follow-up), or a management recommendation. The algorithm addresses most, but not all, pathologies and clinical scenarios. Our goal is to improve quality of care by providing guidance on how to manage incidentally detected pancreatic cysts.

Pancreatic cysts are common and often pose a management dilemma, because some cysts are precancerous, whereas others have little risk of developing into invasive cancers. We used supervised machine learning techniques to develop a comprehensive test, CompCyst, to guide the management of patients with pancreatic cysts. The test is based on selected clinical features, imaging characteristics, and cyst fluid genetic and biochemical markers. Using data from 436 patients with pancreatic cysts, we trained CompCyst to classify patients as those who required surgery, those who should be routinely monitored, and those who did not require further surveillance. We then tested CompCyst in an independent cohort of 426 patients, with histopathology used as the gold standard. We found that clinical management informed by the CompCyst test was more accurate than the management dictated by conventional clinical and imaging criteria alone. Application of the CompCyst test would have spared surgery in more than half of the patients who underwent unnecessary resection of their cysts. CompCyst therefore has the potential to reduce the patient morbidity and economic costs associated with current standard-of-care pancreatic cyst management practices.

Pancreatic cysts are relatively rare lesions, and their diagnosis has increased with the widespread availability and use of cross-sectional imaging. In many cases pancreatic cysts are detected on imaging performed for another indication; however, they can also be seen in patients with symptoms such as abdominal pain or jaundice. The majority of pancreatic cystic lesions are nonneoplastic cysts, which are predominantly pancreatic pseudocysts (PPs) and are mostly seen as a local complication of pancreatitis. Neoplastic cysts of the pancreas are broadly categorized as mucinous and nonmucinous lesions, and the type of epithelial lining determines the risk of malignancy. Once a PP has been eliminated as a possibility, the next step is to determine the type of cyst based on cross-sectional imaging, aspiration cytology, and cyst fluid analysis.

BACKGROUND Mucinous cystic neoplasms (MCNs) of the pancreas present a management conundrum. The majority are benign but all are resected due to their malignant potential. Recent studies have recommended nonsurgical management. In the current study, the authors analyzed the preoperative imaging, cytology, and cyst fluid characteristics of 136 histologically confirmed MCNs to assess predictors of a high-risk (HR) cyst for surgical triage. METHODS MCNs resected at the Massachusetts General Hospital between 1990 and 2014 formed the study cohort. Patient demographics, cyst size, and mural nodules (MNs) by endoscopic ultrasound, cytology, and cyst fluid carcinoembryonic antigen and amylase levels were correlated with histological grade. A HR cyst was defined as high-grade dysplasia or invasive carcinoma on histology. Performance characteristics were assessed for each parameter, with a cyst size ≥3 cm or a MN on imaging and malignant cytology considered to be “true-positive” results for predicting malignancy. RESULTS Only 15 of the 136 cysts had HR histology (11%). On average, patients with HR cysts were older than those with low-risk cysts (55 years vs 49 years, respectively). High-grade cytology was the most accurate predictor of malignancy (95%) followed by MN and cyst size together (88%) and MN alone (83%). The average carcinoembryonic antigen level (in ng/mL) increased with the grade of dysplasia but the ranges overlapped between low risk and HR cysts. CONCLUSIONS To the authors' knowledge, the current study is the largest series to date analyzing the cytological features of histologically confirmed MCN. Cytology is insensitive but very specific for detecting a HR MCN and outperformed imaging for the detection of HR MCN. Endoscopic ultrasound-guided fine-needle aspiration and cytology should be performed on any clinically suspected MCN that is being considered for conservative management. Cancer Cytopathol 2017;125:169–177. © 2016 American Cancer Society.

Objectives The frequency of detecting asymptomatic incidental lesions of the pancreas is increasing. A substantial number of these lesions are either malignant or premalignant, thus mandating pancreatic resection. A less invasive treatment option may be feasible for selected patients. Endoscopic ultrasound-guided radiofrequency ablation (RFA) may be offered as a treatment option for these patients. The objective of this study was to evaluate the performance characteristics of monopolar RFA using a 1-Fr wire electrode in the porcine pancreas, liver, gallbladder, spleen, kidney, stomach, and lymph nodes. Methods Six Yorkshire pigs were used for this study. The internal organs were accessed after a midline laparotomy. Manual monopolar RFAs were performed over a 90-second period using a wide range of power settings (3, 4, 5, 10, 15, and 25 W). The pancreas was exposed at all power settings; the other organs were exposed at power settings of 3, 4, 5, and 10 W. The maximum diameter of coagulative necrosis was measured. Results In all study animals, RFA was performed in the target organs without difficulty. Only the pancreas showed definite coagulative necrosis. The maximum diameter of coagulative necrosis (8.0±1.7 mm) was achieved at 5 W. No definite coagulative necrosis was noted in the other organs. Conclusions Monopolar RFA using a 1-Fr wire electrode resulted in coagulative necrosis in the porcine pancreas. RFA in higher power settings resulted in relatively homogeneous necrosis. At a given power setting, the RFA effect is likely to be differ according to electrical properties of the target tissue. This article is protected by copyright. All rights reserved.

Making a specific diagnosis of pancreatic cysts preoperatively is difficult. The new disposable Moray micro forceps biopsy (MFB) device allows tissue sampling from the pancreatic cyst wall/septum and aims to improve diagnosis. This study compares the diagnostic performance of the MFB with the current conventional analysis of pancreatic cyst fluid (PCF).A total of 48 patients sampled with MFB were identified. Cysts were classified as mucinous on PCF based on extracellular mucin/mucinous epithelium, carcinoembryonic antigen (CEA) levels ≥192 ng/mL, or KRAS/GNAS mutation. A diagnosis of intraductal papillary mucinous neoplasm was supported by GNAS mutation; a diagnosis of serous cystadenoma was supported by Von Hippel-Lindau tumor suppressor (VHL) mutation. A diagnosis of mucinous cystic neoplasm required the presence of subepithelial ovarian-type stroma. A high-risk cyst was defined as a mucinous cyst with high-grade dysplasia or an adenocarcinoma. Comparisons in diagnostic performance between PCF and MFB were made.The mean age of the patients was 69.6 years (range, 27-90 years); 25 of 48 patients (52.1%) were female. Cysts were in the pancreatic head (13 patients), neck (2 patients), body (20 patients), and tail (13 patients), averaging 3.1 cm (range, 1.2-6.0 cm). There was concordance with mucinous versus nonmucinous classification (60.4% for PCF vs 58.3% for MFB; P = .949). Three high-risk cysts were detected by PCF and 2 were detected by MFB (P = .670). However, MFB diagnosed significantly more specific cysts compared with PCF (50.0% for MFB vs 18.8% for PCF; P.001).PCF analysis and MFB have comparable performance in distinguishing between mucinous and nonmucinous cysts and for detecting high-risk cysts. However, MFB was found to be superior for diagnosing specific cyst subtypes, thus adding significant value to preoperative patient management. Cancer Cytopathol 2018;126:414-20. © 2018 American Cancer Society.

Background & Aims The management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients. Methods We performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms). Cyst fluid was analyzed to identify subtle mutations in genes known to be mutated in pancreatic cysts ( BRAF , CDKN2A , CTNNB1 , GNAS , KRAS , NRAS , PIK3CA , RNF43 , SMAD4 , TP53 , and VHL ); to identify loss of heterozygozity at CDKN2A , RNF43 , SMAD4 , TP53 , and VHL tumor suppressor loci; and to identify aneuploidy. The analyses were performed using specialized technologies for implementing and interpreting massively parallel sequencing data acquisition. An algorithm was used to select markers that could classify cyst type and grade. The accuracy of the molecular markers was compared with that of clinical markers and a combination of molecular and clinical markers. Results We identified molecular markers and clinical features that classified cyst type with 90%−100% sensitivity and 92%−98% specificity. The molecular marker panel correctly identified 67 of the 74 patients who did not require surgery and could, therefore, reduce the number of unnecessary operations by 91%. Conclusions We identified a panel of molecular markers and clinical features that show promise for the accurate classification of cystic neoplasms of the pancreas and identification of cysts that require surgery.

Background & Aims Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas occur mostly in older individuals. Individual life expectancy and risk of death from other factors must be carefully considered in analyzing the risks that IPMNs pose. We investigated whether there is a subset of patients with IPMNs and a high risk of dying from other causes who would not benefit from pancreatic surgery. Methods We collected data from 725 patients at Massachusetts General Hospital who underwent resection or have been under observation for IPMNs from 1992 through 2012. Comorbidities were classified according to the age-adjusted Charlson comorbidity index (CACI). Causes of death were recorded, and survival data were analyzed by the Kaplan-Meier method. Results The patients' median CACI score was 3; 10% of patients had CACI of 7 or more. Of the entire cohort, 55% underwent resection, and the remaining 45% have been under observation. After a median follow-up period of 5 years, 177 patients died (24%, 55% of deaths within 5 years of diagnosis); 78% of deaths were not related to IPMNs. The median survival time for all patients with CACI score of 7 or more was 43 months. Multivariate regression analysis revealed that the chance of non-IPMN−related death within 3 years of diagnosis is 11-fold higher for patients with CACI score of 7 or more than for patients with lower scores. Conclusions The CACI can be used to identify patients with a high risk of death from factors other than IPMNs within a few years after diagnosis. These patients are therefore not likely to benefit from further IPMN observation or pancreatic resection.

Background and study aims: Current guidelines recommend using endoscopic ultrasound (EUS), carcinoembryonic antigen (CEA) testing and cytology to manage incidental pancreatic cystic neoplasms (PCN); however, studies suggest a strategy including integrated molecular pathology (IMP) of cyst fluid may further aid in predicting risk of malignancy. Here, we evaluate several strategies for diagnosing and managing asymptomatic PCN using healthcare economic modeling. Patients and methods: A third-party-payer perspective Markov decision model examined four management strategies in a hypothetical cohort of 1000 asymptomatic patients incidentally found to have a 3 cm solitary pancreatic cystic lesion. Strategy I used cross-sectional imaging, recommended surgery only if symptoms or risk factors emerged. Strategy II considered patients for resection without initial EUS. Strategy III (EUS + CEA + Cytology) referred only those with mucinous cysts (CEA > 192 ng/mL) for resection. Strategy IV implemented IMP; a commercially available panel provided a “Benign,” “Mucinous,” or “Aggressive” classification based on the level of mutational change in cyst fluid. “Benign” and “Mucinous” patients were followed with surveillance; “Aggressive” patients were referred for resection. Quality-adjusted life-years (QALY), relative risk with 95 %CI, Number Needed to Treat (NNT), and incremental cost-effectiveness ratios were calculated. Results: Strategy IV provided the greatest increase in QALY at nearly identical cost to the cheapest approach, Strategy I. Relative risk of malignancy compared to the current standard of care and nearest competing strategy, Strategy III, was 0.18 (95 %CI 0.06 – 0.53) with an NNT of 56 (95 %CI 34 – 120). Conclusions: Use of IMP was the most cost-effective strategy, supporting its routine clinical use.

Background and aims: Endobiliary radiofrequency ablation (RFA) has been used to treat occluded self-expandable metal stents (SEMSs). The aim of this study was to determine the characteristics of bipolar RFA in occluded SEMSs using both in vivo and in vitro models. Methods: For the in vivo study, uncovered SEMSs were deployed in the bile ducts of three pigs; another pig was used as the control. RFA was performed at 10 W for 90 seconds. The bile duct was examined for histological changes. For the in vitro simulation of tissue ingrowth in SEMSs, RFA at 10 W for 30 seconds was performed on SEMS-occlusion polyacrylamide-gel phantoms. Results: The ablation depth was markedly reduced in the stented porcine bile duct. RFA of uncovered SEMS-occlusion gel phantoms resulted in early termination of RFA when the coagulated area contacted the SEMS. This phenomenon was not observed in RFA of the covered SEMS-occlusion gel phantoms. Conclusions: The presence of SEMSs attenuated the effect of bipolar endobiliary RFA. Tumorous tissue outside the SEMS is unlikely to be affected.

Radiofrequency ablation of malignant biliary strictures has been offered for the last 3 years, but only limited data have been published. To assess the safety, efficacy, and survival outcomes of patients receiving endoscopic radiofrequency ablation. Between April 2010 and December 2013, 69 patients with unresectable neoplastic lesions and malignant biliary obstruction underwent 98 radiofrequency ablation sessions with stenting. A total of 69 patients (22 male, aged 66.1 ± 13.3) were included in the registry. The etiology of malignant biliary stricture included unresectable cholangiocarcinoma (n = 45), pancreatic cancer (n = 19), gallbladder cancer (n = 2), gastric cancer (n = 1), and liver metastasis from colon cancer (n = 3). Seventy-eight percentage of patients had prior chemotherapy. All strictures were stented post-radiofrequency ablation with either plastic stents or metal stents. The mean stricture length treated was 14.3 mm. There was a statistically significant improvement in stricture diameter post-ablation (p

Background and Aims The tissue acquisition and diagnostic yield of cyst fluid cytology is low-to-moderate and rarely provides a specific diagnosis. The aim of this study was to compare the tissue acquisition and diagnostic tissue yield of microforceps biopsy (MFB) with cyst fluid cytology. Methods In this multicenter study, data of 42 patients who had cysts both aspirated by EUS-guided FNA (EUS-FNA) and biopsy specimens were then obtained with an MFB device, were collected. Cytology analysis of cyst fluid and histologic analysis of biopsy specimens were done. Acquisition yield was defined as percentage of patients with tissue present in the aspirate or biopsy. Diagnostic tissue yield was evaluated at 3 levels: the ability of differentiation between mucinous and/or nonmucinous cysts, detection of high risk for malignancy, and specific cyst type diagnosis. Results The mean patient age was 69 years. Sixteen pancreatic cysts (38.1%) were located in the head, 17 (40.5%) in the body, and 9 (21.4%) in the tail. The mean cyst size was 28.2 mm (12-60 mm); 25 of 42 (60%) were septated. The EUS-FNA tissue (fluid) acquisition yield was 88.1% (37/42). The MFB tissue acquisition yield was 90.4% (38/42). The diagnostic cytology yield to differentiate between mucinous and/or nonmucinous cysts was 47.6% (20/42), and the MFB histologic yield to differentiate between mucinous and/or nonmucinous cysts was 61.9% (26/42) ( P = .188). The percentage of cysts at high risk for malignancy by cytology was 54.7% (23/42), and MFB was 71.5% (30/42) ( P = .113). However, the ability of MFB to provide a specific cyst type diagnosis was 35.7% (15/42), and that for cytology was 4.8% (2/42) ( P = .001). Surgical histology was concordant with that of MFB in 6 of 7 patients (85%), and with that of cytology in 1 of 7 patients (15%). Conclusion The cyst tissue acquisition yield for MFBs was 90%. Although cytology of cyst fluid and MFB were comparable in distinguishing mucinous and nonmucinous cysts and detecting cysts at high risk for malignancy, MFB was far superior to cytology for providing a specific cyst diagnosis.

Endoscopic ultrasound (EUS) plays an important role as a diagnostic and therapeutic modality in gastroenterology. New developments have emerged, especially in the last decade, and are being introduced to endoscopists. The ability to readily visualize and access organs in the gastrointestinal tract has allowed endoscopists to perform new interventional procedures. EUS procedures have taken the place of conventional approaches for the treatment of various gastrointestinal diseases, including pancreatic cystic lesions. This article focuses on the advances and future of diagnostic and therapeutic EUS.

Management of the primary and secondary tumors of the bile ducts still remains as a major clinical challenge. Radiofrequency (RF) ablation (RFA) of these tumors is feasible but the effect of RF energy on the human common bile duct (CBD) and surrounding tissues has not been investigated. This pilot study aimed to determine the relationship between RF energy and the depth of ablation in the normal human CBD. The study was performed on fresh ex vivo human biliary–pancreatic tissue which had been resected for a pancreatic cyst or mass. The study was conducted within 15 min after resection. A bipolar Habib RFA catheter was placed into the middle of the intact CBD, and three different (5, 7, 10 W) power settings were applied over a 90-s period by an RF generator. Gross and histological examinations were performed. The depth of coagulation necrosis in CBD and the effect of RFA on CBD wall and surrounding pancreas tissue were determined by microscopic examination. The study included eight tissue samples. 5 W power was applied to three sites and RFA caused only focal epithelial necrosis limited to the CBD mucosa. 7 and 10 W were applied to five sites and coagulation necrosis occurred in all cases. Microscopically, necrosis was transmural, involved accessory bile duct glands, and extended to the surrounding pancreatic tissue in four of these cases. Macroscopically, RFA resulted in circumferential white-yellowish color change extending approximately 2 cm of the CBD. Bipolar RF energy application with 5 W resulted in limited ablation on CBD wall. However, 7 and 10 W generated tissue necrosis which extended through the CBD wall and into surrounding pancreas tissue. Endoscopic biliary RFA is an effective technique for local biliary tissue ablation but the use of high energy may injure surrounding tissue.

Little is known about the development of branch duct intraductal papillary mucinous neoplasms (BD-IPMNs). We evaluated long-term outcomes of a large cohort of patients with BD-IPMNs to determine risk of malignancy and define a subset of low-risk BD-IPMNs.We performed a retrospective analysis of data from 577 patients with suspected or presumed BD-IPMN under surveillance at the Massachusetts General Hospital. Patients underwent cross-sectional imaging analysis at 3 months or later after their initial diagnosis. The diagnosis of BD-IPMN was based on the presence of unilocular or multilocular cysts of the pancreas and a non-dilated main pancreatic duct (5 mm). We collected demographic, clinical, and pathology data. Cysts were characterized at the time of diagnosis and during the follow-up period. Follow-up duration was time between initial cyst diagnosis and date of last visit or death for patients without development of pancreatic cancer, date of surgery for patients with histologically confirmed malignancy, or date of first discovery of malignancy by imaging analysis for patients with unresectable tumors or who underwent neoadjuvant treatment before surgery. The primary outcome was risk of malignancy, with a focus on patients followed for 5 years or more, compared with that of the US population, based on standardized incidence ratio.Of the 577 patients studied, 479 (83%) were asymptomatic at diagnosis and 363 (63%) underwent endoscopic ultrasound at least once. The median follow-up time was 82 months (range, 6-329 months) for the entire study cohort; 363 patients (63%) underwent surveillance for more than 5 years, and 121 (21%) for more than 10 years. Malignancies (high-grade dysplasia or invasive neoplasm) developed after 5 years in 20 of 363 patients (5.5%), and invasive cancer developed in 16 of 363 patients (4.4%). The standardized incidence ratio for patients with BD-IPMNs without worrisome features of malignancy at 5 years was 18.8 (95% confidence interval, 9.7-32.8; P.001). One hundred and eight patients had cysts ≤1.5 cm for more than 5 years of follow-up; only 1 of these patients (0.9%) developed a distinct ductal adenocarcinoma. By contrast, among the 255 patients with cysts1.5 cm, 19 (7.5%) developed malignancy (P = .01).In a retrospective analysis of patients with BD-IPMNs under surveillance, their overall risk of malignancy, almost 8%, lasted for 10 years or more, supporting continued surveillance after 5 years. Cysts that remain ≤1.5 cm for more than 5 years might be considered low-risk for progression to malignancy.

The differential diagnosis of pancreatic cystic lesions (PCLs) is an increasingly common clinical challenge. Confocal laser endomicroscopy (CLE) may differentiate PCLs by imaging of the cyst wall. However, clinical experience is still limited, and better image definition and characterization of the cyst wall in a spectrum of cysts are needed. This experimental study aimed to expose detailed imaging characteristics of PCLs by CLE. Patients who underwent surgery of a PCL were enrolled. During surgery, intravenous fluorescein (2.5 ml of 10%) was injected just prior to the ligation of blood vessels supplying the pancreas. The freshly excised specimens were transected along the long axis to fully expose the luminal surface. A Gastroflex-UHD CLE probe (pCLE) was used manually to acquire images directly from the surface of cyst wall. The specimen subsequently underwent cross-sectional histology. All recorded data were analyzed by two investigators for predefined and original image findings of PCLs. Ten cases were recruited into the study. All patients underwent surgery because of a mucinous cyst with worrisome features or a symptomatic PCL. Imaging was successful in all patients and differently shaped papillary projections (PP) were visualized in eight patients. Pathological examination of those patients confirmed 6 cases with Intraductal Papillary Mucinous Neoplasm (IPMN) and 2 cases with Mucinous Cystic Neoplasm (MCN). In two patients with serous cystadenoma, typical vascular network was visualized in one patient, and microcystic structures in the other. Three of the IPMNs were malignant. The loss of papillary margin integrity and significant fragmentation together with irregularity was detected in malignant IPMNs by CLE. Pancreatic cyst epithelial wall can be visualized successfully by pCLE in ex vivo surgical specimens. Different papillary projections have been seen in all cases of IPMNs and MCNs. CLE has potential for identifying IPMN subtypes and for grading dysplasia.

Acinar cell cystadenoma is a rare, benign cystic lesion of the pancreas. There have been only a few retrospective reports on its cytological features. We present the first case of acinar cell cystadenoma in a 65-year-old woman, diagnosed pre-operatively by pancreatic cyst fluid cytology and Moray

BACKGROUND Cystic pancreatic neuroendocrine tumors (cPanNETs) account for 13% to 17% of PanNETs. Although the value of endoscopic ultrasound (EUS) imaging and cyst fluid analysis (CFA) in their preoperative diagnosis has been well described, limited information is available about the diagnostic role of cytology samples obtained from fine-needle aspiration (FNA). METHODS Cytopathology records between 1992 and 2013 were searched for all reports of cysts interpreted as PanNET. Patient demographics, clinical and radiologic information, CFA, histopathology, and cytopathology findings were recorded. Performance characteristics of cytology and EUS for the accurate diagnosis of cPanNET were calculated. RESULTS In total, 35 FNAs from 33 patients with cPanNETs were identified, and 34 EUS were performed. Cytology made a specific diagnosis of a cPanNET in 71% of the biopsies compared with a specific diagnosis by EUS in 38% of cases. An interpretation of suspicious for cPanNET was given in 77% of cases by cytology and in 47% by EUS. Cytology identified 86% of the lesions as high-risk pancreatic cysts compared with 56% by EUS. Diagnostic morphology was present on both cytology and cell block preparations in 60% of aspirates, on cytology only in 20%, and on cell block only in 20%. CFA was performed on 51% cyst fluids. All cysts but 1 revealed low carcinoembryonic antigen levels (range, 0.2 to >500 ng/mL; mean, 29.5 ng/mL), and amylase levels were

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.

BACKGROUND Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic cysts obtains cyst fluid for cytologic and biochemical analysis, which may determine whether the cyst is mucinous and malignant, contributing to patient management. Despite this added value, EUS-FNA remains controversial in the preoperative assessment of pancreatic cysts. The objective of this study was to assess the utility of EUS-FNA in a cohort of small pancreatic cysts that were benign on imaging studies. METHODS All pancreatic cysts that underwent initial EUS-FNA in 2006 and 2007 were retrospectively analyzed. Ninety-two patients with pancreatic cysts met the inclusion criteria. Patients who had high-risk or worrisome features on imaging studies were excluded. Cytology, histology, and cyst fluid analysis data were collected. The main outcome measurements were radiologic and clinical follow-up as well as cytopathologic and histologic results. RESULTS EUS-FNA supported a diagnosis of a mucinous cyst in 38 of 92 patients (41%) by carcinoembryonic antigen (CEA) measurement and/or cytology. Cytology demonstrated an absence of high-grade atypia (HGA) in 89 of 92 patients (97%). The mean follow-up was 4.4 years (range, 0-7.7 years), during which 6 cysts were surgically resected and 16 cysts were resampled by at least 1 subsequent EUS-FNA. The overall negative predictive value of cytologic examination for HGA was 99%. CONCLUSIONS EUS-FNA is a screening test that contributes to a triple-negative test for pancreatic cysts—no high-risk stigmata, no worrisome features, and no HGA on cytology—providing a negative predictive value of 99% for conservative management. Cancer (Cancer Cytopathol) 2014;122:412–419. © 2013 American Cancer Society.