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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.

Early detection strategies for pancreatic ductal adenocarcinoma are needed. This article describes a high‐sensitivity platform for detection of epithelial cells shed from preneoplastic lesions at a high risk of becoming malignant and a combination of technologies that could be used for early detection of disease in high‐risk patients., Background. Recent work has demonstrated early shedding of circulating epithelial cells (CECs) from premalignant intraductal papillary mucinous neoplasms (IPMNs). However, the potential use of CECs as a “liquid biopsy” for patients with IPMNs has been limited by antigen dependence of CEC isolation devices and the lack of robust detection biomarkers across CEC phenotypes. Materials and Methods. We utilized a negative depletion microfluidic platform to purify CECs from contaminating leukocytes and coupled this platform with immunofluorescence, RNA in situ hybridization, and RNA sequencing (RNA‐seq) detection and enumeration. Results. Using established protein (EpCAM, cytokeratins) and novel noncoding RNA (HSATII, cytokeratins) biomarkers, we detected CECs in 88% of patients bearing IPMN lesions. RNA‐seq analysis for MUC genes confirm the likely origin of these CECs from pancreatic lesions. Conclusion. Our findings increase the sensitivity of detection of these cells and therefore could have clinical implications for cancer risk stratification. Implications for Practice. This work describes a high‐sensitivity platform for detection of epithelial cells shed from preneoplastic lesions at high risk of malignant transformation. Further research efforts are underway to define the transcriptional programs that might allow discrimination between circulating cells released from tumors that will become malignant and cells released from tumors that will not. After further refinement, this combination of technologies could be deployed for monitoring and early detection of patients at high risk for developing new or recurrent pancreatic malignancies.

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.

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.

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.

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.

Background and Aims Patients with chronic constipation or motility disorders may be referred for rectal suction biopsy (RSB) to rule out Hirschsprung's disease (HD). RSB may not be successful beyond infancy because of the increased thickness of the rectal mucosa. EMR could improve the diagnostic yield for HD when compared with traditional RSB because larger and deeper samples are acquired for analysis. Methods In this prospective, single-center study, patients referred for RSB were offered enrollment for concurrent EMR. Specimens were analyzed pathologically for size, submucosal ganglionic tissue, and acetylcholinesterase or calretinin staining. Biopsy results were compared with transit studies, anorectal manometry, and constipation severity through validated questionnaires. Results Seventeen patients (2 male, 15 female; mean age, 35.8 years; range, 22-61 years) were enrolled in the study from 2008 to 2014. All patients underwent anorectal manometry (88% with anorectal dysfunction, 68% with outlet obstruction) and transit studies (41% with delayed transit). There were no reports of adverse events from the RSB and EMR procedures. The RSB sample volumes were significantly lower than the EMR sample volumes (0.023 cm 3 vs 0.26 cm 3 , P = .001). There was diagnostic tissue for submucosal visualization by RSB in 53% (9/17) of cases compared with 100% (17/17) with EMR ( P = .003). No cases of HD were diagnosed by RSB; one patient had rare ganglions observed by EMR. Conclusions EMR provides greater tissue volume and can improve the characterization of ganglion cells in rectal tissue compared with RSB in patients with moderate to severe constipation with suspected HD.

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

The accurate diagnosis of cystic neoplasms of the pancreas (CNP) with current diagnostic methods is limited. Endoscopic ultrasound (EUS)-guided needle-based confocal laser endomicroscopy (nCLE) is a new technique which can obtain images from the cyst wall during EUS-fine needle aspiration (EUS-FNA). The aim of this study was to assess the safety, feasibility, and diagnostic value of nCLE for CNP. Patients who underwent EUS-FNA to evaluate a CNP larger than 2 cm were enrolled. The cyst was punctured with 19-G FNA needle preloaded with an nCLE probe. The images from different areas of the cyst wall were recorded. Using the final diagnosis defined by surgery or EUS-FNA cyst fluid analysis, the accuracy of the confocal images was defined. The procedure and image acquisition was successful in 18 of the 20 patients. Predefined typical structures for mucinous cysts were visualized in 8 of 12 (66%) cysts but none of the non-mucinous cysts. The superficial vascular network which is a typical finding of serous cysts was observed in 2 of 3 patients. The sensitivity, specificity, and diagnostic accuracy of the findings of epithelial structures by nCLE were 66, 100, and 80%, respectively, for a mucinous cyst diagnosis. All patients tolerated the procedure well, and no adverse effects were determined. nCLE was found to be safe and feasible with high technical success, in this pilot study. With an overall accuracy of 80%, it has the potential to contribute to the diagnosis of CNP with specific imaging.

Our treatment approach for either symptomatic or incidentally found pancreatic cysts continues to improve. The true incidence of pancreatic cysts is not known, and pancreatic cystic neoplasms, especially intraductal papillary mucinous neoplasms, are currently most commonly diagnosed and resected. This is a result of increasing awareness, widespread availability of imaging, and better understanding of the nature of pancreatic cysts as well. Recent studies on molecular analysis and devices such as microbiopsy forceps help us better define and select the treatment approach to alleviate symptoms and to prevent malignant tumors while avoiding unnecessary surgery.

Background and Aims EUS-guided needle-based confocal laser endomicroscopy (nCLE) characteristics of common types of pancreatic cystic lesions (PCLs) have been identified; however, surgical histopathology was available in a minority of cases. We sought to assess the performance characteristics of EUS nCLE for differentiating mucinous from non-mucinous PCLs in a larger series of patients with a definitive diagnosis. Methods Six endosonographers (nCLE experience >30 cases each) blinded to all clinical data, reviewed nCLE images of PCLs from 29 patients with surgical (n = 23) or clinical (n = 6) correlation. After 2 weeks, the assessors reviewed the same images in a different sequence. A tutorial on available and novel nCLE image patterns was provided before each review. The performance characteristics of nCLE and the κ statistic for interobserver agreement (IOA, 95% confidence interval [CI]), and intraobserver reliability (IOR, mean ± standard deviation [SD]) for identification of nCLE image patterns were calculated. Landis and Koch interpretation of κ values was used. Results A total of 29 (16 mucinous PCLs, 13 non-mucinous PCLs) nCLE patient videos were reviewed. The overall sensitivity, specificity, and accuracy for the diagnosis of mucinous PCLs were 95%, 94%, and 95%, respectively. The IOA and IOR (mean ± SD) were κ = 0.81 (almost perfect); 95% CI, 0.71-0.90; and κ = 0.86 ± 0.11 (almost perfect), respectively. The overall specificity, sensitivity, and accuracy for the diagnosis of serous cystadenomas (SCAs) were 99%, 98%, and 98%, respectively. The IOA and IOR (mean ± SD) for recognizing the characteristic image pattern of SCA were κ = 0.83 (almost perfect); 95% CI, 0.73-0.92; and κ = 0.85 ± 0.11 (almost perfect), respectively. Conclusions EUS-guided nCLE can provide virtual histology of PCLs with a high degree of accuracy and inter- and intraobserver agreement in differentiating mucinous versus non-mucinous PCLs. These preliminary results support larger multicenter studies to evaluate EUS nCLE. (Clinical trial registration number: NCT02516488.)

Background and study aim: Obstruction of biliary self-expandable metal stents (SEMSs) is seen frequently. Radiofrequency ablation (RFA) causes tissue necrosis. This study aimed to assess the efficacy of RFA for management of occluded SEMS. Patients and methods: Patients with biliary malignancy and treated for an occluded SEMS were retrospectively reviewed. The study group comprised patients treated with RFA using an Habib endoprobe inside the SEMS. The control group comprised patients treated only with insertion of a plastic stent into an occluded SEMS. The end points were; 90-day stent patency rate, time to stent reocclusion, 30-day mortality, and 3 – and 6-month survival rates. Results: During the 5-year study period 25 patients with an occluded SEMS underwent RFA and 25 patients underwent a plastic stent placement only. Both groups were matched for age and diagnosis. Immediate biliary drainage was restored in all patients. In the RFA group, the stenosis was ablated successfully in 14 patients (56 %); ablation failed in 11 and a plastic stent was then inserted into the SEMS for these. The control group had only placement of a plastic stent across the stenosis. Stent patency rate at 90 days was 56 % and 24 % in the RFA and control groups, respectively (P = 0.04). The mean stent patency time was significantly longer in the RFA group compared to the control group (119.5 vs. 65.3 days, P = 0.03). Conclusion: The application of RFA for occluded SEMS improves stent patency. RFA is an alternative treatment of tissue ingrowth in malignant biliary obstruction.

The aim of this study was to critically analyze the safety of the revised guidelines, with focus on cyst size and worrisome features in the management of BD-IPMN.The Sendai guidelines for management of branch duct (BD) intraductal papillary mucinous neoplasm (IPMN) espouse safety of observation of asymptomatic cysts smaller than 3 cm without nodules (Sendai negative). Revised international consensus guidelines published in 2012 suggest a still more conservative approach, even for lesions of 3 cm or larger. By contrast, 2 recent studies have challenged the safety of both guidelines, describing invasive carcinoma or carcinoma in situ in 67% of BD-IPMN smaller than 3 cm and in 25% of "Sendai-negative" BD-IPMN.Review of a prospective database identified 563 patients with BD-IPMN. A total of 240 patients underwent surgical resection (152 at the time of diagnosis and 88 after being initially followed); the remaining 323 have been managed by observation with median follow-up of 60 months. No patient developed unresectable BD-IPMN carcinoma during follow-up. Invasive cancer arising in BD-IPMN was found in 23 patients of the entire cohort (4%), and an additional 21 patients (3.7%) had or developed concurrent pancreatic ductal adenocarcinoma. According to the revised guidelines, 76% of resected BD-IPMN with carcinoma in situ and 95% of resected BD-IPMN with invasive cancer had high-risk stigmata or worrisome features. The risk of high-grade dysplasia in nonworrisome lesions smaller than 3 cm was 6.5%, but when the threshold was raised to greater than 3 cm, it was 8.8%, and 1 case of invasive carcinoma was found.Expectant management of BD-IPMN following the old guidelines is safe, whereas caution is advised for larger lesions, even in the absence of worrisome features.

Background Pancreatic neuroendocrine tumours are uncommon neoplasms which may rarely be cystic. Differentiation from other more common cystic neoplasms may be difficult. Aims To describe the morphologic, cytologic, and cyst fluid characteristics of cystic pancreatic neuroendocrine tumours. Methods Retrospective analysis of consecutive patients referred for endosonographic evaluation of pancreatic cysts at four centres. Results 27 patients (12 males) with cystic pancreatic neuroendocrine tumours were identified. Prior to endosonography, this tumour was suspected in only 2 patients based on presenting symptoms (7.4%). The median cyst size was 35 mm (range 8–80 mm). Wall thickening was identified in 13 cases. The median carcinoembryonic antigen level was 1.25 (range 0.6–500). Fine needle aspiration cytology in 17 of 24 patients confirmed neuroendocrine tumour (71%). In 8 of 9 patients who had needle targeting of the cyst wall, cytology was consistent with neuroendocrine tumour (88.9%). 18 patients underwent surgical resection. Conclusions Cystic pancreatic neuroendocrine tumour was rarely suspected, including by cross-sectional imaging. Wall thickening was identified in approximately half of cases on endosonography. Cyst fluid was typically non-viscous with very low carcinoembryonic antigen levels. Targeting the wall during fine needle aspiration had a high diagnostic yield and should be performed.

PURPOSE OF REVIEW The purpose of this review is to examine the recent developments in the use of endoscopic retrograde cholangio-pancreatography (ERCP) and endoscopic ultrasound (EUS) in the management of patients with pancreatic-biliary disease. RECENT FINDINGS The use of ERCP to guide selective placement of pancreatic sphincterotomes, stone extraction balloons, and stents enables clinicians to treat pancreatic sphincteric and ductal disorders. Pancreatic stones are a remediable cause of recurrent pancreatitis and small calculi can be easily removed. The gold standard for the diagnosis of pancreas divisum remains ERCP and sphincterotomy is highly effective in the treatment of relapsing pancreatitis. Intraductal papillary mucinous neoplasms are the most common pancreatic malignancy and ERCP, as well as EUS can identify and sample the solid and cystic lesions. Mural nodules can be detected and sampled effectively by EUS-fine needle aspiration (FNA). The sensitivity of EUS-FNA for pancreatic adenocarcinoma is excellent (more than 85%). Although cyst fluid carcinoembryonic antigen is a very good marker for the presence of a mucinous cystic lesion, it is not an indicator of malignancy. SUMMARY In summary, ERCP and EUS are important tools for the management of benign and malignant lesions of the pancreas.

Differentiating between malignant and benign bile duct strictures is often challenging. Endoscopic retrograde cholangiopancreatography with brush cytology and/or endobiliary forceps biopsy is routinely performed. Advanced cytologic methods such as fluorescence in situ hybridization or digital image analysis increases the sensitivity of cytology. Endoscopic ultrasonography enables detailed examination of tissues surrounding the bile duct stricture and offers the advantage of fine-needle aspiration. Intraductal ultrasonography enables detailed evaluation of bile duct wall layers, and cholangioscopy offers direct visualization of the bile duct lesions. Novel techniques of probe-based confocal laser endomicroscopy and optical coherence tomography have introduced the era of in vivo histology.

Background and study aims: Limited data are available on the endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) characteristics of cystic pancreatic neuroendocrine tumors (CPanNets). The aims of this study were to describe the EUS and FNA characteristics of pathologically confirmed CPanNets and to compare these characteristics with mucinous cysts from matched patients. Patients and methods: From an EUS – FNA database (between 1999 and 2011), 19 patients with a pathologically confirmed CPanNet were identified. Patient characteristics, cyst fluid carcinoembryonic antigen (CEA) levels, pathology, and EUS findings were analyzed. For comparison, age- and sex-matched patients with mucinous cysts were randomly chosen from the same database. Results: Of the 19 patients, two had multiple endocrine neoplasia type 1 and two had metastases. The median diameter of the lesions was 24 mm. EUS revealed unilocular lesions in 7 patients, thinly septated lesions with thin walls in 1, and mixed solid-cystic lesions in 11. EUS – FNA cytology confirmed neoplasm in 12 of the 19 patients (63.2 %). The median cyst fluid CEA level (n = 15) was 1.1 ng/mL (range 0.3 – 500 ng/mL). Compared with matched patients with mucinous cysts, the median cyst fluid CEA was lower (1.1 ng/mL vs. 400 ng/mL), thick walls were more common (66.7 % vs. 13.3 %), and diagnostic cytology was more likely (73.3 % vs. 20.0 %). Conclusions: Analysis of EUS and FNA results showed that the cyst fluid from CPanNets had a lower CEA concentration, a higher frequency of thick walls on EUS, and higher diagnostic cytology compared with mucinous cysts. These findings may aid in the diagnosis of CPanNets.

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.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.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.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.

Molecular analysis of pancreatic cyst fluid (PCF) has been proposed as a novel method for differentiating pancreatic cystic lesions (PCL). The present study aimed to investigate the value of GNAS testing when added to KRAS and carcinoembryonic antigen (CEA) testing of PCF for the diagnosis of intraductal papillary mucinous neoplasms (IPMN).Prospectively collected endoscopic ultrasonography fine-needle aspiration (EUS-FNA) data were analyzed retrospectively for GNAS and KRAS mutations and CEA results. IPMN were histologically confirmed or supported by imaging and EUS-FNA findings (KRAS, CEA, cytology). Performance characteristics of GNAS added to KRAS and CEA for the diagnosis of IPMN were calculated.The study population consisted of 197 patients with cyst fluid test results. Cysts were histologically classified in 33 patients and by clinical criteria in 164 patients. The IPMN group included 108 patients and the non-IPMN group included 89 patients. GNAS was positive in 51 patients (47.2%) with IPMN. Forty-two of these patients (82.3%) also had a KRAS mutation. Adding GNAS to KRAS increased the diagnostic accuracy from 76.6% to 79.1% (P 0.05). Adding GNAS to CEA increased the diagnostic accuracy from 66.4% to 80.7 % (P 0.05), but did not achieve a diagnostic superiority to KRAS testing alone (80.7% vs 76.6%, P 0.05). The diagnostic accuracy of the triple combination was significantly better than all single tests (P 0.05).GNAS mutation is a highly specific test for IPMN. When GNAS testing is added to CEA and KRAS, a significantly greater overall accuracy (86.2%) is achieved.

Background and Aims Application of endoscopic submucosal resection (ESMR) in the management of gastric subepithelial lesions (GSLs) less than 20 mm is gradually increasing because it allows diagnosis and treatment at the same operative session. In this study, we compare and evaluate the benefits of ESMR with an endoscopic cap band mucosectomy technique or saline solution–assisted snare technique in GSLs smaller than 20 mm. Methods This was a retrospective analysis of a prospectively maintained database used at 2 academic tertiary care centers. A total of 63 patients (34 females, mean age 52 years) with endoscopically resected GSLs were included in this study. Results The mean tumor size determined by EUS was 12.3 mm (range, 5-20 mm). Sixty-seven percent of the GSLs were localized in the antrum in all groups. The endoscopic cap band mucosectomy technique was used to resect 32 (50.8%) GSLs, whereas 31 (49.2%) were resected with the saline solution–assisted snare technique. The en bloc resection rates were 97% for the saline solution–assisted snare technique and 100% for the endoscopic cap band mucosectomy. Intraoperative bleeding occurred in 1 of 31 patients (3.2%) when ESMR was performed with the saline solution–assisted snare technique. Postoperative bleeding was seen in 1 of 32 patients (3.1%) who underwent the endoscopic cap band mucosectomy technique. Conclusions In GSLs smaller than 20 mm, ESMR with saline solution–assisted snare or endoscopic cap band mucosectomy techniques is safe, the adverse event rate is low, accurate diagnosis is achieved, and treatment with en bloc resection is provided in a single session. Given similar success and adverse event rates, saline solution–assisted ESMR may be the preferred technique because of its lower cost advantages.

Objectives Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. Design Retrospective multinational study including SCN diagnosed between 1990 and 2014. Results 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16–99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2–200)), 9% had resection beyond 1 year of follow-up (3 years (1–20), size at diagnosis: 25 mm (4–140)) and 39% had no surgery (3.6 years (1–23), 25.5 mm (1–200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN9s related mortality was 0.1% (n=1). Conclusions After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. Trial registration number IRB 00006477.

Item does not contain fulltext BACKGROUND AND AIMS: EUS-guided FNA or biopsy sampling is widely practiced. Optimal sonographic visualization of the needle is critical for image-guided interventions. Of the several commercially available needles, bench-top testing and direct comparison of these needles have not been done to reveal their inherent echogenicity. The aims are to provide bench-top data that can be used to guide clinical applications and to promote future device research and development. METHODS: Descriptive bench-top testing and comparison of 8 commonly used EUS-FNA needles (all size 22 gauge): SonoTip Pro Control (Medi-Globe); Expect Slimline (Boston Scientific); EchoTip, EchoTip Ultra, EchoTip ProCore High Definition (Cook Medical); ClearView (Conmed); EZ Shot 2 (Olympus); and BNX (Beacon Endoscopic), and 2 new prototype needles, SonoCoat (Medi-Globe), coated by echogenic polymers made by Encapson. Blinded evaluation of standardized and unedited videos by 43 EUS endoscopists and 17 radiologists specialized in GI US examination who were unfamiliar with EUS needle devices. RESULTS: There was no significant difference in the ratings and rankings of these needles between endosonographers and radiologists. Overall, 1 prototype needle was rated as the best, ranking 10% to 40% higher than all other needles (P < .01). Among the commercially available needles, the EchoTip Ultra needle and the ClearView needle were top choices. The EZ Shot 2 needle was ranked statistically lower than other needles (30%-75% worse, P < .001). CONCLUSIONS: All FNA needles have their inherent and different echogenicities, and these differences are similarly recognized by EUS endoscopists and radiologists. Needles with polymeric coating from the entire shaft to the needle tip may offer better echogenicity.

Objectives Pancreatic ductal adenocarcinoma (PDAC) has not experienced a meaningful mortality improvement for the past few decades. Successful screening is difficult to accomplish because most PDACs present late in their natural history, and current interventions have not provided significant benefit. Our goal was to identify determinants of survival for early PDAC to help inform future screening strategies. Methods Early PDACs from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program database (2000-2010) were analyzed. We stratified by size and included carcinomas in situ (Tis). Overall cancer-specific survival was calculated. A Cox proportional hazards model was developed and the significance of key covariates for survival prediction was evaluated. Results A Kaplan-Meier plot demonstrated significant differences in survival by size at diagnosis; these survival benefits persisted after adjustment for key covariates in the Cox proportional hazards analysis. In addition, relatively weaker predictors of worse survival included older age, male sex, black race, nodal involvement, tumor location within the head of the pancreas, and no surgery or radiotherapy. Conclusions For early PDAC, we found tumor size to be the strongest predictor of survival, even after adjustment for other patient characteristics. Our findings suggest that early PDAC detection can have clinical benefit, which has positive implications for future screening strategies.

BACKGROUND: The Sendai guidelines for risk assessment of malignancy in patients with mucinous cysts lists "positive" cytology as a high-risk feature. In the current study, the authors hypothesized that a cytological threshold of high-grade atypical epithelial cells (AEC) is a more accurate predictor of malignancy. METHODS: The clinical, radiological, and cytological data of 112 patients with histologically confirmed mucinous cysts of the pancreas were reviewed. Cytology slides were blindly reviewed and cells were classified as benign, AEC, or malignant. On histology, neoplasms were grouped as benign (low-grade and moderate dysplasia) and malignant (high-grade dysplasia/carcinoma in situ and invasive carcinoma). RESULTS: There were 92 patients with an intraductal papillary mucinous neoplasm (IPMN) and 20 with a mucinous cystic neoplasm; 39 were malignant and 73 were benign (42 with low-grade dysplasia and 31 with moderate dysplasia). Only 28% (11 of 39) of the malignant cysts were cytologically malignant with a sensitivity of 29%, a specificity of 100%, and an accuracy of 75%. AEC detected 17 additional cancers (44% of all malignant cysts; 16% more than detected on the basis of "positive" cytology). By using AEC as a surgical triage threshold, the sensitivity was 72%, the specificity was 85%, and the accuracy was 80%, with similar values for small (

Background EUS-guided ablation of pancreatic cysts is a minimally invasive technique with reported short-term, CT-defined cyst resolution rates of 33% to 79%. Follow-up results of image-defined, successful pancreatic cyst ablation are not known. Objective To determine the durability of successful cyst resolution after EUS-guided ethanol lavage. Design Prospective cohort study. Setting Two tertiary-care referral hospitals in the United States. Patients This study involved 12 patients with 1-to-5-cm, unilocular, pancreatic cysts that had previously resolved after ethanol lavage. Interventions Follow-up CT after cyst resolution. Main Outcome Measurements The presence or absence of residual pancreatic cysts by CT scanning after previous successful ablation. Results In a previously reported trial, we found that CT scanning documented pancreatic cyst resolution in 12 patients (33%) after one (n = 6) or two (n = 6) ethanol lavages. These 12 cysts (median diameter 18 mm; range 10-34 mm) were located in the head/uncinate of the pancreas in 6 patients (50%) and in the body of the pancreas in 6 patients (50%). The median cyst fluid carcinoembryonic antigen (CEA) level (available in 11 patients) was 463 ng/mL (range 1.6-64,550 ng/mL; normal, 0-2.5 ng/mL). Clinical diagnoses were mucinous cystic neoplasm (MCN) in 9 patients, intraductal papillary mucinous neoplasm in 1 patient, pseudocyst in 1 patient, and serous cystadenoma (SCA) in 1 patient. Follow-up CT in 3 patients (one each of MCN, SCA, and pseudocyst) after the initial diagnosis of cyst resolution was not available. For the remaining 9 patients (75%), follow-up CT performed in a median of 26 months (range 13-39 months) after initial documentation of cyst resolution demonstrated no evidence of cyst recurrence in any patient. Limitations Loss to follow-up of some of the cohort. Conclusions Follow-up after successful EUS-guided ethanol ablation of pancreatic cysts, including suspected mucinous cysts, suggests a durable, image-defined resolution. Longer follow-up in these patients is needed before considering these patients "cured" of their disease.

Background EUS combined with endoluminal resection techniques is increasingly used to provide a definitive diagnosis of small gastric subepithelial lesions seen on standard upper endoscopy. Objective To evaluate the accuracy of EUS in diagnosing small gastric subepithelial lesions by using histology as the criterion standard. Design A retrospective study. Setting Academic tertiary care center. Patients A total of 22 patients (15 women, mean age 62.2 years) with an endoscopically resected gastric subepithelial lesion were included in this 3-year retrospective study. Main Outcome Measurements The size, echogenicity, the layer of origin, and presumptive diagnosis were determined by EUS. The diagnostic accuracy of EUS was determined by using histology as the criterion standard. Results The mean size of the 22 lesions was 13.6 mm (range 8-20 mm). An endoscopic cap band mucosectomy device was used to resect 16 (72.7%) lesions, whereas 6 (27.3%) were resected with a saline solution–assisted and snare technique. Using histology as a criterion standard, we found that the accuracy of the EUS diagnosis was 10 of 22 (45.5%). EUS alone had an accuracy rate of 30.8% and 66.7%, respectively, in the diagnosis of neoplastic and non-neoplastic lesions. Limitations A single-center, retrospective analysis. Conclusion EUS imaging had a low accuracy rate in the diagnosis of gastric subepithelial lesions, and endoscopic submucosal resection should be performed to provide a histologic diagnosis. Resection of small subepithelial lesions of 20 mm or less can be accomplished en bloc with an endoscopic cap band mucosectomy device.

Background EUS-guided FNA has the potential to provide diagnostic cytologic material from pancreatic lesions that are suspicious for malignancy. Objective To determine the operating characteristics of EUS-FNA in the diagnosis of pancreatic adenocarcinoma and pancreatic neuroendocrine neoplasms (PENs). Design Retrospective analysis of a prospectively maintained database. Setting Academic tertiary-care center. Patients This study involved 559 patients undergoing evaluation of pancreatic masses or diffuse pancreatic parenchymal abnormalities. Main Outcome Measurements Performance characteristics of EUS-FNA of pancreatic adenocarcinoma and PEN. Results From January 1997 to December 2005, 737 patients undergoing initial EUS-FNA evaluation for a pancreatic mass were identified. In the final analysis, 559 patients with 560 FNA-sampled lesions were included. Overall, 442 lesions were pancreatic adenocarcinoma, and 40 were PEN. The sensitivity of EUS-FNA in the diagnosis of pancreatic adenocarcinomas and PENs was 77% (95% CI, 72.8%-80.8%) and 68% (95% CI, 50.8%-80.9%), respectively, using strict cytologic criteria. Reclassification of atypical and suspicious cytologies as diagnostic of malignancy resulted in a sensitivity of 93%, (95% CI, 90.9%-99.7%) in adenocarcinoma and 80% (95% CI, 63.9%-90.4%) in PEN. Tumor size, tumor location, and number of needle passes did not significantly influence diagnosis, but immediate cytologic evaluation was influential. Limitations Retrospective analysis at a single center. Conclusions In a large, well-controlled study, EUS-FNA was found to be an accurate test (80%) for the detection of pancreatic adenocarcinoma by using aspiration cytology. The accuracy of the examination is significantly improved (94%) when atypical and suspicious samples are considered positive. Finally, only 2 to 3 FNA passes may be needed to achieve a good diagnostic yield.

Background Surgery for pancreatic cysts is associated with significant morbidity. A pilot study previously demonstrated the safety of EUS-guided ethanol lavage of pancreatic cysts. Objective To determine whether EUS-guided ethanol lavage would decrease pancreatic cyst size more than saline solution lavage. Design Prospective, multicenter, randomized trial. Setting Two tertiary referral hospitals in the United States. Patients Patients referred for EUS with a 1- to 5-cm unilocular pancreatic cyst were randomized to blinded ethanol or saline solution lavage. Three months later, the cyst diameter was remeasured by EUS, and a second unblinded ethanol lavage was performed. Interventions EUS-guided pancreatic cyst lavage. Main Outcome Measurements Cyst ablation based on size changes from follow-up EUS, CT, and histology of resected specimens. Results Of 58 patients randomized, 16 were excluded and 42 underwent initial ethanol (n = 25) or saline solution (n = 17) lavage. Ethanol lavage resulted in a greater mean percentage of decrease in cyst surface area (−42.9; 95% CI, −58.4 to −27.4) compared with saline solution alone (–11.4; 95% CI, −25.0 to 2.2; P = .009). Nineteen (76.0%) of 25 and 14 (82.3%) of 17 patients randomized to ethanol and saline solution, respectively, underwent a second ethanol lavage. A follow-up CT scan demonstrated resolution in 12 (33.3%) of 36 cysts. Histology of 4 resected cysts demonstrated epithelial ablation ranging from 0% (saline solution alone) to 50% to 100% (1 or 2 ethanol lavages). Complication rates were similar in all groups. Limitation Short-term follow-up. Conclusions EUS-guided ethanol lavage results in a greater decrease in pancreatic cyst size compared with saline solution lavage with a similar safety profile. Overall CT-defined complete pancreatic cyst ablation was 33.3%. (This study is registered at ClinicalTrials.gov, identifier NCT00233038.)

Cryoenergy is being increasingly used for atrial fibrillation (AF) ablation, but the thermal effect of cryoenergy on the esophagus remains undefined.This study examines the esophageal effects of cryoenergy used during AF ablation.Catheter ablation was performed using a cryoballoon catheter in 67 AF patients (Cryoballoon group), and a spot cryocatheter to complete irrigated radiofrequency lesion sets at segments in close proximity to the esophagus in 7 AF patients (Cryo-Focal group). A temperature probe monitored the luminal esophageal temperature (LET) in all patients; LET changes did not guide therapy. Post-procedural endoscopy was performed on 35 of 67 (52%) Cryoballoon and all Cryo-Focal patients.Significant LET decreases (1 degrees C) occurred in 62 of 67 (93%) Cryoballoon patients. LET continued to decrease after termination of cryoablation before recovering to normal. Temperature decreases were more pronounced during ablation at the inferior (3.1 degrees C) than superior pulmonary veins (1.5 degrees C); the lowest observed temperature was 0 degrees C. Post-procedural endoscopy showed esophageal ulcerations in 6 of 35 (17%) patients. There were no atrial-esophageal fistulas, and all ulcers had healed on follow-up endoscopy. Patients with and without ulceration differed with respect to mean LET nadir, cumulative LET decrease, and number of LETs30 degrees C. In the Cryo-Focal group, 6 +/- 2 spot cryolesions per patient resulted in 1.3 +/- 1 LET decreases per patient, and an absolute nadir of 32.5 degrees C.Cryoballoon ablation can cause significant LET decreases, resulting in reversible esophageal ulcerations in 17% of patients. No ulcerations occurred with adjunctive spot cryoablation at regions near the esophagus during radiofrequency ablation procedures.

BACKGROUND: The management of patients with pancreatic cysts is based on the preoperative distinction of nonmucinous and mucinous cysts in general and of benign and malignant cysts in particular. An accurate diagnosis is challenging, because endoscopic ultrasound (EUS) and cyst fluid analysis for carcinoembryonic antigen (CEA) and cytology have low sensitivity and specificity. Currently, molecular analysis is a commercially available test that promises an accurate diagnosis. The objective of the current study was to correlate a commercially provided molecular diagnosis (MDx) with a clinical consensus diagnosis (CCD) in the general categories of malignant, benign mucinous, and benign nonmucinous pancreatic cysts. METHODS: Pancreatic cysts that had aspirated fluid submitted for a commercially available molecular test (PathFinderTG) were reviewed. The CCD, defined by histology, malignant cytology, or 2 concordant tests (such as EUS, cytology, or CEA � 192 ng/mL for mucinous cysts), was categorized as malignant, benign mucinous, or benign nonmucinous cyst in 35 patients. Their MDx, based on the PathFinderTG report, including analysis of k-ras mutation, loss of heterozygosity, and quantity/quality of DNA, also was classified as malignant, benign mucinous, or benign nonmucinous cyst. These 2 diagnoses were compared and correlated. RESULTS: The concordance between CCD and MDx was 5 of 6 (83%), 13 of 15 (87%), and 13 of 14 (93%), respectively, for malignant, benign mucinous, and benign nonmucinous cysts, with an overall Cohen kappa statistic of 0.816. The sensitivity, specificity, and positive predictive value of the MDx were 83%, 100%, and 100%, respectively, for a malignant cyst and 86%, 93%, and 95%, respectively for a benign mucinous cyst. CONCLUSIONS: Molecular analysis of pancreatic cyst fluid adds diagnostic value to the preoperative diagnosis with high sensitivity, specificity, and positive predictive value for the diagnosis of malignant and benign mucinous pancreatic cysts. Cancer (Cancer Cytopathol) 2009;117:217–27. V C 2009 American Cancer

Background EUS is increasingly used in the diagnosis of chronic pancreatitis (CP). A number of publications in this field have used different EUS terminology, features, and criteria for CP, making it difficult to reproduce their findings and apply them in clinical practice. Moreover, traditional criteria such as the Cambridge classification for CP are arguably outdated and have lost their relevance. Objective Our purpose was to establish consensus-based criteria for EUS features of CP. Design Consensus study. Main Outcome Measurements Thirty-two internationally recognized endosonographers anonymously voted on terminology of EUS features, rank order, and category (major vs minor criteria). Consensus was defined as greater than two thirds agreement among participants. Results Major criteria for CP were (1) hyperechoic foci with shadowing and main pancreatic duct (PD) calculi and (2) lobularity with honeycombing. Minor criteria for CP were cysts, dilated ducts ≥3.5 mm, irregular PD contour, dilated side branches ≥1 mm, hyperechoic duct wall, strands, nonshadowing hyperechoic foci, and lobularity with noncontiguous lobules. Limitation Lack of broadly accepted reference standard. Conclusion In a complex disease such as CP that has no universally accepted reference standard, an EUS-based criterion for diagnosis can be determined by expert consensus opinion and the existing body of evidence. Here we present the new "Rosemont criteria" for the EUS diagnosis of CP.

Pancreatic cysts encompass a wide spectrum of morphologic and histopathologic types. 1 Broadly, they are classified into 2 main types, mucinous and nonmucinous, which differ in natural history and clinical characteristics. The nonmucinous lesions include serous cystadenomas and cystic endocrine tumors. Mucinous cystic lesions may be benign, borderline, or malignant in nature and include benign mucinous cystic neoplasms and intraductal papillary mucinous neoplasms (IPMN). Mucinous cysts are unique in their predisposition toward malignant transformation. The traditional therapy of cystic neoplasms, particularly mucinous lesions, has been surgical resection. There is now evidence to support clinical monitoring of low-risk mucinous lesions, such as side-branch IPMN lesions or in those patients who are poor surgical candidates. Although small, incidental simple pancreatic cysts 2 cm or smaller may enlarge over a prolonged time. Morbidity or mortality because of these small simple cysts is extremely unlikely, and observation appears to be a safe management option. 2 Sahani et al 3 reported on 86 patients with cystic lesions less than 3 cm in diameter that were resected after EUS-guided FNA. The majority (n = 75) of small pancreatic cysts were benign. Thirty-six cysts were unilocular, and virtually all of these (n = 35) were benign. The presence of septa was associated with borderline or "in situ" malignancy in 20% of cases (10 of 50). Low-risk IPMNs in the elderly are probably best managed with periodic imaging. 4 A report of a recent task force also recommended periodic imaging for cysts less than 3 cm in diameter.5 A general schema for management of pancreatic-cyst neoplasm is shown in Table 1. As an alternative to surgical resection or monitoring, EUS-guided ethanol ablation of pancreatic-cystic lesions may have a role in carefully selected patients. This section of the EUS 2008 Working Group Proceedings will evaluate the current role of EUS-guided ethanol ablation in the management of pancreatic cyst neoplasms and provide recommendations for future research in this area.

The objective of this study was to evaluate the efficacy of EUS-guided CPN for pain relief in patients with chronic pancreatitis and pancreatic cancer. An initial search identified 1,439 reference articles, of which 130 relevant articles were selected and reviewed. Data was extracted from 8 studies (N = 283) for EUS-guided CPN for pain due to pancreatic cancer and nine studies for chronic pancreatitis (N = 376) which met the inclusion criteria. With EUS-guided CPN, the pooled proportion of patients with pancreatic cancer that showed pain relief was 80.12% (95% CI = 74.47-85.22). In patients with pain due to chronic pancreatitis, EUS-guided CPN provided pain relief in 59.45% (95% CI = 54.51-64.30). In conclusion, EUS-guided CPN offers a safe alternative technique for pain relief in patients with chronic pancreatitis or pancreatic cancer. In patients with pain due to chronic pancreatitis, better techniques or injected materials are needed to improve the response.

Autoimmune pancreatitis (AIP) shows a unique spectrum of histologic features and commonly presents with an abundant IgG4-positive (IgG4+) plasma cell infiltration. However, differentiating AIP from other mass lesions, particularly pancreatic cancer [invasive ductal carcinoma (IDC)] can be clinically challenging. In this study, we evaluated the validity of IgG4 and IgG immunohistochemistry of ampullary and periampullary tissue for the diagnosis of AIP. Our study group consisted of 14 resected AIP cases with appropriate ampullary sections. Superficial ampullary tissue and "shouldering" duodenal mucosa were evaluated for several histologic variables. Immunohistochemistry for IgG4 and IgG was performed. The number of IgG4 and IgG-positive plasma cells was counted and an IgG4+ to IgG+ plasma cells ratio (IgG4/IgG ratio) was evaluated. A control cohort was composed of IDC (n=30) and chronic pancreatitis (CP) (n=29). Although an overlap was present between the groups, the overall inflammation and number of plasma cells in and around the ampulla was significantly increased in AIP compared with CP and IDC. Furthermore, although there was some overlap in the crude number of IgG4+ plasma cells of the ampullary and duodenal tissue between AIP, IDC, and CP, an IgG4/IgG ratio, especially of the ampulla, seems diagnostically useful in differentiating AIP from other "mass forming" lesions. When a cut-off of 0.10 was applied, the diagnostic sensitivity and specificity of the ampullary IgG4/IgG ratio was 86% and 95%, respectively. In conclusion, evaluation of ampullary histology and IgG4/IgG ratio might be proven beneficial in discriminating AIP from other mass forming pancreatic lesions.

Purpose of review To review the current state of natural orifice surgery and examine the concerns, challenges, and opportunities presented by translumenal research. Recent findings Translumenal endoscopic procedures have been the focus of extensive research. Researchers have reported natural orifice translumenal endoscopic surgery in a swine model in several areas involving the abdominal cavity. Diagnostic procedures have included endoscopic peritoneoscopy, liver biopsy, lymphadenectomy, and abdominal exploration. Several gynecologic procedures including tubal ligation, oophorectomy, and partial hysterectomy have been demonstrated using current commercial endoscopes. Gastrointestinal surgical procedures, including gastrojejunostomy, cholecystectomy, splenectomy, and distal pancreatectomy have been performed successfully via transgastric and/or transcolonic approaches. There have been no studies of natural orifice translumenal endoscopic surgery procedures published in humans. While fundamental questions about the emerging technology have not been scrutinized, limitations of the large animal model will pose a challenge to the development of large randomized trials. Summary While natural orifice translumenal endoscopic surgery may represent a paradigm shift and may offer significant benefits to patients, rigorous testing of the techniques is lacking and current data have been drawn from case series.